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  • CLASSES

    Adult Multivitamins with Minerals and Iron
    Iron Combination Supplements
    Lactation Multivitamins with Minerals
    Prenatal Multivitamins with Minerals and Iron
    Prenatal Multivitamins with Minerals without Iron
    Prenatal Multivitamins Without Minerals
    Prenatal Supplemental Dietary Agents for Morning Sickness

    BOXED WARNING

    Accidental exposure, children, infants

    Prenatal multivitamins and minerals preparations are not intended for ingestion by pre-pubescent children or adolescent males. The supplement is intended for females of child-bearing potential only. Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children and infants under 6 years of age. Keep this product out of reach of children and infants. In case of accidental exposure via ingested overdose, call a doctor or poison control center immediately.

    DEA CLASS

    Rx, OTC

    DESCRIPTION

    Prenatal multivitamins and minerals consist of a variety of vitamins and minerals intended to be taken before conception, during pregnancy, and after birth in lactating and non-lactating women
    Many vitamins and minerals, such as folic acid, iron, and calcium, help ensure proper fetal growth and development
    Folic acid is especially vital in the prevention of neural tube defects, particularly in the first trimester; use prior to conception may help with early nausea in pregnancy

    COMMON BRAND NAMES

    A-Free Prenatal, B-Nexa, BP FoliNatal Plus B, BP MultiNatal Plus, BP MultiNatal Plus Chewable, Brainstrong, Calcium PNV, CareNatal DHA, Cavan One Omega, Cavan-EC SOD DHA, Centrum Specialist Prenatal, CitraNatal 90 DHA, CitraNatal Assure, CitraNatal B-Calm, CitraNatal DHA, CitraNatal Harmony, CitraNatal Rx, Classic Prenatal, ComBi Rx, Complete Natal DHA, CompleteNate, Concept DHA, Concept OB, CoreNate-DHA, Dothelle, Duet DHA, Duet DHA 400, Duet DHA 430ec, Duet DHA Balanced, Duet DHA EC, Duet DHA Ferrazone, EC Omega-3, Elite OB, Elite-OB 400, Ferrocite Plus, Focalgin 90 DHA, Focalgin CA, Folbecal, Folcal DHA, Folcaps Care One, Folcaps Omega 3, Folet DHA with Quatrefolic, Folet One with Quatrefolic, Folivane OB, Gesticare DHA, HemeNatal OB, HemeNatal OB + DHA, Hemocyte Plus, iNatal Advance, iNatal Ultra, Infanate DHA, Infanate Plus, Kolnatal, MACNATAL CN DHA, Mom's Choice Rx, MyNatal OB Prenatal, NataChew, Natal-V RX, NatalCare Plus, NATALVIRT CA, NataTab FA, Natatab Rx, Natelle One, Natelle Prefer, Neevo DHA, Nestabs, Nestabs ABC, Nestabs DHA, Nestabs FA, Nestabs Rx, NewGen, Nexa Plus, Nexa Select, Niva-Plus, NovaNatal, Nutri-Tab OB, Nutri-Tab OB + DHA, Nutrinate, NutriSpire, O-Cal F.A., OB Complete, OB Complete 400, OB Complete Gold, OB Complete One, OB Complete Petite, OB Complete with DHA, OB-Natal One, Obstetrix EC Prenatal, Obstetrix-100, Obtrex, Obtrex DHA, One-A-Day Women's, One-A-Day Women's Prenatal, Paire OB Tablet Plus DHA, PNV OB + DHA, PNV Prenatal Plus Multivitamin, PNV Tabs 29-1, PNV-DHA, PNV-DHA + Docusate, PNV-Omega, PNV-Select, PNV-Total with DHA, PNV-VP-U, PNV: Ferrous Fumerate/Docusate/Folic Acid, PR Natal 400, PR Natal 400ec, PR Natal 430, PR Natal 430ec, PreCare, PreferaOB, PreferaOB + DHA, Premesis Rx, Prena1, Prena1 PEARL, Prena1 Plus, Prena1 True, Prenaissance, Prenaissance Balance, Prenaissance Harmony DHA, Prenaissance Next, Prenaissance Next-B Prenatal, Prenaissance Plus, PrenaPlus, Prenat with Quatrefolic, PreNata Multivitamin with Iron, Prenatabs FA, Prenatabs OBN, Prenatabs RX, Prenatal, Prenatal 19, Prenatal AD, Prenatal Low Iron, Prenatal Multivitamin + DHA 2, Prenatal Optima Advance, Prenatal Plus, Prenatal Plus Iron, Prenatal Plus Low Iron, Prenatal U, Prenatal Vitamin, PreNatal Vitamins Plus, Prenate Advance, Prenate AM with Quatrefolic, Prenate DHA, Prenate Elite, Prenate Enhance with Quatrefolic, Prenate Essential, Prenate Mini, Prenate Pixie, PreNate Plus, Prenate Restore with Quatrefolic, Prenate Star, Prenavite, Prenavite Protein, PreNexa, PrePLUS, PreTAB, Previte Rx, PrimaCare ONE, Provida OB, PruEt DHAec, PureFe OB Plus, RE Prenatal, RE-Nata 29, RE-Nata 29 OB, Right Step, Rulavite, Se-Care, Se-Care Conceive, Se-Natal 19, Se-Natal 19 Chewable, Se-Natal ONE, Se-Tan Plus, Select-OB + DHA, SetonET, SetonET-EC DHA, StrongStart, Stuart One, Stuart Prenatal, Stuart Prenatal + DHA, Tandem Plus, Taron Prenatal with DHA, Taron-C DHA, Taron-Prex Prenatal with DHA, Thera Natal Complete, Thera Natal Core Nutrition, Thera Natal Lactation Complete, Thera Natal LACTATION ONE, Thera Natal ONE, Thrivite, TL Folate, TL-Select, TriAdvance, TriCare, Trimesis Rx, Trinatal GT, Trinate, Triveen-Duo DHA, Trust Natal DHA, UltimateCare ONE, UltimateCare ONE NF, VemaVite-PRx 2, Venatal-FA, Vinacal B, Vinate AZ Extra, Vinate C, Vinate Calcium, Vinate Care, Vinate DHA, Vinate GT, Vinate IC, Vinate II, Vinate M Low Iron, Vinate One, Vinate PN, Vinate Ultra, Virt-Advance, Virt-C DHA, Virt-PN, Virt-PN DHA, Virt-PN Plus, Virt-Select, Virt-Vite GT, vita True, Vitafol FE, Vitafol PN, Vitafol Ultra, Vitafol-OB, Vitafol-OB and DHA, Vitafol-One, VitaMed MD Plus Rx, VitaMedMD One Rx with Quatrefolic, vitaMedMD RediChew Rx, vitaPearl Prenatal, VitaSpire, VIVA DHA, Vol-Plus, Vol-Tab Rx, VP CH Ultra, VP-CH Plus, VP-CH-PNV, VP-GGR-B6 Prenatal, VP-PNV-DHA, Zatean-CH, Zatean-Pn, Zatean-Pn DHA, Zatean-Pn Plus, Zingiber

    HOW SUPPLIED

    Ascorbic Acid (Vitamin C), Beta-Carotene (Vitamin A), Biotin, Calcium, Cholecalciferol, Copper, Cyanocobalamin (Vitamin B12), Dl-Alpha Tocopheryl Acetate (Vitamin E), Folic Acid (Vitamin B9), Iodine, Iron, L-methylfolate, Magnesium, Niacinamide, Pantothenic Acid (Vitamin B5), Pyridoxine (Vitamin B6), Riboflavin (Vitamin B2), Thiamine (Vitamin B1), Zinc/Ascorbic Acid (Vitamin C), Beta-Carotene (Vitamin A), Biotin, Calcium, Cholecalciferol, Copper, Cyanocobalamin (Vitamin B12), Dl-Alpha Tocopheryl Acetate (Vitamin E), Folic Acid (Vitamin B9), Iodine, Iron, L-methylfolate, Magnesium, Niacinamide, Pantothenic Acid (Vitamin B5), Pyridoxine (Vitamin B6), Riboflavin (Vitamin B2), Thiamine Mononitrate (Vitamin B1), Zinc/PNV-Select/Prenate AM with Quatrefolic/Prenate Elite/Virt-PN/Zatean-Pn Oral Tab
    Ascorbic Acid (Vitamin C), Calcium, Cholecalciferol, Cyanocobalamin (Vitamin B12), D-Alpha Tocopherol (Vitamin E) (Natural), Docosahexaenoic Acid (DHA), Folic Acid (Vitamin B9), Iron, L-methylfolate, Magnesium, Pyridoxine (Vitamin B6)/PNV-DHA/Zatean-Pn DHA Oral Cap

    DOSAGE & INDICATIONS

    For nutritional supplementation of females of child-bearing potential during pre-conception, pregnancy or lactation.
    Oral dosage
    Adult females

    Follow directions for specific product chosen, as per its package label. Usual dose for most products is 1 tablet PO once per day. Use before conception (even just 1 month before fertilization) appears to have benefits, including the reduction of nausea/vomiting in early pregnancy per the American College of Gynecology and Obstetrics (ACOG).

    MAXIMUM DOSAGE

    Adults

    1 tablet or dose, as defined on the product label, PO per day.

    Geriatric

    Not indicated.

    Adolescents

    1 tablet or dose, as defined on the product label, PO per day.

    Children

    Safety and efficacy have not been established.

    Infants

    Do not use.

    Neonates

    Do not use.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    All products: Administer orally. If GI irritation occurs, give with meals.
    Chewable tablets: Chew thoroughly before swallowing.
    Multi-item products: Some prenatal supplements contain packs of 1 or more dose forms, containing the various vitamin or supplement components for the daily dose. The components are intended to be ingested together. Follow the specific package directions.

    STORAGE

    Generic:
    - Avoid temperatures above 86 degrees F
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Active FE:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Active OB:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Advanced-RF NatalCare:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    A-Free Prenatal:
    - Storage information not provided in labeling
    Aminate Fe:
    - Avoid exposure to heat
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    B-Nexa:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    BP FoliNatal Plus B:
    - Store at room temperature (between 59 to 86 degrees F)
    BP MultiNatal Plus :
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    BP MultiNatal Plus Chewable:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Brainstrong:
    - Avoid excessive heat (above 104 degrees F)
    - Avoid excessive humidity
    - Protect from direct sunlight
    Bright Beginnings Prenatal:
    - Avoid excessive heat (above 104 degrees F)
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Calcium PNV:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Cal-Nate :
    - Store at room temperature (between 59 to 86 degrees F)
    CareNatal DHA:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Cavan One Omega :
    - Store at room temperature (between 59 to 86 degrees F)
    Cavan-Alpha :
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Cavan-EC SOD DHA:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Cenogen Ultra:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a dry place
    Centrum Specialist Prenatal:
    - Avoid excessive heat (above 104 degrees F)
    - Store at room temperature (between 59 to 86 degrees F)
    Choice-OB + DHA:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    CitraNatal 90 DHA:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    CitraNatal Assure:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    CitraNatal B-Calm:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    CitraNatal DHA:
    - Brief exposure up to 104 degrees F does not adversely affect product
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    CitraNatal Harmony:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    CitraNatal Rx:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Classic Prenatal:
    - Store at room temperature (between 59 to 86 degrees F)
    ComBi Rx :
    - Store at room temperature (between 59 to 86 degrees F)
    Complete Natal DHA:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    CompleteNate:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Complete-RF :
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Concept DHA:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a cool, dry place
    Concept OB:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a cool, dry place
    CoreNate-DHA:
    - Store at room temperature (between 59 to 86 degrees F)
    Dothelle:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Duet:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Duet Chewable:
    - Avoid exposure to heat
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Duet DHA:
    - Avoid excessive heat (above 104 degrees F)
    - Avoid excessive humidity
    - Protect from freezing
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Duet DHA 400:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from freezing
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Duet DHA 430ec:
    - Avoid excessive heat (above 104 degrees F)
    - Avoid excessive humidity
    - Protect from freezing
    - Protect from moisture
    - Store between 59 to 77 degrees F, excursions permitted to 59 to 86 degrees F
    Duet DHA Balanced:
    - Avoid excessive heat (above 104 degrees F)
    - Avoid excessive humidity
    - Protect from freezing
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Duet DHA Complete:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Duet DHA Complete Gluten Free:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Duet DHA EC:
    - Avoid excessive heat (above 104 degrees F)
    - Avoid excessive humidity
    - Protect from freezing
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Duet DHA Ferrazone, EC Omega-3:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Elite OB :
    - Avoid excessive heat (above 104 degrees F)
    - Store at room temperature (between 59 to 86 degrees F)
    Elite-OB 400:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Extra-Virt Plus:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Ferrocite Plus:
    - Store between 68 to 77 degrees F
    - Store in a cool, dry place
    Focalgin 90 DHA:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Focalgin CA:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Folbecal :
    - Store at room temperature (between 59 to 86 degrees F)
    Folcal DHA :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Folcaps Care One:
    - Store at room temperature (between 59 to 86 degrees F)
    Folcaps Omega 3 :
    - Store at room temperature (between 59 to 86 degrees F)
    Folet DHA with Quatrefolic:
    - Avoid excessive heat (above 104 degrees F)
    - Avoid extreme temperatures
    - Protect from freezing
    - Store at room temperature (between 59 to 86 degrees F)
    Folet One with Quatrefolic:
    - Avoid excessive heat (above 104 degrees F)
    - Avoid extreme temperatures
    - Protect from freezing
    - Store at room temperature (between 59 to 86 degrees F)
    Folivane OB:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a cool, dry place
    Gesticare:
    - Store at room temperature (between 59 to 86 degrees F)
    Gesticare DHA :
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Gesticare DHA Delayed-Release :
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    HemeNatal OB:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    HemeNatal OB + DHA:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Hemocyte Plus:
    - Store between 68 to 77 degrees F
    - Store in a cool, dry place
    ICAR Prenatal Rx:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    iNatal Advance :
    - Store at room temperature (between 59 to 86 degrees F)
    iNatal GT:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    iNatal Ultra:
    - Store at room temperature (between 59 to 86 degrees F)
    Infanate DHA :
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Infanate Plus:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Kolnatal :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in a cool, dry place
    Lactocal-F:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Levomefolate PNV:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    MACNATAL CN DHA:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Marnatal-F :
    - Store at room temperature (between 59 to 86 degrees F)
    Mission Prenatal :
    - Store at room temperature (between 59 to 86 degrees F)
    Mission Prenatal F.A.:
    - Store at room temperature (between 59 to 86 degrees F)
    Mission Prenatal H.P.:
    - Store at room temperature (between 59 to 86 degrees F)
    Mom's Choice Rx:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from freezing
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    MyNatal OB Prenatal:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Nata Komplete:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    NataChew:
    - Store at room temperature (between 59 to 86 degrees F)
    Natafort:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    NatalCare GlossTabs:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    NatalCare PIC :
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    NatalCare PIC Forte :
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    NatalCare Plus :
    - Store at room temperature (between 59 to 86 degrees F)
    NatalCare Rx:
    - Avoid exposure to heat
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    NatalCare Three:
    - Avoid exposure to heat
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Natal-V RX:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    NATALVIRT 90 DHA:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    NATALVIRT CA:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    NataTab CFe:
    - Store at room temperature (between 59 to 86 degrees F)
    NataTab FA:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Natatab Rx :
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Natelle:
    - Store at room temperature (between 59 to 86 degrees F)
    Natelle One:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Natelle Prefer:
    - Store at room temperature (between 59 to 86 degrees F)
    Natelle-ez:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Neevo:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in original container
    Neevo DHA :
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Nestabs:
    - Store at room temperature (between 59 to 86 degrees F)
    Nestabs ABC:
    - Store at room temperature (between 59 to 86 degrees F)
    Nestabs CBF:
    - Storage information not available
    Nestabs DHA:
    - Store at room temperature (between 59 to 86 degrees F)
    Nestabs FA:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Nestabs Rx:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    New Advanced Formula Prenatal Z :
    - Storage information not available
    NewGen:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Nexa Plus:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Nexa Select:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Niva-Plus:
    - Store at room temperature (between 59 to 86 degrees F)
    NovaNatal:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Nu-Natal :
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    NutraCare :
    - Storage information not available
    Nutrinate :
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    NutriSpire:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Nutri-Tab OB:
    - Store at room temperature (between 59 to 86 degrees F)
    Nutri-Tab OB + DHA:
    - Store at room temperature (between 59 to 86 degrees F)
    OB Complete:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    OB Complete 400:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    OB Complete Gold:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    OB Complete One :
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    OB Complete Petite:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    OB Complete with DHA :
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Obegyn:
    - Storage information not available
    OB-Natal One:
    - Store at room temperature (between 59 to 86 degrees F)
    Obstetrix EC Prenatal:
    - Store at room temperature (between 59 to 86 degrees F)
    Obstetrix-100 :
    - Storage information not provided in labeling
    Obtrex:
    - Store at room temperature (between 59 to 86 degrees F)
    Obtrex DHA:
    - Store at room temperature (between 59 to 86 degrees F)
    O-Cal F.A. :
    - Storage information not listed
    O-Cal Prenatal :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    One-A-Day Women's:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a dry place
    One-A-Day Women's Prenatal:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a dry place
    Paire OB Tablet Plus DHA:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from freezing
    - Store in a cool, dry place
    PNV OB + DHA:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in a cool, dry place
    PNV Prenatal Plus Multivitamin:
    - Store at room temperature (between 59 to 86 degrees F)
    PNV Tabs 29-1:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    PNV: Ferrous Fumerate/Docusate/Folic Acid:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from freezing
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    PNV-DHA :
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    PNV-DHA + Docusate:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    PNV-DHA Plus :
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    PNV-First:
    - Avoid excessive heat (above 104 degrees F)
    - Store at room temperature (between 59 to 86 degrees F)
    PNV-OB with DHA:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    PNV-Omega:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    PNV-Select:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    PNV-Total with DHA :
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    PNV-VP-U:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    PR Natal 400:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    PR Natal 400ec:
    - Avoid exposure to heat
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    PR Natal 430:
    - Protect from extreme heat
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    PR Natal 430ec:
    - Protect from extreme heat
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    PreCare:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    PreferaOB:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    PreferaOB + DHA:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from freezing
    - Store in a cool, dry place
    PreferaOB One:
    - Protect from light
    - Store and dispense in original container
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Premesis Rx:
    - Store at room temperature (between 59 to 86 degrees F)
    Prena1 :
    - Store in a cool, dry place
    Prena1 PEARL:
    - Store in a cool, dry place
    Prena1 Plus:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Prena1 True:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    PrenaCare:
    - Store at room temperature (between 59 to 86 degrees F)
    Prenafirst:
    - Storage information not available
    Prenaissance:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Prenaissance 90 DHA:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Prenaissance Balance:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Prenaissance DHA:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Prenaissance Harmony DHA:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Prenaissance Next:
    - Protect from extreme heat
    - Protect from light
    - Store at room temperature (between 59 to 86 degrees F)
    Prenaissance Next-B Prenatal:
    - Protect from extreme heat
    - Protect from light
    - Store at room temperature (between 59 to 86 degrees F)
    Prenaissance Plus :
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Prenaissance Promise:
    - Store between 59 to 77 degrees F, excursions permitted to 59 to 86 degrees F
    PrenaPlus:
    - Store at room temperature (between 59 to 86 degrees F)
    Prenat with Quatrefolic:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    PreNata Multivitamin with Iron:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Prenatabs CBF:
    - Storage information not available
    Prenatabs FA:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Prenatabs OBN:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Prenatabs RX:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Prenatal:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Prenatal 19:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from freezing
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Prenatal AD:
    - Store at room temperature (between 59 to 86 degrees F)
    Prenatal Formula 3:
    - Storage information not available
    Prenatal H:
    - Storage information not available
    Prenatal Low Iron:
    - Store at room temperature (between 59 to 86 degrees F)
    Prenatal MR 90 Fe:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Prenatal MTR with Selenium:
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Prenatal Multivitamin + DHA 2:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from freezing
    - Store in a cool, dry place
    Prenatal Plus:
    - Store at room temperature (between 59 to 86 degrees F)
    Prenatal Plus Iron:
    - Store at room temperature (between 59 to 86 degrees F)
    Prenatal Plus Low Iron:
    - Store at room temperature (between 59 to 86 degrees F)
    Prenatal Vitamin :
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    PreNatal Vitamins Plus :
    - Store at room temperature (between 59 to 86 degrees F)
    Prenate Advance:
    - Store at room temperature (between 59 to 86 degrees F)
    Prenate AM with Quatrefolic:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Prenate DHA:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Prenate Elite:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Prenate Enhance with Quatrefolic:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Prenate Essential :
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Prenate GT:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Prenate Mini:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Prenate Pixie:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    PreNate Plus:
    - Store at room temperature (between 59 to 86 degrees F)
    Prenate Restore with Quatrefolic:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Prenate Star:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Prenate Ultra:
    - Store at room temperature (between 59 to 86 degrees F)
    Prenavite :
    - Store in a cool, dry place
    Prenavite Protein :
    - Store at room temperature (between 59 to 86 degrees F)
    PreNexa:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    PreNexa Premier :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    PrePLUS:
    - Store at room temperature (between 59 to 86 degrees F)
    PreQue:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    PreTAB:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Previte Rx :
    - Store at room temperature (between 59 to 86 degrees F)
    PrimaCare:
    - Store at room temperature (between 59 to 86 degrees F)
    PrimaCare Advantage:
    - Store at room temperature (between 59 to 86 degrees F)
    PrimaCare ONE:
    - Store at room temperature (between 59 to 86 degrees F)
    Provida DHA:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a cool, dry place
    Provida OB:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a cool, dry place
    PruEt DHAec:
    - Protect from extreme heat
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    PureFe OB Plus :
    - Store between 68 to 77 degrees F
    - Store in a cool, dry place
    RE Prenatal:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Reaphrim:
    - Avoid excessive heat (above 104 degrees F)
    - Store at room temperature (between 59 to 86 degrees F)
    RE-Nata 29:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    RE-Nata 29 OB:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Right Step:
    - Protect from light
    - Store in a cool, dry place
    Rovin-Nv DHA:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Rulavite:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Se-Care:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Se-Care Conceive:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Select-OB:
    - Avoid excessive heat (above 104 degrees F)
    - Store at room temperature (between 59 to 86 degrees F)
    Select-OB + DHA:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Se-Natal 19 :
    - Avoid excessive heat (above 104 degrees F)
    - Protect from freezing
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Se-Natal 19 Chewable:
    - Avoid excessive heat (above 104 degrees F)
    - Do not freeze
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Se-Natal ONE:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Se-Tan DHA:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a cool, dry place
    Se-Tan Plus:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a cool, dry place
    SetonET:
    - Protect from extreme heat
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    SetonET-EC DHA:
    - Protect from extreme heat
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    StrongStart:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from freezing
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Strongstart Chewable:
    - Storage information not available
    StrongStart Chewable Tablet:
    - Storage information not available
    Stuart One:
    - Store at room temperature (between 59 to 86 degrees F)
    Stuart Prenatal:
    - Store in a cool, dry place
    Stuart Prenatal + DHA:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Stuartnatal Plus 3:
    - Storage information not available
    Tandem DHA:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a cool, dry place
    Tandem OB:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a dry place
    Tandem Plus:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a cool, dry place
    Taron Prenatal with DHA:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Taron-BC:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Taron-C DHA:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a cool, dry place
    Taron-Prex Prenatal with DHA:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Thera Natal Complete:
    - Protect from extreme heat
    - Protect from moisture
    Thera Natal Core Nutrition:
    - Avoid exposure to heat
    Thera Natal Lactation Complete:
    - Avoid exposure to heat
    - Protect from moisture
    Thera Natal LACTATION ONE:
    - Avoid exposure to heat
    - Protect from moisture
    Thera Natal Lactation Support:
    - Avoid exposure to heat
    - Protect from moisture
    Thera Natal ONE:
    - Avoid exposure to heat
    - Protect from moisture
    Thrivite:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    TL Folate:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    TL-Select :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    TL-Select DHA:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    TriAdvance:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    TriCare:
    - Store at room temperature (between 59 to 86 degrees F)
    TriCare Prenatal DHA ONE :
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Trimesis Rx:
    - Store at room temperature (between 59 to 86 degrees F)
    Trinatal GT:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Trinatal Rx 1 :
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Trinate :
    - Storage information not available
    Triveen-Duo DHA:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Triveen-PRx RNF:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Triveen-Ten:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Trust Natal DHA:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    UltimateCare ONE:
    - Store at room temperature (between 59 to 86 degrees F)
    UltimateCare ONE NF:
    - Store at room temperature (between 59 to 86 degrees F)
    Ultra NatalCare :
    - Store at room temperature (between 59 to 86 degrees F)
    VemaVite-PRx 2:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Vena-Bal DHA:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Venatal-FA:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Vinacal:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Vinacal B:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Vinate 90:
    - Storage information not provided in labeling
    Vinate AZ :
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Vinate AZ Extra:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Vinate C :
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Vinate Calcium:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Vinate Care:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Vinate DHA:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Vinate GT:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Vinate IC :
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Vinate II:
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Vinate M Low Iron:
    - Storage information not provided in labeling
    Vinate One:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Vinate PN:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Vinate Ultra:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Virt-Advance:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Virt-C DHA:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Virt-Care One:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Virt-Nate:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Virt-PN:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Virt-PN DHA:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Virt-PN Plus:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    VirtPrex:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Virt-Select:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Virt-Vite GT:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    vita True:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Vitafol FE:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Vitafol PN:
    - Avoid excessive heat (above 104 degrees F)
    - Store at room temperature (between 59 to 86 degrees F)
    Vitafol Ultra:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Vitafol-OB + DHA:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Vitafol-OB and DHA:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in a cool, dry place
    Vitafol-One :
    - Avoid excessive heat (above 104 degrees F)
    - Store at room temperature (between 59 to 86 degrees F)
    Vitafol-Plus:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    VitaMed MD Plus Rx :
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    VitaMedMD One Rx with Quatrefolic:
    - Store in a cool, dry place
    vitaMedMD RediChew Rx:
    - Store in a cool, dry place
    VitaMedMD RediChew Rx with Quatrefolic:
    - Store in a cool, dry place
    vitaPearl Prenatal:
    - Store in a cool, dry place
    VitaSpire:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Viva CT:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    VIVA DHA:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Vol-Plus:
    - Store at room temperature (between 59 to 86 degrees F)
    Vol-Tab Rx:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    VP CH Ultra:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    VP-CH Plus:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    VP-CH-PNV:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    VP-GGR-B6 Prenatal:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    VP-HEME OB:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    VP-HEME OB+ DHA:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    VP-HEME One:
    - Protect from light
    - Store and dispense in original container
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    VP-PNV-DHA:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Zatean-CH:
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Zatean-Pn:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Zatean-Pn DHA:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Zatean-Pn Plus:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Zingiber:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    NOTE: This monograph discusses prenatal multivitamin and mineral products when taken as marketed. Clinicians may wish to refer to individual component monographs for more information regarding individual supplements contained in the products of interest.
     
    Prenatal multivitamins and minerals products are contraindicated in patients hypersensitive to any particular product components. Carefully review product components prior to selecting a particular product for a given patient.

    Accidental exposure, children, infants

    Prenatal multivitamins and minerals preparations are not intended for ingestion by pre-pubescent children or adolescent males. The supplement is intended for females of child-bearing potential only. Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children and infants under 6 years of age. Keep this product out of reach of children and infants. In case of accidental exposure via ingested overdose, call a doctor or poison control center immediately.

    Anticoagulant therapy, bleeding

    Certain prenatal multivitamins and minerals products contain fish oils or omega-3-fatty acids. Ingestion of more than 3 grams of omega-3 fatty acids (such as DHA) per day has been shown to have potential antithrombotic effects, including an increased bleeding time and International Normalized Ratio (INR). Administsration of omega-3 fatty acids should generally be avoided in patients taking anticoagulant therapy and in those known to have an inherited or acquired predisposition to bleeding.

    Breast-feeding, pregnancy

    Prenatal multivitamins and minerals are generally recognized as safe (GRAS) for meeting nutritional requirements of females during pre-conception, pregnancy and breast-feeding. No particular precautions are advised. Use before conception (even just 1 to 3 months before fertilization) appears to have benefits, including the reduction of neural tube defects in the fetus, and reduction in symptoms of nausea/vomiting in early pregnancy.

    Pernicious anemia, vitamin B12 deficiency megaloblastic anemia

    Folic acid alone is improper therapy in the treatment of pernicious anemia and other vitamin B12 deficiency megaloblastic anemia where vitamin B12 is deficient. Folic acid in doses above 1 mg daily may obscure pernicious anemia in that hematologic remission can occur while neurological manifestations progress.

    Hemochromatosis, hemosiderosis, hepatic disease, sideroblastic anemia, thalassemia

    Those suffering from hereditary/genetic hemochromatosis or hemochromatosis due to secondary iron overload (e.g., as in iron-loading anemias such as thalassemia or sideroblastic anemia) need to avoid prenatal multivitamins and minerals containing iron supplements. Hemochromatosis causes the body to lose its ability to regulate the amount of iron that is absorbed, leading to excess iron absorption and tissue storage. Massive deposition of iron (hemosiderosis) in parenchymal tissues in these conditions may damage the liver, heart, pancreas and other tissues. Porphyria cutanea tarda (PCT) is sometimes associated with parenchymal iron deposits; patients with PCT should avoid iron supplements unless prescribed by a physician. Excess iron supplementation in patients with PCT can contribute to hepatic uroporphinogen decarboxylase deficiency, but the mechanism is not clear. Some patients with chronic hepatic disease may have hemochromatosis or moderate iron overload in hepatic tissues. The liver is one of the main storage sites for iron, and advanced chronic liver disease may result in excess storage iron in the liver. Thus patients with hepatic disease should receive iron supplementation with caution and only under the direction of a health care prescriber.

    ADVERSE REACTIONS

    Moderate

    gastritis / Delayed / 1.0-10.0
    dyspnea / Early / 0-1.0
    constipation / Delayed / 10.0

    Mild

    rash / Early / 0-1.0
    pruritus / Rapid / 0-1.0
    urticaria / Rapid / 0-1.0
    dyspepsia / Early / 10.0
    stool discoloration / Delayed / 10.0
    nausea / Early / 10.0

    DRUG INTERACTIONS

    Abacavir; Dolutegravir; Lamivudine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir. (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
    Acarbose: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Acetaminophen; Guaifenesin; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Acetaminophen; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Acetohexamide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added.
    Acetohydroxamic Acid: (Moderate) Acetohydroxamic acid chelates heavy metals, including iron. Absorption of orally administered iron salts or polysaccharide-iron complex and acetohydroxamic acid from the intestinal lumen may be reduced when both drugs are administered concomitantly. If iron therapy is required in a patient currently taking acetohydroxamic acid, intramuscular iron is recommended.
    Acrivastine; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Albiglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Alendronate: (Moderate) Oral magnesium-containing products may significantly reduce the absorption of alendronate. All medications should be administered at least 30 minutes after an alendronate dose to help prevent these absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after oral bisphosphonates or at a completely different time of day.
    Alendronate; Cholecalciferol: (Moderate) Magnesium-containing drug products and magnesium salts should be used cautiously in patients receiving vitamin D. Because vitamin D can increase serum magnesium concentrations, the combined use of vitamin D and magnesium-containing drug products should be avoided, if possible, in patients with chronic renal failure. (Moderate) Oral magnesium-containing products may significantly reduce the absorption of alendronate. All medications should be administered at least 30 minutes after an alendronate dose to help prevent these absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after oral bisphosphonates or at a completely different time of day.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Alogliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Alogliptin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Alogliptin; Pioglitazone: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Alpha-blockers: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Alpha-glucosidase Inhibitors: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added.
    Altretamine: (Major) Data from a randomized trial of altretamine and cisplatin plus or minus pyridoxine, vitamin B6 in ovarian cancer indicated that pyridoxine significantly reduced drug-induced neurotoxicity; however, it adversely affected response duration suggesting that pyridoxine should not be administered with altretamine and/or cisplatin.
    Aluminum Hydroxide: (Moderate) The chronic use of aluminum-containing antacids (e.g., aluminum hydroxide-containing antacids) for hyperphosphatemia in conjunction with vitamin D can lead to aluminum retention and possible toxicity. This is of primary significance in patients with renal failure. (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) The chronic use of aluminum-containing antacids (e.g., aluminum hydroxide-containing antacids) for hyperphosphatemia in conjunction with vitamin D can lead to aluminum retention and possible toxicity. This is of primary significance in patients with renal failure. (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Magnesium-containing antacids, such as magnesium hydroxide, should be used cautiously in patients receiving vitamin D (cholecalciferol). Because vitamin D can increase serum magnesium concentrations, the combined use of vitamin D and magnesium-containing drug products should be avoided, if possible, in patients with chronic renal failure. (Moderate) The chronic use of aluminum-containing antacids (e.g., aluminum hydroxide-containing antacids) for hyperphosphatemia in conjunction with vitamin D can lead to aluminum retention and possible toxicity. This is of primary significance in patients with renal failure. (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Magnesium-containing antacids, such as magnesium hydroxide, should be used cautiously in patients receiving vitamin D (cholecalciferol). Because vitamin D can increase serum magnesium concentrations, the combined use of vitamin D and magnesium-containing drug products should be avoided, if possible, in patients with chronic renal failure. (Moderate) The chronic use of aluminum-containing antacids (e.g., aluminum hydroxide-containing antacids) for hyperphosphatemia in conjunction with vitamin D can lead to aluminum retention and possible toxicity. This is of primary significance in patients with renal failure. (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) The chronic use of aluminum-containing antacids (e.g., aluminum hydroxide-containing antacids) for hyperphosphatemia in conjunction with vitamin D can lead to aluminum retention and possible toxicity. This is of primary significance in patients with renal failure. (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Aminoglycosides: (Minor) Ginger may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Amlodipine; Atorvastatin: (Major) There is no clear indication for routine use of niacin in combination with atorvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with atorvastatin. Carefully weigh the potential benefits and risk of combined therapy. If coadministered, use the lowest atorvastatin dose necessary and closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Discontinue atorvastatin immediately if myopathy is diagnosed or suspected. (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
    Amlodipine; Celecoxib: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Amphetamines: (Moderate) Concurrent use of amphetamines and gastrointestinal acidifying agents, such as ascorbic acid, vitamin C, should be used with caution. Vitamin C lowers the absorption of amphetamines, resulting in reduced efficacy. It may be advisable to separate times of administration. In addition, ascorbic acid acts as a urinary acidifier, which reduces the renal tubular reabsorption of amphetamines, accelerating amphetamine clearance and reducing the duration of effect. If combined use is necessary, the amphetamine dose should be adjusted according to clinical response as needed.
    Amprenavir: (Major) Amprenavir contains more than the Reference Daily Intake of vitamin E for adults and children. Concurrent use of vitamin E supplements and amprenavir should be avoided.
    Angiotensin II receptor antagonists: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Angiotensin-converting enzyme inhibitors: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Antacids: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
    Anticoagulants: (Moderate) Additive bleeding may occur if anticoagulants are given in combination with ginger, zingiber officinale. Ginger inhibits thromboxane synthetase (platelet aggregation inducer) and is a prostacyclin agonist. Patients taking ginger and an anticoagulant should be monitored closely for bleeding.
    Articaine; Epinephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of inotropic agents, however, no clinical data are available.
    Aspirin, ASA: (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
    Aspirin, ASA; Caffeine: (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
    Aspirin, ASA; Carisoprodol: (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal. (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
    Aspirin, ASA; Dipyridamole: (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
    Aspirin, ASA; Omeprazole: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts. (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
    Aspirin, ASA; Oxycodone: (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
    Aspirin, ASA; Pravastatin: (Major) There is no clear indication for routine use of niacin in combination with pravastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with pravastatin. If coadministered, consider lower starting and maintenance does of pravastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue pravastatin immediately if myopathy is diagnosed or suspected. (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy. (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal.
    Atenolol: (Minor) Calcium antacids (e.g., calcium carbonate) and supplements (e.g., other oral calcium salts) have been reported to reduce the mean peak concentrations by 51% and the AUC of atenolol by 32%. In another study, antacids reduced the AUC of atenolol by 33%. Separate doses of atenolol and calcium-containing antacids or supplements by at least 2 hours to minimize this potential interaction,. However, most clinicians consider the interaction of atenolol with antacids to be of minor clinical significance, since clinical efficacy (heart rate and blood pressure parameters) appear to be unchanged under usual intermittent clinical use.
    Atenolol; Chlorthalidone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended. (Minor) Calcium antacids (e.g., calcium carbonate) and supplements (e.g., other oral calcium salts) have been reported to reduce the mean peak concentrations by 51% and the AUC of atenolol by 32%. In another study, antacids reduced the AUC of atenolol by 33%. Separate doses of atenolol and calcium-containing antacids or supplements by at least 2 hours to minimize this potential interaction,. However, most clinicians consider the interaction of atenolol with antacids to be of minor clinical significance, since clinical efficacy (heart rate and blood pressure parameters) appear to be unchanged under usual intermittent clinical use.
    Atorvastatin: (Major) There is no clear indication for routine use of niacin in combination with atorvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with atorvastatin. Carefully weigh the potential benefits and risk of combined therapy. If coadministered, use the lowest atorvastatin dose necessary and closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Discontinue atorvastatin immediately if myopathy is diagnosed or suspected. (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
    Atorvastatin; Ezetimibe: (Major) There is no clear indication for routine use of niacin in combination with atorvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with atorvastatin. Carefully weigh the potential benefits and risk of combined therapy. If coadministered, use the lowest atorvastatin dose necessary and closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that periodic monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Discontinue atorvastatin immediately if myopathy is diagnosed or suspected. (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
    Atracurium: (Moderate) Concomitant use of neuromuscular blockers and magnesium may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) The therapeutic action of methenamine requires an acidic urine. Ascorbic acid, vitamin C can produce unpredictable changes in urine pH and should be avoided as a urinary acidifier. In addition, orange juice also should be avoided because citric acid ultimately may raise urine pH. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
    Azilsartan; Chlorthalidone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Baloxavir Marboxil: (Major) Do not administer baloxavir with products that contain calcium. Polyvalent cations, such as calcium, can chelate with baloxavir, reducing its absorption. (Major) Do not administer baloxavir with products that contain zinc. Polyvalent cations, such as zinc, can chelate with baloxavir, reducing its absorption. (Major) Do not administer baloxavir with selenium. Polyvalent cations, such as selenium, can chelate with baloxavir, reducing its absorption.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Numerous studies indicate that folate status is impaired with the chronic use of phenobarbital, presumably via inhibition of the intestinal absorption of folic acid. The studies available suffer from poor methodologic control and definitive conclusions cannot be drawn relative to adverse effects of phenobarbital on folate status. In addition, high doses of folate may result in decreased serum concentrations of phenobarbital resulting in a decrease in effectiveness and, possibly, an increase in the frequency of seizures in susceptible patients. Although no decrease in effectiveness of anticonvulsants has been reported with the concurrent use of L-methylfolate, caution still should be exercised with the coadministration of these agents and patients should be monitored closely for seizure activity. (Moderate) Phenobarbital use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like phenobarbital, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly. (Minor) Concurrent use of folic acid, vitamin B9 and phenobarbital may result in decreased folic acid serum concentrations and decreased anticonvulsant effect. It is important to maintain adequate folic acid concentrations in epileptic patients taking enzyme-inducing anticonvulsants, and maintenance doses may require upward adjustment. However, in large amounts, folic acid may counteract the anticonvulsant effect of some agents, including phenobarbital. Therefore, it has been recommended that oral folic acid supplementation not exceed 1 mg/day in epileptic patients taking anticonvulsants. If large doses are used, monitor phenobarbital concentrations upon folic acid initiation, dose titration, and discontinuation. Adjust the anticonvulsant dosage as appropriate. (Minor) In a limited case report, the administration of pyridoxine, vitamin B6 (200 mg once daily x 4 weeks) resulted in reduced serum phenobarbital concentrations in 5 patients with epilepsy; the reductions approached 50%. The evidence for the interaction is limited, and there is no data to suggest that lower supplemental doses would result in alterations in the pharmacokinetics of phenobarbital. The clinical significance of this potential interaction is questionable. If a patient is using large doses of pyridoxine, then the clinician should be alert to possible alterations.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Bendroflumethiazide; Nadolol: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) The therapeutic action of methenamine requires an acidic urine. Ascorbic acid, vitamin C can produce unpredictable changes in urine pH and should be avoided as a urinary acidifier. In addition, orange juice also should be avoided because citric acid ultimately may raise urine pH. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
    Beta-adrenergic blockers: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of inotropes; however, no clinical data are available.
    Beta-blockers: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Administer bictegravir on an empty stomach 2 hours before or 6 hours after taking oral medications containing magnesium. Routine administration of bictegravir simultaneously with, or 2 hours after, oral medications containing magnesium is not recommended as the bioavailability of bictegravir may be reduced. (Moderate) Administer bictegravir with food at the same time as iron supplements. Routine administration of bictegravir under fasting conditions simultaneously with, or 2 hours after, iron supplements is not recommended. Iron is a polyvalent cation that can bind bictegravir in the GI tract. Taking these drugs simultaneously without food results in reduced bioavailability of bictegravir. In drug interaction studies, simultaneous administration of bictegravir and ferrous fumarate under fasted conditions decreased the mean AUC of bictegravir by approximately 63%. (Moderate) Administer bictegravir with food at the same time as oral calcium supplements. Routine administration of bictegravir under fasting conditions simultaneously with, or 2 hours after, calcium supplements is not recommended. Calcium is a polyvalent cation that can bind bictegravir in the GI tract. Taking these drugs simultaneously without food results in reduced bioavailability of bictegravir. In drug interaction studies, simultaneous administration of bictegravir with another calcium supplement under fasted conditions decreased the mean AUC of bictegravir by approximately 33%.
    Bile acid sequestrants: (Major) In vitro studies have shown that bile acid sequestrants bind niacin. The results suggest that at least 4 to 6 hours should elapse between the ingestion of bile-acid-binding resins and the administration of niacin. (Moderate) In vitro studies have shown that bile acid sequestrants bind niacin. Roughly 98% of niacin was bound to colestipol, and 10 to 30% of niacin was bound to cholestyramine. These results suggest that at least 4 to 6 hours should elapse between the ingestion of bile-acid-binding resins and the administration of niacin.
    Bismuth Subsalicylate: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Bisphosphonates: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product. (Moderate) Separating times of administration of the oral bisphosphonate from iron-containing supplements and medications will maximize absorption and clinical benefit. Iron will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any iron containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any iron containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Bleomycin: (Moderate) Monitor for decreased efficacy of bleomycin during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration of ascorbic acid and bleomycin may result in decreased efficacy of bleomycin.
    Brompheniramine; Carbetapentane; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Brompheniramine; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Brompheniramine; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Bupivacaine; Lidocaine: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of antiarrhythmics, however, no clinical data are available.
    Bupivacaine; Meloxicam: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Cabotegravir: (Moderate) Administer oral calcium at least two hours before or four hours after taking oral cabotegravir. Calcium is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir. (Moderate) Administer oral iron at least two hours before or four hours after taking oral cabotegravir. Iron is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir. (Moderate) Administer oral zinc at least two hours before or four hours after taking oral cabotegravir. Zinc is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir.
    Cabotegravir; Rilpivirine: (Moderate) Administer oral calcium at least two hours before or four hours after taking oral cabotegravir. Calcium is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir. (Moderate) Administer oral iron at least two hours before or four hours after taking oral cabotegravir. Iron is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir. (Moderate) Administer oral zinc at least two hours before or four hours after taking oral cabotegravir. Zinc is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir.
    Calcipotriene: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
    Calcipotriene; Betamethasone: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
    Calcitonin: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
    Calcium Carbonate: (Major) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Calcium Carbonate; Magnesium Hydroxide: (Major) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction.
    Calcium Carbonate; Risedronate: (Major) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. (Moderate) Oral magnesium may significantly reduce the absorption of the oral bisphosphonates (e.g. risedronate). All medications should be administered at least 30 minutes after a risedronate dose to help prevent these absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after oral bisphosphonates or at a completely different time of day. (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of risedronate therapy.
    Calcium Carbonate; Simethicone: (Major) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction.
    Calcium Phosphate, Supersaturated: (Moderate) The concomitant use of oral sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous preparations in conjunction with antacids containing calcium (e.g., calcium carbonate, calcium salts) may bind the phosphate in the stomach and reduce its absorption. If the patient requires multiple mineral supplements or concurrent use of antacids, it is prudent to separate the administration of sodium phosphate salts from calcium containing products by at least one hour.
    Calcium: (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of supplementation with calcium salts.
    Calcium; Vitamin D: (Moderate) Magnesium-containing drug products and magnesium salts should be used cautiously in patients receiving vitamin D. Because vitamin D can increase serum magnesium concentrations, the combined use of vitamin D and magnesium-containing drug products should be avoided, if possible, in patients with chronic renal failure.
    Calcium-channel blockers: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially calcium-channel blockers. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents.
    Canagliflozin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Canagliflozin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Capecitabine: (Moderate) Monitor for an increase in capecitabine-related adverse reactions if coadministration with folic acid is necessary. Capecitabine is an orally administered prodrug of fluorouracil; leucovorin enhances the binding of fluorouracil to thymidylate synthase, increasing exposure to fluorouracil. Folic acid (vitamin B9) is converted to folinic acid in vivo; leucovorin is the calcium salt of folinic acid. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil. (Moderate) Monitor for an increase in capecitabine-related adverse reactions if coadministration with L-methylfolate is necessary. Capecitabine is an orally administered prodrug of fluorouracil; leucovorin enhances the binding of fluorouracil to thymidylate synthase, increasing exposure to fluorouracil. L-methylfolate is the biologically active form of folic acid, which is converted to folinic acid in vivo; leucovorin is the calcium salt of folinic acid. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Carbamazepine: (Moderate) Carbamazepine use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like carbamazepine, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly. (Moderate) High doses of folate may cause decreased serum concentrations of carbamazepine resulting in a decrease in effectiveness and, possibly, an increase in the frequency of seizures in susceptible patients. In addition, L-methylfolate plasma levels may be decreased when administered with carbamazepine. Although no decrease in effectiveness of anticonvulsants has been reported with the concurrent use of L-methylfolate, caution still should be exercised with the coadministration of these agents and patients should be monitored closely for seizure activity. (Moderate) Niacin may inhibit the CYP3A4 metabolism of carbamazepine, resulting in elevated carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored if niacin is added during carbamazepine therapy. It may be necessary to reduce the dose of carbamazepine.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) Orally administered zinc salts compete with copper salts for absorption from the intestines. Since a large portion of administered zinc doses are excreted via biliary and pancreatic secretions, parenteral zinc therapy may also interfere with the oral absorption of copper salts. (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Carbetapentane; Phenylephrine: (Major) Orally administered zinc salts compete with copper salts for absorption from the intestines. Since a large portion of administered zinc doses are excreted via biliary and pancreatic secretions, parenteral zinc therapy may also interfere with the oral absorption of copper salts. (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Carbetapentane; Phenylephrine; Pyrilamine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Carbetapentane; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Carbidopa; Levodopa: (Contraindicated) Pyridoxine, vitamin B6, in doses as low as 10 mg/day, can accelerate the rate of aromatic amino acid decarboxylation, thus increasing the peripheral conversion of levodopa to dopamine. This action diminishes levodopa's therapeutic effects by decreasing the amount of levodopa that is available to cross into the CNS. Patients receiving levodopa single-agent therapy should avoid vitamin B6 supplements. (Major) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
    Carbidopa; Levodopa; Entacapone: (Contraindicated) Pyridoxine, vitamin B6, in doses as low as 10 mg/day, can accelerate the rate of aromatic amino acid decarboxylation, thus increasing the peripheral conversion of levodopa to dopamine. This action diminishes levodopa's therapeutic effects by decreasing the amount of levodopa that is available to cross into the CNS. Patients receiving levodopa single-agent therapy should avoid vitamin B6 supplements. (Major) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Carbinoxamine; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Carbinoxamine; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Cardiac glycosides: (Moderate) Monitor serum calcium regularly in patients receiving digoxin. Calcium salts augment the actions of digoxin. In addition, when calcium is administered via rapid intravenous injection, the risk of serious arrhythmias in digitalized patients is increased. (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of inotropes; however, no clinical data are available.
    Castor Oil: (Moderate) Absorption of fat-soluble vitamins may be decreased with coadministration of castor oil.
    Cefdinir: (Moderate) If oral iron supplements are required during cefdinir therapy, cefdinir should be taken at least 2 hours before or 2 hours after the iron supplement. Concomitant administration of cefdinir with therapeutic iron supplements containing 60 mg of elemental iron or vitamins supplemented with 10 mg of elemental iron reduced extent of cefdinir absorption by 80% and 31%, respectively. The effect highly iron-fortified food (primarily iron-fortified breakfast cereals) on cefdinir absorption has not been studied. Further, concomitantly administered iron-fortified infant formula (2.2 mg elemental iron/6 oz) has no significant effect on cefdinir pharmacokinetics; therefore, cefdinir oral suspension can be administered with iron-fortified infant formula. However, several case reports describe nonbloody, reddish stool discoloration in infants being treated with cefdinir who were also receiving iron-fortified infant formulas. This reddish color may occur as a result of the formation of a nonabsorbable complex between ferric ions and cefdinir or one of its metabolites. Parents of infants receiving cefdinir should be counseled about this potential interaction.
    Celecoxib: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Central-acting adrenergic agents: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. Clonidine has been shown to inhibit niacin-induced flushing. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
    Cephalexin: (Minor) Caution may be warranted with coadminstration of cephalexin and zinc salts as zinc may decrease the absorption of cephalexin. In a randomized, single-dose, four-way crossover study (n = 12), patients received cephalexin alone, in combination with zinc sulfate (250 mg), 3 hours after zinc sulfate, or 3 hours before zinc sulfate. When administered in combination with zinc, the cephalexin Cmax decreased from 18.07 +/- 4.27 mcg/ml to 12.46 +/- 2.73 mcg/ml (p < 0.05) and the AUC decreased from 41.97 +/- 6.04 mcg x h/ml to 30.47 +/- 3.52 mcg x h/ml (p < 0.05). When cephalexin was administered 3 hours after zinc, the Cmax and AUC were 16 +/- 4.06 mcg/ml (p < 0.05) and 34.37 +/- 1.58 mcg x h/mL (p < 0.05), respectively. When cephalexin was administered 3 hours before zinc, there were no significant differences in the cephalexin Cmax or AUC. One in vitro study suggested that zinc is a competitive inhibitor of the intestinal peptide transporter, PEPT1, which may inhibit the uptake of oral cephalosporins. An additional in vitro study suggested that trace elements may have an antagonistic effect on cephalosporins.
    Cerivastatin: (Contraindicated) The risk of myopathy increases when HMG-Co-A reductase inhibitors are administered concurrently with antilipemic doses of niacin.
    Cetirizine; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Chlophedianol; Guaifenesin; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Chloramphenicol: (Moderate) If use together is necessary, monitor for reduced efficacy of cyanocobalamin (vitamin B12), and if needed, consider an alternative therapy. Chloramphenicol can cause bone marrow depression and inhibit red blood cell maturation, which may reduce the efficacy of vitamin B12 in the treatment of anemia. (Minor) Concurrent use of chloramphenicol with folic acid can antagonize the hematopoietic response to folic acid. Hematologic response should be monitored in patients requiring folic acid if chloramphenicol is administered concomitantly.
    Chlorothiazide: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available. (Minor) L-methylfolate should be used cautiously in patients taking high doses of ibuprofen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of ibuprofen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Chlorpheniramine; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Chlorpheniramine; Pseudoephedrine: (Major) Orally administered zinc salts compete with copper salts for absorption from the intestines. Since a large portion of administered zinc doses are excreted via biliary and pancreatic secretions, parenteral zinc therapy may also interfere with the oral absorption of copper salts. (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Chlorpropamide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added.
    Chlorthalidone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Chlorthalidone; Clonidine: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Cholestyramine: (Major) In vitro studies have shown that bile acid sequestrants bind niacin. The results suggest that at least 4 to 6 hours should elapse between the ingestion of bile-acid-binding resins and the administration of niacin. (Major) L-methylfolate and cholestyramine should be used together cautiously. Cholestyramine administration may decrease L-methylfolate plasma concentrations. Patients taking both drugs should take L-methylfolate 1 hour before or 4 to 6 hours after a dose of cholestyramine. (Moderate) Cholestyramine can decrease the intestinal absorption of fat and fat-soluble vitamins. If used concurrently, administration of the two agents should be staggered for the longest time interval possible. (Moderate) Chronic administration of cholestyramine may interfere with folic acid, vitamin B9 oral absorption. Patients receiving both drugs should take folic acid 1 hour before or 4 to 6 hours after a dose of cholestyramine. (Moderate) Concurrent administration of cholestyramine and oral iron supplements may reduce the oral absorption of iron. To avoid any oral absorption interference, administration of other drugs is recommended 1 hour before or at least 4 to 6 hours after cholestyramine administration.
    Choline Salicylate; Magnesium Salicylate: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
    Cimetidine: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Ciprofloxacin: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain magnesium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain magnesium. (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc. (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain iron. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron.
    Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and magnesium may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Class IA Antiarrhythmics: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of antiarrhythmics, however, no clinical data are available.
    Class IC Antiarrhythmics: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of antiarrhythmics; however, no clinical data are available.
    Codeine; Guaifenesin; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Codeine; Phenylephrine; Promethazine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Co-Enzyme Q10, Ubiquinone: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of antiarrhythmics, inotropes and vasopressors; however, no clinical data are available.
    Colchicine: (Minor) Colchicine has been shown to induce reversible malabsorption of vitamin B12. Patients receiving these agents concurrently should be monitored for the desired therapeutic response to vitamin B12. (Minor) L-methylfolate and colchicine should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with colchicine. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Colesevelam: (Major) In vitro studies have shown that bile acid sequestrants bind niacin. The results suggest that at least 4 to 6 hours should elapse between the ingestion of bile-acid-binding resins and the administration of niacin. (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Colestipol: (Major) In vitro studies have shown that bile acid sequestrants bind niacin. The results suggest that at least 4 to 6 hours should elapse between the ingestion of bile-acid-binding resins and the administration of niacin. (Major) L-methylfolate and colestipol should be used together cautiously. Colestipol administration may decrease L-methylfolate plasma concentrations. Patients taking both agents should take L-methylfolate 1 hour before or 4 to 6 hours after a dose of colestipol. (Moderate) Separate administration of fat-soluble vitamins by 1 hour before or 4 hours after a colestipol dose to limit effects on oral absorption. Because it sequesters bile acids, colestipol may interfere with normal fat absorption and thus may reduce absorption of fat-soluble vitamins.
    Conjugated Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Cycloserine: (Moderate) Cycloserine can either interfere with the actions of pyridoxine, vitamin B6 or increase its clearance, which may result in a secondary niacin deficiency. It may be necessary to administer pyridoxine to patients receiving prolonged therapy with cycloserine to prevent the development of anemia or peripheral neuritis.
    Dapagliflozin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Dapagliflozin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Dapagliflozin; Saxagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacinamide interferes with glucose metabolism and can result in hyperglycemia. Monitor patients taking antidiabetic agents for changes in glycemic control if niacinamide is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Darbepoetin Alfa: (Minor) It is important that iron stores be replete before beginning therapy with darbepoetin alfa due to increased iron utilization. Inadequate iron stores will interfere with the therapeutic response to these agents (e.g., red blood cell production). Supplemental iron may be needed during maintenance therapy to facilitate erythropoiesis. Iron supplementation (e.g., iron dextran; iron salts; iron sucrose, sucroferric oxyhydroxide; polysaccharide-iron complex; sodium ferric gluconate complex) may be required.
    Deferasirox: (Contraindicated) Deferasirox chelates iron and is indicated as a treatment of iron toxicity or overdose. It is illogical for a patient to receive both iron supplementation and deferasirox simultaneously. Do not give iron supplementation during Deferasirox treatment.
    Deferiprone: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, iron sucrose, sodium ferric gluconate complex, or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. However, since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used. (Moderate) Concurrent use of deferiprone with food, mineral supplements, and antacids that contain polyvalent (trivalent) cations has not been studied. However, since deferiprone has the potential to bind polyvalent cations (e.g., iron, aluminum, and zinc), allow at least a 4-hour interval between deferiprone and other medications or dietary supplements containing these polyvalent cations. Such medications can include antacids, iron salts, aluminum hydroxide, dietary supplements containing polyvalent minerals, and zinc salts.
    Deferoxamine: (Contraindicated) Deferoxamine chelates iron from ferritin or hemosiderin. A stable complex is formed that prevents iron from entering into further chemical reactions. The chelate is excreted in the urine and in the feces via bile. Deferoxamine is indicated as a treatment of iron toxicity or overdose. It would be illogical for a patient to receive both iron supplementation and deferoxamine simultaneously. (Major) Patients should be advised not to take ascorbic acid, vitamin C supplements along with deferoxamine chelation therapy unless such supplements are prescribed with the approval of their health care professional. Patients with iron overload usually become vitamin C deficient, probably because iron oxidizes the vitamin. Vitamin C can be a beneficial adjunct in iron chelation therapy because it facilitates iron chelation and iron complex excretion. As an adjuvant to iron chelation therapy (e.g., deferoxamine), vitamin C (in doses up to 200 mg/day for adults, 50 mg/day in children < 10 years of age or 100 mg/day in older children) may be given in divided doses, starting after an initial month of regular treatment with deferoxamine. However, higher doses of ascorbic acid, vitamin C can facilitate iron deposition, particularly in the heart tissue, causing cardiac decompensation. In patients with severe chronic iron overload, the concomitant use of deferoxamine with > 500 mg/day PO of vitamin C in adults has lead to impairment of cardiac function; the dysfunction was reversible when vitamin C was discontinued. The manufacturer of deferoxamine recommends certain precautions for the coadministration of vitamin C with deferoxamine. First, vitamin C supplements should not be given concurrently with deferoxamine in patients with heart failure. Secondly, in other patients, such supplementation should not be started until 1 month of regular treatment with deferoxamine, and should be given only to patients receiving regular deferoxamine treatments. Do not exceed vitamin C doses of 200 mg/day for adults, 50 mg/day in children < 10 years of age, or 100 mg/day in older children, given in divided doses. Clinically monitor all patients, especially the elderly, for signs or symptoms of decreased cardiac function.
    Delafloxacin: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium. (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain iron. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain magnesium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain magnesium. (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc.
    Desloratadine; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Desogestrel; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Dexbrompheniramine; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Dexlansoprazole: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Dichlorphenamide: (Moderate) Use dichlorphenamide and pyridoxine, vitamin B6 together with caution. Metabolic acidosis is associated with the use of dichlorphenamide and has been reported with the rapid infusion of large pyridoxine doses. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
    Diclofenac: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Diclofenac; Misoprostol: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Didanosine, ddI: (Moderate) Iron salts should not be administered simultaneously with didanosine, ddI chewable tablets or powder for oral solution. Oral absorption of iron supplements is reduced if given with antacids; the buffering agents contained in didanosine tablets and powder likewise reduce iron salt absorption. Administer oral doses of iron salts 1 hour before or 4 hours after didanosine tablet or powder administration. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with iron salts.
    Dienogest; Estradiol valerate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Diethylstilbestrol, DES: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Diflunisal: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Diltiazem: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of inotropes; however, no clinical data are available.
    Dimercaprol: (Contraindicated) Dimercaprol forms toxic-chelates with iron, cadmium, and selenium. These dimercaprol-metal complexes are more toxic than the metal alone, especially to the kidneys. (Contraindicated) Dimercaprol forms toxic-chelates with iron. These dimercaprol-metal complexes are more toxic than the metal alone, especially to the kidneys. Iron therapy should not be administered concomitantly with dimercaprol. Therapy with iron should generally be delayed until 24 hours after the cessation of dimercaprol therapy.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Diphenhydramine; Ibuprofen: (Minor) L-methylfolate should be used cautiously in patients taking high doses of ibuprofen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of ibuprofen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Diphenhydramine; Naproxen: (Minor) L-methylfolate should be used cautiously in patients taking high doses of naproxen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of naproxen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Diphenhydramine; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Disulfiram: (Moderate) As ascorbic acid, vitamin C has on occasion been used as a specific antidote for symptoms resulting from interaction between ethanol and disulfiram, it may be expected that the administration of large doses of vitamin C may interfere with the effectiveness of disulfiram given to patients to encourage abstinence from alcohol.
    Dobutamine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of inotropes; however, no clinical data are available.
    Dolutegravir: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir. (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
    Dolutegravir; Lamivudine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir. (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
    Dolutegravir; Rilpivirine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir. (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
    Dopamine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of inotropes; however, no clinical data are available.
    Doxacurium: (Moderate) Concomitant use of neuromuscular blockers and magnesium may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Doxazosin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents.
    Doxycycline: (Moderate) Monitor for decreased efficacy of doxycycline during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration may result in decreased efficacy of doxycycline.
    Drospirenone; Estetrol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Drospirenone; Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Drospirenone; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Dulaglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Edetate Calcium Disodium, Calcium EDTA: (Major) Administration of oral magnesium with edetate disodium, disodium EDTA may result in binding of magnesium. Do not administer oral magnesium salts within 1 hour of edetate disodium, EDTA (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly. (Major) Concomitant use of zinc supplements with calcium EDTA can decrease the effectiveness of both agents due to chelation. Zinc salts should not be administered until edetate calcium therapy is completed.
    Edetate Disodium, Disodium EDTA: (Major) Administration of oral magnesium with edetate disodium, disodium EDTA may result in binding of magnesium. Do not administer oral magnesium salts within 1 hour of edetate disodium, EDTA (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly. (Major) Concomitant use of zinc supplements with calcium EDTA can decrease the effectiveness of both agents due to chelation. Zinc salts should not be administered until edetate calcium therapy is completed.
    Elagolix; Estradiol; Norethindrone acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Eltrombopag: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts. (Major) Eltrombopag chelates polyvalent cations (e.g., iron) in foods and mineral supplements. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as iron salts, multivitamins that contain iron, or polysaccharide-iron complex. (Major) Eltrombopag chelates polyvalent cations (e.g., selenium) in foods, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag 2 hours before or 4 hours after any oral products containing selenium. (Major) Eltrombopag chelates polyvalent cations (e.g., zinc salts) in foods, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag 2 hours before or 4 hours after any oral products containing zinc salts.
    Elvitegravir: (Moderate) Separate administration of elvitegravir and calcium by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations. (Moderate) Separate administration of elvitegravir and iron by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations. (Moderate) Separate administration of elvitegravir and zinc by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Separate administration of elvitegravir and calcium by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations. (Moderate) Separate administration of elvitegravir and iron by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations. (Moderate) Separate administration of elvitegravir and zinc by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Separate administration of elvitegravir and calcium by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations. (Moderate) Separate administration of elvitegravir and iron by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations. (Moderate) Separate administration of elvitegravir and zinc by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
    Empagliflozin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Empagliflozin; Linagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750-2000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on linagliptin for changes in blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750-2000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on linagliptin for changes in blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Empagliflozin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Enteral Feedings: (Minor) Absorption of zinc from enteral feedings may be impaired, despite the presence of zinc as a component of the enteral feeding formula; patients on chronic enteral feeding therapy may require additional zinc supplementation to ensure adequate nutritional intake. (Minor) Ferrous sulfate elixir has an acidic pH and has been reported to form precipitates with enteral feedings and may clog feeding tubes.
    Epinephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of inotropic agents, however, no clinical data are available.
    Eplerenone: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Epoetin Alfa: (Minor) Inadequate iron stores will interfere with the therapeutic response to epoetin alfa (e.g., red blood cell production). Most patients with chronic kidney disease will require supplemental iron (e.g., iron dextran; iron salts; iron sucrose, sucroferric oxyhydroxide; polysaccharide-iron complex; sodium ferric gluconate complex) during epoetin alfa receipt. Evaluate transferrin saturation and serum ferritin before and during epoetin alfa treatment. Administer supplemental iron therapy when serum ferritin is < 100 mcg/L or when serum transferrin saturation is < 20%. After initiation of therapy and after each dose adjustment, monitor hemoglobin weekly until the hemoglobin concentration is stable and sufficient to minimize the need for RBC transfusion.
    Epoprostenol: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially epoprostenol. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Ertugliflozin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Ertugliflozin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Ertugliflozin; Sitagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacinamide interferes with glucose metabolism and can result in hyperglycemia. Monitor patients taking antidiabetic agents for changes in glycemic control if niacinamide is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Erythromycin: (Moderate) Monitor for decreased efficacy of erythromycin during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration may result in decreased efficacy of erythromycin.
    Erythromycin; Sulfisoxazole: (Moderate) Monitor for decreased efficacy of erythromycin during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration may result in decreased efficacy of erythromycin.
    Esomeprazole: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Esterified Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Esterified Estrogens; Methyltestosterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estradiol Cypionate; Medroxyprogesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estradiol; Levonorgestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estradiol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estradiol; Norgestimate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estradiol; Progesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estramustine: (Major) Administration of estramustine with calcium impairs the oral absorption of estramustine significantly, due to formation of a calcium-phosphate complex. Calcium-containing drugs must not be taken simultaneously with estramustine. Patients should be instructed to take estramustine with water at least 1 hour before or 2 hours after calcium supplements.
    Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estropipate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethanol: (Moderate) Alcohol-containing beverages or hot beverages/foods can exacerbate cutaneous vasodilation caused by niacin and should be avoided around the time of niacin ingestion. (Moderate) Alcohol-containing beverages or hot beverages/foods can exacerbate cutaneous vasodilation caused by niacin and should be avoided around the time of niacin ingestion. In general, this interaction would not be harmful, but might decrease patient tolerance of niacin. alcohol and niacin, particularly sustained-release niacin, are both potentially hepatotoxic. Although no data are available regarding enhanced hepatotoxicity, excessive alcohol use should be discouraged. (Moderate) Ethanol-containing beverages or hot beverages/foods can exacerbate cutaneous vasodilation caused by niacin and should be avoided around the time of niacin ingestion. (Moderate) Ethanol-containing beverages or hot beverages/foods can exacerbate cutaneous vasodilation caused by niacin and should be avoided around the time of niacin ingestion. In general, this interaction would not be harmful, but might decrease patient tolerance of niacin. Ethanol and niacin, particularly sustained-release niacin, are both potentially hepatotoxic. Although no data are available regarding enhanced hepatotoxicity, excessive ethanol use should be discouraged. (Moderate) The heavy consumption of alcohol for greater than 2 weeks has been reported to reduce the absorption of cyanocobalamin, vitamin B12. Patients should be aware that heavy, chronic alcohol use may counteract the therapeutic effects of vitamin B12; such patients with regular and chronic alcohol consumption be monitored for the desired therapeutic response to vitamin B12. (Moderate) The heavy consumption of ethanol for greater than 2 weeks has been reported to reduce the absorption of cyanocobalamin, vitamin B12. Patients should be aware that heavy, chronic ethanol use may counteract the therapeutic effects of vitamin B12; such patients with regular and chronic ethanol consumption be monitored for the desired therapeutic response to vitamin B12. (Minor) Folate deficiency may result in patients with chronic alcohol consumption, and especially in alcoholic cirrhosis. Such patients may derive most of their caloric intake from alcohol-containing beverages which do not contain adequate amounts of folic acid; in addition alcohol may affect folate metabolism increasing folate loss. Supplementation in patients known to have excessive alcohol intake is prudent. Avoidance of excessive intake of alcohol would be recommended to help treat the deficiency. (Minor) Folate deficiency may result in patients with chronic alcohol or alcohol consumption, and especially in patients with alcoholic cirrhosis. Such patients may derive most of their caloric intake from alcohol-containing beverages, which do not contain adequate amounts of folic acid. In addition, alcohol may affect folate metabolism increasing folate loss. Supplementation in patients known to have excessive alcohol intake is prudent. Avoidance of excessive intake of alcohol would be recommended to help treat the deficiency. (Minor) Folate deficiency may result in patients with chronic alcohol or ethanol consumption, and especially in patients with alcoholic cirrhosis. Such patients may derive most of their caloric intake from alcoholic beverages, which do not contain adequate amounts of folic acid; in addition ethanol may affect folate metabolism increasing folate loss. Supplementation in patients known to have excessive alcohol intake is prudent. Avoidance of excessive intake of alcohol would be recommended to help treat the deficiency.
    Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Norelgestromin: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Norethindrone Acetate: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Norgestrel: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethotoin: (Major) Oral absorption of phenytoin can be reduced by calcium salts. Calcium salts can form complexes that are nonabsorbable. Separating the administration of phenytoin and calcium salts by at least 2 hours to help avoid this interaction. A similar interaction may occur with ethotoin.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Etidronate: (Moderate) Do not administer any oral magnesium-containing products within 2 hours of etidronate; oral magnesium may significantly reduce the absorption of etidronate. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after any oral bisphosphonates or at a completely different time of day.
    Etodolac: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Etonogestrel; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Exenatide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Ezetimibe; Simvastatin: (Major) There is no clear indication for routine use of niacin in combination with simvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with simvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue simvastatin immediately if myopathy is diagnosed or suspected. Coadministration is not recommended in Chinese patients, as the risk of myopathy is greater in this population. It is unknown if this risk applies to other Asian patients. (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
    Famotidine: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Famotidine; Ibuprofen: (Minor) L-methylfolate should be used cautiously in patients taking high doses of ibuprofen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of ibuprofen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity. (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Fenoprofen: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Ferric carboxymaltose: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
    Ferric Derisomaltose: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
    Ferric Maltol: (Moderate) Orally administered zinc salts compete with iron supplements for absorption from the intestine. To minimize the interaction, separate oral iron and zinc doses by at least 2 hours. The oral receipt of 100 mg of iron as ferrous gluconate with 12 mg zinc in 11 patients with normal iron status and comparable total exchangeable zinc pools yielded a mean zinc absorption of 26.4% +/- 14.4% of the administered dose as compared with 44.5% +/- 22.5% of the dose given without concomitant iron. Concomitant use of iron 400 mg as ferrous gluconate yielded a mean zinc absorption of 22.9% +/- 6.4% of the zinc dose.
    Ferumoxytol: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
    Fexofenadine; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Floxuridine: (Moderate) L-methylfolate is the biologically active form of folic acid; leucovorin is a reduced form of folic acid. Coadministration of leucovorin with 5-FU may potentiate the adverse effects associated with 5-FU. Since floxuridine is metabolized to 5-FU, a similar interaction may occur with concomitant administration of floxuridine and L-methylfolate.
    Fluorouracil, 5-FU: (Moderate) L-methylfolate is the biologically active form of folic acid; leucovorin is a reduced form of folic acid. Coadministration of leucovorin with Fluorouracil, 5-FU may potentiate the adverse effects associated with 5-FU. Although no interaction between L-methylfolate and fluorouracil, 5-FU has been reported, caution still should be exercised with the coadministration of these agents.
    Fluoxetine: (Minor) Levomefolate and fluoxetine should be used together cautiously. Fluoxetine is a noncompetitive inhibitor of levomefolate active transport in the intestines. Monitor patients for decreased efficacy of levomefolate if these agents are used together.
    Fluphenazine: (Moderate) Monitor for decreased efficacy of fluphenazine during coadministration. Coadministration of ascorbic acid and fluphenazine may result in decreased plasma concentrations of fluphenazine due to acidification of the urine by ascorbic acid and increased excretion of fluphenazine.
    Flurbiprofen: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Fluvastatin: (Major) There is no clear indication for routine use of niacin in combination with fluvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with fluvastatin. If coadministered, consider lower starting and maintenance does of fluvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue fluvastatin immediately if myopathy is diagnosed or suspected. (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
    Food: (Contraindicated) Foods, seasonings, or medicines containing high potassium or sodium content, such as dietary salt substitutes, 'low salt' milk products (which contain potassium), or tomato juice (which has high sodium content), could increase the risk of complications of hyperkalemia or sodium excess. Regularly monitor the serum potassium and/or sodium concentration in patients taking food or medications with high potassium and/or sodium content. Muscle weakness, chest pain, or an abnormal heart rhythm can indicate hyperkalemia. Abdominal pain, diarrhea, metabolic alkalosis, nausea, vomiting, and seizures can indicate sodium excess. (Major) For better iron absorption, administer iron salts 1 hour before or 2 hours after meals. If GI irritation occurs, the iron supplement may be administered with meals. However, where possible, avoid administering coffee, tea, or dairy products within 1 hour before or 2 hours after giving iron. (Moderate) Breads, vegetables, fruits, eggs, and beverages appear to interfere with the oral absorption of Zinc. For optimal absorption, oral zinc salts should be separated from food and beverages, other than water, by at least 1 hour. (Moderate) Food or medicines containing a high sodium content (e.g., tomato juice) could increase the risk of complications of sodium excess when given with sodium citrate (see Adverse Reactions). (Moderate) Hot beverages and foods can exacerbate cutaneous vasodilation caused by niacin and should be avoided around the time of niacin ingestion. In general, this interaction would not be harmful, but might decrease patient tolerance of niacin. (Minor) Dietary avidin, a glycoprotein in raw egg whites (food), binds tightly to dietary biotin and prevents its absorption in the gastrointestinal tract. Cooking denatures the avidin, disabling it from interfering with biotin absorption. (Minor) The intranasal forms of cyanocobalamin, vitamin B12, should be administered at least one hour before or one hour after ingestion of hot foods or liquids. Hot foods may cause nasal secretions and a resulting loss of medication or medication efficacy. Interactions between foods and oral or injectable forms of cyanocobalamin are not expected.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Fosphenytoin: (Moderate) Fosphenytoin use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like fosphenytoin, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly. (Moderate) Numerous studies indicate that folate status is impaired with the chronic use of diphenylhydantoin (phenytoin or fosphenytoin). Prolonged administration of phenytoin reportedly has resulted in a folate deficiency. In addition, folic acid replacement has resulted in an increase in metabolism of phenytoin and a decrease in phenytoin concentration in some patients, apparently through increased metabolism and/or redistribution of phenytoin in the brain and CSF. Although no decrease in effectiveness of anticonvulsants has been reported with the concurrent use of L-methylfolate, caution still should be exercised with the coadministration of these agents, and patients should be monitored closely for seizure activity. (Minor) Concurrent use of folic acid, vitamin B9 and phenytoin (and fosphenytoin) may result in decreased folic acid serum concentrations and decreased anticonvulsant effect. It is important to maintain adequate folic acid concentrations in epileptic patients taking enzyme-inducing anticonvulsants, and maintenance doses may require upward adjustment. However, in large amounts, folic acid may counteract the anticonvulsant effect of some agents, including phenytoin. Therefore, it has been recommended that oral folic acid supplementation not exceed 1 mg/day in epileptic patients taking anticonvulsants. If large doses are used, monitor phenytoin concentrations upon folic acid initiation, dose titration, and discontinuation and adjust the anticonvulsant dosage as appropriate. Prolonged administration of phenytoin reportedly has resulted in a folate deficiency in 27% to 91% of patients. Megaloblastic anemia occurs in fewer than 1% of patients receiving phenytoin. The proposed mechanisms of this phenomenon include an increase in folate catabolism, folate malabsorption, or use of folic acid secondary to enzyme induction by phenytoin. Some evidence suggests that the anticonvulsant effect of phenytoin is partially the result of a reduction in folic acid concentrations. Folic acid replacement has resulted in an increase in metabolism of phenytoin and a decrease in phenytoin concentration in some patients, apparently through increased metabolism and/or redistribution of phenytoin in the brain and CSF. A clinically significant increase in seizure activity has occurred with this drug combination in rare instances, especially when doses of 4 mg/day or more were utilized. (Minor) In a limited case report, the administration of pyridoxine, vitamin B6 (range of 80 to 400 mg PO) once daily for 2-4 weeks, resulted in approximate 35% (range 17 to 70%) reductions in serum phenytoin concentrations. The authors postulated that pyridoxine increased the metabolism of phenytoin anticonvulsants. The evidence for the interaction is limited, and there is no data to suggest that lower supplemental doses would result in alterations in the pharmacokinetics of phenytoin or fosphenytoin. The clinical significance of this potential interaction is questionable. If a patient is using large doses of pyridoxine, then the clinician should be alert to possible alterations.
    Gallium Ga 68 Dotatate: (Moderate) Diuretics may interfere with the kidneys ability to regulate magnesium concentrations. Long-term use of diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia.
    Gallium: (Moderate) Concurrent administration products containing calcium salts may antagonize the effects of gallium nitrate.
    Garlic, Allium sativum: (Minor) Garlic, Allium sativum may produce clinically-significant antiplatelet effects; until more data are available, garlic should be used cautiously in patients receiving other supplements with a potential risk for bleeding such as ginger.
    Gemifloxacin: (Major) Administer oral products that contain iron at least 3 hours before or 2 hours after gemifloxacin. Gemifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. (Major) Administer oral products that contain magnesium at least 3 hours before or 2 hours after gemifloxacin. Gemifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain magnesium. (Major) Administer oral products that contain zinc at least 3 hours before or 2 hours after gemifloxacin. Gemifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc.
    Ginkgo, Ginkgo biloba: (Moderate) Ginkgo is reported to inhibit platelet aggregation and several case reports describe bleeding complications with Ginkgo biloba, with or without concomitant drug therapy. In theory, Ginkgo, Gingko biloba may interact with other herbs or dietary supplements that exhibit antiplatelet effects or anticoagulant activity, such as ginger.
    Ginseng, Panax ginseng: (Moderate) Ginseng exerts antiplatelet activity and theoretically may interact with other herbs and dietary supplements that exhibit antiplatelet effects or anticoagulant activity, such as ginger.
    Glimepiride: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added.
    Glimepiride; Rosiglitazone: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added.
    Glipizide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added.
    Glipizide; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Glyburide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added.
    Glyburide; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Green Tea: (Major) Green tea has been shown to inhibit the absorption of nonheme iron. When possible, do not consume green tea or green tea extract within 1 hour before or 2 hours after giving iron salts. (Moderate) Green tea has demonstrated antiplatelet and fibrinolytic actions in animals. Use caution when combining green tea with herbs that exhibit antiplatelet effects or anticoagulant activity, such as ginger.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Guaifenesin; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Guaifenesin; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    H2-blockers: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    HMG-CoA reductase inhibitors: (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
    Hydantoins: (Moderate) Phenytoin and fosphenytoin can decrease the activity of vitamin D (e.g., cholecalciferol) by increasing its metabolism. In rare cases, this has caused anticonvulsant-induced rickets and osteomalacia. Vitamin D supplementation or dosage adjustments may be required in patients who are receiving chronic treatment with anticonvulsants.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Major) Coadministration of methyldopa with iron salts or polysaccharide-iron complex is not recommended. If iron supplementation is necessary, administer a methyldopa dose at least 2 hours prior to the iron supplement. Iron salts have been reported to dramatically reduce the oral absorption of methyldopa. Several studies demonstrate decreased bioavailability of methyldopa when coadministered with ferrous sulfate or ferrous gluconate. This interaction may result in decreased antihypertensive effect of methyldopa. (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrocodone; Ibuprofen: (Minor) L-methylfolate should be used cautiously in patients taking high doses of ibuprofen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of ibuprofen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Hydrocodone; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Hydrocodone; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) The therapeutic action of methenamine requires an acidic urine. Ascorbic acid, vitamin C can produce unpredictable changes in urine pH and should be avoided as a urinary acidifier. In addition, orange juice also should be avoided because citric acid ultimately may raise urine pH. (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
    Ibandronate: (Moderate) Magnesium-containing products may significantly reduce the absorption of ibandronate. All medications should be administered at least 60 minutes after an ibandronate dose to help prevent these absorption interactions. However, some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after ibandronate or at a completely different time of day.
    Ibritumomab Tiuxetan: (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphates by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions. (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphorus salts by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions. (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
    Ibuprofen: (Minor) L-methylfolate should be used cautiously in patients taking high doses of ibuprofen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of ibuprofen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Ibuprofen; Oxycodone: (Minor) L-methylfolate should be used cautiously in patients taking high doses of ibuprofen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of ibuprofen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Ibuprofen; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available. (Minor) L-methylfolate should be used cautiously in patients taking high doses of ibuprofen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of ibuprofen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Iloprost: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Inamrinone: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of inotropic agents, however, no clinical data are available.
    Incretin Mimetics: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Indomethacin: (Minor) L-methylfolate should be used cautiously in patients taking high doses of indomethacin. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of indomethacin. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Insulin Degludec; Liraglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Insulin Glargine; Lixisenatide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Insulins: (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when niacin, niacinamide is instituted or discontinued. Dosage adjustments may be necessary. Niacin interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added.
    Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Iron - Injectable Only: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
    Iron Dextran: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
    Iron Salts: (Moderate) Orally administered zinc salts compete with iron supplements for absorption from the intestine. To minimize the interaction, separate oral iron and zinc doses by at least 2 hours. The oral receipt of 100 mg of iron as ferrous gluconate with 12 mg zinc in 11 patients with normal iron status and comparable total exchangeable zinc pools yielded a mean zinc absorption of 26.4% +/- 14.4% of the administered dose as compared with 44.5% +/- 22.5% of the dose given without concomitant iron. Concomitant use of iron 400 mg as ferrous gluconate yielded a mean zinc absorption of 22.9% +/- 6.4% of the zinc dose.
    Iron Sucrose, Sucroferric Oxyhydroxide: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
    Iron: (Moderate) Orally administered zinc salts compete with iron supplements for absorption from the intestine. To minimize the interaction, separate oral iron and zinc doses by at least 2 hours. The oral receipt of 100 mg of iron as ferrous gluconate with 12 mg zinc in 11 patients with normal iron status and comparable total exchangeable zinc pools yielded a mean zinc absorption of 26.4% +/- 14.4% of the administered dose as compared with 44.5% +/- 22.5% of the dose given without concomitant iron. Concomitant use of iron 400 mg as ferrous gluconate yielded a mean zinc absorption of 22.9% +/- 6.4% of the zinc dose.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of cholecalciferol, Vitamin D3. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of cholecalciferol, Vitamin D3 may be required.
    Isoniazid, INH; Rifampin: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of cholecalciferol, Vitamin D3. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of cholecalciferol, Vitamin D3 may be required.
    Isoproterenol: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of inotropic agents, however, no clinical data are available.
    Isotretinoin: (Minor) L-methylfolate and isotretinoin should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with isotretinoin. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Kanamycin: (Moderate) Monitor for decreased efficacy of kanamycin during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration may result in decreased efficacy of kanamycin.
    Ketoprofen: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Ketorolac: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Lamotrigine: (Minor) L-methylfolate concentrations may be reduced when administered concomitantly with lamotrigine. Patients should be monitored closely for decreased efficacy of L-methylfolate if these agents are used together.
    Lansoprazole: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Lansoprazole; Naproxen: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts. (Minor) L-methylfolate should be used cautiously in patients taking high doses of naproxen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of naproxen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Lanthanum Carbonate: (Major) Oral compounds known to interact with antacids, like iron salts, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
    Levodopa: (Contraindicated) Pyridoxine, vitamin B6, in doses as low as 10 mg/day, can accelerate the rate of aromatic amino acid decarboxylation, thus increasing the peripheral conversion of levodopa to dopamine. This action diminishes levodopa's therapeutic effects by decreasing the amount of levodopa that is available to cross into the CNS. Patients receiving levodopa single-agent therapy should avoid vitamin B6 supplements. (Major) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
    Levofloxacin: (Major) Administer oral products that contain calcium at least 2 hours before or 2 hours after orally administered levofloxacin. Levofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Chelation of divalent cations with levofloxacin is less than with other quinolones. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. (Major) Administer oral products that contain iron at least 2 hours before or 2 hours after orally administered levofloxacin. Levofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Chelation of divalent cations with levofloxacin is less than with other quinolones. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. (Major) Administer oral products that contain magnesium at least 2 hours before or 2 hours after orally administered levofloxacin. Levofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Chelation of divalent cations with levofloxacin is less than with other quinolones. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain magnesium. (Major) Administer oral products that contain zinc at least 2 hours before or 2 hours after orally administered levofloxacin. Levofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Chelation of divalent cations with levofloxacin is less than with other quinolones. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc.
    Levonorgestrel; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Levothyroxine: (Moderate) Administer thyroid hormones at least 4 hours before or after antacids, dietary supplements, or other drugs containing magnesium. Magnesium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of levothyroxine with products containing oral cations, such as antacids or dietary supplements.
    Levothyroxine; Liothyronine (Porcine): (Moderate) Administer thyroid hormones at least 4 hours before or after antacids, dietary supplements, or other drugs containing magnesium. Magnesium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of levothyroxine with products containing oral cations, such as antacids or dietary supplements.
    Levothyroxine; Liothyronine (Synthetic): (Moderate) Administer thyroid hormones at least 4 hours before or after antacids, dietary supplements, or other drugs containing magnesium. Magnesium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of levothyroxine with products containing oral cations, such as antacids or dietary supplements.
    Lidocaine: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of antiarrhythmics, however, no clinical data are available.
    Lidocaine; Prilocaine: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of antiarrhythmics, however, no clinical data are available.
    Linagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750-2000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on linagliptin for changes in blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Linagliptin; Metformin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750-2000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on linagliptin for changes in blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Lincomycin: (Moderate) Monitor for decreased efficacy of lincomycin during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration may result in decreased efficacy of lincomycin.
    Liothyronine: (Moderate) Administer thyroid hormones at least 4 hours before or after antacids, dietary supplements, or other drugs containing magnesium. Magnesium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of levothyroxine with products containing oral cations, such as antacids or dietary supplements.
    Liraglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Lixisenatide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Loop diuretics: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Loratadine; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Losartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Lovastatin: (Major) There is no clear indication for routine use of niacin in combination with lovastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with lovastatin. If coadministered, consider lower starting and maintenance does of lovastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue lovastatin immediately if myopathy is diagnosed or suspected. (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
    Lovastatin; Niacin: (Major) There is no clear indication for routine use of niacin in combination with lovastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with lovastatin. If coadministered, consider lower starting and maintenance does of lovastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue lovastatin immediately if myopathy is diagnosed or suspected. (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
    Magnesium Citrate: (Moderate) Concurrent use of magnesium salts with other magnesium-containing products, such as magnesium citrate, may result in magnesium toxicity, especially in patients with renal impairment. Single use of magnesium citrate solution for bowel cleansing may warrant caution if significant renal impairment exists. Magnesium citrate should not be used chronically as a laxative due to the risk of hypermagnesemia. (Moderate) Magnesium-containing drug products, such as magnesium citrate, should be used cautiously in patients receiving vitamin D. Because vitamin D can increase serum magnesium concentrations, the combined use of vitamin D and magnesium-containing drug products should be avoided, if possible, in patients with chronic renal failure.
    Magnesium Hydroxide: (Moderate) Magnesium-containing antacids, such as magnesium hydroxide, should be used cautiously in patients receiving vitamin D (cholecalciferol). Because vitamin D can increase serum magnesium concentrations, the combined use of vitamin D and magnesium-containing drug products should be avoided, if possible, in patients with chronic renal failure. (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
    Magnesium Salicylate: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
    Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Major) Administer iron at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of iron may be reduced by chelation with magnesium sulfate.
    Magnesium: (Moderate) Magnesium-containing drug products and magnesium salts should be used cautiously in patients receiving vitamin D. Because vitamin D can increase serum magnesium concentrations, the combined use of vitamin D and magnesium-containing drug products should be avoided, if possible, in patients with chronic renal failure.
    Mannitol: (Moderate) Diuretics may interfere with the kidneys ability to regulate magnesium concentrations. Long-term use of diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia.
    Mecamylamine: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Meclofenamate Sodium: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Mefenamic Acid: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Meloxicam: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Mestranol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Metformin: (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Metformin; Repaglinide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Metformin; Rosiglitazone: (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Metformin; Saxagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacinamide interferes with glucose metabolism and can result in hyperglycemia. Monitor patients taking antidiabetic agents for changes in glycemic control if niacinamide is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Metformin; Sitagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacinamide interferes with glucose metabolism and can result in hyperglycemia. Monitor patients taking antidiabetic agents for changes in glycemic control if niacinamide is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Methenamine: (Moderate) The therapeutic action of methenamine requires an acidic urine. Ascorbic acid, vitamin C can produce unpredictable changes in urine pH and should be avoided as a urinary acidifier. In addition, orange juice also should be avoided because citric acid ultimately may raise urine pH.
    Methenamine; Sodium Acid Phosphate: (Moderate) The therapeutic action of methenamine requires an acidic urine. Ascorbic acid, vitamin C can produce unpredictable changes in urine pH and should be avoided as a urinary acidifier. In addition, orange juice also should be avoided because citric acid ultimately may raise urine pH.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) The therapeutic action of methenamine requires an acidic urine. Ascorbic acid, vitamin C can produce unpredictable changes in urine pH and should be avoided as a urinary acidifier. In addition, orange juice also should be avoided because citric acid ultimately may raise urine pH.
    Methotrexate: (Moderate) Folic acid may compete with methotrexate for entry into cells. However, in some situations, folic acid supplementation may be used to decrease adverse reactions such as mouth sores in patients receiving methotrexate for arthritis and other non-malignant diseases. Folic acid, vitamin B9, is NOT effective for methotrexate rescue therapy since folic acid requires dihydrofolate reductase for bioactivation and methotrexate inhibits this enzyme. Therefore folic acid should not be used to prevent toxicity of moderate- to high-dose methotrexate therapy. (Minor) L-methylfolate should be used cautiously in patients taking methotrexate. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with methotrexate. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Methoxsalen: (Moderate) Use methoxsalen and retinoids together with caution; the risk of severe burns/phototoxicity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Methoxy polyethylene glycol-epoetin beta: (Minor) Iron stores should be replete before and during treatment with an ESA. Iron stores are utilized in erythropoiesis and can be depleted during therapy even in patients with normal pre-treatment iron concentrations. Achieving and maintaining adequate iron stores are essential to attaining an optimal response to MPG-epoetin beta. Iron supplementation may be needed before and during therapy (e.g. iron dextran; iron salts; sodium ferric gluconate complex; iron sucrose, sucroferric oxyhydroxide; and polysaccharide-iron complex.
    Methyclothiazide: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Methyldopa: (Major) Coadministration of methyldopa with iron salts or polysaccharide-iron complex is not recommended. If iron supplementation is necessary, administer a methyldopa dose at least 2 hours prior to the iron supplement. Iron salts have been reported to dramatically reduce the oral absorption of methyldopa. Several studies demonstrate decreased bioavailability of methyldopa when coadministered with ferrous sulfate or ferrous gluconate. This interaction may result in decreased antihypertensive effect of methyldopa.
    Methylprednisolone: (Minor) L-methylfolate and methylprednisolone should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with methylprednisolone. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Methylsulfonylmethane, MSM: (Moderate) Increased bruising or blood in the stool from concomitant anticoagulant drugs have been reported in patients taking methylsulfonylmethane. Avoid other herbs that exhibit antiplatelet or anticoagulant activity, such as ginger.
    Metolazone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Mexiletine: (Minor) Ascorbic acid, vitamin C in doses greater than 2 grams per day can lower urinary pH, potentially causing enhanced the plasma clearance of mexiletine. (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of antiarrhythmics, however, no clinical data are available.
    Midodrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of antiarrhythmics, inotropes and vasopressors; however, no clinical data are available.
    Miglitol: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added.
    Milrinone: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of inotropic agents, however, no clinical data are available.
    Mineral Oil: (Moderate) Absorption of fat-soluble vitamins is reported to be decreased with prolonged oral administration of mineral oil. However, despite warnings in various texts, there is little direct evidence that the interaction is of practical/clinical importance with limited use as directed. It may be prudent for those taking dietary supplements of Vitamin A, D, E, or K to separate administration by 1 hour before or 4 hours after a mineral oil oral dosage to help limit absorption interactions. Theoretically, the effect on fat-soluble vitamin absorption may more likely occur with prolonged or chronic administration of mineral oil. (Moderate) Absorption of fat-soluble vitamins is reported to be decreased with prolonged oral administration of mineral oil. However, despite warnings in various texts, there is little direct evidence that the interaction is of practical/clinical importance with limited use as directed. It may be prudent for those taking dietary supplements of Vitamin A, D, E, or K to separate administration by 1 hour before or 4 hours after a mineral oil oral dosage to help limit absorption interactions. Theoretically, the effect on fat-soluble vitamin absorption may more likely occur with prolonged or chronic administration of mineral oil.
    Mivacurium: (Moderate) Concomitant use of neuromuscular blockers and magnesium may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Moxifloxacin: (Major) Administer oral moxifloxacin at least 4 hours before or 8 hours after oral products that contain calcium. Moxifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. (Major) Administer oral moxifloxacin at least 4 hours before or 8 hours after oral products that contain iron. Moxifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. (Major) Administer oral moxifloxacin at least 4 hours before or 8 hours after oral products that contain magnesium. Moxifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain magnesium. (Major) Administer oral moxifloxacin at least 4 hours before or 8 hours after oral products that contain zinc. Moxifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc.
    Mycophenolate: (Major) Conflicting information has been reported regarding coadministration of mycophenolate and iron salts. Due to the discrepant findings and study differences, additional data are needed to clarify the potential interaction between iron salts and MMF. Until more information is available, avoid concurrent administration of mycophenolate mofetil and oral iron salts, including polysaccharide-iron complex, if possible.
    Nabumetone: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Naproxen: (Minor) L-methylfolate should be used cautiously in patients taking high doses of naproxen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of naproxen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Naproxen; Esomeprazole: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts. (Minor) L-methylfolate should be used cautiously in patients taking high doses of naproxen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of naproxen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Naproxen; Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available. (Minor) L-methylfolate should be used cautiously in patients taking high doses of naproxen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of naproxen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Nateglinide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Neomycin: (Minor) Oral neomycin has been shown to inhibit the gastrointestinal absorption of cyanocobalamin, Vitamin B12. Caution is warranted with concomitant use.
    Nesiritide, BNP: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of antiarrhythmics, inotropes and vasopressors; however, no clinical data are available.
    Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade. (Moderate) Concomitant use of neuromuscular blockers and magnesium may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Niacin; Simvastatin: (Major) There is no clear indication for routine use of niacin in combination with simvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with simvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue simvastatin immediately if myopathy is diagnosed or suspected. Coadministration is not recommended in Chinese patients, as the risk of myopathy is greater in this population. It is unknown if this risk applies to other Asian patients. (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
    Nifedipine: (Major) Clinically significant drug interactions including neuromuscular blockade and hypotension have occurred when IV magnesium salts were given concurrently with nifedipine during the treatment of hypertension or premature labor during pregnancy. The effects have been attributed to nifedipine potentiation of the neuromuscular blocking effects of magnesium. It is recommended that nifedipine not be given concurrently with magnesium therapy for pre-eclampsia, hypertension, or tocolytic treatment during pregnancy.
    Nitrofurantoin: (Moderate) L-methylfolate and nitrofurantoin should be used together cautiously. Nitrofurantoin is a folate antagonist. Plasma concentrations of both medications may be reduced when used concomitantly. (Moderate) Nitrofurantoin is a folate antagonist. Patients taking nitrofurantoin may develop folate deficiency. Further study is needed to confirm these interactions.
    Nizatidine: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Nonsteroidal antiinflammatory drugs: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Norepinephrine: (Minor) In vitro studies have demonstrated the positive inotropic effect ginger, Zingiber officinale. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like norepinephrine; however, no clinical data are available.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Orally administered zinc salts compete with iron supplements for absorption from the intestine. To minimize the interaction, separate oral iron and zinc doses by at least 2 hours. The oral receipt of 100 mg of iron as ferrous gluconate with 12 mg zinc in 11 patients with normal iron status and comparable total exchangeable zinc pools yielded a mean zinc absorption of 26.4% +/- 14.4% of the administered dose as compared with 44.5% +/- 22.5% of the dose given without concomitant iron. Concomitant use of iron 400 mg as ferrous gluconate yielded a mean zinc absorption of 22.9% +/- 6.4% of the zinc dose. (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Norethindrone; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Orally administered zinc salts compete with iron supplements for absorption from the intestine. To minimize the interaction, separate oral iron and zinc doses by at least 2 hours. The oral receipt of 100 mg of iron as ferrous gluconate with 12 mg zinc in 11 patients with normal iron status and comparable total exchangeable zinc pools yielded a mean zinc absorption of 26.4% +/- 14.4% of the administered dose as compared with 44.5% +/- 22.5% of the dose given without concomitant iron. Concomitant use of iron 400 mg as ferrous gluconate yielded a mean zinc absorption of 22.9% +/- 6.4% of the zinc dose. (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Norfloxacin: (Major) Administer oral products that contain calcium at least 2 hours before or 2 hours after norfloxacin. Norfloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. (Major) Administer oral products that contain iron at least 2 hours before or 2 hours after norfloxacin. Norfloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. (Major) Administer oral products that contain magnesium at least 2 hours before or 2 hours after norfloxacin. Norfloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain magnesium. (Major) Administer oral products that contain zinc at least 2 hours before or 2 hours after norfloxacin. Norfloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc.
    Norgestimate; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Octreotide: (Minor) Depressed levels of cyanocobalamin, vitamin B12, and abnormal Schilling's test have been reported in patients receiving octreotide.
    Ofloxacin: (Major) Administer oral products that contain calcium at least 2 hours before or 2 hours after ofloxacin. Ofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. (Major) Administer oral products that contain iron at least 2 hours before or 2 hours after ofloxacin. Ofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron. (Major) Administer oral products that contain magnesium at least 2 hours before or 2 hours after ofloxacin. Ofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain magnesium. (Major) Administer oral products that contain zinc at least 2 hours before or 2 hours after ofloxacin. Ofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc.
    Olanzapine; Fluoxetine: (Minor) Levomefolate and fluoxetine should be used together cautiously. Fluoxetine is a noncompetitive inhibitor of levomefolate active transport in the intestines. Monitor patients for decreased efficacy of levomefolate if these agents are used together.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Omeprazole: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Omeprazole; Amoxicillin; Rifabutin: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Omeprazole; Sodium Bicarbonate: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts. (Minor) Because antacids can alkalinize the urine, they can interact with urinary acidifiers, such as ascorbic acid. Frequent use of high doses of antacids should be avoided by patients receiving urinary acidifiers.
    Orlistat: (Moderate) Administer vitamin E at least 2 hours before or after the administration of orlistat to limit effects on oral absorption. Orlistat has been shown to inhibit the absorption of a vitamin E acetate supplement by 60%. (Moderate) Due to orlistat's mechanism of action, the potential exists for the malabsorption of drugs and dietary supplements. Patients should be advised to take a multivitamin supplement once per day that contains fat soluble vitamins A, D, E, K and beta-carotene. The manufacturer recommends that fat-soluble vitamin supplements be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption. (Moderate) Orlistat reduced the absorption of fat-soluble vitamins during clinical trials. The bioavailability of orally administered vitamin D may also be decreased. In patients receiving orally-administered vitamin D with orlistat, close monitoring is recommended. In addition, the manufacturer recommends that fat-soluble vitamins be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption.
    Oxaprozin: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and magnesium may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Pantoprazole: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Penicillamine: (Major) In general, oral mineral supplements should not be given since they may block the oral absorption of penicillamine. However, iron deficiency may develop, especially in children and menstruating or pregnant women, or as a result of the low copper diet recommended for Wilson's disease. If necessary, iron may be given in short courses, but since iron and penicillamine each inhibit oral absorption of the other, 2 hours should elapse between administration of penicillamine and iron doses. (Moderate) Pyridoxine, vitamin B6 excretion can be increased during the administration of penicillamine, possibly causing anemia or peripheral neuritis. Pyridoxine dosages may need to be increased during concomitant administration of penicillamine.
    Pentamidine: (Minor) L-methylfolate and pentamidine should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with pentamidine. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Pentoxifylline: (Moderate) Ginger inhibits thromboxane synthetase, a platelet aggregation inducer, and is a prostacyclin agonist so additive effects on hemostasis might occur if pentoxifylline is given in combination with ginger.
    Phenobarbital: (Moderate) Numerous studies indicate that folate status is impaired with the chronic use of phenobarbital, presumably via inhibition of the intestinal absorption of folic acid. The studies available suffer from poor methodologic control and definitive conclusions cannot be drawn relative to adverse effects of phenobarbital on folate status. In addition, high doses of folate may result in decreased serum concentrations of phenobarbital resulting in a decrease in effectiveness and, possibly, an increase in the frequency of seizures in susceptible patients. Although no decrease in effectiveness of anticonvulsants has been reported with the concurrent use of L-methylfolate, caution still should be exercised with the coadministration of these agents and patients should be monitored closely for seizure activity. (Moderate) Phenobarbital use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like phenobarbital, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly. (Minor) Concurrent use of folic acid, vitamin B9 and phenobarbital may result in decreased folic acid serum concentrations and decreased anticonvulsant effect. It is important to maintain adequate folic acid concentrations in epileptic patients taking enzyme-inducing anticonvulsants, and maintenance doses may require upward adjustment. However, in large amounts, folic acid may counteract the anticonvulsant effect of some agents, including phenobarbital. Therefore, it has been recommended that oral folic acid supplementation not exceed 1 mg/day in epileptic patients taking anticonvulsants. If large doses are used, monitor phenobarbital concentrations upon folic acid initiation, dose titration, and discontinuation. Adjust the anticonvulsant dosage as appropriate. (Minor) In a limited case report, the administration of pyridoxine, vitamin B6 (200 mg once daily x 4 weeks) resulted in reduced serum phenobarbital concentrations in 5 patients with epilepsy; the reductions approached 50%. The evidence for the interaction is limited, and there is no data to suggest that lower supplemental doses would result in alterations in the pharmacokinetics of phenobarbital. The clinical significance of this potential interaction is questionable. If a patient is using large doses of pyridoxine, then the clinician should be alert to possible alterations.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Numerous studies indicate that folate status is impaired with the chronic use of phenobarbital, presumably via inhibition of the intestinal absorption of folic acid. The studies available suffer from poor methodologic control and definitive conclusions cannot be drawn relative to adverse effects of phenobarbital on folate status. In addition, high doses of folate may result in decreased serum concentrations of phenobarbital resulting in a decrease in effectiveness and, possibly, an increase in the frequency of seizures in susceptible patients. Although no decrease in effectiveness of anticonvulsants has been reported with the concurrent use of L-methylfolate, caution still should be exercised with the coadministration of these agents and patients should be monitored closely for seizure activity. (Moderate) Phenobarbital use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like phenobarbital, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly. (Minor) Concurrent use of folic acid, vitamin B9 and phenobarbital may result in decreased folic acid serum concentrations and decreased anticonvulsant effect. It is important to maintain adequate folic acid concentrations in epileptic patients taking enzyme-inducing anticonvulsants, and maintenance doses may require upward adjustment. However, in large amounts, folic acid may counteract the anticonvulsant effect of some agents, including phenobarbital. Therefore, it has been recommended that oral folic acid supplementation not exceed 1 mg/day in epileptic patients taking anticonvulsants. If large doses are used, monitor phenobarbital concentrations upon folic acid initiation, dose titration, and discontinuation. Adjust the anticonvulsant dosage as appropriate. (Minor) In a limited case report, the administration of pyridoxine, vitamin B6 (200 mg once daily x 4 weeks) resulted in reduced serum phenobarbital concentrations in 5 patients with epilepsy; the reductions approached 50%. The evidence for the interaction is limited, and there is no data to suggest that lower supplemental doses would result in alterations in the pharmacokinetics of phenobarbital. The clinical significance of this potential interaction is questionable. If a patient is using large doses of pyridoxine, then the clinician should be alert to possible alterations.
    Phenoxybenzamine: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents.
    Phentolamine: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents.
    Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Phenytoin: (Moderate) Numerous studies indicate that folate status is impaired with the chronic use of diphenylhydantoin (phenytoin or fosphenytoin). Prolonged administration of phenytoin reportedly has resulted in a folate deficiency. In addition, folic acid replacement has resulted in an increase in metabolism of phenytoin and a decrease in phenytoin concentration in some patients, apparently through increased metabolism and/or redistribution of phenytoin in the brain and CSF. Although no decrease in effectiveness of anticonvulsants has been reported with the concurrent use of L-methylfolate, caution still should be exercised with the coadministration of these agents, and patients should be monitored closely for seizure activity. (Moderate) Phenytoin use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like phenytoin, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly. (Minor) Concurrent use of folic acid, vitamin B9 and phenytoin may result in decreased folic acid serum concentrations and decreased anticonvulsant effect. It is important to maintain adequate folic acid concentrations in epileptic patients taking enzyme-inducing anticonvulsants, and maintenance doses may require upward adjustment. However, in large amounts, folic acid may counteract the anticonvulsant effect of some agents, including phenytoin. Therefore, it has been recommended that oral folic acid supplementation not exceed 1 mg/day in epileptic patients taking anticonvulsants. If large doses are used, monitor phenytoin concentrations upon folic acid initiation, dose titration, and discontinuation and adjust the anticonvulsant dosage as appropriate. Prolonged administration of phenytoin reportedly has resulted in a folate deficiency in 27% to 91% of patients. Megaloblastic anemia occurs in fewer than 1% of patients receiving phenytoin. The proposed mechanisms of this phenomenon include an increase in folate catabolism, folate malabsorption, or use of folic acid secondary to enzyme induction by phenytoin. Some evidence suggests that the anticonvulsant effect of phenytoin is partially the result of a reduction in folic acid concentrations. Folic acid replacement has resulted in an increase in metabolism of phenytoin and a decrease in phenytoin concentration in some patients, apparently through increased metabolism and/or redistribution of phenytoin in the brain and CSF. A clinically significant increase in seizure activity has occurred with this drug combination in rare instances, especially when doses of 4 mg/day or more were utilized. (Minor) Limited data suggests that large doses (greater than 80 mg per day) of pyridoxine, vitamin B6 may result in reduced serum phenytoin concentrations. Regular doses, such as in multivitamins, probably will have little effect. Monitor for reduced serum phenytoin concentrations or changes in seizure control if large doses of pyridoxine, vitamin B6 are coadminsitered.
    Phosphorated Carbohydrate Solution: (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphates by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions. (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphorus salts by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions. (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
    Phosphorus: (Major) High intake of phosphates concomitantly with vitamin D or vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphates by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions. (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphorus salts by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions. (Moderate) Phosphate may bind magnesium salts and magnesium-containing antacids (e.g., magnesium carbonate, magnesium hydroxide) may limit phosphorus absorption or phosphorus may limit magnesium absorption. If the patient requires magnesium supplements or a magnesium-containing antacid, it may be wise to separate the administration of phosphates from magnesium-containing products. (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue. (Minor) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of potassium phosphate; sodium phosphateby as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions.
    Pioglitazone; Glimepiride: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added.
    Pioglitazone; Metformin: (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin may interfere with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated.
    Piroxicam: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Pitavastatin: (Major) There is no clear indication for routine use of niacin in combination with pitavastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with pitavastatin. If coadministered, consider lower starting and maintenance does of pitavastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue pitavastatin immediately if myopathy is diagnosed or suspected. (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
    Platelet Inhibitors: (Moderate) Ginger inhibits thromboxane synthetase, a platelet aggregation inducer, and is a prostacyclin agonist so additive bleeding may occur if platelet inhibitors are given in combination with ginger, zingiber officinale.
    Polycarbophil: (Moderate) Oral calcium-containing medications, such as calcium polycarbophil, may increase serum calcium or magnesium concentrations in susceptible patients, primarily in patients with renal insufficiency. Calcium and magnesium salts are often combined together in nutritional supplements and vitamin products. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg).
    Polyethylene Glycol; Electrolytes: (Major) Administer iron at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of iron may be reduced by chelation with magnesium sulfate.
    Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Major) Administer iron at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of iron may be reduced by chelation with magnesium sulfate.
    Polysaccharide-Iron Complex: (Moderate) Orally administered zinc salts compete with iron supplements for absorption from the intestine. To minimize the interaction, separate oral iron and zinc doses by at least 2 hours. The oral receipt of 100 mg of iron as ferrous gluconate with 12 mg zinc in 11 patients with normal iron status and comparable total exchangeable zinc pools yielded a mean zinc absorption of 26.4% +/- 14.4% of the administered dose as compared with 44.5% +/- 22.5% of the dose given without concomitant iron. Concomitant use of iron 400 mg as ferrous gluconate yielded a mean zinc absorption of 22.9% +/- 6.4% of the zinc dose.
    Porfimer: (Major) Avoid coadministration of porfimer with retinoids due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like retinoids may increase the risk of a photosensitivity reaction.
    Potassium Phosphate: (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphates by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions. (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphorus salts by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions. (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
    Potassium Phosphate; Sodium Phosphate: (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphates by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions. (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphorus salts by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions. (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
    Potassium-sparing diuretics: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Pramlintide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Pravastatin: (Major) There is no clear indication for routine use of niacin in combination with pravastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with pravastatin. If coadministered, consider lower starting and maintenance does of pravastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue pravastatin immediately if myopathy is diagnosed or suspected. (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
    Prazosin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents.
    Prilocaine; Epinephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of inotropic agents, however, no clinical data are available.
    Primidone: (Moderate) High doses of folate may cause decreased serum concentrations of primidone resulting in a decrease in effectiveness and, possibly, an increase in the frequency of seizures in susceptible patients. In addition, L-methylfolate plasma levels may be decreased when administered with primidone. Although no decrease in effectiveness of anticonvulsants has been reported with the concurrent use of L-methylfolate, caution still should be exercised with the coadministration of these agents and patients should be monitored closely for seizure activity. (Moderate) Primidone use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like primidone, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly. (Minor) Concurrent use of folic acid, vitamin B9 and phenobarbital and primidone may result in decreased folic acid serum concentrations and decreased anticonvulsant effect. It is important to maintain adequate folic acid concentrations in epileptic patients taking enzyme-inducing anticonvulsants, and maintenance doses may require upward adjustment. However, in large amounts, folic acid may counteract the anticonvulsant effect of some agents, including phenobarbital and primidone. Therefore, it has been recommended that oral folic acid supplementation not exceed 1 mg/day in epileptic patients taking anticonvulsants. If large doses are used, monitor phenobarbital concentrations upon folic acid initiation, dose titration, and discontinuation. Adjust the anticonvulsant dosage as appropriate.
    Probenecid; Colchicine: (Minor) Colchicine has been shown to induce reversible malabsorption of vitamin B12. Patients receiving these agents concurrently should be monitored for the desired therapeutic response to vitamin B12. (Minor) L-methylfolate and colchicine should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with colchicine. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Promethazine; Phenylephrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like phenylephrine; however, no clinical data are available.
    Propranolol: (Minor) Ascorbic acid may reduce the oral bioavailability of propranolol. Advise patients against taking large doses of ascorbic acid with doses of propranolol.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended. (Minor) Ascorbic acid may reduce the oral bioavailability of propranolol. Advise patients against taking large doses of ascorbic acid with doses of propranolol.
    Proton pump inhibitors: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Pseudoephedrine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Pseudoephedrine; Triprolidine: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of vasopressors like pseudoephedrine; however, no clinical data are available.
    Pyridostigmine: (Moderate) Magnesium salts may enhance the neuromuscular blockade and may interfere with the restoration of neuromuscular function. Consider the possibility of enhanced neuromuscular blockade from magnesium salts during pyridostigmine administration.
    Pyrimethamine: (Moderate) L-methylfolate and pyrimethamine should be used together cautiously. Pyrimethamine is a folate antagonist. Plasma concentrations of both medications may be reduced when used concomitantly. (Moderate) Pyrimethamine is a folate antagonist. Some evidence suggests that administration of folic acid to leukemia patients receiving pyrimethamine for Pneumocystis carinii resulted in exacerbation of leukemia symptoms. Folic acid, vitamin B9 reportedly interferes with the action of pyrimethamine in treating toxoplasmosis. Further study is needed to confirm these interactions.
    Pyrimethamine; Sulfadoxine: (Moderate) L-methylfolate and pyrimethamine should be used together cautiously. Pyrimethamine is a folate antagonist. Plasma concentrations of both medications may be reduced when used concomitantly. (Moderate) Pyrimethamine is a folate antagonist. Some evidence suggests that administration of folic acid to leukemia patients receiving pyrimethamine for Pneumocystis carinii resulted in exacerbation of leukemia symptoms. Folic acid, vitamin B9 reportedly interferes with the action of pyrimethamine in treating toxoplasmosis. Further study is needed to confirm these interactions.
    Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Rabeprazole: (Moderate) Proton pump inhibitors may cause a decrease in the oral absorption of cyanocobalamin, vitamin B12. Patients receiving long-term therapy with proton pump inhibitors should be monitored for signs of B12 deficiency. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Ranitidine: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Rapacuronium: (Moderate) Concomitant use of neuromuscular blockers and magnesium may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Red Yeast Rice: (Major) Since compounds in red yeast rice are chemically similar to and possess actions similar to lovastatin, patients should avoid this dietary supplement if they currently take drugs known to increase the risk of myopathy when coadministered with HMG-CoA reductase inhibitors. Niacin (as nicotinic acid, vitamin B3 in antilipemic doses) directly increases the risk of myopathy. (Major) Since compounds in red yeast rice are chemically similar to and possess actions similar to lovastatin, patients should avoid this dietary supplement if they currently take drugs known to increase the risk of myopathy when coadministered with HMG-CoA reductase inhibitors. Niacin (as nicotinic acid, vitamin B3 in antilipemic doses) directly increases the risk of myopathy.
    Relugolix; Estradiol; Norethindrone acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Repaglinide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia; monitor patients on antidiabetic agents for loss of blood glucose control if niacin therapy is added.
    Reserpine: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Rifampin: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of cholecalciferol, Vitamin D3. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of cholecalciferol, Vitamin D3 may be required.
    Risedronate: (Moderate) Oral magnesium may significantly reduce the absorption of the oral bisphosphonates (e.g. risedronate). All medications should be administered at least 30 minutes after a risedronate dose to help prevent these absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after oral bisphosphonates or at a completely different time of day. (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of risedronate therapy.
    Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and magnesium may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Rofecoxib: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity.
    Rosuvastatin: (Major) There is no clear indication for routine use of niacin in combination with rosuvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with rosuvastatin. If coadministered, consider lower starting and maintenance does of rosuvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue rosuvastatin immediately if myopathy is diagnosed or suspected. (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
    Rosuvastatin; Ezetimibe: (Major) There is no clear indication for routine use of niacin in combination with rosuvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with rosuvastatin. If coadministered, consider lower starting and maintenance does of rosuvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue rosuvastatin immediately if myopathy is diagnosed or suspected. (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
    Salicylic Acid: (Moderate) Dryness of the skin and mucus membranes are common side effects of retinoid therapy. Simultaneous use of retinoids and topical drying agents, such as salicylic acid, can potentiate the drying effects of retinoids on the skin. Be alert for signs of skin irritation, the offending topical agents may need to be used less often or discontinued during retinoid therapy.
    Salsalate: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. If the urine is acidic prior to administration of an acidifying agent, the interaction should be minimal.
    Saxagliptin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary. (Moderate) Niacinamide interferes with glucose metabolism and can result in hyperglycemia. Monitor patients taking antidiabetic agents for changes in glycemic control if niacinamide is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Segesterone Acetate; Ethinyl Estradiol: (Minor) Ascorbic acid, vitamin C acts as a competitive inhibitor of the sulfation of ethinyl estradiol in the gastrointestinal tract wall and may increase the bioavailability by 50%. Patients who ingest ascorbic acid supplements may experience an increase in estrogen related side effects. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Selumetinib: (Moderate) Coadministration of selumetinib with supplemental vitamin E is not recommended if the total daily dose of vitamin E (amount in selumetinib plus the supplement) exceeds the recommended or safe daily limit; high dose vitamin E may increase the bleeding risk by antagonizing vitamin K dependent clotting factors and inhibiting platelet aggregation. Selumetinib contains 32 mg of vitamin E in the 10 mg capsules and 36 mg of vitamin E in the 25 mg capsules.
    Semaglutide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
    Simvastatin: (Major) There is no clear indication for routine use of niacin in combination with simvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with simvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue simvastatin immediately if myopathy is diagnosed or suspected. Coadministration is not recommended in Chinese patients, as the risk of myopathy is greater in this population. It is unknown if this risk applies to other Asian patients. (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of my