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  • CLASSES

    Calcium Supplements
    Mineral Binding Agents

    DEA CLASS

    OTC, Rx

    DESCRIPTION

    Inorganic salt; used as an antacid or calcium supplement; also used to bind dietary phosphate in patients with hyperphosphatemia; has improved bioavailability of calcium versus other oral calcium salts.

    COMMON BRAND NAMES

    Calphron, Eliphos, PhosLo, Phoslyra

    HOW SUPPLIED

    Calcium/Calcium Acetate/Calphron/Eliphos/PhosLo Oral Tab: 667mg, 668mg
    Calcium/Calcium Acetate/PhosLo Oral Cap: 667mg
    Phoslyra Oral Sol: 5mL, 667mg

    DOSAGE & INDICATIONS

    For the treatment of chronic hypocalcemia.
    NOTE: Dosage is based on the clinical condition of the patient and the serum calcium concentration. Serum concentrations of ionized calcium may be necessary to guide dosage adjustments in some patients, especially those with hypoalbuminemia.
    Oral dosage
    Adults

    2 to 4 g/day PO of elemental calcium (5 to 10 grams calcium carbonate) given in 3 to 4 divided doses.

    Infants, Children, and Adolescents

    40 to 80 mg elemental calcium/kg/day PO in 3 to 4 divided doses (Usual Max: 2000 mg/day; 500 mg/dose). Titrate dose based on serum calcium concentrations; higher doses may be necessary.

    Neonates

    40 to 100 mg elemental calcium/kg/day PO in 4 to 6 divided doses, given with feedings. Titrate dose based on serum calcium concentrations; higher doses may be necessary.

    For nutritional supplementation (as adequate intake (AI)) for maximum calcium retention in healthy individuals, including osteoporosis prophylaxis.
    NOTE: Recommended dietary allowances (RDAs) for calcium have not been established. Adequate intakes (AIs) should be used in place of RDAs.
    For osteoporosis prophylaxis in patients receiving chronic corticosteroid therapy.
    Oral dosage (in combination with vitamin D)
    Adults

    The combination of calcium carbonate with vitamin D3 (the product 'Os-Cal 250 + D' was used) not only prevented loss of bone mineral density but actually improved it at some anatomic sites in patients with rheumatoid arthritis who were receiving low doses of prednisone (5.6 mg/day) during the 2-year study. Improvement was seen mainly in areas rich in trabecular bone (e.g., lumbar spine, trochanter). The equivalent of 1,000 mg/day PO of elemental calcium was administered in this study.

    Oral dosage (in combination with calcitriol)
    Adults

    In another study, calcium (1,000 mg/day PO of elemental calcium) alone was not as beneficial as the combination of calcium with calcitriol. However, some benefit was seen, but only in the lumbar spine. In this study, the mean daily dose of prednisone was 13.5 mg/day.

    Oral dosage (in combination with etidronate)
    Adults

    500 mg/day PO of elemental calcium has been studied in combination with etidronate. Ambulatory patients, 18 to 90 years of age, who were to receive at least 12 months of therapy with prednisone (not less than 7.5 mg/day for the first 90 days, followed by not less than 2.5 mg/day for the remainder) were randomized to either placebo or etidronate with calcium. Bone density of the lumbar spine and trochanter increased in the etidronate/calcium group while it decreased in the placebo group and these differences were significant. Changes in the femoral neck and radius were not significant between groups. Etidronate was given once daily for 14 days, followed by 76 days of calcium. This 3-month cycle was then repeated 3 times during the year of treatment.

    Oral dosage
    Adults 51 years and older

    1,000 to 1,500 mg/day elemental calcium PO (2,500 to 3,750 mg calcium carbonate). The IOM Food and Nutrition Board recommends using the AI for osteoporosis prophylaxis. To prevent the development of osteoporosis in postmenopausal women, most reference texts recommend an intake of 1,000 to 1,500 g/day PO of elemental calcium; the 2006 guidelines of the North American Menopause Society recommend a target intake of 1,200 mg/day of elemental calcium PO in postmenopausal women. A dose of 1,000 mg/day PO of elemental calcium was superior to placebo in a randomized study of 122 women however, this same dose of elemental calcium was less effective than calcitriol in preventing new vertebral fractures in a separate study of postmenopausal women.

    Adults 19 to 50 years

    1,000 mg/day elemental calcium PO (2,500 mg calcium carbonate).

    Children and Adolescents 9 to 18 years

    1,300 mg/day elemental calcium PO (3,250 mg calcium carbonate).

    Children 4 to 8 years

    1,000 mg/day elemental calcium PO (2,500 mg calcium carbonate).

    Children 1 to 3 years

    700 mg/day elemental calcium PO (1,750 mg calcium carbonate).

    Infants 6 to 12 months

    260 mg/day elemental calcium PO based on adequate intake. A recommended dietary allowance (RDA) has not been established.

    Neonates and Infants 1 to 5 months

    200 mg/day elemental calcium PO based on adequate intake. A recommended dietary allowance (RDA) has not been established.

    Premature Neonates

    150 to 220 mg/kg/day PO based on adequate intake. A recommended dietary allowance (RDA) has not been established.

    For the treatment of hyperphosphatemia associated with chronic renal failure.
    NOTE: Calcium carbonate has been designated as orphan drug by the FDA for this purpose.
    Oral dosage
    Adults

    1,000 to 2,000 mg PO 3 times daily (1,200 to 2,250 mg elemental calcium/day), given with each meal, based on limited data. Titrate dose according to serum phosphorus concentrations. Doses as high as 7,500 mg/day (3,000 mg/day of elemental calcium) were reported in one study. Calcium carbonate lowers serum phosphate concentrations similarly to calcium acetate; however, calcium carbonate contains more elemental calcium and hypercalcemia has been noted more frequently with calcium carbonate compared with calcium acetate.

    Infants, Children, and Adolescents

    1,000 to 2,000 mg PO 3 times daily (1,200 to 2,250 mg elemental calcium/day), given with each meal, based on limited data. Titrate dose according to serum phosphorus concentrations. Doses as high as 7,500 mg/day (3,000 mg/day of elemental calcium) were reported in one study. Calcium carbonate lowers serum phosphate concentrations similarly to calcium acetate; however, calcium carbonate contains more elemental calcium and hypercalcemia has been noted more frequently with calcium carbonate compared with calcium acetate.

    For temporary relief of pyrosis (heartburn) or dyspepsia, or for symptomatic relief of hyperacidity associated with peptic ulcer, gastritis, esophagitis, gastric hyperacidity, or hiatal hernia.
    NOTE: Calcium carbonate can cause gastric hypersecretion and is not the preferred antacid for the adjunctive treatment of peptic ulcer disease.
    Oral dosage
    Adults

    1,000 to 3,000 mg (400 to 1,200 mg elemental calcium) PO; repeat as needed (Max: 7,000 to 7,500 mg/day; 2,800 to 3,000 mg elemental calcium). Tablets per dose varies depending on formulation.

    Children and Adolescents 12 to 17 years

    1,000 to 3,000 mg (400 to 1,200 mg elemental calcium) PO; repeat as needed (Max: 7,000 to 7,500 mg/day; 2,800 to 3,000 mg elemental calcium). Tablets per dose varies depending on formulation.

    Children 6 to 11 years

    750 to 800 mg (300 to 320 mg of elemental calcium) PO; repeat as needed (Max: 2,400 to 3,000 mg/day; 960 to 1,200 mg of elemental calcium). Tablets per dose varies depending on formulation.

    Children 2 to 5 years

    375 to 750 mg (150 to 300 mg of elemental calcium) PO; repeat as needed (Max: 1,200 to 1,500 mg/day; 480 to 600 mg of elemental calcium). Tablets per dose varies depending on formulation.

    For use as an antacid in the adjunctive treatment of peptic ulcer disease such as duodenal ulcer†.
    NOTE: Calcium carbonate can cause gastric hypersecretion and is not the preferred antacid for the adjunctive treatment of peptic ulcer disease.
    Oral dosage
    Adults

    Dosage is variable; however, an acid neutralizing capacity of 80 to 140 mEq/dose PO is often required. Doses should be given every 3 to 6 hours, or 1 and 3 hours after meals and at bedtime.

    For the adjunctive management of stress gastritis† or for stress gastritis prophylaxis†.
    Oral dosage
    Adults

    Dosage is variable; however, an acid neutralizing capacity of 80 to 140 mEq/dose PO is often required. Doses may need to be given as frequently as every 1 to 3 hours. Titrate to maintain the nasogastric aspirate above pH 5 to 7 in patients with active GI bleeding/gastritis and 3.5 to 7 for prevention of stress gastritis.

    For the treatment of premenstrual syndrome (PMS)†.
    Oral dosage (Tums E-X or Tums Calcium for Life PMS - OTC products)
    Adult females

    2 tablets PO twice per day (1,200 mg of elemental calcium/day). This dosage was studied in one multicenter, randomized, parallel-group clinical trial of 720 women meeting the NIH Premenstrual Syndrome criteria. This calcium dosage, administered over 3 menstrual cycles, resulted in a 48% reduction in PMS symptoms versus a 30% placebo-treatment effect. The difference was statistically significant.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Because of its limited intestinal absorption, excessive dosage with calcium carbonate is unlikely. However, prolonged use of very high doses can lead to hypercalcemia. Dosage must be individualized according to indication, serum calcium concentrations, and patient response.

    Adults

    Generally, 4,000 mg/day PO elemental calcium for hypocalcemia; tolerable upper intake level as a nutrient is 2,500 mg/day of elemental calcium (6,250 mg/day as calcium carbonate).

    Geriatric

    Generally, 4,000 mg/day PO elemental calcium for hypocalcemia; tolerable upper intake level as a nutrient is 2,500 mg/day of elemental calcium (6,250 mg/day as calcium carbonate).

    Adolescents

    Generally, 80 mg elemental calcium/kg/day PO for hypocalcemia; tolerable upper intake level as a nutrient is 2,500 mg/day of elemental calcium (6,250 mg/day as calcium carbonate).

    Children

    Generally, 80 mg elemental calcium/kg/day PO for hypocalcemia; tolerable upper intake level as a nutrient is 2,500 mg/day of elemental calcium (6,250 mg/day as calcium carbonate).

    Infants

    Generally, 80 mg elemental calcium/kg/day PO for hypocalcemia; tolerable upper intake level as a nutrient has not been established.

    Neonates

    Generally, 100 mg elemental calcium/kg/day PO for hypocalcemia; tolerable upper intake level as a nutrient has not been established.

    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. Adjust dosage based on patient response and serum calcium concentrations.

    ADMINISTRATION

    Oral Administration

    Generally, administer with meals or feedings for improved absorption. Follow each dose with appropriate fluid intake.
    Because calcium carbonate, like other antacids or calcium-containing products, may interfere with the absorption of other medicines, separate administration of calcium carbonate from other medications according to recommendations for the potentially interacting medication.

    Oral Solid Formulations

    Chewable tablets: Have patient chew tablets thoroughly before swallowing.

    Oral Liquid Formulations

    Oral Suspension: Shake well prior to each administration. Measure dosage with an oral syringe or other calibrated oral dosage device to ensure accurate dosing.

    STORAGE

    Generic:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a cool, dry place
    Calphron:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Eliphos:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    PhosLo:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Phoslyra:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Dehydration, hypercalcemia, hypercalciuria, hyperparathyroidism, neoplastic disease, nephrolithiasis, renal disease, sarcoidosis

    Hypercalcemia from any cause including, but not limited to, hyperparathyroidism, hypercalcemia of malignancy (neoplastic disease), or sarcoidosis would contraindicate therapy with calcium carbonate. Patients with a history of preexisting hypercalcemia, renal disease, or dehydration are predisposed to developing milk-alkali syndrome and calcinosis. Symptoms of this syndrome include hypercalcemia, nausea/vomiting, headache, weakness, metabolic alkalosis, and change in mental status. Calcium blood concentrations should be monitored routinely in such patients who are receiving calcium carbonate therapy. In administration of calcium carbonate is needed in patients with a history of nephrolithiasis (kidney stones) or hypercalciuria, urinary calcium excretion and other appropriate testing should be monitored periodically.

    Peptic ulcer disease

    Administration of calcium carbonate can cause gastric hypersecretion and acid rebound. For this reason, calcium carbonate is not a good choice for use as an antacid for the adjunctive treatment of peptic ulcer disease.

    Constipation, GI bleeding, GI obstruction, ileus

    The use of calcium carbonate can be constipating and it should be used cautiously in patients with preexisting constipation or with GI bleeding, GI obstruction or ileus, or decreased gastric motility.

    Pregnancy

    When chronic high doses are avoided, calcium carbonate appears to be safe and effective to use during pregnancy to relieve occasional dyspepsia or to help meet maternal nutritional requirements. Adverse effects have not been reported with the normal daily intake of calcium carbonate within the recommended dietary daily intakes for a pregnant female. The use of calcium carbonate in excess of the recommended dietary allowance during normal pregnancy should be avoided unless, in the judgment of the physician, potential benefits in a specific, unique case outweigh the significant hazards involved.

    Breast-feeding

    Calcium carbonate appears to be safe and effective to use during breast-feeding to relieve occasional dyspepsia in the lactating mother or to help meet maternal nutritional requirements. Human breast milk naturally contains calcium and other minerals; maternal calcium intake appears to have no significant effect on the amount of calcium normally found in human milk.

    Necrotizing enterocolitis

    In infants at high risk for necrotizing enterocolitis, oral liquid calcium formulations should be avoided due to the high osmolality.

    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.
    Acalabrutinib: (Moderate) Separate the administration of acalabrutinib and calcium carbonate by at least 2 hours if these agents are used together; decreased acalabrutinib exposure occurred when acalabrutinib and calcium carbonate were coadministered in a drug interaction study. Acalabrutinib solubility decreases with increasing pH values. In healthy subjects, the AUC of acalabrutinib was decreased by 53% when acalabrutinib was coadministered with calcium carbonate 1 gram.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Acetaminophen; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Acrivastine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    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.
    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.
    Amlodipine; Atorvastatin: (Moderate) Concomitant administration of atorvastatin with antacids (Maalox TC) reduced the plasma concentrations of atorvastatin by approximately 35%. However, LDL-cholesterol reduction was not altered.
    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.
    Amphetamine: (Moderate) Calcium carbonate is a gastrointestinal alkalinizing agent that may iincrease the oral absorption of amphetamines and increase amphetamine concentrations. To help limit an interaction, do not take caclium carbonate at the same time as the amphetamine product. It is recommended to separate times of administration.
    Amphetamine; Dextroamphetamine: (Moderate) Calcium carbonate is a gastrointestinal alkalinizing agent that may iincrease the oral absorption of amphetamines and increase amphetamine concentrations. To help limit an interaction, do not take caclium carbonate at the same time as the amphetamine product. It is recommended to separate times of administration.
    Amphetamines: (Moderate) Calcium carbonate is a gastrointestinal alkalinizing agent that may iincrease the oral absorption of amphetamines and increase amphetamine concentrations. To help limit an interaction, do not take caclium carbonate at the same time as the amphetamine product. It is recommended to separate times of administration.
    Anticholinergics: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Atazanavir: (Major) Atazanavir solubility decreases as gastric pH increases. Although drug interactions between atazanavir and antacids have not been specifically studied, based on data with other protease inhibitors, it is recommended that antacids not be given at the same time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
    Atazanavir; Cobicistat: (Major) Atazanavir solubility decreases as gastric pH increases. Although drug interactions between atazanavir and antacids have not been specifically studied, based on data with other protease inhibitors, it is recommended that antacids not be given at the same time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid.
    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: (Moderate) Concomitant administration of atorvastatin with antacids (Maalox TC) reduced the plasma concentrations of atorvastatin by approximately 35%. However, LDL-cholesterol reduction was not altered.
    Atorvastatin; Ezetimibe: (Moderate) Concomitant administration of atorvastatin with antacids (Maalox TC) reduced the plasma concentrations of atorvastatin by approximately 35%. However, LDL-cholesterol reduction was not altered. (Minor) Antacids (e.g., 20 ml aluminum hydroxide; magnesium hydroxide) have no significant effect on the oral bioavailability of total ezetimibe (ezetimibe plus ezetimibe-glucuronide), ezetimibe-glucuronide, or ezetimibe based on AUC values. However, the peak plasma concentration (Cmax) of total ezetimibe is decreased by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
    Atropine: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Avoid the concomitant use of calcium carbonate and methenamine. Calcium carbonate may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Atropine; Difenoxin: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Atropine; Edrophonium: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Azelastine; Fluticasone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
    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.
    Beclomethasone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Belladonna; Opium: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Bempedoic Acid; Ezetimibe: (Minor) Antacids (e.g., 20 ml aluminum hydroxide; magnesium hydroxide) have no significant effect on the oral bioavailability of total ezetimibe (ezetimibe plus ezetimibe-glucuronide), ezetimibe-glucuronide, or ezetimibe based on AUC values. However, the peak plasma concentration (Cmax) of total ezetimibe is decreased by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
    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: (Major) Avoid the concomitant use of calcium carbonate and methenamine. Calcium carbonate may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Benzphetamine: (Moderate) Calcium carbonate is a gastrointestinal alkalinizing agent that may iincrease the oral absorption of amphetamines and increase amphetamine concentrations. To help limit an interaction, do not take caclium carbonate at the same time as the amphetamine product. It is recommended to separate times of administration.
    Benztropine: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Betamethasone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
    Bictegravir; Emtricitabine; Tenofovir Alafenamide: (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%.
    Bisacodyl: (Moderate) By increasing intragastric pH, calcium carbonate can affect the dissolution of oral bisacodyl tablets; administration should be separated by 1 hour.
    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.
    Bosutinib: (Major) Bosutinib displays pH-dependent aqueous solubility; therefore, concomitant use of bosutinib and antacids may result in decreased plasma exposure of bosutinib. Separate the administration of bosutinib and antacids by more than 2 hours.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Brompheniramine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Budesonide: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
    Budesonide; Formoterol: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
    Budesonide; Glycopyrrolate; Formoterol: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    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.
    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) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
    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 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.
    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.
    Captopril: (Major) Antacids can decrease the GI absorption of captopril if administered simultaneously.
    Captopril; Hydrochlorothiazide, HCTZ: (Major) Antacids can decrease the GI absorption of captopril if administered simultaneously. (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.
    Carbetapentane; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Carbinoxamine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    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.
    Cefdinir: (Major) Antacids containing magnesium or aluminum can interfere with the absorption of cefdinir. If aluminum or magnesium containing antacids are required during cefdinir therapy, cefdinir should be taken at least 2 hours before or after the antacid.
    Cefpodoxime: (Moderate) Because cefpodoxime proxetil requires a low gastric pH for dissolution, drugs which increase gastric pH, such as antacids, can decrease the bioavailability of cefpodoxime.
    Cefuroxime: (Moderate) Antacids can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy. If an antacid must be used while a patient is taking cefuroxime, administer the oral dosage of cefuroxime at least 1 hour before or 2 hours after the antacid.
    Cetirizine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Chlordiazepoxide; Clidinium: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Chloroquine: (Major) Chloroquine absorption may be reduced by antacids. Administer chloroquine and antacids at least 4 hours apart.
    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; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Chlorpheniramine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    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.
    Ciprofloxacin: (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.
    Codeine; Guaifenesin; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    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.
    Corticotropin, ACTH: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. Patients taking systemic corticosteroids should ensure proper intake of calcium as directed by their health care provider.
    Cortisone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
    Cysteamine: (Major) In general, cysteamine may be administered with electrolyte and mineral replacements necessary for managing Fanconi syndrome, as well as with vitamin D and thyroid hormone. However, delayed-release cysteamine (Procysbi) should be administered at least 1 hour before or 1 after medications that increase gastric pH, including those containing bicarbonate or carbonate (i.e.calcium carbonate). Drugs that increase the gastric pH, such as bicarbonate and carbonate, may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
    Dabrafenib: (Moderate) Space the administration of antacids from dabrafenib by at least 2 hours. Antacids elevate the gastric pH and may alter the solubility of dabrafenib. Therefore, the concomitant use of dabrafenib and antacids may reduce the systemic exposure and bioavailability of dabrafenib. No formal trials have been performed to evaluate this interaction and it is not known how this interaction affects the efficacy of dabrafenib.
    Dasatinib: (Moderate) Separate the administration of dasatinib and calcium carbonate by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    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.
    Delavirdine: (Major) Coadministration of delavirdine with antacids results in decreased absorption of delavirdine. Administration of delavirdine and antacids should be separated by at least 1 hour.
    Desloratadine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Desogestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Dexamethasone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
    Dexbrompheniramine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Dextroamphetamine: (Moderate) Calcium carbonate is a gastrointestinal alkalinizing agent that may iincrease the oral absorption of amphetamines and increase amphetamine concentrations. To help limit an interaction, do not take caclium carbonate at the same time as the amphetamine product. It is recommended to separate times of administration.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Dextromethorphan; Quinidine: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
    Diazepam: (Moderate) The coadministration of diazepam with antacids results in delayed diazepam absorption due to the fact that antacids delay gastric emptying. It may be prudent to separate dosing by 2 hours to limit any potential interaction.
    Dicyclomine: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    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: (Moderate) Concurrent use of diflunisal with antacids, such as calcium carbonate, may reduce plasma diflunisal concentrations. The effect may be clinically significant if antacids are used on a continuous schedule.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Diphenoxylate; Atropine: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    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.
    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.
    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) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
    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) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Edetate Calcium Disodium, Calcium EDTA: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
    Edetate Disodium, Disodium EDTA: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
    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.
    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.
    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.
    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.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
    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.
    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.
    Erdafitinib: (Major) Avoid coadministration of calcium carbonate with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Calcium carbonate decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by calcium carbonate may interfere with the determination of this initial dose increase.
    Erlotinib: (Major) Separate administration by several hours if concomitant use of erlotinib with calcium carbonate is necessary. Erlotinib displays pH-dependent solubility with decreased solubility at a higher pH; the increased gastric pH resulting from calcium carbonate therapy may reduce the bioavailability of erlotinib. Increasing the dose of erlotinib without modifying the administration schedule is unlikely to compensate for loss of exposure. The effects of antacids on erlotinib pharmacokinetics has not been evaluated.
    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.
    Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Norelgestromin: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Norgestrel: (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) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Etonogestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ezetimibe: (Minor) Antacids (e.g., 20 ml aluminum hydroxide; magnesium hydroxide) have no significant effect on the oral bioavailability of total ezetimibe (ezetimibe plus ezetimibe-glucuronide), ezetimibe-glucuronide, or ezetimibe based on AUC values. However, the peak plasma concentration (Cmax) of total ezetimibe is decreased by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
    Ezetimibe; Simvastatin: (Minor) Antacids (e.g., 20 ml aluminum hydroxide; magnesium hydroxide) have no significant effect on the oral bioavailability of total ezetimibe (ezetimibe plus ezetimibe-glucuronide), ezetimibe-glucuronide, or ezetimibe based on AUC values. However, the peak plasma concentration (Cmax) of total ezetimibe is decreased by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
    Ferric Maltol: (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.
    Fexofenadine: (Major) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
    Fexofenadine; Pseudoephedrine: (Major) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended. (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Flavoxate: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Fludrocortisone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
    Flunisolide: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
    Fluticasone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
    Fluticasone; Salmeterol: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
    Fluticasone; Vilanterol: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
    Food: (Moderate) Food or medicines containing a high potassium content such as salt substitutes could increase the risk of complications of potassium excess when given with potassium-based phosphorous salts. (Moderate) Foods containing oxalates (found in vegetables like rhubarb, tomatoes, celery, and spinach; as well as berries, beans, nuts and chocolate) or phytates (found in bran and whole-grain cereals) may reduce the absorption of phosphorus by forming complexes with the phosphorus salt.
    Fosamprenavir: (Moderate) The administration of an aluminum hydroxide and magnesium hydroxide containing antacid with fosamprenavir decreased fosamprenavir Cmax and AUC. It is recommended that the administration of fosamprenavir and antacids be separated by at least 1 hour.
    Fosinopril: (Moderate) Coadministration of antacids with fosinopril may impair absorption of fosinopril. Therefore, if concomitant administration of these agents is indicated, dosing should be separated by 2 hours.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of antacids with fosinopril may impair absorption of fosinopril. Therefore, if concomitant administration of these agents is indicated, dosing should be separated by 2 hours. (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.
    Gabapentin: (Moderate) Antacids (e.g., aluminum hydroxide; magnesium hydroxide) have been shown to reduce the oral bioavailability of gabapentin by roughly 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after the antacid. It is recommended that gabapentin be taken at least 2 hours following the administration of antacids in order to avoid a significant interaction.
    Gallium: (Moderate) Concurrent administration products containing calcium salts may antagonize the effects of gallium nitrate.
    Gastrointestinal Enzymes: (Major) The effectiveness of gastrointestinal enzymes can be diminished with concurrent administration of antacids. In-vitro studies suggest that calcium and magnesum cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.
    Gefitinib: (Major) Avoid coadministration of calcium carbonate with gefitinib if possible due to decreased exposure to gefitinib, which may lead to reduced efficacy. If concomitant use is unavoidable, take gefitinib 6 hours after the last dose or 6 hours before the next dose of calcium carbonate. Gefitinib exposure is affected by gastric pH. Coadministration with another drug to maintain gastric pH above 5 decreased gefitinib exposure by 47%.
    Glipizide: (Moderate) Antacids have been reported to increase the absorption of glipizide, enhancing their hypoglycemic effects. Although the exact mechanism is not known, theoretically it may be due to alterations in gastric pH. Consider closely monitoring blood glucose concentrations.
    Glipizide; Metformin: (Moderate) Antacids have been reported to increase the absorption of glipizide, enhancing their hypoglycemic effects. Although the exact mechanism is not known, theoretically it may be due to alterations in gastric pH. Consider closely monitoring blood glucose concentrations.
    Glyburide: (Moderate) Antacids have been reported to increase the absorption of non-micronized glyburide, enhancing their hypoglycemic effects. Although the exact mechanism is not known, theoretically it may be due to alterations in gastric pH. Consider closely monitoring blood glucose concentrations.
    Glyburide; Metformin: (Moderate) Antacids have been reported to increase the absorption of non-micronized glyburide, enhancing their hypoglycemic effects. Although the exact mechanism is not known, theoretically it may be due to alterations in gastric pH. Consider closely monitoring blood glucose concentrations.
    Glycopyrrolate: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Glycopyrrolate; Formoterol: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Guaifenesin; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Homatropine; Hydrocodone: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    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: (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; Potassium Guaiacolsulfonate; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Hydrocodone; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Hydrocortisone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
    Hydroxychloroquine: (Major) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
    Hyoscyamine: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Avoid the concomitant use of calcium carbonate and methenamine. Calcium carbonate may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Ibritumomab Tiuxetan: (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; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Indacaterol; Glycopyrrolate: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Indomethacin: (Moderate) Antacids may inhibit the oral absorption of indomethacin. Simultaneous administration should be avoided; separate dosing by at least 2 hours to limit an interaction.
    Infigratinib: (Moderate) Separate the administration of infigratinib and locally acting antacids such as calcium carbonate if concomitant use is necessary. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Administer infigratinib two hours before or after calcium carbonate.
    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 Salts: (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.
    Iron: (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.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Isoniazid, INH; Rifampin: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Itraconazole: (Moderate) When administering antacids with the 100 mg itraconazole capsule and 200 mg itraconazole tablet formulations, systemic exposure to itraconazole is decreased. Conversely, exposure to itraconazole is increased when antacids are administered with the 65 mg itraconazole capsule. Administer antacids at least 2 hours before or 2 hours after the 100 mg capsule or 200 mg tablet. Monitor for increased itraconazole-related adverse effects if antacids are administered with itraconazole 65 mg capsules.
    Ketoconazole: (Major) By increasing intragastric pH, calcium carbonate can reduce the oral absorption of ketoconazole; administer calcium carbonate and other antacids 2 hours after oral administration of ketoconazole or itraconazole to minimize this interaction.
    Lactulose: (Minor) Oral, nonabsorbable antacids may interfere with the decrease in colon pH necessary for lactulose's action.
    Ledipasvir; Sofosbuvir: (Moderate) Separate administration of ledipasvir and antacids by at least 4 hours. Solubility of ledipasvir decreases as gastric pH increases; thus, simultaneous administration of these drugs may result in lower ledipasvir plasma concentrations.
    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.
    Levonorgestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Lisdexamfetamine: (Moderate) Calcium carbonate is a gastrointestinal alkalinizing agent that may iincrease the oral absorption of amphetamines and increase amphetamine concentrations. To help limit an interaction, do not take caclium carbonate at the same time as the amphetamine product. It is recommended to separate times of administration.
    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.
    Loratadine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    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.
    Mefenamic Acid: (Moderate) Ingestion of mefenamic acid with antacids is not recommended. Administration with an antacid containing 1.7 grams of magnesium hydroxide resulted in a 36 percent increase in the area under the time versus concentration curve of mefenamic acid.
    Mefloquine: (Moderate) Antacids, H2-blockers, and proton pump inhibitors (PPIs) may increase plasma concentrations of mefloquine. In a small study involving 6 healthy subjects and 6 peptic ulcer patients, cimetidine increased the Cmax and AUC of mefloquine. In the study, the pharmacokinetics of mefloquine were determined after receiving a single oral mefloquine 500 mg dose alone and after 3-days of cimetidine 400 mg PO bid. In both healthy subjects and peptic ulcer patients, mefloquine Cmax was increased 42.4% and 20.5%, respectively, and AUC was increased by 37.5% in both groups. Elimination half-life, total clearance, and volume of distribution were not significantly affected. An increase in adverse reactions was not noted. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially in patients with a neurological or psychiatric history.
    Mepenzolate: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Mesalamine, 5-ASA: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
    Mestranol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Methamphetamine: (Moderate) Calcium carbonate is a gastrointestinal alkalinizing agent that may iincrease the oral absorption of amphetamines and increase amphetamine concentrations. To help limit an interaction, do not take caclium carbonate at the same time as the amphetamine product. It is recommended to separate times of administration.
    Methenamine: (Major) Avoid the concomitant use of calcium carbonate and methenamine. Calcium carbonate may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde.
    Methenamine; Sodium Acid Phosphate: (Major) Avoid the concomitant use of calcium carbonate and methenamine. Calcium carbonate may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Avoid the concomitant use of calcium carbonate and methenamine. Calcium carbonate may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Methscopolamine: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    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.
    Methylprednisolone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
    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.
    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.
    Mycophenolate: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum or magnesium hydroxide antacids decrease AUC of mycophenolic acid by about 17%. Avoid administration of mycophenolate mofetil with agents that may decrease its absorption.
    Naproxen; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Neratinib: (Major) Administer neratinib at least 3 hours after administration of calcium carbonate if concomitant use is necessary due to decreased absorption and systemic exposure of neratinib; the solubility of neratinib decreases with increasing pH of the GI tract.
    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.
    Nilotinib: (Moderate) If concomitant use of these agents is necessary, administer the antacid approximately 2 hours before or approximately 2 hours after the nilotinib dose. Nilotinib displays pH-dependent solubility with decreased solubility at a higher pH; therefore, concomitant use of nilotinib and antacids may result in decreased bioavailability of nilotinib. In a study in healthy subjects, there was no significant change in nilotinib pharmacokinetics when an antacid (aluminum hydroxide/magnesium hydroxide/simethicone) was administered approximately 2 hours before or approximately 2 hours after a single 400-mg nilotinib dose.
    Nitrofurantoin: (Moderate) Separate administration of antacids and nitrofurantoin by at least 1 hour. Antacids can delay both the rate and the extent of GI absorption of nitrofurantoin. This interaction may be due to surface absorption of the antibacterial onto the antacid.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (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) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Norethindrone; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (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) 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.
    Norgestimate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Octreotide: (Moderate) Coadministration of oral octreotide with antacids may require increased doses of octreotide. Coadministration of oral octreotide with drugs that alter the pH of the upper GI tract, including antacids, may alter the absorption of octreotide and lead to a reduction in bioavailability.
    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.
    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.
    Oxybutynin: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Pancrelipase: (Major) The effectiveness of gastrointestinal enzymes can be diminished with concurrent administration of antacids. In-vitro studies suggest that calcium and magnesum cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.
    Pazopanib: (Moderate) Separate administration of pazopanib and antacids by several hours if coadministration is necessary in order to avoid a reduction in pazopanib exposure, which may decrease efficacy.
    Penicillamine: (Moderate) Because penicillamine chelates heavy metals, it is possible that antacids could reduce penicillamine bioavailability, which can decrease the therapeutic effects of penicillamine. Simultaneous administration should be avoided; separate dosing by at least 2 hours to limit an interaction.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Phenytoin: (Moderate) Calcium carbonate can significantly decrease the oral bioavailability of phenytoin. Calcium carbonate should not affect the pharmacokinetics of parenteral phenytoin. If calcium carbonate is to be used with oral phenytoin, calcium carbonate should be administered at least 1 hour before or 6 hours after the phenytoin dose.
    Phosphorated Carbohydrate Solution: (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: (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.
    Polyethylene Glycol; Electrolytes; Bisacodyl: (Moderate) By increasing intragastric pH, calcium carbonate can affect the dissolution of oral bisacodyl tablets; administration should be separated by 1 hour.
    Polysaccharide-Iron Complex: (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.
    Potassium Phosphate: (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) 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.
    Prednisolone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
    Prednisone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
    Propantheline: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Propranolol: (Major) Antacids may reduce the absorption of propranolol. The need to stagger doses of propranolol has not been established, but may be prudent. Monitor clinical response, and adjust propranolol dosage if needed to attain therapeutic goals.
    Propranolol; Hydrochlorothiazide, HCTZ: (Major) Antacids may reduce the absorption of propranolol. The need to stagger doses of propranolol has not been established, but may be prudent. Monitor clinical response, and adjust propranolol dosage if needed to attain therapeutic goals. (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.
    Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    Pseudoephedrine; Triprolidine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
    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.
    Quinidine: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
    Quinine: (Major) Antacids may delay or decrease the absorption of quinine.
    Raltegravir: (Major) Coadministration of calcium carbonate with raltegravir administered as a once daily dose (high dose regimen) is not recommended. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. Calcium carbonate may be given with other dosage regimens of raltegravir with no dose adjustments necessary. In a drug interaction study (n = 19), the AUC of raltegravir, given as a single 1200 mg dose, was decreased by 72% (90% CI, 68% to 76%) when administered with a calcium carbonate antacid.
    Relugolix; Estradiol; Norethindrone acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Rifampin: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
    Rilpivirine: (Moderate) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
    Riociguat: (Major) Separate administration of riociguat from antacids by at least 1 hour. Antacids such as aluminum hydroxide/magnesium hydroxide decrease riociguat absorption.
    Rosuvastatin: (Major) While not specifically reported with calcium carbonate, antacids (aluminum hydroxide; magnesium hydroxide combination) have been shown to reduce rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed.
    Rosuvastatin; Ezetimibe: (Major) While not specifically reported with calcium carbonate, antacids (aluminum hydroxide; magnesium hydroxide combination) have been shown to reduce rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed. (Minor) Antacids (e.g., 20 ml aluminum hydroxide; magnesium hydroxide) have no significant effect on the oral bioavailability of total ezetimibe (ezetimibe plus ezetimibe-glucuronide), ezetimibe-glucuronide, or ezetimibe based on AUC values. However, the peak plasma concentration (Cmax) of total ezetimibe is decreased by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
    Scopolamine: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Segesterone Acetate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Selpercatinib: (Major) Avoid coadministration of selpercatinib with calcium carbonate due to the risk of decreased selpercatinib exposure which may reduce its efficacy. If concomitant use is unavoidable, take selpercatinib 2 hours before or 2 hours after administration of calcium carbonate. Coadministration with acid-reducing agents decreases selpercatinib plasma concentrations.
    Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (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.
    Sodium Fluoride: (Moderate) Absorption of sodium fluoride may be reduced by concomitant use of antacids that contain magnesium, aluminum, or calcium. An interval of at least 2 hours is advisable between administration of sodium fluoride and antacids.
    Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (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.
    Sodium Polystyrene Sulfonate: (Major) Simultaneous oral administration of cation-donating antacids or laxatives may reduce the potassium exchange capability of sodium polystyrene sulfonate. Examples of cation-donating antacids and laxatives include aluminum hydroxide, calcium carbonate, magnesium carbonate, magnesium citrate, and magnesium hydroxide. Patients who received concomitant oral sodium polystyrene sulfonate and non-absorbable cation-donating antacids and laxatives have developed systemic alkalosis. Intestinal obstruction due to concretions of aluminum hydroxide when used in combination with sodium polystyrene sulfonate has also been reported. One case of grand mal seizure has been reported in a patient with chronic hypocalcemia of renal failure who was given sodium polystyrene with magnesium hydroxide as laxative. Normally, antacids like magnesium hydroxide and calcium carbonate neutralize hydrochloric acid in the stomach, forming magnesium chloride and calcium chloride. As these compounds enter the small intestine, they react with bicarbonate, forming magnesium carbonate and calcium carbonate, which are insoluble. If polystyrene is administered, it blocks this reaction by binding to the magnesium and calcium ions before they can react with the bicarbonate. More hydrogen ions are lost from the stomach than are lost from the intestine, resulting in metabolic alkalosis. Rectal administration of sodium polystyrene sulfonate may reduce the severity of these interactions.
    Sofosbuvir; Velpatasvir: (Moderate) Separate the use of antacids (e.g., calcium carbonate) and sofosbuvir; velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Separate the use of antacids (e.g., calcium carbonate) and sofosbuvir; velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
    Sotalol: (Major) Coadministration of antacids with sotalol reduces the Cmax and AUC of sotalol by 26% and 20%, respectively. This interaction results in a 25% reduction in the bradycardic effect of sotalol (measured at rest). Administer antacids two hours after the sotalol dose to avoid altering sotalol pharmacokinetics or pharmacodynamics.
    Sotorasib: (Moderate) Avoid coadministration of sotorasib and gastric-reducing agents, such as antacids including calcium carbonate. Coadministration may decrease sotorasib exposure resulting in decreased efficacy. If coadministration with calcium carbonate is necessary, administer sotorasib 4 hours before or 10 hours after calcium carbonate.
    Spironolactone; 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.
    Sucralfate: (Major) Oral antacids, including calcium carbonate, potentially interfere with gastric mucosal binding of sucralfate. This interaction can be minimized by staggering the doses of these agents as much as possible.
    Telmisartan; 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.
    Tetracyclines: (Major) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Thiazide diuretics: (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.
    Thiothixene: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
    Thyroid hormones: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium 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 thyroid hormones with oral calcium supplements.
    Ticlopidine: (Major) Administration of ticlopidine after antacids results in a decrease in plasma levels of ticlopidine. Staggering the times of administration may avoid this pharmacokinetic interaction.
    Tipranavir: (Moderate) Concurrent administration of tipranavir and ritonavir with antacids results in decreased tipranavir concentrations. Administer tipranavir and ritonavir 2 hours before or 1 hour after antacids.
    Triamcinolone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
    Triamterene; 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.
    Trientine: (Major) In general, oral mineral supplements should not be given since they may block the oral absorption of trientine. 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 trientine each inhibit oral absorption of the other, 2 hours should elapse between administration of trientine and iron doses.
    Trihexyphenidyl: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Valproic Acid, Divalproex Sodium: (Minor) Antacids may increase valproic acid AUC. Patients should be monitored for adverse effects in this situation.
    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.
    Vitamin A: (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.
    Vitamin D analogs: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.

    PREGNANCY AND LACTATION

    Pregnancy

    When chronic high doses are avoided, calcium carbonate appears to be safe and effective to use during pregnancy to relieve occasional dyspepsia or to help meet maternal nutritional requirements. Adverse effects have not been reported with the normal daily intake of calcium carbonate within the recommended dietary daily intakes for a pregnant female. The use of calcium carbonate in excess of the recommended dietary allowance during normal pregnancy should be avoided unless, in the judgment of the physician, potential benefits in a specific, unique case outweigh the significant hazards involved.

    Calcium carbonate appears to be safe and effective to use during breast-feeding to relieve occasional dyspepsia in the lactating mother or to help meet maternal nutritional requirements. Human breast milk naturally contains calcium and other minerals; maternal calcium intake appears to have no significant effect on the amount of calcium normally found in human milk.

    MECHANISM OF ACTION

    Calcium is the fifth most abundant element in the body. Calcium is a divalent metal essential for the maintenance of the nervous, muscular, and skeletal systems and for cell membrane and capillary permeability. Its role in bone structure and muscle contraction is well known, but calcium is also important for blood coagulation, nerve conduction, and electrical conduction in the heart. Calcium stimulates gastrin secretion, which offsets the utility of oral calcium carbonate as a treatment of peptic ulcer disease. Growing evidence suggests that calcium accumulates readily in atherosclerotic plaques, although this does not appear to be related to exogenous calcium administration. Parathyroid hormone (PTH), vitamin D, and, to a lesser extent, calcitonin, glucocorticoids, and magnesium influence calcium balance.
     
    Antacids neutralize gastric acid, increasing the pH of the gastric contents, which reduces GI mucosal irritation. The composition of available commercial products determines the acid neutralizing capacity (ANC). For example, Tums tablets have an ANC of 10 mEq/500 mg tablet. Each Tums Extra-Strength tablet has an ANC of 15 mEq and each Tums Ultra tablet has an ANC of 20 mEq. Suspensions have a greater acid neutralizing capacity (ANC) than tablets or powders because suspensions are more rapidly and effectively solubilized. The increase in gastric pH from the antacid inhibits the proteolytic activity of pepsin, which is beneficial to patients with peptic ulcers. The role of calcium carbonate in the treatment of peptic ulcers is questionable, however, because the drug can cause acid rebound. Most clinicians do not use calcium carbonate to treat peptic ulcers, and antacids in general have fallen out of favor due to the availability of H2-blockers.
     
    Calcium carbonate and calcium citrate are useful in treating hyperphosphatemia secondary to chronic renal failure. Oral calcium salts do not extract phosphate from the circulation, as charcoal does to some drugs, but rather bind to dietary phosphate in the gut, preventing its absorption. To accomplish this, it is important to administer the oral calcium salt with meals or snacks because it exerts minimal effects on phosphate once phosphate has been absorbed into the circulation. Calcium binds with phosphate in the gut, forming the insoluble calcium phosphate, which is subsequently eliminated in the stool. Some free calcium, however, can be absorbed, potentially elevating the calcium-phosphorus product. For this reason, it is important to avoid using calcium salts as phosphate binders when serum phosphorus is extremely elevated.

    PHARMACOKINETICS

    Calcium carbonate is administered orally. After absorption, approximately 50% of calcium in the serum is in the physiologically active ionized form; about 10% is complexed to phosphate, citrate or other anions. The remaining 40% is bound to proteins, primarily albumin. Unabsorbed calcium from the small intestine is excreted in the feces. Renal excretion depends largely on glomerular filtration and calcium tubular reabsorption with more than 98% of calcium reabsorbed from the glomerular filtrate. This process is regulated by active vitamin D and parathyroid hormone (PTH). The amount excreted in the urine varies with the degree of calcium absorption, the rate of bone turnover, and renal conservation status. Calcium is excreted in the urine (roughly 20%); urinary excretion of calcium is often measured as a marker for calcium bioavailability in clinical studies.

    Oral Route

    In general, the absorption of calcium from the intestine is never complete, and demands that the calcium be in a soluble, ionized form.The intestinal pH, the presence of food, the dosage administered, and the presence of calcium deficiency all influence oral bioavailability of calcium. Because of the hormonal influence of PTH and vitamin D on calcium absorption, there is only so much calcium that can be absorbed at any one time from the gastrointestinal tract; absorption is increased in patients with calcium deficiency or low-calcium diets. The normal bioavailability of calcium from supplements like calcium carbonate is usually only 25—35%. The intestinal pH for dissolution and absorption of calcium salts and complexes is typically in the optimal range of 5—7 a little while after a meal in the patient with normal stomach acid status, as the acidic stomach contents empty into the upper small intestine (duodenum). Thus, it is often recommended that calcium carbonate be administered with or 1—1.5 hours after a meal to enhance absorption of the supplement. Of course, when used as a dietary phosphate binder, calcium carbonate is effective administered with or after food. In patients with achlorhydria or other conditions of low stomach acid, calcium carbonate absorption is enhanced by taking the supplement with meals versus after meals so that the small amount of acid produced to aid digestion can also help aid calcium absorption. The anions (ex: oxalate, phylates or sulfates) present or high fiber percentage in certain foods may reduce the bioavailability of calcium from a supplement product. This may also explain why some foods (e.g., dark green leafy vegetables), although containing calcium, are not the best sources of calcium in the diet; the oral bioavailability of calcium from such foods is not as high as the oral bioavailability from dairy products due to the presence of fiber or listed anions.