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    Iron Supplements

    BOXED WARNING

    Accidental exposure, children, infants

    Infants and children should receive iron salts only under the advice and supervision of a qualified health care professional. Accidental exposure to excessive amounts of iron-containing products (i.e., overdose) is the leading cause of fatal poisoning in children under the age of 6 years. Products that contain 30 milligrams (mg) or more of iron per dosage unit are packaged as individual unit-doses. This is to limit the number of pills or capsules a small child could accidentally consume once the package is opened. The FDA published the final rule on the packaging of iron in the January 15, 1997 Federal Register. Under U.S. Consumer Product Safety Commission regulations, most drugs and dietary supplements with more than 250 mg of iron per container must have child-resistant packages. Always store any iron-containing products out of the reach of children and pets. In the case of accidental exposure by ingestion, call a physician or poison control center immediately.

    DEA CLASS

    Rx

    DESCRIPTION

    Essential mineral important to several metabolic functions including erythropoiesis; used as a dietary supplement or to treat iron-deficiency anemia; different salts available (carbonyl iron, ferrous sulfate, ferrous gluconate, ferrous fumarate).

    COMMON BRAND NAMES

    Auryxia

    HOW SUPPLIED

    Auryxia Oral Tab: 210mg

    DOSAGE & INDICATIONS

    For the US recommended dietary allowance (RDA) of iron for oral nutritional supplementation in otherwise healthy individuals.
    NOTE: All dosages are expressed in terms of elemental iron. These RDAs were revised by the IOM Food and Nutrition Board in 2001.
    Oral dosage
    Adult and Adolescent pregnant females

    15 mg PO once daily in the first trimester; 27 mg PO once daily during the last 2 trimesters.

    Adult and Adolescent females during lactation

    9 to 10 mg PO once daily.

    Adult males

    8 mg PO once daily.

    Adult females older than 50 years

    8 mg PO once daily.

    Adult females 19 to 50 years

    18 mg PO once daily.

    Adolescent males 14 years and older

    11 mg PO once daily.

    Adolescent females 14 years and older

    15 mg PO once daily.

    Children 9 to 13 years

    8 mg PO once daily.

    Children 4 to 8 years

    10 mg PO once daily.

    Children 1 to 3 years

    7 mg PO once daily.

    Infants 7 to 12 months

    11 mg PO once daily.

    Term Infants birth to 5 months

    RDA is not established. An adequate intake is 0.27 mg per day PO and is based on the average iron intake of breast-fed infants.

    Preterm neonates birth to 5 months

    2 mg elemental iron/kg/day PO. Up to 4 mg elemental iron/kg/day PO may be required for premature infants weighing less than 1,500 g at birth. Do not exceed 15 mg/day PO of elemental iron.

    For the treatment of iron-deficiency anemia.
    Oral dosage
    Adults

    60 mg elemental iron PO 1 to 3 times daily for 4 weeks . Repeat anemia screening. An increase in hemoglobin of 1 g/dL or more or an increase in hematocrit of 3% or more confirms the diagnosis of iron deficiency anemia. If iron deficiency anemia is confirmed, continue iron treatment for another 2 to 3 months, then repeat anemia screening. Repeat anemia screening again 6 months after successful treatment is completed. Smaller dosages may be used if GI intolerance occurs; however, correction of the deficiency will occur at a slower rate.

    Adolescents

    60 mg elemental iron PO 1 to 3 times daily for 4 weeks . Repeat anemia screening. An increase in hemoglobin of 1 g/dL or more or an increase in hematocrit of 3% or more confirms the diagnosis of iron deficiency anemia. If iron deficiency anemia is confirmed, continue iron treatment for another 2 to 3 months, then repeat anemia screening. Repeat anemia screening again 6 months after successful treatment is completed. Smaller dosages may be used if GI intolerance occurs; however, correction of the deficiency will occur at a slower rate.

    Infants and Children

    3 to 6 mg elemental iron/kg/day PO in 1 to 3 divided doses for 4 weeks. In school-aged children, a dose of 60 mg elemental iron/day has also been recommended. Repeat anemia screening. An increase in hemoglobin of 1 g/dL or more or an increase in hematocrit of 3% or more confirms the diagnosis of iron-deficiency anemia. If iron deficiency anemia is confirmed, continue iron treatment for another 2 to 3 months, then repeat anemia screening. Repeat anemia screening again 6 months after successful treatment is completed.

    Term Neonates

    3 to 6 mg elemental iron/kg/day PO in 1 to 3 divided doses for 4 weeks. Repeat anemia screening. An increase in hemoglobin of 1 g/dL or more or an increase in hematocrit of 3% or more confirms the diagnosis of iron-deficiency anemia. If iron deficiency anemia is confirmed, continue iron treatment for another 2 to 3 months then repeat anemia screening. Repeat anemia screening again 6 months after successful treatment is completed.

    For anemia of prematurity.
    For the prevention of anemia of prematurity.
    Oral dosage
    Premature Neonates

    Usual initial dose is 2 to 4 mg elemental iron/kg/day PO. If erythropoietin alfa is used, doses up to 6 mg elemental iron/kg/day is needed as active erythropoiesis requires additional iron. Begin supplementation between age 2 and 8 weeks and continue for 12 months; starting supplementation at 2 weeks of life may reduce the risk of anemia between age 2 and 6 months. Preterm infants on iron-fortified specialized formula for preterm infants do not require additional iron supplementation. NOTE: Prior to administering iron drops, verify the concentration on the bottle; multiple concentrations are available.

    For the treatment of anemia of prematurity.
    Oral dosage
    Premature Neonates

    3 to 6 mg elemental iron/kg/day PO for 3 months. If erythropoietin alfa is used, up to 6 mg elemental iron/kg/day is needed as active erythropoiesis requires additional iron. NOTE: Prior to administering iron drops, verify the concentration on the bottle; multiple concentrations are available.

    MAXIMUM DOSAGE

    Dosage with iron must be individualized according to the patients age, dietary intake requirements, and the degree of the iron-deficiency anemia. Excess accumulation may occur if iron therapy is continued after the correction of the dietary deficiency.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Patients with hepatic disease should receive iron supplementation with caution and only under the direction of a health care prescriber. The liver is one of the main storage sites for iron, and some patients with chronic liver disease may have excessive iron storage. Specific guidelines for dosage adjustments in hepatic impairment are not available.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
     
    Intermittent hemodialysis
    Before supplementing hemodialysis patients with iron, a diagnosis of absolute or functional iron deficiency should be made. Follow normal recommended doses; it appears that no dosage adjustments are needed. Iron supplements are not hemodialyzable.

    ADMINISTRATION

     
    NOTE: Serum iron, hemoglobin and hematocrit should be evaluated prior to iron therapy and at regular intervals during therapy. Serum ferritin and transferrin-saturation may also be helpful monitoring parameters in some patients.

    Oral Administration

    For better absorption, administer 1 hour before or 2 hours after meals. If GI irritation occurs, give with meals. Avoid administering antacids, coffee, tea, dairy products, eggs, or whole grain breads within 1 hour before or 2 hours after giving iron salts.

    Oral Solid Formulations

    Tablets and capsules: Administer with a full glass of water or juice. Enteric-coated tablets should not be crushed or chewed and capsules should not be opened.

    Oral Liquid Formulations

    Solutions: May cause temporary staining of the teeth. May be diluted in water or fruit juice and administered with a straw to lessen contact with the tooth enamel. Do not mix in dairy milk.
    Iron drops: May cause temporary staining of the teeth. Drops may be diluted in infant formula for ease of administration. Do not mix in dairy milk. NOTE: Prior to giving ferrous sulfate drops, verify the concentration on the bottle; two concentrations are available: 15 mg elemental iron/1 mL and 15 mg elemental iron/0.6 mL.

    STORAGE

    Auryxia:
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Anemia, hemolytic anemia

    Iron salts are only useful for those anemia types where iron-deficiency co-exists. The type of anemia and the underlying cause or causes should be determined before starting therapy with iron. Unnecessary administration of iron salts may lead to iron overload and iron toxicity. Since anemia may be a result of a systemic disturbance, such as recurrent blood loss, the underlying cause(s) should be corrected, if possible. Exogenous Iron salts are only useful for those anemia types where iron-deficiency co-exists. The type of anemia and the underlying cause or causes should be determined before starting therapy with iron. Unnecessary administration of iron salts may lead to iron overload and iron toxicity. Since anemia may be a result of a systemic disturbance, such as recurrent blood loss, the underlying cause(s) should be corrected, if possible. Exogenous administration of iron salts will not alleviate hemolytic anemia and should only be administered to patients with hemolysis if an iron-deficiency is also present. Iron supplementation should be used cautiously in patients receiving blood transfusions because iron overload may occur.

    Neonates

    Administration of iron salts to premature neonates can increase the risk of developing hemolytic anemia because these neonates may have a low vitamin E serum concentration. In general, iron supplementation should not begin until adequate vitamin E is supplied in the diet; human breast milk and modern infant formulas usually supply adequate dietary vitamin E.

    Accidental exposure, children, infants

    Infants and children should receive iron salts only under the advice and supervision of a qualified health care professional. Accidental exposure to excessive amounts of iron-containing products (i.e., overdose) is the leading cause of fatal poisoning in children under the age of 6 years. Products that contain 30 milligrams (mg) or more of iron per dosage unit are packaged as individual unit-doses. This is to limit the number of pills or capsules a small child could accidentally consume once the package is opened. The FDA published the final rule on the packaging of iron in the January 15, 1997 Federal Register. Under U.S. Consumer Product Safety Commission regulations, most drugs and dietary supplements with more than 250 mg of iron per container must have child-resistant packages. Always store any iron-containing products out of the reach of children and pets. In the case of accidental exposure by ingestion, call a physician or poison control center immediately.

    Hemochromatosis, hemosiderosis, hepatic disease, porphyria, sideroblastic anemia, thalassemia

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

    Colitis, dysphagia, GI disease, GI obstruction, ileus, inflammatory bowel disease, peptic ulcer disease

    Orally administered iron salts may have a corrosive effect that may exacerbate the symptoms associated with certain GI disease states such as peptic ulcer disease or inflammatory bowel disease (e.g., ulcerative colitis). Patients with dysphagia have, on rare occasions, developed oral or esophageal ulcerations from difficulty in swallowing solid oral iron dosage forms. Iron salts may produce constipation and should be used with care in patients with GI obstruction or ileus. Iron products may cause false-positive results on stool guaiac tests for blood.

    Pregnancy

    When ingested in amounts according to the recommended daily allowances (RDA), iron salts are considered safe for use during pregnancy. Routine iron supplementation during pregnancy appears to prevent low maternal hemoglobin at birth and in the immediate postpartum period. The effect of routine iron supplementation on fetal or maternal outcomes is not clear, but is thought to be beneficial. Pregnant women should supplement iron salts during pregnancy only when advised to do so by a qualified health care professional.

    Breast-feeding

    Use of iron supplements within the recommended daily dietary intake for lactating women is generally recognized as safe. While iron is excreted into breast-milk, the iron content of breast milk is not readily affected by the iron content of the maternal diet or the maternal serum iron level. Therefore, the use of iron salts, under the direction of a health care prescriber, is compatible with breast-feeding if the lactating mother needs treatment for iron deficiency. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Sulfite hypersensitivity

    Some iron products contain sulfites and should be used with caution in patients with a known sulfite hypersensitivity. Although the overall prevalence of sulfite hypersensitivity is low, it is seen more frequently in asthmatics or in atopic non-asthmatic persons.

    Geriatric

    The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities (LTCFs). According to the OBRA guidelines, iron therapy is not indicated in anemia of chronic disease when iron stores and transferrin levels are normal or elevated. Clinical rationale should be documented for long-term use (greater than 2 months) or more than once daily administration for longer than a week, because of side effects and the risk of iron accumulation in tissues. Monitoring should include a baseline serum iron or ferritin level and periodic complete blood count (CBC) or hematocrit/hemoglobin measurements. Adverse consequences of iron therapy include constipation and dyspepsia. Iron can accumulate in tissues and cause multiple complications if given chronically in the presence of normal or high iron stores.

    ADVERSE REACTIONS

    Severe

    esophageal stricture / Delayed / Incidence not known
    esophageal ulceration / Delayed / Incidence not known
    odynophagia / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known

    Moderate

    constipation / Delayed / Incidence not known
    esophagitis / Delayed / Incidence not known
    oral ulceration / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    hemosiderosis / Delayed / Incidence not known

    Mild

    anorexia / Delayed / Incidence not known
    nausea / Early / Incidence not known
    vomiting / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    diarrhea / Early / Incidence not known
    stool discoloration / Delayed / Incidence not known
    dyspepsia / Early / Incidence not known
    tooth discoloration / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abacavir; Dolutegravir; Lamivudine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
    Acetohydroxamic Acid: (Moderate) Acetohydroxamic acid chelates heavy metals, including iron. Absorption of orally administered iron salts or polysaccharide-iron complex and acetohydroxamic acid from the intestinal lumen may be reduced when both drugs are administered concomitantly. If iron therapy is required in a patient currently taking acetohydroxamic acid, intramuscular iron is recommended.
    Alendronate: (Moderate) Separate administration of alendronate and iron supplements by at least 30 minutes. Iron will interfere with the absorption of alendronate.
    Alendronate; Cholecalciferol: (Moderate) Separate administration of alendronate and iron supplements by at least 30 minutes. Iron will interfere with the absorption of alendronate.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Antacids: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed.
    Aspirin, ASA; Omeprazole: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Administer bictegravir with food at the same time as iron supplements. Routine administration of bictegravir under fasting conditions simultaneously with, or 2 hours after, iron supplements is not recommended. Iron is a polyvalent cation that can bind bictegravir in the GI tract. Taking these drugs simultaneously without food results in reduced bioavailability of bictegravir. In drug interaction studies, simultaneous administration of bictegravir and ferrous fumarate under fasted conditions decreased the mean AUC of bictegravir by approximately 63%.
    Cabotegravir: (Moderate) Administer oral iron at least two hours before or four hours after taking oral cabotegravir. Iron is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir.
    Cabotegravir; Rilpivirine: (Moderate) Administer oral iron at least two hours before or four hours after taking oral cabotegravir. Iron is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir.
    Calcium Carbonate: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction.
    Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction.
    Calcium Carbonate; Risedronate: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. (Moderate) Separate administration of oral risedronate and iron supplements by at least 2 hours. Iron will interfere with the absorption of oral risedronate.
    Calcium Carbonate; Simethicone: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction.
    Calcium; Vitamin D: (Moderate) 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.
    Carbidopa; Levodopa: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
    Carbidopa; Levodopa; Entacapone: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
    Cefdinir: (Moderate) Administer cefdinir at least 2 hours before or 2 hours after iron supplements. Cefdinir absorption may be reduced. Coadministration of cefdinir with a therapeutic iron supplement containing 60 mg of elemental iron or vitamins supplemented with 10 mg of elemental iron reduced extent of absorption by 80% and 31%, respectively.
    Cholestyramine: (Moderate) Concurrent administration of cholestyramine and oral iron supplements may reduce the oral absorption of iron. To avoid any oral absorption interference, administration of other drugs is recommended 1 hour before or at least 4 to 6 hours after cholestyramine administration.
    Cimetidine: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Ciprofloxacin: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain iron. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
    Darbepoetin Alfa: (Minor) It is important that iron stores be replete before beginning therapy with darbepoetin alfa due to increased iron utilization. Inadequate iron stores will interfere with the therapeutic response to these agents (e.g., red blood cell production). Supplemental iron may be needed during maintenance therapy to facilitate erythropoiesis. Iron supplementation (e.g., iron dextran; iron salts; iron sucrose, sucroferric oxyhydroxide; polysaccharide-iron complex; sodium ferric gluconate complex) may be required.
    Deferasirox: (Contraindicated) Deferasirox chelates iron and is indicated as a treatment of iron toxicity or overdose. It is illogical for a patient to receive both iron supplementation and deferasirox simultaneously. Do not give iron supplementation during Deferasirox treatment.
    Deferiprone: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, iron sucrose, sodium ferric gluconate complex, or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. However, since deferiprone has the potential to bind polyvalent cations (e.g., iron), allow at least a 4-hour interval between deferiprone and other oral medications or dietary supplements containing these polyvalent cations when they are used.
    Deferoxamine: (Contraindicated) Deferoxamine chelates iron from ferritin or hemosiderin. A stable complex is formed that prevents iron from entering into further chemical reactions. The chelate is excreted in the urine and in the feces via bile. Deferoxamine is indicated as a treatment of iron toxicity or overdose. It would be illogical for a patient to receive both iron supplementation and deferoxamine simultaneously.
    Delafloxacin: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain iron. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron.
    Dexlansoprazole: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Didanosine, ddI: (Moderate) Iron salts should not be administered simultaneously with didanosine, ddI chewable tablets or powder for oral solution. Oral absorption of iron supplements is reduced if given with antacids; the buffering agents contained in didanosine tablets and powder likewise reduce iron salt absorption. Administer oral doses of iron salts 1 hour before or 4 hours after didanosine tablet or powder administration. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with iron salts.
    Dimercaprol: (Contraindicated) Dimercaprol forms toxic-chelates with iron. These dimercaprol-metal complexes are more toxic than the metal alone, especially to the kidneys. Iron therapy should not be administered concomitantly with dimercaprol. Therapy with iron should generally be delayed until 24 hours after the cessation of dimercaprol therapy.
    Dolutegravir: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
    Dolutegravir; Lamivudine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
    Dolutegravir; Rilpivirine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing iron if given under fasting conditions. When taken with food, dolutegravir and supplements containing iron can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
    Eltrombopag: (Major) Eltrombopag chelates polyvalent cations (e.g., iron) in foods and mineral supplements. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as iron salts, multivitamins that contain iron, or polysaccharide-iron complex.
    Elvitegravir: (Moderate) Separate administration of elvitegravir and iron by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Separate administration of elvitegravir and iron by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Separate administration of elvitegravir and iron by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
    Enteral Feedings: (Minor) Ferrous sulfate elixir has an acidic pH and has been reported to form precipitates with enteral feedings and may clog feeding tubes.
    Epoetin Alfa: (Minor) Inadequate iron stores will interfere with the therapeutic response to epoetin alfa (e.g., red blood cell production). Most patients with chronic kidney disease will require supplemental iron (e.g., iron dextran; iron salts; iron sucrose, sucroferric oxyhydroxide; polysaccharide-iron complex; sodium ferric gluconate complex) during epoetin alfa receipt. Evaluate transferrin saturation and serum ferritin before and during epoetin alfa treatment. Administer supplemental iron therapy when serum ferritin is < 100 mcg/L or when serum transferrin saturation is < 20%. After initiation of therapy and after each dose adjustment, monitor hemoglobin weekly until the hemoglobin concentration is stable and sufficient to minimize the need for RBC transfusion.
    Esomeprazole: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Etidronate: (Moderate) Separate administration of oral etidronate and iron supplements by at least 2 hours. Iron will interfere with the absorption of oral etidronate.
    Famotidine: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Ferric carboxymaltose: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
    Ferric Derisomaltose: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
    Ferumoxytol: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
    Food: (Major) For better iron absorption, administer iron salts 1 hour before or 2 hours after meals. If GI irritation occurs, the iron supplement may be administered with meals. However, where possible, avoid administering coffee, tea, or dairy products within 1 hour before or 2 hours after giving iron.
    Gemifloxacin: (Major) Administer oral products that contain iron at least 3 hours before or 2 hours after gemifloxacin. Gemifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron.
    Green Tea: (Major) Green tea has been shown to inhibit the absorption of nonheme iron. When possible, do not consume green tea or green tea extract within 1 hour before or 2 hours after giving iron salts.
    H2-blockers: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Major) Coadministration of methyldopa with iron salts or polysaccharide-iron complex is not recommended. If iron supplementation is necessary, administer a methyldopa dose at least 2 hours prior to the iron supplement. Iron salts have been reported to dramatically reduce the oral absorption of methyldopa. Several studies demonstrate decreased bioavailability of methyldopa when coadministered with ferrous sulfate or ferrous gluconate. This interaction may result in decreased antihypertensive effect of methyldopa.
    Ibandronate: (Moderate) Separate administration of oral ibandronate and iron supplements by at least 1 hour. Iron will interfere with the absorption of oral ibandronate.
    Ibritumomab Tiuxetan: (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphates by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions.
    Ibuprofen; Famotidine: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Iron - Injectable Only: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
    Iron Dextran: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
    Iron Sucrose, Sucroferric Oxyhydroxide: (Major) Parenteral iron formulas are generally only indicated for use in patients with documented iron deficiency in whom oral administration is either impossible or unsatisfactory. In general, do not administer parenteral iron concomitantly with other iron preparations (e.g., other parenteral iron products or oral iron supplements). Parenteral iron preparations (e.g., iron dextran; iron sucrose, sucroferric oxyhydroxide; sodium ferric gluconate complex; ferric carboxymaltose; ferumoxytol) may reduce the absorption of concomitantly administered oral iron preparations. Oral iron supplementation should be discontinued before parenteral administration of iron. Too much iron can be toxic, and iron is not easily eliminated from the body.
    Lansoprazole: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Lansoprazole; Naproxen: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Lanthanum Carbonate: (Major) Oral compounds known to interact with antacids, like iron salts, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
    Levodopa: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
    Levofloxacin: (Moderate) Administer oral products that contain iron at least 2 hours before or 2 hours after orally administered levofloxacin. Levofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Chelation of divalent cations with levofloxacin is less than with other quinolones.
    Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Major) Administer iron at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of iron may be reduced by chelation with magnesium sulfate.
    Methoxy polyethylene glycol-epoetin beta: (Minor) Iron stores should be replete before and during treatment with an ESA. Iron stores are utilized in erythropoiesis and can be depleted during therapy even in patients with normal pre-treatment iron concentrations. Achieving and maintaining adequate iron stores are essential to attaining an optimal response to MPG-epoetin beta. Iron supplementation may be needed before and during therapy (e.g. iron dextran; iron salts; sodium ferric gluconate complex; iron sucrose, sucroferric oxyhydroxide; and polysaccharide-iron complex.
    Methyldopa: (Major) Coadministration of methyldopa with iron salts or polysaccharide-iron complex is not recommended. If iron supplementation is necessary, administer a methyldopa dose at least 2 hours prior to the iron supplement. Iron salts have been reported to dramatically reduce the oral absorption of methyldopa. Several studies demonstrate decreased bioavailability of methyldopa when coadministered with ferrous sulfate or ferrous gluconate. This interaction may result in decreased antihypertensive effect of methyldopa.
    Moxifloxacin: (Major) Administer oral moxifloxacin at least 4 hours before or 8 hours after oral products that contain iron. Moxifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain iron.
    Mycophenolate: (Moderate) Separate administration of mycophenolate and iron by at least 4 hours. Iron may decrease the oral bioavailability of mycophenolate. Mycophenolate recovery was reduced by up to 16% under certain pH conditions in drug interaction studies.
    Naproxen; Esomeprazole: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Nizatidine: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Ofloxacin: (Moderate) Administer oral products that contain iron at least 2 hours before or 2 hours after ofloxacin. Ofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
    Omeprazole: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Omeprazole; Amoxicillin; Rifabutin: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Omeprazole; Sodium Bicarbonate: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Pantoprazole: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Penicillamine: (Major) In general, oral mineral supplements should not be given since they may block the oral absorption of penicillamine. However, iron deficiency may develop, especially in children and menstruating or pregnant women, or as a result of the low copper diet recommended for Wilson's disease. If necessary, iron may be given in short courses, but since iron and penicillamine each inhibit oral absorption of the other, 2 hours should elapse between administration of penicillamine and iron doses.
    Phosphorated Carbohydrate Solution: (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphates by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions.
    Phosphorus: (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphates by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions.
    Polyethylene Glycol; Electrolytes: (Major) Administer iron at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of iron may be reduced by chelation with magnesium sulfate.
    Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Major) Administer iron at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of iron may be reduced by chelation with magnesium sulfate.
    Potassium Phosphate: (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphates by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions.
    Potassium Phosphate; Sodium Phosphate: (Moderate) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of phosphates by as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions.
    Proton pump inhibitors: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Rabeprazole: (Moderate) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of proton pump inhibitors can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Proton pump inhibitors have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Ranitidine: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
    Risedronate: (Moderate) Separate administration of oral risedronate and iron supplements by at least 2 hours. Iron will interfere with the absorption of oral risedronate.
    Sodium Bicarbonate: (Moderate) Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. Antacids may decrease the absorption of oral iron preparations. At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed.
    Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Iron salts may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, products containing iron should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
    Tetracyclines: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
    Thyroid hormones: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
    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.
    Vonoprazan; Amoxicillin: (Moderate) Monitor for decreased efficacy of oral iron salts if coadministered with vonoprazan. Vonoprazan reduces intragastric acidity, which may decrease the absorption of iron reducing its efficacy.
    Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Monitor for decreased efficacy of oral iron salts if coadministered with vonoprazan. Vonoprazan reduces intragastric acidity, which may decrease the absorption of iron reducing its efficacy.
    Zinc: (Moderate) Orally administered zinc salts compete with iron supplements for absorption from the intestine. To minimize the interaction, separate oral iron and zinc doses by at least 2 hours. The oral receipt of 100 mg of iron as ferrous gluconate with 12 mg zinc in 11 patients with normal iron status and comparable total exchangeable zinc pools yielded a mean zinc absorption of 26.4% +/- 14.4% of the administered dose as compared with 44.5% +/- 22.5% of the dose given without concomitant iron. Concomitant use of iron 400 mg as ferrous gluconate yielded a mean zinc absorption of 22.9% +/- 6.4% of the zinc dose.

    PREGNANCY AND LACTATION

    Pregnancy

    When ingested in amounts according to the recommended daily allowances (RDA), iron salts are considered safe for use during pregnancy. Routine iron supplementation during pregnancy appears to prevent low maternal hemoglobin at birth and in the immediate postpartum period. The effect of routine iron supplementation on fetal or maternal outcomes is not clear, but is thought to be beneficial. Pregnant women should supplement iron salts during pregnancy only when advised to do so by a qualified health care professional.

    Use of iron supplements within the recommended daily dietary intake for lactating women is generally recognized as safe. While iron is excreted into breast-milk, the iron content of breast milk is not readily affected by the iron content of the maternal diet or the maternal serum iron level. Therefore, the use of iron salts, under the direction of a health care prescriber, is compatible with breast-feeding if the lactating mother needs treatment for iron deficiency. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Normal erythropoiesis is dependent on the concentration of iron and erythropoietin available in the plasma. Approximately two-thirds of total body iron is in the circulating red blood cell mass as hemoglobin, the major factor in oxygen transport. Administration of iron does not stimulate the production of red blood cells, nor does it correct abnormalities not caused by iron deficiency. A therapeutic response to treatment with iron products is dependent on the patient's ability to absorb and use the iron. The response to iron therapy is also influenced by the cause of the deficiency as well as other illnesses that can affect normal erythropoiesis. A positive response to iron treatment can be noted by an increase in the reticulocyte count within 1 week of therapy and an increase in hemoglobin at roughly 3—4 weeks, assuming that transfusion or other interventions cannot explain the improvements in the patients clinical status.
     
    Iron-containing proteins and enzymes are important in oxidation-reduction reactions, especially those of the mitochondria. Iron is a component of myoglobin and several heme-enzymes, including the cytochromes, catalase, and peroxidase. Iron is an essential component of the metalloflavoprotein enzymes and the mitochondrial enzyme alpha-glycerophosphate oxidase. Furthermore, iron is a cofactor for enzymes such as aconitase and tryptophan pyrrolase. Iron deficiency not only causes anemia and decreased oxygen delivery, it also reduces the metabolism of muscle and decreases mitochondrial activity. Iron deficiency can also lead to defects in learning or thermoregulation. Thus iron is important to several metabolic functions which are independent of its importance to erythropoiesis.

    PHARMACOKINETICS

    Iron salts are administered orally. Once absorbed, the amount of total body iron content is used to form essential iron-dependent compounds and any excess iron is stored. Most of the essential iron in the body is contained in hemoglobin. Roughly 80% of plasma iron goes to the bone marrow to produce new erythrocytes. Other iron-dependent essential compounds include myoglobin and iron-dependent enzymes. The internal transport of iron to essential sites depends on the plasma protein transferrin. Transferrin delivers iron to specific transferrin receptors at target tissues, which then deliver iron to intracellular sites. Transferrin is extruded from the cell once iron is delivered intracellularly. The production of transferrin receptors is regulated according to body needs; when iron is deficient, transferrin receptors increase and iron storage via ferritin decreases. Ferritin is the storage protein for iron. The main sites of iron storage are the liver, spleen, bone marrow, and the reticuloendothelial system; a minor portion is stored in the muscle. After a life-cycle of roughly 120 days, roughly 0.8%/day of the circulating erythrocytes are catabolized by the reticuloendothelial system (RES); at that time, some of the iron is recirculated to the plasma bound to transferrin. The remaining iron from erythrocyte breakdown is incorporated into ferritin stores in the RES and hepatocytes. The utilization of iron by the body is designed to maintain body stores, so very little physiologic loss of iron occurs once it is in the body. In healthy adults, daily loss of iron occurs primarily through GI losses (e.g., bile, exfoliated mucosal or red cells); minor amounts are lost through skin desquamation or the urine. Physiologic losses in adult males average roughly 1 mg/day. Iron status will determine the magnitude of iron loss; less iron is lost in those individuals with iron deficiency. Those patients with excessive iron intake may lose up to 2 mg/day.

    Oral Route

    When iron is taken orally, the acidic environment of the stomach maintains iron in its more soluble ferrous (and more readily absorbed) state. Iron is then absorbed through the duodenum and upper small intestines. Although orally administered iron is absorbed in the duodenum, iron directly instilled into the duodenum is poorly absorbed. Intraduodenal pH is much higher than intragastric pH due to the high concentration of pancreatic secretions in the duodenum. Both ascorbic acid and meat (heme iron) will increase the absorption of non-heme iron. A hematopoietic transcription factor, known as NF-E2, regulates the absorption of iron by the oral route in response to erythropoiesis. Increased oral uptake into the systemic circulation occurs when iron deficiency or increased erythropoiesis (e.g., epoetin alfa therapy) is present. When iron stores are adequate, less iron is absorbed across the intestinal mucosa. The absorptive process across the intestine is finite, limiting the amount of entry of iron into the systemic circulation on a daily basis, even in deficiency. Oral iron absorption rarely exceeds 2 mg/day.