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  • CLASSES

    Iron Supplements
    Mineral Binding Agents

    DEA CLASS

    Rx

    DESCRIPTION

    IV iron supplement and oral phosphate binder
    Used IV for the treatment of iron deficiency anemia in patients with chronic kidney disease and orally for control of serum phosphorus levels in patients with chronic kidney disease on dialysis
    Can cause serious, even fatal, hypersensitivity reactions when administered IV; although less likely to cause hypersensitivity than iron dextran, facilities for cardiopulmonary resuscitation must be available during dosing

    COMMON BRAND NAMES

    Velphoro, Venofer

    HOW SUPPLIED

    Iron Sucrose/Venofer Intravenous Inj Sol
    Velphoro Oral Tab Chew: 500mg

    DOSAGE & INDICATIONS

    For the treatment of iron-deficiency anemia in patients with chronic kidney disease.
    NOTE: A test dose is not required, but has been used at the physician's discretion in 1 of 3 clinical U.S. premarketing trials of hemodialysis patients. In another clinical study, 131 patients received a 50 mg (2.5 mL) test dose of iron sucrose, sucroferric oxyhydroxide diluted in 50 mL of 0.9% Sodium Chloride Injection administered IV over 3 to 10 minutes.
    In patients with hemodialysis dependent-chronic kidney disease.
    Intravenous dosage
    Adults

    100 mg elemental iron IV. Administer undiluted by slow IV injection over 2 to 5 minutes or diluted in up to 100 mL of 0.9% Sodium Chloride Injection over at least 15 minutes, per consecutive hemodialysis session. Administer early during the dialysis session (generally within the first hour). The usual total treatment course is 1,000 mg elemental iron. Treatment may be repeated if iron deficiency recurs.

    Children and Adolescents 2 to 17 years

    Dosing for iron replacement treatment in pediatric patients is not established. For iron maintenance treatment, 0.5 mg/kg/dose IV every 2 weeks (Max: 100 mg/dose) for 12 weeks. Administer by slow IV injection (undiluted) over 5 minutes or diluted in 0.9% Sodium Chloride Injection at a concentration of 1 to 2 mg/mL and administered over 5 to 60 minutes. Do not dilute to concentrations less than 1 mg/mL. Treatment may be repeated if necessary.

    In patients with peritoneal dialysis dependent-chronic kidney disease.
    Intravenous dosage
    Adults

    Administer a total dose of 1,000 mg in 3 divided doses by IV infusion within a 28-day period; each dose is administered 14 days apart. The first 2 doses of 300 mg each are administered by IV infusion over 1.5 hours; the last dose of 400 mg is administered by IV infusion over 2.5 hours. Dilute in up to 250 mL of 0.9% Sodium Chloride Injection. Treatment may be repeated if iron deficiency recurs.

    Children and Adolescents 2 to 17 years

    Dosing for iron replacement treatment in pediatric patients is not established. For iron maintenance treatment, 0.5 mg/kg/dose IV every 4 weeks (Max: 100 mg/dose) for 12 weeks. Administer by slow IV injection (undiluted) over 5 minutes or diluted in 0.9% Sodium Chloride Injection at a concentration of 1 to 2 mg/mL and administered over 5 to 60 minutes. Do not dilute to concentrations less than 1 mg/mL. Treatment may be repeated if necessary.

    In patients with non-dialysis dependent-chronic kidney disease.
    Intravenous dosage
    Adults

    200 mg elemental iron IV. Administer undiluted by slow IV injection over 2 to 5 minutes or diluted in up to 100 mL of 0.9% Sodium Chloride Injection over 15 minutes. Administer on 5 different occasions within a 14-day period. The total cumulative dose administered is 1,000 mg. Treatment may be repeated if iron deficiency recurs. There is limited experience with 500 mg of elemental iron diluted in up to 250 mL of 0.9% Sodium Chloride Injection, given as an IV infusion over 3.5 to 4 hours on day 1 and day 14. In addition, in 107 chronic kidney disease patients, 500 mg of elemental iron has been administered over 3 hours on 2 consecutive days. Two patients experienced drug-related adverse events; 1 patient experienced first-dose epigastric discomfort, nausea, vomiting, and lightheadedness and did not receive further doses, and 1 patient experienced abdominal cramps and moderate nausea lasting 3 days after completing the entire dosage regimen.

    Children and Adolescents 2 to 17 years

    Dosing for iron replacement treatment in pediatric patients is not established. For iron maintenance treatment, 0.5 mg/kg/dose IV every 4 weeks (Max: 100 mg/dose) for 12 weeks. Administer by slow IV injection (undiluted) over 5 minutes or diluted in 0.9% Sodium Chloride Injection at a concentration of 1 to 2 mg/mL and administered over 5 to 60 minutes. Do not dilute to concentrations less than 1 mg/mL. Treatment may be repeated if necessary.

    For the management of hyperphosphatemia in patients with chronic kidney disease on dialysis.
    Oral dosage
    Adults

    Initially, 500 mg PO 3 times daily with meals. To maximize the dietary phosphate binding, the total daily dose should be divided across the meals of the day. Monitor serum phosphorus concentration, and at weekly intervals, titrate the dose by 500 mg per day as needed until an acceptable serum phosphorus concentration (5.5 mg/dL or less) is reached; continue monitoring regularly. Patients enrolled in clinical studies generally required an average of 1,500 to 2,000 mg/day PO to control serum phosphorus concentration. The maximum daily dosage evaluated in a phase 3 trial in end stage renal disease patients was 3,000 mg/day PO.

    MAXIMUM DOSAGE

    Adults

    500 mg/dose IV has been administered on 2 consecutive days in patients with chronic kidney disease. Up to 3000 mg/day PO has been studied in patients with end stage renal disease.

    Geriatric

    500 mg/dose IV has been administered on 2 consecutive days in patients with chronic kidney disease. Up to 3000 mg/day PO has been studied in patients with end stage renal disease.

    Adolescents

    0.5 mg/kg IV up to a max of 100 mg/dose IV. Safety and efficacy of iron sucrose chewable tablets have not been established.

    Children

    >= 2 years: 0.5 mg/kg IV up to a max of 100 mg/dose IV. Safety and efficacy of iron sucrose chewable tablets have not been established.
    < 2 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Patients with hepatic disease should receive IV iron sucrose with caution. 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 are not available.

    Renal Impairment

    Dosage adjustments are not necessary.
     
    Intermittent hemodialysis
    Before supplementing hemodialysis patients with iron, a diagnosis of absolute or functional iron deficiency should be made. Follow recommended dosage for IV iron sucrose in hemodialysis patients. IV iron sucrose is not dialyzable.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Chewable tablets
    Chew or crush before swallowing; do not swallow whole.
    Take with meals. No additional fluid above the amount usually taken by the patient is required.
    If 1 or more doses are missed, resume the medication with the next meal. Do not attempt to replace a missed dose.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    The dosage of iron sucrose is expressed in mg of elemental iron.
    Each mL contains 20 mg of elemental iron.
    A test dose is not required but has been used in some premarketing clinical trials (50 mg (2.5 mL) diluted in 50 mL of 0.9% Sodium Chloride Injection and administered IV over 3 to 10 minutes).
    Discard any unused portions; contains no preservatives.
    Do NOT mix iron sucrose with other medications or TPN solution.
    Prior to and at regular intervals during parenteral iron therapy, evaluate serum iron, hemoglobin, and hematocrit. Ferritin and transferrin are also recommended monitoring parameters.[44801]

    Intravenous Administration

    Slow Intravenous Injection
    No dilution necessary.
    In adults, a 100 to 200 mg dose may be given undiluted (into the dialysis line for hemodialysis patients) over 2 to 5 minutes.
    In pediatric patients, the maintenance dose may be given undiluted over 5 minutes.
    Storage: When stored undiluted in a plastic syringe, solution is stable for 7 days at controlled room temperature (25 +/- 2 degrees C) and under refrigeration (4 +/- 2 degrees C).
     
    Intravenous Infusion
    May be administered by IV infusion (into the dialysis line for hemodialysis patients). This may reduce the risk of hypotensive episodes.
    For doses of 100 or 200 mg (adults): Dilute in a maximum of 100 mL of 0.9% Sodium Chloride Injection and infuse over a period of at least 15 minutes.
    For doses of 300 to 500 mg (adults): Dilute in a maximum of 250 mL of 0.9% Sodium Chloride Injection. Per FDA-approved labeling, infuse doses of 300 mg over a period of 1.5 hours; infuse doses of 400 mg over 2.5 hours. During clinical experiences, doses of 500 mg have been administered over 3.5 to 4 hours.
    In pediatric patients, maintenance dose may be diluted in 0.9% Sodium Chloride Injection at a concentration of 1 to 2 mg/mL and administered over 5 to 60 minutes. Do not dilute to concentrations less than 1 mg/mL.
    Storage: When diluted at a concentration of 2 to 10 mg/mL elemental iron and stored in a plastic syringe, solution is stable for 7 days at controlled room temperature (25 +/- 2 degrees C) and under refrigeration (4 +/- 2 degrees C). When added to IV infusion bags (PVC or non-PVC) containing 0.9% Sodium Chloride Injection at a concentration of 1 to 2 mg/mL elemental iron, solution is stable for 7 days at controlled room temperature (25 +/- 2 degrees C).

    STORAGE

    Velphoro:
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    - Store in original container
    Venofer:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - See package insert for detailed storage information
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in original container

    CONTRAINDICATIONS / PRECAUTIONS

    Requires a specialized care setting

    The use of IV iron sucrose requires a specialized care setting in which facilities for cardiopulmonary resuscitation must be available during dosing and where the patient can be observed during administration. Serious hypersensitivity reactions, including life-threatening and fatal anaphylactic-type reactions, have been reported in patients receiving IV iron sucrose. Patients may present with shock, loss of consciousness, collapse and/or significantly low blood pressure, wheezing, dyspnea, rashes, or pruritus. IV iron sucrose is contraindicated in patients with known hypersensitivity to iron sucrose or any of its inactive components. Close patient monitoring is advised during IV iron administration. Observe for signs and symptoms of hypersensitivity during and for at least 30 minutes after administration. If hypersensitivity reactions occur, stop iron sucrose administration. Serious anaphylactoid reactions require appropriate resuscitation measures.[44801]

    Cardiac disease, hypotension, intramuscular administration, subcutaneous administration

    Hypotension has been reported frequently in patients receiving intravenous iron products and may be unrelated to hypersensitivity. Use caution in administering IV iron sucrose in patients with pre-existing hypotension. Hypotension (36% incidence in pre-marketing hemodialysis trials) following administration of IV iron sucrose may be related to rate of infusion, the total dose administered, and patient risk factors. Patients with preexisting cardiac disease may have exacerbation of cardiovascular symptoms if adverse effects such as hypotension occur following IV iron sucrose administration. Iron sucrose injection is strongly alkaline and should not be administered by intramuscular administration or subcutaneous administration.[44801]

    Hemochromatosis, hemoglobinopathy, hemosiderosis

    Do not administer IV iron sucrose to patients with evidence of iron overload (e.g., patients with hemochromatosis). Oral sucroferric oxyhydroxide has not been studied in patients with hemochromatosis or other diseases with iron accumulation. Unnecessary or prolonged administration of iron may lead to iron overload and consequently the possibility of exogenous hemosiderosis. Patients with hemoglobinopathy and other refractory anemias that might be erroneously diagnosed as iron deficiency anemias are at particular risk for such iron overload.[42291] The type of anemia and the underlying cause or causes should be determined before starting therapy with IV iron sucrose. Since the anemia may be a result of a systemic disturbance, such as recurrent blood loss, the underlying cause(s) should be corrected, if possible. Patients receiving exogenous iron therapy require periodic monitoring of hematologic and hematinic parameters (i.e., hemoglobin, hematocrit, serum ferritin, and transferrin saturation) to avoid iron overload.[44801]

    Hepatic disease

    Some patients with chronic hepatic disease may also have hemochromatosis or moderate iron overload in hepatic tissues. Use IV iron sucrose with caution in patients with hepatic disease. The liver is one of the main storage sites for iron, and advanced chronic liver disease may result in excess storage of iron in the liver.

    Pregnancy

    Fetal adverse reactions, including fetal bradycardia, have been associated with maternal hypersensitivity reactions, especially during the second and third trimester of pregnancy. Data with intravenous iron sucrose use during human pregnancy have not shown adverse maternal or fetal outcomes; however, reports of intravenous iron sucrose use in pregnant women during the first trimester are insufficient to assess the risk of major birth defects or miscarriage. Treat iron deficiency anemia during pregnancy because there are risks to the mother and fetus associated with untreated iron deficiency anemia during pregnancy.[44801] There are no adequate and well-controlled studies of oral sucroferric oxyhydroxide use in pregnant women; however, animal studies have not shown any evidence of impaired fertility or fetal harm at doses up to 16 and 4 times, respectively, the human maximum recommended clinical dose. Sucroferric oxyhydroxide is not absorbed systemically following oral administration, and maternal use is not expected to result in fetal exposure to the drug.[56601]

    Breast-feeding

    Iron sucrose is present in human milk, and available data after exposure to 100 to 300 mg of intravenous iron sucrose have not reported adverse reactions in breast-fed infants. Limited data indicate iron found in breast milk is not increased after intravenous administration of iron sucrose. There are no data on the effects of iron sucrose on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for intravenous iron sucrose and any potential adverse effects on the breast-fed infant from intravenous iron sucrose or the underlying maternal condition. Monitor breastfed infants exposed to intravenous iron sucrose for gastrointestinal toxicity (i.e., constipation, diarrhea).[44801] [49198] [49199] Sucroferric oxyhydroxide is not absorbed systemically following oral administration and breast-feeding is not expected to result in exposure of the child to sucroferric oxyhydroxide.[56601]

    Children, infants, neonates

    Intravenous iron sucrose has not been studied in neonates, infants, and children younger than 2 years. In a country where it is available for use in children, fatal necrotizing enterocolitis was reported in premature neonates (weight less than 1,250 g) who received IV iron sucrose, several other medications, and erythropoietin; causality was not established. The dosing of IV iron sucrose for iron replacement treatment in pediatric patients with hemodialysis-dependent chronic kidney disease has not been established.[44801] The safety and efficacy of oral sucroferric oxyhydroxide have also not been established in pediatric patients.[56601]
     

    Peritonitis

    Patients with peritonitis during peritoneal dialysis, significant gastric disorders, or those following major gastrointestinal surgery were not included in clinical trials evaluating oral sucroferric oxyhydroxide therapy. When administering oral sucroferric oxyhydroxide, monitor effect and iron homeostasis in these patients.[56601]

    ADVERSE REACTIONS

    Severe

    heart failure / Delayed / 1.0
    anaphylactoid reactions / Rapid / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    bradycardia / Rapid / Incidence not known
    seizures / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known

    Moderate

    hypotension / Rapid / 2.0-39.4
    hypertension / Early / 2.1-8.0
    peripheral edema / Delayed / 2.6-7.2
    chest pain (unspecified) / Early / 1.4-6.1
    dyspnea / Early / 1.3-5.8
    hypoglycemia / Early / 0.4-4.0
    hypervolemia / Delayed / 1.3-3.0
    gout / Delayed / 2.9-2.9
    hyperglycemia / Delayed / 2.9-2.9
    conjunctivitis / Delayed / 0.4-2.7
    edema / Delayed / Incidence not known
    hemosiderosis / Delayed / Incidence not known
    confusion / Early / Incidence not known

    Mild

    muscle cramps / Delayed / 0.7-29.4
    diarrhea / Early / 5.2-24.0
    stool discoloration / Delayed / 12.0-16.0
    sinusitis / Delayed / 2.2-16.0
    infection / Delayed / 2.2-16.0
    pharyngitis / Delayed / 2.2-16.0
    nausea / Early / 5.3-14.7
    headache / Early / 2.9-12.6
    vomiting / Early / 5.0-9.1
    dysgeusia / Early / 0.9-7.9
    dizziness / Early / 1.3-6.5
    injection site reaction / Rapid / 2.2-5.8
    fever / Early / 0.7-4.0
    abdominal pain / Early / 1.4-4.0
    arthralgia / Delayed / 1.4-4.0
    cough / Delayed / 1.3-4.0
    pruritus / Rapid / 2.2-3.9
    myalgia / Early / 1.3-3.6
    asthenia / Delayed / 0.7-2.7
    back pain / Delayed / 1.3-2.2
    nasal congestion / Early / 1.3-1.4
    rash / Early / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    constipation / Delayed / Incidence not known
    musculoskeletal pain / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    tooth discoloration / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
    Alendronate: (Moderate) Concomitant administration of alendronate with oral iron sucrose, sucroferric oxyhydroxide may interfere with the absorption of alendronate. To minimize the potential for this interaction, consider separating the administration of the two drugs and monitor for clinical response to alendronate.
    Alendronate; Cholecalciferol: (Moderate) Concomitant administration of alendronate with oral iron sucrose, sucroferric oxyhydroxide may interfere with the absorption of alendronate. To minimize the potential for this interaction, consider separating the administration of the two drugs and monitor for clinical response to alendronate.
    Aspirin, ASA: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
    Aspirin, ASA; Caffeine: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
    Aspirin, ASA; Carisoprodol: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
    Aspirin, ASA; Dipyridamole: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
    Aspirin, ASA; Omeprazole: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
    Aspirin, ASA; Oxycodone: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
    Aspirin, ASA; Pravastatin: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption.
    Baloxavir Marboxil: (Major) Do not administer baloxavir with products that contain oral iron sucrose, sucroferric oxyhydroxide. Polyvalent cations, such as iron, can chelate with baloxavir, reducing its absorption.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
    Cephalexin: (Moderate) Administer cephalexin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of cephalexin, leading to decreased absorption.
    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: (Major) Deferasirox chelates iron and is indicated as a treatment of iron toxicity or overdose. It would be illogical for a patient to receive both iron supplementation and deferasirox simultaneously.
    Deferiprone: (Major) Deferiprone chelates iron. Therapeutically, it is typically illogical for a patient to receive both iron supplementation (e.g., iron salts, iron dextran, ferric carboxymaltose, ferric citrate, sodium ferric gluconate complex, iron sucrose, sucroferric oxyhydroxide or polysaccharide-iron complex) and deferiprone simultaneously. Concurrent use of deferiprone with iron supplements has not been studied. 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 together.
    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.
    Demeclocycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
    Dimercaprol: (Contraindicated) Dimercaprol forms toxic chelates with iron. These dimercaprol-iron complexes are more toxic than the metal alone, especially to the kidneys. Do not administer iron during dimercaprol treatment. Therapy with iron should generally be delayed until 24 hours after the cessation of dimercaprol therapy.
    Doxycycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
    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.
    Erdafitinib: (Major) Avoid coadministration of iron sucrose; sucroferric oxyhydroxide with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Iron sucrose; sucroferric oxyhydroxide 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 iron sucrose; sucroferric oxyhydroxide may interfere with the determination of this initial dose increase.
    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.
    Iron: (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.
    Levothyroxine: (Moderate) Administer oral thyroid hormones at least 4 hours before or after oral iron sucrose, sucroferric oxyhydroxide. Oral iron 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 iron supplements.
    Levothyroxine; Liothyronine (Porcine): (Moderate) Administer oral thyroid hormones at least 4 hours before or after oral iron sucrose, sucroferric oxyhydroxide. Oral iron 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 iron supplements.
    Levothyroxine; Liothyronine (Synthetic): (Moderate) Administer oral thyroid hormones at least 4 hours before or after oral iron sucrose, sucroferric oxyhydroxide. Oral iron 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 iron supplements.
    Liothyronine: (Moderate) Administer oral thyroid hormones at least 4 hours before or after oral iron sucrose, sucroferric oxyhydroxide. Oral iron 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 iron supplements.
    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.
    Minocycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
    Omadacycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
    Paricalcitol: (Moderate) According to the manufacturer of oral iron sucrose, sucroferric oxyhydroxide an interaction was seen with paricalcitol in in vitro studies. Consider separating the administration of the two drugs and monitor for clinical response to paricalcitol.
    Sarecycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
    Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
    Tetracyclines: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
    Thyroid hormones: (Moderate) Administer oral thyroid hormones at least 4 hours before or after oral iron sucrose, sucroferric oxyhydroxide. Oral iron 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 iron supplements.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    Fetal adverse reactions, including fetal bradycardia, have been associated with maternal hypersensitivity reactions, especially during the second and third trimester of pregnancy. Data with intravenous iron sucrose use during human pregnancy have not shown adverse maternal or fetal outcomes; however, reports of intravenous iron sucrose use in pregnant women during the first trimester are insufficient to assess the risk of major birth defects or miscarriage. Treat iron deficiency anemia during pregnancy because there are risks to the mother and fetus associated with untreated iron deficiency anemia during pregnancy.[44801] There are no adequate and well-controlled studies of oral sucroferric oxyhydroxide use in pregnant women; however, animal studies have not shown any evidence of impaired fertility or fetal harm at doses up to 16 and 4 times, respectively, the human maximum recommended clinical dose. Sucroferric oxyhydroxide is not absorbed systemically following oral administration, and maternal use is not expected to result in fetal exposure to the drug.[56601]

    Iron sucrose is present in human milk, and available data after exposure to 100 to 300 mg of intravenous iron sucrose have not reported adverse reactions in breast-fed infants. Limited data indicate iron found in breast milk is not increased after intravenous administration of iron sucrose. There are no data on the effects of iron sucrose on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for intravenous iron sucrose and any potential adverse effects on the breast-fed infant from intravenous iron sucrose or the underlying maternal condition. Monitor breastfed infants exposed to intravenous iron sucrose for gastrointestinal toxicity (i.e., constipation, diarrhea).[44801] [49198] [49199] Sucroferric oxyhydroxide is not absorbed systemically following oral administration and breast-feeding is not expected to result in exposure of the child to sucroferric oxyhydroxide.[56601]

    MECHANISM OF ACTION

    IV Iron Sucrose
    Normal erythropoiesis depends on the concentration of iron and erythropoietin available in the plasma, both being decreased in renal failure. Exogenous administration of erythropoietin increases red blood cell production and iron utilization, contributing to iron deficiency in hemodialysis patients. Intravenous iron has been used to treat the anemia associated with hemodialysis and may reduce the need for erythropoietin dosage by about 40%. Following IV administration of iron sucrose, the complex of polynuclear iron (III)-hydroxide in sucrose is dissociated into iron and sucrose by the reticuloendothelial system. In addition, a competitive exchange of iron takes place from the iron sucrose complex to the iron-binding protein transferrin. A therapeutic response to treatment with iron therapy is dependent upon the patient's iron stores and the ability to use the iron. Use of iron is influenced by the cause of the deficiency as well as other illnesses that can affect normal erythropoiesis. Protein-energy malnutrition can prevent the incorporation of iron into the erythrocyte regardless of the quantity of iron stored. Only when lean body mass expands will iron be used. Iron therapy alone does not increase red blood cell production. Administration of iron only improves anemia which is associated with iron deficiency.
    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. Iron-containing proteins and enzymes are important in oxidation-reduction reactions, especially those of the mitochondria. Furthermore, iron is a cofactor for enzymes such as aconitase and tryptophan pyrrolase. Iron deficiency not only causes anemia and decreased oxygen delivery, but 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.
     
    Oral Sucroferric Oxyhydroxide
    In the management of serum phosphorus concentrations in patients with chronic kidney disease, oral sucroferric oxyhydroxide is a phosphate binder. Oral sucroferric oxyhydroxide binds dietary phosphate within the gastrointestinal tract via ligand exchange between hydroxyl groups and water in sucroferric oxyhydroxide and the phosphate in the diet. Bound phosphate is eliminated in the feces. As a result of reduced absorption of dietary phosphate, both serum phosphorus and calcium-phosphorus product concentrations are reduced.[56601]

    PHARMACOKINETICS

    Iron sucrose is administered intravenously while sucroferric oxyhydroxide is administered orally. The dose of intravenous iron sucrose is individualized according to patient goals for serum iron levels, iron storage parameters (e.g., ferritin, transferrin saturation) and serum hemoglobin concentrations whereas the dose of oral sucroferric oxyhydroxide is guided by serum phosphorus. Iron toxicity may occur with excessive or unnecessary iron therapy. The absorption of iron from oral sucroferric oxyhydroxide is low, and the risk of systemic iron toxicity with the oral formulation is negligible. Systemic iron is stored in compounds called ferritin and hemosiderin, which are used for future production of hemoglobin. The absorption of iron depends upon the route of entry. The tissue that first clears parenterally administered iron from the bloodstream determines the bioavailability. If the reticuloendothelial system clears iron, only small amounts will be available over time to the bone marrow. Transferrin accepts iron from the intestinal tract or from sites of storage or hemoglobin destruction. Iron is then transported in plasma bound to transferrin and distributed to the bone marrow for hemoglobin synthesis, to the reticuloendothelial system for storage, to all cells for enzymes containing iron, and to placental cells if needed to meet fetal needs. Transferrin eventually becomes available for reuse. There is no destructive metabolism of iron because it takes place in a closed system. In normal adults, 90% of metabolized iron is conserved and reutilized repeatedly. Very little iron is eliminated. In normal, healthy adults, some daily loss of iron occurs through normal skin, hair, and nail loss, and GI losses. Menstruating women have an increased loss as do other persons with loss of blood.

    Oral Route

    The active moiety of oral sucroferric oxyhydroxide, polynuclear iron (III)-oxyhydroxide (pn-FeOOH), is essentially insoluble and therefore not absorbed or metabolized. The mononuclear iron species, a degradation product, can be released from the surface of pn-FeOOH and absorbed. The median uptake of radiolabeled iron in the blood on day 21 after administration of 2,000 mg oral sucroferric oxyhydroxide in 1 day was 0.04% in patients with chronic kidney disease compared with 0.43% in healthy subjects with low iron stores (serum ferritin less than 100 mcg/L). The sucrose and starch components of oral sucroferric oxyhydroxide can be digested to glucose and fructose, and maltose and glucose, respectively. These compounds can be absorbed into the blood. One tablet is equivalent to 1.4 g of carbohydrates.[56601]

    Intravenous Route

    In healthy adults receiving IV doses of iron sucrose, the iron component appears to distribute mainly in blood and to some extent in extravascular fluid. A significant amount of the administered iron distributes in the liver, spleen and bone marrow. The bone marrow is considered an iron trapping compartment and not a reversible volume of distribution. Following IV administration, iron sucrose is dissociated into iron and sucrose by the reticuloendothelial system. The sucrose component is eliminated primarily by urinary excretion (75.4% in 24 hours). Approximately 5% of the iron is excreted in the urine over 24 hours. In healthy adults treated with IV iron sucrose, the iron component exhibits linear kinetics with an elimination half-life of about 6 hours and a systemic clearance of 1.2 L/hour.[44801]