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    Iron Supplements

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral iron supplement of ferric oxyhydroxide complexed with dextrans; rapidly repletes iron stores in deficiency from anemia or blood loss; sometimes associated with severe hypersensitivity.

    COMMON BRAND NAMES

    INFeD

    HOW SUPPLIED

    INFeD Intramuscular Inj Sol: 1mL, 50mg
    INFeD Intravenous Inj Sol: 1mL, 50mg

    DOSAGE & INDICATIONS

    For the treatment of iron-deficiency anemia in patients in whom oral iron administration is unsatisfactory or impossible.
    Instructions for test dose administration for all indications.
    Intramuscular or Intravenous dosage
    Adults

    Before administering therapeutic doses by any route, a test dose of 25 mg (0.5 mL) of iron dextran should be given by the route and method of administration for which therapeutic doses will be administered. Observe patient for at least 1 hour after test dose administration. Because anaphylactic reactions are known to occur after uneventful test doses, subsequent test doses should be considered.

    Infants, Children, and Adolescents

    Before administering therapeutic doses by any route, a test dose of of iron dextran should be given by the route and method of administration for which therapeutic doses are to be administered. Consult specialized references for amount of test dose to be given. While the manufacturer recommends 25 mg (0.5 mL) for all patients, this amount may be greater than or equal to the required calculated daily dose for the pediatric patient. Observe patient for at least 1 hour after test dose administration. Because anaphylactic reactions are known to occur after uneventful test doses, subsequent test doses should be considered.

    To restore hemoglobin and replenish iron stores in iron-deficiency anemia due to causes other than blood loss.
    NOTE: The formula is based on hemoglobin (Hb) expressed as g/dL and lean body weight (LBW) in kg or actual body weight (ABW) in kg if the actual body weight is less than LBW or for children 15 kg or less.
    Intramuscular or Intravenous dosage
    Adults, Adolescents, and Children weighing more than 15 kg

    Total iron dextran dose in mL = [0.0442 x (desired Hb - observed Hb) x LBW] + (0.26 x LBW). Use actual body weight if less than lean body weight. A value of 14.8 may be used as a target normal hemoglobin. NOTE: Iron dextran injection contains 50 mg of elemental iron per mL. If test dose uneventful, give the remainder of the total dose as 100 mg elemental iron per day IM or IV until the total calculated dose is given. The maximum IV/IM dose of undiluted iron dextran is 100 mg (2 mL) per day.

    Infants and Children 4 months and older weighing 10 to 15 kg

    Total iron dextran dose in mL = [0.0442 x (desired Hb - observed Hb) x LBW] + (0.26 x ABW). A value of 12 may be used as a target normal hemoglobin. NOTE: Iron dextran injection contains 50 mg of elemental iron per mL. If test dose uneventful, give the remainder of the total dose as 100 mg elemental iron per day IM or IV until the total calculated dose is given. The maximum IV/IM dose of undiluted iron dextran is 100 mg (2 mL) per day.

    Infants and Children 4 months and older weighing 5 to 9.9 kg

    Total iron dextran dose in mL = [0.0442 x (desired Hb - observed Hb) x LBW] + (0.26 x ABW). A value of 12 may be used as a target normal hemoglobin. NOTE: Iron dextran injection contains 50 mg of elemental iron per mL. If test dose uneventful, give the remainder of the total dose as 50 mg of elemental iron per day IM or slow IV until the total calculated dose is given.

    Infants 4 months and older weighing less than 5 kg

    Total iron dextran dose in mL = [0.0442 x (desired Hb - observed Hb) x LBW] + (0.26 x ABW). A value of 12 may be used as a target normal hemoglobin. NOTE: Iron dextran injection contains 50 mg of elemental iron per mL. If test dose uneventful, give the remainder of the total dose as 25 mg of elemental iron per day IM or slow IV until the total calculated dose needed given.

    Intravenous infusion dosage†
    Adults, Adolescents, and Children weighing more than 15 kg

    Total iron dextran dose in mL = [0.0442 x (desired Hb - observed Hb) x LBW] + (0.26 x LBW). Use actual body weight if less than lean body weight. A value of 14.8 may be used as a target normal hemoglobin. NOTE: Iron dextran injection contains 50 mg of elemental iron per mL. If test dose uneventful, infuse the remainder of the total calculated dose IV over 2 to 6 hours.

    Infants and Children 4 months and older weighing less than 15 kg

    Total iron dextran dose in mL = [0.0442 x (desired Hb - observed Hb) x LBW] + (0.26 x ABW). A value of 12 may be used as a target normal hemoglobin. NOTE: Iron dextran injection contains 50 mg of elemental iron per mL. If test dose uneventful, infuse the remainder of the total calculated dose IV over 2 to 6 hours.

    To restore hemoglobin and replenish iron stores due to blood loss.
    Intramuscular or Intravenous dosage
    Adults, Adolescents, and Children weighing 10 kg or more

    Total iron dextran dose in mL = blood loss (mL) x hematocrit (expressed as a decimal fraction) x 0.02. NOTE: Iron dextran injection contains 50 mg of elemental iron per mL. If test dose uneventful, give the remainder of the total dose as 100 mg of elemental iron per day IM or slow IV until the total calculated dose is given. The maximum IV/IM dose of undiluted iron dextran is 100 mg (2 mL) per day.

    Infants and Children 4 months and older weighing 5 to 9.9 kg

    Total iron dextran dose in mL = blood loss (mL) x hematocrit (expressed as a decimal fraction) x 0.02. NOTE: Iron dextran injection contains 50 mg of elemental iron per mL. If test dose uneventful, give the remainder of the total dose as 50 mg of iron dextran per day IM or slow IV until the total calculated dose is given.

    Infants 4 months and older weighing less than 5 kg

    Total iron dextran dose in mL = blood loss (mL) x hematocrit (expressed as a decimal fraction) x 0.02. NOTE: Iron dextran injection contains 50 mg of elemental iron per mL. If test dose uneventful, give the remainder of the total dose as 25 mg of iron dextran per day IM or slow IV until the total calculated dose (see equation) is given.

    Intravenous infusion dosage†
    Adults, Adolescents, Children, and Infants 4 months and older

    Total iron dextran dose in mL = blood loss (mL) x hematocrit (expressed as a decimal fraction) x 0.02. NOTE: Iron dextran injection contains 50 mg of elemental iron per mL. If test dose uneventful, infuse the remainder of the total calculated dose (see equation) IV over 2 to 6 hours.

    For nutritional supplementation† and to prevent iron deficiency in patients receiving long-term total parenteral nutrition.
    Intravenous dosage
    Adult men, Adolescent males, and Postmenopausal women

    In general, the dosage of parenteral iron for maintenance of nutritional intake is 10% of the oral RDA, since dietary iron is roughly 10% bioavailable. If test dose uneventful, give 1 mg/day IV. NOTE: Patients who require parenteral nutrition for a limited period of time and who are not iron-deficient do not need parenteral iron supplementation. The use of iron dextran to prevent iron deficiency in patients requiring long-term parenteral nutrition support is controversial; some experts advocate the use of iron to treat a deficiency if it occurs vs. maintenance dosing to prevent deficiency, particularly given the potential risks of parenteral iron therapy. NOTE:The stability of iron dextran in TPN solutions has not been well established. Do not add therapeutic doses of iron dextran to total parenteral nutrition (TPN) solutions; iron dextran may destabilize the mixture or cause the cracking of the TPN emulsion.

    Adult and Adolescent menstruating, premenopausal women

    In general, the dosage of parenteral iron for maintenance of nutritional intake is 10% of the oral RDA, since dietary iron is roughly 10% bioavailable. If test dose uneventful, doses of 1.5 to 1.8 mg/day IV have been administered. NOTE: Patients who require parenteral nutrition for a limited period of time and who are not iron-deficient do not need parenteral iron supplementation. The use of iron dextran to prevent iron deficiency in patients requiring long-term parenteral nutrition support is controversial; some experts advocate the use of iron to treat a deficiency if it occurs vs. maintenance dosing to prevent deficiency, particularly given the potential risks of parenteral iron therapy. NOTE: The stability of iron dextran in TPN solutions has not been well established. Do not add therapeutic doses of iron dextran to total parenteral nutrition (TPN) solutions; iron dextran may destabilize the mixture or cause the cracking of the TPN emulsion.

    For the treatment of anemia of prematurity†.
    Intravenous dosage
    Premature Neonates

    1 mg/kg/day IV added to total parenteral nutrition (TPN) has been used in very low birth weight premature neonates (n = 26 with birth weight 1,005 +/- 302 g and gestational age 28 +/- 2.3 weeks in 1 study and n = 28 with birth weight 662 +/- 14 g and gestational age 24.7 +/- 0.3 weeks in a second study). Some patients received epoetin in conjunction with parenteral iron. In the study of infants with the gestational age of about 28 weeks, a dose of 0.2 mg/day IV added to the TPN was not a sufficient amount of iron. The authors concluded that 1 mg/kg/day IV added to the TPN would more closely maintain iron balance. Alternatively, a weekly dose of 5 mg/kg IV added to TPN and administered over 24 hours or diluted in several milliliters of normal saline or 10% dextrose in water and infused over 4 to 6 hours also has been used in low birth weight neonates.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Total dosage with iron dextran must be individualized according to the patients age, weight, and the degree of the iron-deficiency anemia. Excess accumulation may occur if iron therapy is continued after the correction of the deficiency. The following are generally accepted limits in the treatment of iron-deficient patients.

    Adults

    100 mg/day IV or IM. See individual dosage if using total dose IV infusion methods.

    Geriatric

    100 mg/day IV or IM. See individual dosage if using total dose IV infusion methods.

    Adolescents

    100 mg/day IV or IM. See individual dosage if using total dose IV infusion methods.

    Children

    10 kg or more: 100 mg/day IV or IM. See individual dosage if using total dose IV infusion methods.
    5 to 9.9 kg: 50 mg/day IV or IM.

    Infants

    4 months and older (weight 5 to 9.9 kg): 50 mg/day IV or IM.
    4 months and older (weight less than 5 kg): 25 mg/day IV or IM.
    1 to 3  months: 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 iron dextran 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 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 dextran, a diagnosis of absolute or functional iron deficiency should be made. Follow recommended dosage. Iron dextran is not hemodialyzable.

    ADMINISTRATION

     
    NOTE: Serum iron, hemoglobin and hematocrit should be evaluated prior to iron therapy and at regular intervals during therapy. Ferritin and transferrin are also recommended monitoring parameters.

    Injectable Administration

    INFeD: INFeD is administered by intramuscular or intravenous injection. Before administering therapeutic doses, a test dose of 25 mg (0.5 mL) should be given. Give INFeD test doses gradually over at least 30 seconds. Observe the patient for at least 1 hour after test dose administration. Because anaphylactic reactions are known to occur after uneventful test doses, test doses before subsequent doses should be considered.
    DexFerrum: DexFerrum is administered by intravenous injection only. Before administering therapeutic doses, a test dose of 25 mg (0.5 mL) should be given. Give DexFerrum test doses gradually over at least 5 minutes. Observe the patient for at least 1 hour after test dose administration. Because anaphylactic reactions are known to occur after uneventful test doses, test doses before subsequent doses should be considered.
    DO NOT mix iron dextran with other medications.
    Do not add therapeutic doses of iron dextran to total parenteral nutrition (TPN) solutions; iron dextran may destabilize the mixture or cause the cracking of the TPN emulsion.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Slow intermittent intravenous (IV) injection:
    NOTE: Each 1 mL of iron dextran injection contains 50 mg of elemental iron.
    No dilution necessary.
    Inject via slow IV at a gradual rate not to exceed 50 mg (1 mL) per minute for adults; take care to inject dosage very slowly in children and infants.
    There are limits to the volume of iron dextran that may be injected IV undiluted per 24 hours based on patient age and weight; see dosage guidelines.
     
    Total Dose Intravenous Infusion [26236]:
    Iron dextran is not FDA-approved to be administered as a total dose infusion.
    Dilute the total calculated dose (see Dosage) in 250 to 1000 mL of 0.9% sodium chloride injection. 5% dextrose injection may be used for dilution; however, use of 5% dextrose injection for iron dextran dilution has been associated with a higher incidence of local pain and phlebitis upon administration.
    A test dose should be administered before the administration of the therapeutic dose.
    If test dose is uneventful after 1 hour of observation, then infuse the remaining dose over 4 to 6 hours (usually no faster than 2 to 6 mg/min). Once the infusion is completed, flush vein with NS injection.

    Intramuscular Administration

    NOTE: Each 1 mL of iron dextran injection contains 50 mg of elemental iron.
    No dilution necessary.
    To avoid staining of subcutaneous tissue, use the Z-track technique of injection.
    There are limits to the volume of iron dextran that may be injected IM per 24 hours based on patient age and weight; see dosage guidelines.
    Inject deeply into the upper outer quadrant of the buttock (gluteus maximus) only using a 2- or 3-inch, 19- or 20-gauge needle. DO NOT USE THE DELTOID MUSCLE OR OTHER EXPOSED AREAS. If the patient is standing, inject iron dextran into the buttock opposite the weight-bearing leg. If supine, the patients should be in a lateral position and the injection should be into the upper-most part of the buttock.

    STORAGE

    Dexferrum:
    - Store at room temperature (between 59 to 86 degrees F)
    INFeD:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Iron dextran hypersensitivity, serious hypersensitivity reactions or anaphylaxis

    Parenteral iron dextran therapy is associated with a risk of serious hypersensitivity reactions or anaphylaxis. Iron dextran should only be used in patients with a clear and confirmed need for parenteral iron therapy. Iron dextran is contraindicated in patients with iron dextran hypersensitivity. Fatal anaphylactoid reactions have occurred during the parenteral administration of iron dextran. These reactions have been characterized by sudden onset of respiratory difficulty and/or cardiovascular collapse. A test dose should be given prior to administration of the initial therapeutic dose. Reactions are usually evident within a few minutes of administration; however, observe patients for at least 1 hour after the administration of the test dose before administering the remainder of the therapeutic dose. Fatal reactions have occurred following the test dose of iron dextran and also have occurred after other doses when the test dose was tolerated. Monitor patients for signs and symptoms of anaphylactoid reactions during all iron dextran administrations. Patients with a history of drug allergy may be at increased risk for anaphylactoid reactions. Furthermore, concomitant use of angiotensin-converting enzyme inhibitors may increase the risk for serious reactions to iron dextran. Serious anaphylactoid reactions require appropriate resuscitative measures. Facilities for cardiopulmonary resuscitation and personnel trained in the detection and treatment of anaphylactoid reactions must be available during administration. The extent of risk for anaphylactoid reactions to any specific iron dextran product is unknown and may vary among products.

    Ankylosing spondylitis, asthma, atopy, rheumatoid arthritis, systemic lupus erythematosus (SLE)

    Patients with a significant history of allergies (e.g., atopy), asthma, or other inflammatory conditions appear to be susceptible to experiencing adverse effects from iron dextran treatment. Parenteral administration of iron dextran may exacerbate joint pain and swelling in patients with rheumatoid arthritis, ankylosing spondylitis, or systemic lupus erythematosus (SLE).

    Cardiac disease, hypotension, intravenous administration

    Cardiovascular adverse effects may also occur with iron dextran therapy, and do not necessarily indicate hypersensitivity. Flushing and hypotension are more common following rapid intravenous administration; do not exceed recommended IV infusion rates. Patients with preexisting cardiac disease may have exacerbation of cardiovascular symptoms if adverse effects occur following iron dextran administration.

    Anemia, hemochromatosis, hemoglobinopathy, hemosiderosis

    Iron dextran is contraindicated for use in patients with anemia not associated with iron deficiency. Do not administer iron dextran to patients with evidence of iron overload (e.g., patients with hemochromatosis). 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. The type of anemia and the underlying cause or causes should be determined before starting therapy with parenteral iron dextran. 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.

    Dialysis, renal disease, renal failure

    Hemosiderosis secondary to long-term iron dextran treatment has primarily been reported in patients with renal failure receiving dialysis. Periodic monitoring of serum ferritin levels may be helpful in recognizing a progressive accumulation of iron resulting from impaired iron uptake from the reticuloendothelial system in patients with renal failure. The contribution of iron to infectious processes is unclear, but iron dextran should not be administered during the acute phase of infectious renal disease (manufacturer's information).

    Hepatic disease

    Some patients with chronic hepatic disease may also 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. Use iron dextran with caution in patients with hepatic disease.

    Infants, neonates

    Use of iron dextran in infants younger than 4 months of age and neonates is not recommended; there have been reports from other countries of an increased incidence of gram-negative sepsis (e.g., E. coli sepsis) in infants receiving iron dextran. Administration of iron dextran to premature infants/neonates can increase the risk of developing hemolytic anemia because these infants may have a low vitamin E serum concentration. In general, iron supplementation should not begin in premature infants until adequate vitamin E is supplied in the diet; human breast milk and modern infant formulas usually supply adequate dietary vitamin E.

    Pregnancy

    Fetal adverse reactions, including fetal bradycardia, have been associated with maternal hypersensitivity reactions to parenteral iron products, especially during the second and third trimester of pregnancy. There are no adequate and well-controlled studies of iron dextran in pregnant women. Administer iron dextran during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Various human and animal studies have demonstrated inconclusive results regarding the ability of iron dextran to cross the placenta; it appears some iron does reach the fetus, but the form in which it crosses the placenta is not clear. Iron dextran has been shown to be teratogenic and embryocidal in animals (mice, rats, rabbits, dogs, and monkeys) when given in doses approximately 3 times the maximum human dose. No consistent adverse fetal effects were observed in non-iron deficient animals at doses of 50 mg iron/kg or less. Fetal and maternal toxicity has been reported in monkeys receiving a total dose of 90 mg iron/kg administered over a 14-day period. Similar effects were observed in mice and rats after administration of a single 125 mg iron/kg dose. Fetal abnormalities were also observed in rats and dogs at doses of 250 mg iron/kg or higher.[42291]

    Breast-feeding

    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 therapeutic prescription use of iron is usually compatible with breast-feeding if the lactating mother needs treatment for iron deficiency. However, trace amounts of unmetabolized iron dextran are excreted in breast milk. According to FDA-approved labeling, caution should be exercised if iron dextran is administered to a nursing mother.[42291] Potential alternatives include iron salts, polysaccharide-iron complex, and iron sucrose. 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.

    Laboratory test interference

    Laboratory test interference may occur with iron dextran therapy. Specifically, the drug may cause falsely elevated concentrations of serum bilirubin and falsely decreased concentrations of serum calcium. Additionally, the drug may affect bone scans. Bone scans involving 99m Tc-diphosphonate have been reported to show a dense, crescentic area of activity in the buttocks, following the contour of the iliac crest, 1 to 6 days after intramuscular injections of iron dextran. Bone scans with 99m Tc-labeled bone-seeking agents, in the presence of high serum ferritin concentrations or following iron dextran infusions, have been reported to show a reduction of bony uptake, marked renal activity, and excessive blood pool and soft tissue accumulation.[42291]

    ADVERSE REACTIONS

    Severe

    seizures / Delayed / Incidence not known
    bradycardia / Rapid / Incidence not known
    cardiac arrest / Early / Incidence not known
    skin necrosis / Early / Incidence not known
    skin atrophy / Delayed / Incidence not known
    serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    cyanosis / Early / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    pulmonary edema / Early / Incidence not known
    bronchospasm / Rapid / Incidence not known
    respiratory arrest / Rapid / Incidence not known

    Moderate

    confusion / Early / Incidence not known
    hypertension / Early / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    phlebitis / Rapid / Incidence not known
    edema / Delayed / Incidence not known
    hemosiderosis / Delayed / Incidence not known
    hematuria / Delayed / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    wheezing / Rapid / Incidence not known

    Mild

    weakness / Early / Incidence not known
    headache / Early / Incidence not known
    syncope / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    dizziness / Early / Incidence not known
    flushing / Rapid / Incidence not known
    fever / Early / Incidence not known
    leukocytosis / Delayed / Incidence not known
    vomiting / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    metallic taste / Early / Incidence not known
    diarrhea / Early / Incidence not known
    nausea / Early / Incidence not known
    dysgeusia / Early / Incidence not known
    injection site reaction / Rapid / Incidence not known
    skin discoloration / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    rash / Early / Incidence not known
    purpura / Delayed / Incidence not known
    myalgia / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    arthralgia / Delayed / Incidence not known
    diaphoresis / Early / Incidence not known
    chills / Rapid / Incidence not known
    malaise / Early / Incidence not known

    DRUG INTERACTIONS

    Amlodipine; Benazepril: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Angiotensin-converting enzyme inhibitors: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Benazepril: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Captopril: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    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.
    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.
    Enalapril, Enalaprilat: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Enalapril; Felodipine: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    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.
    Fosinopril: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    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.
    Lisinopril: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    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.
    Moexipril: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Perindopril: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Perindopril; Amlodipine: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Quinapril: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Ramipril: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Trandolapril: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    Trandolapril; Verapamil: (Moderate) The concomitant use of angiotensin-converting enzyme inhibitors (ACE inhibitors) with iron dextran may increase the risk for anaphylactic-type reactions. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Patients should be monitored for signs and symptoms of anaphylactic-type reactions during all iron dextran administrations.
    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 to parenteral iron products, especially during the second and third trimester of pregnancy. There are no adequate and well-controlled studies of iron dextran in pregnant women. Administer iron dextran during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Various human and animal studies have demonstrated inconclusive results regarding the ability of iron dextran to cross the placenta; it appears some iron does reach the fetus, but the form in which it crosses the placenta is not clear. Iron dextran has been shown to be teratogenic and embryocidal in animals (mice, rats, rabbits, dogs, and monkeys) when given in doses approximately 3 times the maximum human dose. No consistent adverse fetal effects were observed in non-iron deficient animals at doses of 50 mg iron/kg or less. Fetal and maternal toxicity has been reported in monkeys receiving a total dose of 90 mg iron/kg administered over a 14-day period. Similar effects were observed in mice and rats after administration of a single 125 mg iron/kg dose. Fetal abnormalities were also observed in rats and dogs at doses of 250 mg iron/kg or higher.[42291]

    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 therapeutic prescription use of iron is usually compatible with breast-feeding if the lactating mother needs treatment for iron deficiency. However, trace amounts of unmetabolized iron dextran are excreted in breast milk. According to FDA-approved labeling, caution should be exercised if iron dextran is administered to a nursing mother.[42291] Potential alternatives include iron salts, polysaccharide-iron complex, and iron sucrose. 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. 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, and it is influenced by the cause of the deficiency as well as other illnesses that can affect normal erythropoiesis.
     
    There is some concern that intravenously administered iron is not used appropriately by the body. Both animal and human data indicate that the bulk of intravenous iron is sequestered in the reticuloendothelial system (i.e., liver, spleen), and little is available to the iron-deficient bone marrow.

    PHARMACOKINETICS

    Iron dextran is administered intramuscularly or intravenously.  Approximately 60% of an injected dose is absorbed within 3 days and up to 90% within 1—3 weeks. Subcutaneous injection results in slow absorption and staining of subcutaneous tissue. Distribution of iron dextran following intramuscular or intravenous injection involves uptake by reticuloendothelial cells of the liver, spleen, and bone marrow. Uptake by these cells occurs at a rate of about 10—20 mg per hour. Iron crosses the placenta, and pregnancy increases iron-intake requirements. Once taken into reticuloendothelial cells, the iron from the iron dextran complex is separated and added to the body's total iron stores. Ferric iron is then gradually released into the plasma where it combines rapidly with transferrin.
     
    Transferrin delivers iron to specific receptors for deposit, where it is either incorporated into hemoglobin or oxidized and stored in combination with apoferritin as ferritin. Transferrin eventually becomes available for reuse. There is no destructive metabolism of iron because it takes place in a closed system. In normal, healthy adults, some daily loss of iron occurs through normal skin, hair, and nail loss, and GI losses.

    Intramuscular Route

    Following intramuscular injection of iron dextran, the drug is slowly absorbed in two stages primarily through the lymphatic system. The first stage involves an inflammatory reaction at the site of injection which aids the passage of the drug into the lymphatic system. In the second stage, macrophages ingest the iron dextran and enter the lymphatic system and eventually the blood.

    Subcutaneous Route

    Subcutaneous injection of iron dextran results in slow absorption and staining of subcutaneous tissue.