VA Class:TN410
Iron dextran injection, a sterile, colloidal solution of ferric hydroxide100 or ferric oxyhydroxide101 in a complex with partially hydrolyzed low molecular weight dextran, corrects the erythropoietic abnormalities that are due to a deficiency of iron.
Iron Deficiency Not Amenable to Oral Iron Therapy
Iron dextran is used in the treatment of iron deficiency when oral iron preparations are ineffective or cannot be used.100, 101 There are relatively few indications for parenteral iron therapy. Occasionally, however, parenteral administration may be required in iron-deficient patients in whom oral administration of iron is infeasible or ineffective because of intolerance, poor absorption, GI disease, refusal or inability to take the oral medication, or when rapid replenishment of iron stores is necessary as in hypochromic anemia of infancy or the last trimester of pregnancy. In addition, most chronic kidney disease patients who receive therapy with erythropoiesis-stimulating agents (ESAs) (e.g., epoetin alfa, darbepoetin alfa) will require oral or parenteral iron therapy because of the dramatic decrease in iron stores associated with erythrocyte formation. In several randomized controlled studies comparing IV and oral administration of iron in patients with chronic kidney disease on hemodialysis, IV iron was superior to orally administered iron in increasing hemoglobin concentrations and/or minimizing the dosage of ESA required to maintain target hemoglobin levels; guidelines from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) state that the IV route is preferred for administration of iron in patients with chronic kidney disease undergoing hemodialysis.117 (See Uses: Anemia of Chronic Kidney Disease, in Epoetin Alfa 20:16.) The response to iron dextran is quantitatively similar to that produced by other iron preparations administered parenterally.
Since parenteral use of complexes of iron and carbohydrates has resulted in fatal anaphylactoid reactions, iron dextran should be used only in patients in whom a clearly established indication for parenteral iron therapy exists, confirmed by appropriate laboratory tests.
Iron dextran injection is administered undiluted by slow (50 mg/minute or less if undiluted) IV injection;100, 101 some preparations (i.e., INFeD®) also are FDA-labeled for IM injection.100 Iron dextran injection also has been diluted in 0.9% sodium chloride injection and administered by IV infusion† (e.g., over 1-6 hours).121, 122, 123
Before administration of the first therapeutic dose of iron dextran, a test dose of iron should be given by the chosen route and appropriate method of administration .100, 101 If iron dextran is to be administered IV, the manufacturer of INFeD® recommends that a test dose of 25 mg (0.5 mL) of iron dextran be given IV over at least 30 seconds; the manufacturer of Dexferrum® recommends a 25-mg (0.5 mL) test dose given IV over at least 5 minutes.100, 101 If administered IM, a test dose of 25 mg (0.5 mL) of iron dextran (InFeD®) should be administered into the buttock using the IM injection technique recommended by the manufacturer.100 It has been recommended that the test dose and subsequent doses of iron dextran be administered by individuals trained to provide emergency treatment of serious allergic reactions should they occur and that immediate access to drugs and resuscitation equipment needed to treat such reactions be available.100, 101, 117 Although anaphylactic reactions usually are evident within a few minutes when they occur, it is recommended that a period of 1 hour or longer elapse before the remaining portion of the initial dose is given.100, 101
IV administration may be preferred to IM administration when there is insufficient muscle mass for IM administration, when there is impaired absorption from the muscle because of stasis or edema, when there is a possibility of uncontrolled IM bleeding (as in hemophilia), or when massive and prolonged parenteral therapy is indicated (as in chronic substantial blood loss), and to avoid the pain, irritation, and staining of the skin at the injection site secondary to IM administration. IM administration may be preferred when venous access is difficult or infeasible (e.g., in infants or in adults with poor veins).
For IM administration, the manufacturer of INFeD® recommends that iron dextran be injected deeply with a 2- or 3-inch, 19- or 20-gauge needle into the upper outer quadrant of the buttock only; the drug should never be administered into the arm or any other exposed area.100 When the drug is administered IM, if the patient is standing, the injection should be made in the buttock of the leg opposite the patient's weight-bearing leg; if supine, the patient should be in a lateral position with the injection site uppermost.100 To avoid injection or leakage into subcutaneous tissue, the Z-track technique of injection in which the subcutaneous tissue over the site of injection is firmly pushed aside before inserting the needle is recommended.100
The manufacturers state that iron dextran should not be mixed with other drugs or added to parenteral nutrition solutions for IV infusion.100, 101 Iron dextran solutions should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.100, 101
Dosage of iron dextran is expressed in terms of mg of elemental iron. Iron dextran injection contains the equivalent of 50 mg of elemental iron per mL.
Before initiating therapy for iron deficiency anemia, total iron requirements (allowing for storage iron) are calculated by using a dose formula or table. Calculations are based on the amount of iron needed to restore hemoglobin concentration to normal or near normal plus an additional amount to provide adequate replenishment of iron stores in most individuals with moderately or severely reduced levels of hemoglobin.100 In the formula recommended by the manufacturers, the total dose of iron dextran injection (in mL) containing the equivalent of 50 mg/mL of iron is calculated as follows:100, 101
[0.0442 × (Hbd - Hbo) × Wt] + (0.26 × Wt) = total dose of iron dextran injection (mL)
Where Wt is the patient's lean body weight in kg, Hbd is the desired hemoglobin concentration in g/dL (14.8 for patients weighing more than 15 kg and 12 for patients weighing 15 kg or less), Hbo is the patient's observed hemoglobin concentration in g/dL, and (0.26 × lean body weight) is a factor that accounts for storage iron.100, 101
In patients with chronic kidney disease who are receiving supplemental therapy with an erythropoiesis-stimulating agent (ESA), sufficient iron should be administered to maintain certain indices of iron therapy (i.e., transferrin saturation and serum ferritin concentrations) at target levels; periodic monitoring of these iron indices is recommended, and the results should be used (in conjunction with hemoglobin concentrations and ESA dosage) to guide iron therapy.117
Iron Replacement Secondary to Blood Loss
For iron replacement secondary to blood loss (e.g., in patients with hemorrhagic diatheses or patients on long-term renal hemodialysis), total iron requirements are based on estimates of the amount of iron represented in the blood loss; the formula above for iron deficiency anemia is not applicable. Instead, the following formula, based on the approximation that 1 mL of normocytic, normochromic erythrocytes contains 1 mg of elemental iron, may be used to calculate the required total dosage in mL of iron dextran injection containing the equivalent of 50 mg of iron per mL:100, 101
0.02 × blood loss (in mL) × hematocrit (expressed as a decimal fraction) = total dosage of iron dextran injection in mL
Iron dextran may be injected IV, undiluted, at a slow, gradual rate not exceeding 50 mg of iron per minute (1 mL/minute).100, 101 If adverse reactions to the test dose do not occur, subsequent IV doses may be increased to up to 100 mg of iron daily until the total calculated dose has been administered.100, 101 The manufacturers recommend that the maximum daily IV dosage of undiluted iron dextran not exceed 25 mg (0.5 mL) of iron in infants weighing less than 5 kg; 50 mg (1 mL) of iron in children weighing less than 10 kg; and 100 mg (2 mL) of iron in other patients.100, 101
Although the manufacturers do not recommend dilution of iron dextran injection† or administration of the drug in single IV doses exceeding 100 mg†, numerous reports have been made in which the total dose of an iron dextran preparation was administered as a single dose either by direct IV injection or as an IV infusion.121, 122, 123 Large IV doses of iron dextran, such as those used in total-dose infusions†, reportedly have been associated with an increased frequency of adverse effects, especially delayed reactions (e.g., arthralgia, myalgia, fever). In the total-dose infusion technique, the total calculated dose of iron dextran is diluted in 250-1000 mL of 0.9% sodium chloride injection.121, 122, 123 The use of 5% dextrose injection instead of 0.9% sodium chloride injection has been reported to be associated with a higher incidence of local pain and phlebitis. With the total-dose infusion technique, if no reaction occurs after administration of a 25-mg IV test dose over 5 minutes, the remainder of the dose may be infused (e.g., over 1-6 hours).121, 122, 123 After the infusion is completed, the vein is often flushed with 0.9% sodium chloride injection.121, 122, 123
Iron dextran labeled for IM use (i.e., INFeD®) may be injected IM daily or less frequently until the calculated amount has been given. If adverse reactions to the test dose do not occur, subsequent doses may be given. The manufacturer of INFeD® recommends that the maximum daily IM dosage of undiluted iron dextran not exceed 25 mg (0.5 mL) of iron in infants weighing less than 5 kg, 50 mg (1 mL) of iron in children weighing less than 10 kg, and 100 mg (2 mL) of iron in other patients.100
Sensitivity (e.g., anaphylactoid or anaphylactic) reactions appear to be the most common adverse effects of iron dextran, occurring with either IV or IM administration, and such reactions vary widely in severity and can be immediate or delayed.100, 101, 102, 103, 104, 105, 106, 107 Incidences of such reactions are difficult to ascertain since some studies only reported severe or potentially serious reactions whereas others reported a wide range of severity.100, 101, 102, 103, 104, 105 Sensitivity reactions may be severe enough to require discontinuance of iron dextran therapy100, 101, 102, 103, 104, 105 and can be fatal.100, 101, 102, 106, 107 (See Cautions: Sensitivity Reactions.) Local reactions associated with IV or IM administration also appear to be relatively common.100, 103, 104 Adverse reactions associated with IV administration of the drug generally resemble those associated with IM administration.100, 101, 104 Large IV doses of iron dextran, such as those used in total-dose infusions, have been associated with an increased incidence of adverse effects,100, 101, 104 and such adverse effects frequently have been delayed (1-2 days).100, 101, 103, 104
Anaphylactic or anaphylactoid reactions to iron dextran, including fatal anaphylaxis, have been reported.100, 101, 107 These reactions occur most frequently within the first several minutes of administration and are generally characterized by sudden onset of respiratory difficulty (e.g., wheezing, bronchospasm, rigor, dyspnea, cyanosis), tachycardia, hypotension, respiratory arrest, and/or cardiovascular collapse.100, 101, 102, 103, 104 The manufacturers state that concomitant use of angiotensin-converting enzyme (ACE) inhibitors may increase the risk for reactions to iron dextran.100, 101 The level of risk for anaphylactic-type reactions following exposure to specific iron dextran preparations is not known and may vary.100, 101 Iron dextran preparations differ in chemical characteristics and may differ in clinical effects; the manufacturers state that such preparations are not clinically interchangeable.100, 101
Acute hypersensitivity reactions to iron dextran have been estimated to occur in 0.2-3% of patients. These reactions have been reported after administration of uneventful test doses of iron dextran as well as after therapeutic doses of the drug.100, 101, 107 Although it has been suggested that severe systemic reactions, including anaphylactoid reactions, are more common following IV rather than IM administration of iron dextran, the risk of severe systemic reactions following IV or IM administration has not been directly compared and there appears to be no well-substantiated evidence of a difference in the frequency of anaphylactoid reactions following either route of administration. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) guidelines state that direct observation of the patient after IV administration of an iron agent permits the most reliable assessment of the frequency of associated adverse drug reactions.117 Relatively large IV doses such as those employed with total-dose infusions have been associated with an increased risk of adverse effects,100, 101, 104 mainly delayed effects.100, 101, 103, 104 The risk of anaphylactic or anaphylactoid reactions to iron dextran appears to be increased in patients with a positive history of drug allergy, particularly those with multiple drug allergies.100, 101, 102 Other hypersensitivity reactions may include sweating, dyspnea, urticaria, other rashes and pruritus, arthralgia, myalgia, and febrile episodes.
The mechanism of anaphylactic/anaphylactoid reactions to iron dextran has not been elucidated, but because of the rapid nature of their onset and similarity to anaphylactoid reactions observed with radiographic contrast media they probably result from a direct effect on mast cells and basophils leading to their degranulation and release of mediators (e.g., histamine).102, 104, 108 An immunoglobulin E-mediated reaction appears unlikely.102, 108
Musculoskeletal and Delayed Adverse Effects
Large IV doses of iron dextran, such as those used in total-dose infusions†, may be associated with an increased frequency of adverse effects,100, 101, 104, 117 especially delayed (1-2 days) reactions manifested by arthralgia, backache, myalgia, adenopathy, moderate to high fever, backache, chills, dizziness, headache, malaise, nausea, and/or vomiting.100, 101, 103, 104, 117 The onset of these adverse effects is usually 24-48 hours after administration of the drug, and the effects generally subside within 3-4 days.100, 101 Delayed adverse effects have also occurred following IM administration and usually subsided within 3-7 days.100 The etiology of delayed adverse effects is not known,100, 101, 104 but the symptom complex resembles that of a serum sickness reaction.104 Patients with rheumatoid arthritis and possibly other inflammatory diseases (e.g., ankylosing spondylitis, lupus erythematosus) may be at particular risk for delayed reactions.100, 101, 103, 104, 109 IV administration of iron dextran has caused fever and exacerbation or reactivation of joint pain and swelling in patients with rheumatoid arthritis;100, 101, 103, 104, 109 in addition, exacerbation of ankylosing spondylitis in one patient and arthralgia, myalgia, erythema nodosum, and fever in a patient with lupus erythematosus have been reported. Such exacerbations of underlying inflammatory conditions may respond to nonsteroidal anti-inflammatory agent (NSAIA) therapy103 and may be prevented with corticosteroid pretreatment.103
Local reactions may occur at the injection site of iron dextran and are more common following IM administration. Local reactions at the injection site following IM injection include soreness or pain (in rare cases persisting longer than a year), inflammation, sterile abscesses, necrosis, atrophy, fibrosis, cellulitis, swelling, and harmless but persistent brown staining of the skin and/or underlying tissue. Phlebitis, pain along the course of the vein, and venospasm may occur following IV injection. Inadvertent intra-arterial injection of a 1-g undiluted dose over 20 minutes resulted in marked erythema, warmth, and tingling in the hand and arm distal to the brachial artery injection site during infusion.104
Chest pain, chest tightness, shock, hypotension, hypertension, tachycardia, bradycardia, flushing, edema, cardiac arrest, thrombophlebitis, pulmonary embolus, and arrhythmias have occurred in patients receiving iron dextran.100 Flushing and hypotension may occur when the drug is administered IV too rapidly.100, 101
Abdominal pain, dyspepsia, nausea, vomiting, diarrhea, metallic taste in the mouth, altered taste,100 and transient loss of taste perception have occurred in patients receiving iron dextran.
Headache, transient paresthesia, weakness, dizziness, faintness, syncope, unresponsiveness, disorientation, numbness, malaise, and seizures (which may accompany anaphylaxis) have been reported in patients receiving iron dextran.
Latent folic acid deficiency may occasionally become apparent in patients receiving iron dextran. Leukocytosis, frequently with fever, may occur. One case of leukocytosis was reported in a severely iron-deficient infant who received the drug. Purpura has also occurred.
Other adverse effects of iron dextran include chills, shivering, regional lymphadenopathy (generally inguinal and associated with IM injection of the drug), and hematuria.
Precautions and Contraindications
Because anaphylactic reactions to iron dextran, including fatal anaphylaxis, have been reported, an initial test dose should be administered prior to administration of the first therapeutic dose of the drug and the patient should be observed for manifestations of anaphylactic-type reactions.100, 101, 102, 103, 104, 105, 106, 107 Because anaphylaxis and other hypersensitivity reactions have been reported after administration of uneventful test doses of iron dextran as well as after therapeutic doses of the drug, the manufacturers state that administration of subsequent test doses should be considered during iron dextran therapy.100, 101 (See Dosage and Administration: Administration.) It is recommended that the test dose and subsequent doses of iron dextran be administered by personnel trained to provide emergency treatment101, 117 and that appropriate resuscitation equipment and drugs for the treatment of a severe allergic or anaphylactic reaction (e.g., epinephrine) be readily available when iron dextran is administered.100, 101, 102, 103, 104, 117 Patients receiving β-adrenergic blocking agents may not respond adequately to epinephrine, and use of isoproterenol or a similar β-adrenergic agonist may be required in these patients.100, 101
The fact that large IV doses of iron dextran, such as those used in total-dose infusions, have been associated with an increased incidence of adverse effects, especially delayed reactions, should be considered when evaluating the benefits and risks of such therapy.100, 101, 104 Patients should be advised of potential effects associated with the use of iron dextran.100
Iron dextran should be used with caution in patients with a history of serious allergies and/or asthma.100 Iron dextran should be used with extreme caution in patients with serious impairment of hepatic function.100 Adverse effects following administration of iron dextran may exacerbate cardiovascular complications in patients with preexisting cardiovascular disease.100, 101
Extreme caution should also be used in administering the drug IV in patients with rheumatoid arthritis, since IV administration may cause fever and exacerbation or reactivation of joint pain and swelling in these patients; the possibility of an increased risk of delayed reactions (e.g., arthralgia, myalgia, fever) should also be considered in patients with other inflammatory diseases (e.g., ankylosing spondylitis, lupus erythematosus). (See Cautions: Musculoskeletal and Delayed Adverse Effects.)
Unwarranted administration of parenteral iron preparations may cause excess storage of iron and a syndrome similar to hemosiderosis in patients whose anemia is not attributable to iron deficiency (e.g., those with hemoglobinopathies and other refractory anemias that might be erroneously diagnosed as iron deficiency anemias).100, 101
Because iron can increase the pathogenicity of certain microorganisms110, 111, 112, 113 and has been postulated as potentially adversely affecting prognosis in certain HIV-infected individuals,111, 112 some clinicians recommend that HIV-infected individuals who do not have documented iron-deficiency anemia avoid iron supplementation for the management of HIV-associated anemia.111, 112 Iron dextran should not be administered concomitantly with oral iron preparations. Determinations of hematologic response, such as serum ferritin, blood hemoglobin concentration, hematocrit, and reticulocyte count, should be performed periodically during the course of therapy with iron dextran. Serum ferritin has been shown to correlate with iron stores, at least in nonuremic patients; while a correlation between serum ferritin and iron stores has been reported in hemodialysis patients, other data suggest that elevated serum ferritin can result from hepatosplenic siderosis in some of these patients, and may not reliably indicate bone marrow iron stores.
Iron dextran should not be used during the acute phase of infectious renal disease.100, 101 The drug is contraindicated in patients with any anemia other than iron deficiency anemia and in patients who are hypersensitive to iron dextran.100, 101
The manufacturers state that the use of iron dextran in children younger than 4 months of age is not recommended.100, 101 Use of IM iron dextran in neonates† in other countries (e.g., New Zealand) reportedly has been associated with an increased incidence of gram-negative sepsis, principally infections caused by Escherichia coli .100 However, the drug has been administered IV in a limited number of neonates in the US without evidence of unusual adverse effect or risk of sepsis.114
IM administration of iron-carbohydrate complexes may be associated with a risk of carcinogenesis.100, 101 Subcutaneous injection of very large doses of iron dextran or small doses injected repeatedly at the same site have been shown to produce sarcomas in mice, rats, rabbits, and possibly hamsters.100 Such tumors have not been produced in guinea pigs. Animal studies suggest that sarcomas may result from high tissue concentrations of iron remaining at the site of injection and that the latent period between administration of the drug and appearance of the tumor may be one-quarter to one-third of the life span of the particular species. Sarcoma at the site of injection has been reported rarely in patients approximately 4-14 years after receiving IM iron dextran or other complexes of iron and carbohydrates; however, a causal relationship has not been proven. Although the carcinogenic potential of iron dextran is generally considered remote by most authorities, it may require years before the carcinogenic potential in humans can be clearly defined.
Reproduction studies in mice, rats, rabbits, dogs, and monkeys using iron dextran doses about 3 times the maximum human dose have shown the drug to be teratogenic and embryocidal.100, 101 At doses equivalent to 50 mg/kg or less of iron, no consistent adverse fetal effects were observed in mice, rats, rabbits, dogs, or monkeys.100, 101 At a total IV dose equivalent to 90 mg/kg of iron given over a 14-day period, fetal and maternal toxicity has been reported in monkeys; similar effects were observed in mice and rats with a single dose equivalent to 125 mg/kg of iron.100, 101 In dogs and rats, fetal abnormalities were observed at doses equivalent to 250 mg/kg or higher of iron.100, 101 The animals used in reproduction studies were not iron deficient.100, 101 The effect of iron dextran on the human fetus is not known. Results of various studies in pregnant animals and humans have been inconclusive regarding placental transfer of intact iron dextran.100, 101 Small amounts of iron apparently cross the placenta (the form in which it crosses the placenta has not been clearly established)100, 101 and increase neonatal serum iron concentrations when iron dextran is administered within 2 weeks of delivery; however, no adverse effects on the neonate have been reported. There are no adequate and well-controlled studies using iron dextran in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.100, 101
Only traces of unmetabolized iron dextran are distributed into milk, but the drug should be used with caution in nursing women.100, 101
Large IV doses (250 mg or more of iron) of iron dextran may cause serum from blood samples obtained 4 hours after administration of the drug to have a brown color.100, 101 The drug may cause falsely elevated values of serum bilirubin and falsely decreased values of serum calcium.100, 101 Serum iron determinations (especially colorimetric assays) may not be meaningful for 3 weeks following the administration of iron dextran.100, 101 Results of serum iron measurements obtained within 1-2 weeks of administration of large doses of the drug should be interpreted with caution. Serum ferritin concentrations peak approximately 7-9 days following an IV dose of iron dextran and slowly return to baseline over a period of about 3 weeks.100 Examination of the bone marrow for iron stores may not be meaningful for prolonged periods following iron dextran therapy because residual iron dextran may remain in the reticuloendothelial cells.100, 101
Prolongation of the partial thromboplastin time has been reported to occur after IV administration of iron dextran when the blood sample for the test is mixed with anticoagulant citrate dextrose solution. This interference apparently does not occur when anticoagulant sodium citrate solution is used. Blood typing and cross-matching are not affected by iron dextran.
Bone scans involving technetium Tc 99m diphosphonate have been reported to exhibit dense, crescentic areas of activity along the contour of the iliac crest, visualized 1-6 days after IM injections of iron dextran.100, 101 Bone scans using imaging agents labeled with technetium Tc 99m, in the presence of high serum ferritin concentrations or following IV infusions of iron dextran, have been reported to show reduced bone uptake, marked renal activity, and excessive blood pool and soft tissue accumulation.100, 101
The LD50 of iron dextran in mice is 500 mg/kg or greater.100, 101 Overdosage of iron dextran is unlikely to be associated with any acute manifestations; however, dosage of the drug in excess of that required for restoration of hemoglobin and replenishment of iron stores may lead to hemosiderosis.100, 101 Periodic monitoring of serum ferritin concentrations may be useful in recognizing a deleterious, progressive accumulation of iron resulting from impaired iron uptake from the reticuloendothelial system that may occur in some patients (e.g., those with chronic kidney disease, Hodgkin's disease, rheumatoid arthritis).100, 101 Only negligible amounts of iron dextran are removed by hemodialysis.101, 115, 116
Iron is a constituent of hemoglobin, and administration of iron dextran corrects the erythropoietic abnormalities that are due to a deficiency of iron. Some iron also may be utilized for synthesis of myoglobin or nonhemoglobin heme units. In iron-deficient patients, reticulocytosis may begin by the fourth day following an IV infusion of the total calculated dose of iron dextran and reaches a maximum by about the tenth day. Iron does not stimulate erythropoiesis nor does it correct hemoglobin disturbances not caused by iron deficiency.
Administration of iron may reverse esophageal, gastric, and other tissue changes associated with iron deficiency. Iron therapy also relieves other symptoms associated with iron deficiency such as soreness of the tongue, cheilosis, dysphagia, and dystrophy of the nails and skin. Some of the toxic effects of iron dextran may be due to a pharmacologic or allergenic effect of dextran; however, conclusive studies have not been performed to establish the importance of this effect.
Following IM injection, iron dextran is absorbed from the site of injection principally through the lymphatic system. Absorption takes place in two stages. In the initial phase lasting about 3 days, a local inflammatory reaction facilitates passage of the drug from the site of IM injection into the lymphatic system. In the second, slower phase, iron dextran is ingested by macrophages, which then enter the lymphatic system and eventually the blood. Results of studies using radiolabeled iron dextran have shown that about 60% of an IM dose of iron dextran is absorbed after 3 days and up to 90% is absorbed after 1-3 weeks; the remainder is gradually absorbed over a period of several months or longer. Absorption of iron dextran from subcutaneous tissue is very slow, and the skin may be stained brown for up to 2 years if the drug is deposited in this tissue.
Following IM or IV injection, iron dextran is gradually cleared from the plasma by the reticuloendothelial cells of the liver, spleen, and bone marrow. Results of several studies indicate that a variable portion of an IV dose of iron dextran may be stored in an unusable form in bone marrow. Following IV doses containing more than 500 mg of elemental iron, the uptake of iron dextran by the reticuloendothelial system appears to be constant and amounts to 10-20 mg per hour. Reticuloendothelial cells separate iron from the iron dextran complex and the iron becomes a part of the body's total iron stores.
Ferric iron is gradually released into the plasma where it rapidly combines with transferrin and is carried to the bone marrow and incorporated into hemoglobin. Rate of incorporation of iron into hemoglobin is determined by the extent of iron deficiency, with greater rates of hemoglobin synthesis occurring in iron deficient patients than in normal or mildly anemic patients. Following an IV infusion of the total calculated dose of iron dextran in iron-deficient patients, the rate of increase in hemoglobin concentration appears to be most rapid during the first 1-2 weeks and ranges from 1.5-2.2 g/dL per week. Subsequently, hemoglobin concentration increases at a rate of 0.7-1.6 g/dL per week until normal hemoglobin concentrations are attained.
Small amounts of iron apparently reach the fetus following administration of iron dextran during pregnancy, but the form in which it crosses the placenta is not clearly established.100 Only traces of unmetabolized iron dextran are distributed into breast milk.100
In doses of 500 mg or less, iron dextran plasma concentrations decrease exponentially with a half-life of about 6 hours. In studies in iron-deficient patients with coexistent end-stage renal disease and other clinical problems, the serum elimination half-life of iron averaged 58.9 hours (range: 9.4-87.4 hours) following IV administration of iron dextran;101 these studies measured the total serum iron directly as well as transferrin bound iron non-radioisotopically.101 It should be recognized that elimination of iron from serum, including elimination half-life, does not correspond to clearance of the mineral from the body.100, 101
Dextran, a polyglucose, is either metabolized or excreted.100, 101 Only traces of unmetabolized iron dextran are excreted in urine, bile, or feces.
Iron dextran is negligibly removed by hemodialysis.101, 115, 116 Several dialyzer membranes have been studied (e.g., polysulphone, cuprophane, cellulose acetate, cellulose triacetate, polymethylmethacrilate, polyacrylonitrile), including those considered high efficiency and high flux.100, 101, 115, 116
Iron dextran injection is a sterile, colloidal solution of ferric hydroxide100 or oxyhydroxide101 in a complex with partially hydrolyzed low molecular weight dextran. During the manufacture of iron dextran, polymerization occurs resulting in a complex with a molecular weight estimated to be approximately 165,000.100 Approximately 98-99% of the iron in iron dextran is present as a stable ferric-dextran complex; the remainder is present as a weak ferrous complex. Iron dextran injection occurs as a dark brown, slightly viscous liquid100, 101 that is completely miscible with water and 0.9% sodium chloride injection. The commercially available injection of InFed®100 or Dexferrum®101 has a pH of 5.2-6.5 or 4.5-7, respectively; sodium hydroxide and/or hydrochloric acid may have been added to adjust pH.100, 101
Iron dextran injection should be stored at a controlled room temperature of 20-25°C,100, 101 with excursions permitted to 15-30°C.101
Iron dextran injection has been reported to be physically incompatible with oxytetracycline and with sulfadiazine sodium in IV infusions.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IV use | equivalent to 50 mg of elemental iron per mL | ||
Injection, for IV or IM use | equivalent to 50 mg of elemental iron per mL |
Only references cited for selected revisions after 1984 are available electronically.
100. Watson Pharmaceuticals. INFeD® (iron dextran injection, USP) prescribing information. Corona, CA; 2009 Sept.
101. American Regent Laboratories, Inc. Dexferrum® (iron dextran injection, USP) prescribing information. Shirley, NY; 2008 Aug.
102. Fishbane S, Ungureanu VD, Maesaka JK et al. The safety of intravenous iron dextran in hemodialysis patients. Am J Kidney Dis . 1996; 28:1529-34.
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114. Friel JK, Andrews WL, Hall MS et al. Intravenous iron administration to very-low-birth-weight newborns receiving total and partial parenteral nutrition. J Parenter Enteral Nutr . 1995; 19:114-8.
115. Hatton RC, Portales IT, Finley A et al. Removal of iron dextran by hemodialysis: an in vivo study. Am J Kidney Dis . 1995; 26:327-330. [PubMed 7645537]
116. Manuel MA, Stewart WK, St. Clair Neill GD et al. Loss of iron-dextran through cuprophane membrane of disposable coil dialyser. Nephron . 1972; 9:94-8. [PubMed 4634565]
117. National Kidney Foundation. KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. Am J Kidney Dis . 2006; 47(suppl 3):S1-S146.
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119. Bregman D. Dear healthcare professional letter: Important drug warning for Dexferrum® (iron dextran injection, USP). Shirley, NY: American Regent; 2009 Sep 25.
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