General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Test dose: A test dose, given by the route and method of administration for which therapeutic doses will be administered, is recommended for all patients prior to therapeutic dose administration.Give INFed test doses gradually over at least 30 seconds; give DexFerrum test doses gradually over at least 5 minutes.
-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.
-Do not mix iron dextran with other medications.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-No dilution necessary.
-Inject via slow IV at a gradual rate. The maximum rate of administration is 50 mg/minute; take care to inject dosage very slowly in children and infants.
Total Dose Intravenous Infusion:
-Iron dextran is not FDA-approved to be administered as a total dose infusion.
-Dilute the total calculated dose in 50-1000 ml of NS injection. D5W may be used for dilution; however, use of D5W for iron dextran dilution has been associated with a higher incidence of local pain and phlebitis upon administration.
-If the test dose is uneventful after 1 hour of observation, then infuse the remaining dose over 2-6 hours (usually no faster than 2-6 mg/min). Once the infusion is completed, flush vein with NS injection.
Total Parenteral Nutrition Infusion:
-Iron dextran is not FDA-approved to be administered in parenteral nutrition (PN) formulations.
-Studies evaluating stability and compatibility in PN solutions are inconsistent. Iron dextran may destabilize the mixture or cause cracking of the TPN emulsion.
-Neonatal PN solutions containing iron dextran and at least 2% amino acids were visually compatible for 48 hours at room temperature.
-Only INFeD is approved for administration via IM injection.
-No dilution necessary.
-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.
-To avoid staining of subcutaneous tissue, use the Z-track technique (displacement of the skin laterally before injection).
Patients who receive parenteral iron, rarely, if ever, develop hemochromatosis unless a genetic predisposition to the disorder is also present. Hemochromatosis results in aberrations of iron absorption, metabolism and storage; iron accumulates in the body and excess iron deposition occurs in the parenchymal tissues. With hemochromatosis, the liver becomes enlarged, and skin discoloration, specifically a bronze hue, occurs. Pancreatic dysfunction, diabetes mellitus, cardiac failure, liver failure and other tissue disorders may occur secondary to hemochromatosis.
Central nervous system effects that may occur with iron dextran therapy include headache, transient paresthesias, weakness, dizziness, syncope, unresponsiveness, disorientation (confusion), unconsciousness, numbness, and seizures. Headache and dizziness may also occur as part of a delayed reaction that is associated with large intravenous doses (e.g., total dose infusions). The onset of the delayed reaction is usually 24-48 hours after administration and symptoms generally subside within 3-4 days.
Cardiovascular adverse effects associated with iron dextran administration include chest pain (unspecified) or tightness, cardiac arrest, shock, hypotension, hypertension, sinus tachycardia, bradycardia, flushing, and cardiac arrhythmias. Flushing and hypotension may occur when the drug is administered too rapidly intravenously.
Iron dextran therapy may expose latent folic acid deficiency. Leukocytosis and lymphadenopathy have been reported with iron dextran therapy.
Gastrointestinal effects that may occur during iron dextran therapy include abdominal pain, nausea, vomiting, diarrhea, and altered taste (dysgeusia). Nausea and vomiting may also occur as part of a delayed reaction that is associated with large intravenous doses (e.g., total dose infusion). The onset of the delayed reaction is usually 24-48 hours after administration and symptoms generally subside within 3-4 days.
Serious hypersensitivity reactions or anaphylaxis, including fatal reactions, has occurred with iron dextran therapy. These reactions can occur with either IM or IV administration, are usually apparent within minutes of administration, and are usually characterized by sudden onset of dyspnea and/or anaphylactic shock. Hypersensitivity or dermatological reactions also include urticaria, pruritus, rash, purpura and cyanosis. Angioedema has been reported with another parenteral iron product, sodium ferric gluconate complex (Ferrlecit). Administer iron dextran therapy only when resuscitation techniques and treatment for anaphylactoid reactions are readily available.
Iron is not easily eliminated from the body and acute overdose may result in toxicity. Overdosage of iron dextran, per the manufacturer, is unlikely to cause any acute manifestations. Iron overload, which can occur after long-term use of iron dextran, may cause exogenous hemosiderosis. Hemosiderosis is the result of deposition of hemosiderin, an iron-containing pigment, in the tissues of the liver and spleen. Hemosiderosis has primarily been reported in dialysis patients who receive long-term iron dextran treatment. 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.
Adverse reactions associated with iron dextran therapy include malaise, diaphoresis, respiratory arrest, dyspnea, wheezing, bronchospasm, fever, chills, shivering, arthralgia, myalgia, back pain, and hematuria. Arthralgia, myalgia, back pain, chills, and moderate to high fever may also occur as part of a delayed reaction that is associated with large intravenous doses (e.g., total dose infusion). The onset of the delayed reaction is usually 24-48 hours after administration and symptoms generally subside within 3-4 days.
Injection site reactions may occur following intramuscular administration of iron dextran. Local reactions may include soreness or pain, inflammation, sterile abscesses, cellulitis, edema, and persistent brown staining of the skin and/or the underlying tissue (skin discoloration). Intravenous injection of iron dextran may cause local phlebitis near the injection site. The administration of large intravenous doses (e.g., total dose infusion) is associated with an increased incidence of adverse effects. The onset of reaction is usually delayed by 24-48 hours after administration and symptoms generally subside within 3-4 days. Delayed reactions reported include arthralgia, myalgia, back pain, chills, dizziness moderate to high fever, headache, malaise, nausea and vomiting.
Parenteral iron dextran therapy is associated with a risk of serious hypersensitivity reactions or anaphylaxis. Parenteral iron dextran therapy 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 have also occurred in situations 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.
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.
Patients with pre-existing cardiac disease may experience an exacerbation of cardiovascular complications after administration of iron dextran. Cardiovascular adverse effects (e.g., flushing, hypotension) may occur with iron dextran therapy, and do not necessarily indicate hypersensitivity.
Iron dextran is contraindicated for use in patients who have anemia not associated with iron-deficiency. Unnecessary administration of iron may lead to iron overload and iron toxicity. The type of anemia and the underlying cause or causes should be determined before starting therapy with 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. Iron dextran is only useful for those anemia types where iron-deficiency co-exists. Exogenous administration of iron dextran will not alleviate hemolytic anemia and iron should only be administered to patients with hemolysis if an iron-deficiency is also present. Parenteral iron products should be used cautiously in patients receiving blood transfusions because iron overload may occur. Prolonged use of iron dextran should be restricted to avoid iron overload. Oral iron preparations should be discontinued prior to the use of iron dextran.
Unnecessary administration of iron dextran to patients with hemoglobinopathies may result in excessive storage of iron. Iron dextran should not be used in patients with hereditary/genetic hemochromatosis or hemochromatosis due to secondary iron overload (e.g., as in iron-loading anemias such as thalassemia or sideroblastic anemia). Hemochromatosis is a disease that causes the body to lose its ability to regulate the amount of iron that is absorbed, leading to excess iron absorption and tissue storage. Massive deposition of iron (hemosiderosis) in parenchymal tissues in these conditions may damage the liver, heart, pancreas and other tissues. Porphyria cutanea tarda (PCT) is sometimes associated with parenchymal iron deposits; patients with PCT should generally avoid iron therapies. Excess iron supplementation in PCT patients can contribute to hepatic uroporphinogen decarboxylase deficiency but the mechanism is not clear.
The contribution of iron to infectious processes is unclear, but iron dextran should not be administered during the acute phase of infectious renal disease. 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.
Use iron dextran with caution in patients with 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 of iron in the liver.
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.
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.
Description: Iron dextran is used parenterally to treat iron-deficiency anemia. Iron dextran consists of a complex of ferric oxyhydroxide with dextrans of 5000-7000 daltons. Because anaphylactic reactions, including fatalities, have occurred with the parenteral use, iron dextran is usually reserved for iron-deficient patients unable to take or intolerant to oral iron preparations. Test doses are recommended prior to the first therapeutic dose of iron dextran. Parenteral iron produces therapeutic responses similar to those of oral iron. One advantage of parenteral iron is that iron stores are rapidly restored, which may take months to achieve with oral iron therapy. Iron dextran was approved by the FDA prior to 1982.
Test Dose Information
-For all patients, the manufacturer recommends a test dose of 25 mg be given by the route and method of administration for which therapeutic doses will be administered; however, this amount may be more than the required calculated daily dose for some pediatric patients. Administering the test dose based on weight has been suggested.-Patients weighing < 10 kg: administer 10 mg
-Patients weighing 10-20 kg: administer 15 mg
-Patients weighing > 20 kg: administer 25 mg
-After the test dose, observe patients for at least 1 hour; because anaphylactic reactions are known to occur after an uneventful test doses, subsequent test doses should be considered.
For the treatment of iron-deficiency anemia in patients in whom oral iron administration is unsatisfactory or impossible:
-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:
Infants >= 4 months and weighing < 5 kg: Total iron dextran dose in mL = (0.0442 x [desired Hb - observed Hb] x LBW) + (0.26 x LBW). A value of 12 g/dL may be used as a target normal hemoglobin. If the test dose is uneventful, give daily doses of 25 mg IM (INFeD only) or via slow IV (INFeD or Dexferrum) until the total calculated dose is given.
Infants >= 4 months and Children weighing 5-< 10 kg: Total iron dextran dose in mL = (0.0442 x [desired Hb - observed Hb] x LBW) + (0.26 x LBW). A value of 12 g/dL may be used as a target normal hemoglobin. If the test dose is uneventful, give daily doses of 50 mg IM (INFeD only) or via slow IV (INFeD or Dexferrum) until the total calculated dose is given.
Infants >= 4 months and Children weighing 10-15 kg: Total iron dextran dose in mL = (0.0442 x [desired Hb - observed Hb] x LBW) + (0.26 x LBW). A value of 12 g/dL may be used as a target normal hemoglobin. If the test dose is uneventful, give daily doses of 100 mg IM (INFeD only) or via slow IV (INFeD or Dexferrum) until the total calculated dose is given.
Children and Adolescents weighing > 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 g/dL may be used as a target normal hemoglobin. If the test dose is uneventful, give daily doses of 100 mg IM (INFeD only) or via slow IV (INFeD or Dexferrum) until the total calculated dose is given.
Intravenous infusion dosage*:
Infants >= 4 months and Children weighing < 15 kg: Total iron dextran dose in mL = (0.0442 x [desired Hb - observed Hb] x LBW) + (0.26 x LBW). A value of 12 g/dL may be used as a target normal hemoglobin. If the test dose is uneventful, infuse the remainder of the total calculated dose IV over 2 to 6 hours.
Children and Adolescents weighing >= 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 g/dL may be used as a target normal hemoglobin. 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:
Intermittent Intramuscular or Intravenous injection dosage:
Infants >= 4 months and weighing < 5 kg: Total iron dextran dose in mL = blood loss (mL) x hematocrit (expressed as a decimal fraction) x 0.02. If the test dose is uneventful, give daily doses of 25 mg IM (INFeD only) or via slow IV (INFeD or Dexferrum) until the total calculated dose is given.
Infants >= 4 months and Children weighing 5-<10 kg: Total iron dextran dose in mL = blood loss (mL) x hematocrit (expressed as a decimal fraction) x 0.02. If the test dose is uneventful, give daily doses of 50 mg IM (INFeD only) or via slow IV (INFeD or Dexferrum) until the total calculated dose is given.
Children and Adolescents weighing >= 10 kg: Total iron dextran dose in mL = blood loss (mL) x hematocrit (expressed as a decimal fraction) x 0.02.If the test dose is uneventful, give daily doses of 100 mg IM (INFeD only) or via slow IV (INFeD or Dexferrum) until the total calculated dose is given.
Intravenous infusion dosage*:
Infants >= 4 months, Children, and Adolescents: Total iron dextran dose in mL = blood loss (mL) x hematocrit (expressed as a decimal fraction) x 0.02. If test dose uneventful, infuse the remainder of the total calculated dose (see equation) IV over 2 to 6 hours.
For the treatment of anemia of prematurity*:
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.
Therapeutic Drug Monitoring:
-Serum iron, hemoglobin, and hematocrit should be evaluated prior to iron therapy and at regular intervals during therapy. Ferritin, transferrin, total iron binding capacity, and percent saturation of transferrin are also recommended monitoring parameters.
-Serum iron concentrations, especially measured by colorimetric assays, may not be meaningful for 3 weeks following iron dextran administration.
-Examination of the bone marrow for iron stores may also not be meaningful for prolonged periods following iron dextran therapy because residual iron dextran may remain in the reticuloendothelial cells.
-Serum ferritin peaks approximately 7 to 9 days after an IV dose of iron dextran and slowly returns to baseline after approximately 3 weeks.
Maximum Dosage Limits:
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.
Safety and efficacy have not been established.
< 4 months: Safety and efficacy have not been established.
>= 4 months (weight < 5 kg): 25 mg/day IV or IM.
>= 4 months (weight 5-<10 kg): 50 mg/day IV or IM.
>= 10 kg: 100 mg/day IV or IM.
5-9.99 kg: 50 mg/day IV or IM.
100 mg/day IV or IM.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available. However, 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.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Iron dextran is not hemodialyzable. Before supplementing hemodialysis patients with iron dextran, a diagnosis of absolute or functional iron deficiency should be made. Follow recommended dosage.
Monograph content under development
Mechanism of Action: After administration, circulating iron dextran is split into iron and dextran by cells of the reticuloendothelial system. Iron is bound immediately to various proteins to the physiological form of iron, hemosiderin or ferritin, or to a lesser extent, to transferrin. The iron available for physiological use replenishes hemoglobin and depleted iron stores. Normal erythropoiesis is dependent on the concentration of iron and erythropoietin available in the plasma. Approximately two-thirds of total body iron is in the circulating erythrocytes as hemoglobin, the major factor in oxygen transport to the tissues. Stored iron, in the form of ferritin and hemosiderin, accumulates during periods of positive iron balance and can be mobilized to meet iron requirements when iron intake is low. The majority of iron present in a newborn term infant is accrued during the third trimester of pregnancy. Term infants are born with enough stored iron to meet requirements until about 4-6 months of age. Infants born prematurely miss the rapid accretion and are deficient in total body iron. This deficit increases with decreasing gestational age and is worsened by rapid postnatal growth and frequent phlebotomies without adequate blood replacement. Due to low iron stores and a high growth rate, iron stores of premature infants are depleted by 2-3 months of age. Therefore premature infants and low birth weight infants are at an increased risk of iron deficiency. Administration of iron does not stimulate the production of red blood cells, nor does it correct abnormalities not caused by iron deficiency. A therapeutic response to treatment with iron products is dependent on the patient's ability to absorb and use the iron. The response to iron therapy is also influenced by the cause of the deficiency as well as other illnesses that can affect normal erythropoiesis. A positive response to iron treatment can be noted by an increase in the hemoglobin concentration by 1 g/dl or more 4 weeks after initiating oral therapy, assuming that transfusion or other interventions cannot explain the improvements in the patients clinical status.
Iron-containing proteins and enzymes are important in oxidation-reduction reactions, especially those of the mitochondria. Iron is a component of iron-containing heme proteins (e.g., hemoglobin, myoglobin), iron-sulfur enzymes (e.g., flavoproteins), proteins for iron storage and transport (e.g., transferrin) and other iron-containing enzymes. Iron deficiency not only causes anemia and decreased oxygen delivery, it also reduces the metabolism of muscle and decreases mitochondrial activity. In infants and children, early iron deficiency has been associated with long-term neurodevelopmental deficiencies (e.g., cognitive development, behavior) that may be irreversible. Iron deficiency can also lead to deficits in temperature regulation and motor deficits in preterm infants. Thus iron is important to several metabolic functions which are independent of its importance to erythropoiesis.
Pharmacokinetics: Iron dextran is administered intramuscularly or intravenously. Iron dextran is absorbed into the capillaries and the lymphatic system. The majority of an intramuscularly injected dose is absorbed within 3 days; most of the remaining iron is absorbed over 3-4 weeks. Circulating iron dextran is removed by cells of the reticuloendothelial system (RES) and split into iron and dextran. Ferric iron is then gradually released into the plasma where it combines rapidly to form hemosiderin or ferritin, or to a lesser extent, with transferrin. Negligible amounts of iron are excreted via the urinary or alimentary pathways.
The internal transport of iron to essential sites depends on the plasma protein transferrin. Transferrin delivers iron to specific transferrin receptors at target tissues, which then deliver iron to intracellular sites. Transferrin is extruded from the cell once iron is delivered intracellularly. The production of transferrin receptors is regulated according to body needs; when iron is deficient, transferrin receptors increase and iron storage via ferritin decreases. Ferritin is the storage protein for iron. The main sites of iron storage are the liver, spleen, bone marrow, and the RES; a minor portion is stored in the muscle. Iron is excreted in small amounts. The majority of absorbed iron is lost in the feces. Menstrual losses are highly variable. After a life-cycle of roughly 120 days, circulating erythrocytes are catabolized by the RES, and some of the iron is recirculated to the plasma bound to transferrin. The remaining iron from erythrocyte breakdown is incorporated into ferritin stores in the RES and hepatocytes. The utilization of iron by the body is designed to maintain body stores, so very little physiologic loss of iron occurs once it is in the body.
Affected cytochrome P450 isoenzymes: none