INDICATIONS AND USAGE Intravenous or intramuscular injections of iron dextran are indicated for treatment of patients with documented iron deficiency in whom oral administration is unsatisfactory or impossible. CONTRAINDICATIONS Hypersensitivity to the product. All anemias not associated with iron deficiency. WARNINGS See WARNING ABOVE. A risk of carcinogenesis may attend the intramuscular injection of iron-carbohydrate complexes. Such complexes have been found under experimental conditions to produce sarcoma when large doses or small doses injected repeatedly at the same site were given to rats, mice, and rabbits, and possibly in hamsters. The long latent period between the injection of a potential carcinogen and the appearance of a tumor makes it impossible to measure accurately the risk in man. There have, however, been several reports in the literature describing tumors at the injection site in humans who had previously received intramuscular injections of iron-carbohydrate complexes. Large intravenous doses, such as used with total dose infusions (TDI), have been associated with an increased incidence of adverse effects. The adverse effects frequently are delayed (1-2 days) reactions typified by one or more of the following symptoms: arthralgia, backache, chills, dizziness, moderate to high fever, headache, malaise, myalgia, nausea, and vomiting. The onset is usually 24-48 hours after administration and symptoms generally subside within 3-4 days. These symptoms have also been reported following intramuscular injection and generally subside within 3-7 days. The etiology of these reactions is not known. The potential for a delayed reaction must be considered when estimating the risk/benefit of treatment. The maximum daily dose should not exceed 2 mL undiluted iron dextran. This preparation should be used with extreme care in patients with serious impairment of liver function. It should not be used during the acute phase of infectious kidney disease. Adverse reactions experienced following administration of INFeD may exacerbate cardiovascular complications in patients with preexisting cardiovascular disease.
Pregnancy Pregnancy Category C: Iron dextran has been shown to be teratogenic and embryocidal in mice, rats, rabbits, dogs, and monkeys when given in doses of about 3 times the maximum human dose. No consistent adverse fetal effects were observed in mice, rats, rabbits, dogs and monkeys at doses of 50 mg iron/kg or less. Fetal and maternal toxicity has been reported in monkeys at a total intravenous dose of 90 mg iron/kg over a 14 day period. Similar effects were observed in mice and rats on administration of a single dose of 125 mg iron/kg. Fetal abnormalities in rats and dogs were observed at doses of 250 mg iron/kg and higher. The animals used in these tests were not iron deficient. There are no adequate and well-controlled studies in pregnant women. INFeD should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Placental Transfer Various animal studies and studies in pregnant humans have demonstrated inconclusive results with respect to the placental transfer ofiron dextran as iron dextran. It appears that some iron does reach the fetus, but the form in which it crosses the placenta is not clear. Nursing Mothers Caution should be exercised when INFeD is administered to a nursing woman. Traces of unmetabolized iron dextran are excreted in human milk. Pediatric Use Not recommended for use in infants under 4 months of age (See DOSAGE AND ADMINISTRATION).
Oral iron should be discontinued prior to administration of INFeD. Dosage I. Iron Deficiency Anemia: Periodic hematologic determination (hemoglobin and hematocrit) is a simple and accurate technique for monitoring hematological response, and should be used as a guide in therapy. It should be recognized that iron storage may lag behind the appearance of normal blood morphology. Serum iron, total iron binding capacity (TIBC) and percent saturation of transferrin are other important tests for detecting and monitoring the iron deficient state. After administration of iron dextran complex, evidence of a therapeutic response can be seen in a few days as an increase in the reticulocyte count. Although serum ferritin is usually a good guide to body iron stores, the correlation of body iron stores and serum ferritin may not be valid in patients on chronic renal dialysis who are also receiving iron dextran complex. Although there are significant variations in body build and weight distribution among males and females, the accompanying table and formula represent a convenient means for estimating the total iron required. This total iron requirement reflects the amount of iron needed to restore hemoglobin concentration to normal or near normal levels plus an additional allowance to provide adequate replenishment of iron stores in most individuals with moderately or severely reduced levels of hemoglobin. It should be remembered that iron deficiency anemia will not appear until essentially all iron stores have been depleted. Therapy, thus, should aim at not only replenishment of hemoglobin iron but iron stores as well. Factors contributing to the formula are shown below.
a) Blood volume.......................... 65 mL/kg of body weight b) Normal hemoglobin (males and females) over 15 kg (33 lbs)................... 14.8 g/dl 15 kg (33 lbs) or less............... 12.0 g/dl c) Iron content of hemoglobin ....................0.34% d) Hemoglobin deficit e) Weight Based on the above factors, individuals with normal hemoglobin levels will have approximately 33 mg of blood iron per kilogram of body weight (15 mg/lb). Note: The table and accompanying formula are applicable for dosage determinations only in patients with iron deficiency anemia; they are not to be used for dosage determinations in patients requiring iron replacement for blood loss. TOTAL INFeD® REQUIREMENT FOR HEMOGLOBIN RESTORATION AND IRON STORES REPLACEMENT*
Based on: Desired Hb = the target Hb in g/dl. Observed Hb = the patient’s current hemoglobin in g/dl. LBW = Lean body weight in kg. A patient’s lean body weight (or actual body weight if less than lean body weight) should be utilized when determining dosage. For males: LBW = 50 kg + 2.3 kg for each inch of patient’s height over 5 feet For females: LBW = 45.5 kg + 2.3 kg for each inch of patient’s height over 5 feet To calculate a patient’s weight in kg when lbs are known: patient’s weight in pounds = weight in kilograms/2.2
II. Iron Replacement for Blood Loss: Some individuals sustain blood losses on an intermittent or repetitive basis. Such blood losses may occur periodically in patients with hemorrhagic diatheses (familial telangiectasia; hemophilia; gastrointestinal bleeding) and on a repetitive basis from procedures such as renal hemodialysis. Iron therapy in these patients should be directed toward replacement of the equivalent amount of iron represented in the blood loss. The table and formula described under I. Iron Deficiency Anemia are not applicable for simple iron replacement values. Quantitative estimates of the individual’s periodic blood loss and hematocrit during the bleeding episode provide a convenient method for the calculation of the required iron dose. The formula shown below is based on the approximation that 1 mL of normocytic, normochromic red cells contains 1 mg of elemental iron: Replacement iron (in mg) = Blood loss (in mL) x hematocrit Example: Blood loss of 500 mL with 20% hematocrit Replacement Iron = 500 x 0.20 = 100 mg INFeD dose = 100 mg/50 = 2 mL
Administration: The total amount of INFeD required for the treatment of iron deficiency anemia or iron replacement for blood loss is determined from the table or appropriate formula (See Dosage). I. Intravenous Injection - PRIOR TO RECEIVING THEIR FIRST INFeD THERAPEUTIC DOSE, ALL PATIENTS SHOULD BE GIVEN AN INTRAVENOUS TEST DOSE OF 0.5 mL. (See PRECAUTIONS: General.) THE TEST DOSE SHOULD BE ADMINISTERED AT A GRADUAL RATE OVER AT LEAST 30 SECONDS. Although anaphylactic reactions known to occur following INFeD administration are usually evident within a few minutes, or sooner, it is recommended that a period of an hour or longer elapse before the remainder of the initial therapeutic dose is given. Individual doses of 2 mL or less may be given on a daily basis until the calculated total amount required has been reached. INFeD is given undiluted at a slow gradual rate not to exceed 50 mg (1 mL) per minute. 2. Intramuscular Injection - PRIOR TO RECEIVING THEIR FIRST INFeD THERAPEUTIC DOSE, ALL PATIENTS SHOULD BE GIVEN AN INTRAMUSCULAR TEST DOSE OF 0.5 mL. (See PRECAUTIONS: General.) The test dose should be administered in the same recommended test site and by the same technique as described in the last paragraph of this section. Although anaphylactic reactions known to occur following INFeD administration are usually evident within a few minutes or sooner, it is recommended that at least an hour or longer elapse before the remainder of the initial therapeutic dose is given. If no adverse reactions are observed, INFeD can be given according to the following schedule until the calculated total amount required has been reached. Each day’s dose should ordinarily not exceed 0.5 mL (25 mg of iron) for infants under 5 kg (11 lbs); 1.0 mL (50 mg of iron) for children under 10 kg (22 lbs); and 2.0 mL (100 mg of iron) for other patients. INFeD should be injected only into the muscle mass of the upper outer quadrant of the buttock - never into the arm or other exposed areas - and should be injected deeply, with a 2-inch or 3-inch 19 or 20 gauge needle. If the patient is standing, he/she should be bearing his/her weight on the leg opposite the injection site, or if in bed, he/she should be in the lateral position with injection site uppermost. To avoid injection or leakage into the subcutaneous tissue, a Z-track technique (displacement of the skin laterally prior to injection) is recommended. NOTE: Do not mix INFeD with other medications or add to parenteral nutrition solutions for intravenous infusion. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit. HOW SUPPLIED: INFeD® (Iron Dextran Injection USP) containing 50 mg of elemental iron per mL, is available in 2 mL single dose amber vials (for intramuscular or intravenous use) in cartons of 10 (NDC 52544-931-02). Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature]. Rx Only REFERENCES: 1. Hatton RC, Portales IT, Finlay A, Ross EA. Removal of Iron Dextran by Hemodialysis: An In Vitro Study. Am J Kid Dis. 1995; 26(2):327-330. 2. Manuel MA, Stewart WK, St. Clair Neill GD, Hutchinson F. Loss of Iron-Dextran through Cuprophane Membrane of a Disposable Coil Dialyser. Nephron. 1972;9:94-98. Literature revised: March 2006
Parenterally administered iron does not give a faster response compared to oral administration, therefore, the rate of recovery from anemia should be the same. Reticulocyte count will increase in 3-4 days and peak in 7-10 days. Hemoglobin may increase at a rate of 1.5-2.2 g/dl/week for the first 2 weeks, followed by 0.7 to 1.6 g/dl/week until normal hemoglobin levels are achieved. Parenteral iron treatment should be administered only when iron deficiency is not correctable with oral treatment. Note: Iron dextran is cleared by the reticuloendothelial system. Smaller doses (50-500mg) are cleared within 3 days, however, larger doses(>500mg) are cleared at a constant rate of 10-20mg/hr and are associated with increased plasma concentration of iron dextran for as long as 3 weeks.
Iron replacement for blood loss: Dose (mg)= Blood loss (ml) x Hematocrit %. Total mg of iron/50 = dose in ml. Reactions to IV administration include: fever, chills, backache, myalgia, dizziness, syncope,rash and anaphylaxis-immediate or delayed.
Total dose infusion: the overall consensus regarding IV administration of iron dextran is that total dose infusion is the preferred method. If severe reactions develop, multiple bolus injections over several days may be required. Average total body content of iron in adult male: 4 grams (70% in Hgb, 25% in storage).
The first changes seen with treatment is an increase in reticulocytes (4-6 days initially, peak: 9-12 days) Hemoglobin will rise slowly--it should rise by 2 g/dl after 3 weeks. The plasma iron will gradually increase, and the initially elevated TIBC will return to normal in about one month. Blood levels return to normal in about 4-6 months (ferritin levels will return to normal). Laboratory: Transferrin: delivers iron to bone marrow and storage sites. Circulating transferrin is normally only about 30% saturated with iron. The remaining 70% in unbound and represents the TIBC. Iron is stored as either ferritin or hemosiderin within macrocytes (reticuloendothelial system). Normal RBC survival time: 120 days.
In iron deficiency anemia (microcytic-hypochromic=decreased Hemoglobin), iron stores are depleted prior to anemia; therefore, the earliest change observed is usually decreased ferritin. Hemoglobin: Normal (female): 12-16 g/dL ; Male 14-18 g/dL. Hematocrit: Normal (female): 35-40% ; (Male): 42-52%. A low Hematocrit indicates a decrease in number or size of RBC or increase in plasma volume. RBC count: 4.5 to 6 million/ml (4 to 5.5 female). MCV(mean corpuscular volume): indicates microcytic, normocytic or macrocytic morphology. MCH(mean corpuscular hemoglobin): Average weight of Hgb in RBC. Decreased in microcytosis and hypochromia(low hgb). MCH alone cannot distinguish between the two. MCHC(mean corpuscular hemoglobin conc.): (Nml: 31-36%): weight of Hemoglobin/volume of cells. Independent of cell size and, therefore, is more useful than MCH in distinguishing between microcytosis and hypochromia. A low MCHC always indicates hypochromia, as a microcyte with a normal Hemoglobin concentration will have a low MCH but a normal MCHC. Red cell distribution width (RDW): Normal: 11.4 - 14.5% Indicates how much the RBC's vary in size. Elevated in anemia's resulting from nutritional deficiencies (iron,folic acid, B12). Serum iron concentration: concentration of iron bound to transferrin. Unfortunately, the serum level of many patients with iron deficiency anemia remains within the lower limits of normal. There is a 20-30% diurnal variation in serum iron levels--it is best to draw levels in the morning. Total iron binding capacity (TIBC): indirect measurement of serum transferrin. Unlike the serum iron level, the TIBC is remarkably constant. The finding of a low serum iron and a high TIBC indicates iron deficiency anemia. Serum ferritin: the concentration of ferritin (storage iron) in the serum is proportional to total iron stores. Low ferritin levels are virtually diagnostic of iron deficiency anemia as they are decreased only in iron deficiency anemia. Liver disease causes an elevation in serum ferritin; thus ferritin should not be used for diagnostic purposes in patients with even mild hepatic pathology.
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