DEXIRON
Genpharm
Iron Dextran
Hematinic – Iron Supplement
Action And Clinical Pharmacology: Iron dextran is absorbed from i.m. injection sites into the capillaries and the lymphatic system. Circulating iron dextran is removed from the plasma by cells of the reticuloendothelial system, which split the complex into its components of iron and dextran. The iron is immediately bound to the available protein moieties to form hemosiderin or ferritin, the physiologic forms of iron, and to a lesser extent transferrin. This iron, which is subject to physiologic control, replenishes hemoglobin and depleted iron stores.
Dextran, a polyglucose, is either metabolized or excreted. Negligible amounts of iron are lost via the urinary or alimentary pathways after administration of iron dextran.
The major portion of iron dextran is absorbed within 72 hours after i.m. injection. Most of the remaining iron dextran is absorbed over the ensuing 3 to 4 weeks.
Studies involving i.v. administered iron dextran to iron deficient subjects who had co-existing end-stage renal disease and other clinical problems, yielded individual plasma half-lives ranging from 9.4 to 87.4 hours. The average half-life was 58.9 hours. These studies measured the total serum iron directly as well as the transferrin-bound iron, non-radioisotopically. It should be understood that these half-life values do not represent clearance of iron from the body. Iron is not easily eliminated from the body, and accumulation of iron can be toxic.
The availability of iron for erythropoiesis and replenishment of iron stores after administration of iron dextran was evaluated in a study of 20 renal dialysis patients. A total dose equivalent to 500 mg of iron, divided into five 100 mg doses was administered i.v. over a period of 10 days. (The dosing schedule varied according to each patient’s clinical situation.) Hemoglobin increased from a pretreatment mean of 10.3 g/dL to 11.4 g/dL 2 weeks after completion of the series of injections. Serum ferritin and transferrin saturation peaked in 1 week at 620 ng/mL and 32%, respectively. Total iron binding capacity remained well within the physiological range (245 to 400 g/dL) for the duration of the 30 day observation period, an indication that free ionic iron is not released from iron dextran. The mean percent utilization of iron from iron dextran was calculated to be 47±20%.
Indications And Clinical Uses: For the treatment of patients with documented iron deficiency in whom oral iron administration is unsatisfactory or impossible (see Warnings and Dosage).
Contra-Indications: Hypersensitivity to the drug product. All anemias not associated with iron deficiency.
Manufacturers’ Warnings In Clinical States: The parenteral use of complexes of iron and carbohydrates has resulted in anaphylactic-type reactions. Deaths associated with such administration have been reported. Therefore, iron dextran should be used only in those patients in whom the indications have been clearly established and laboratory investigations confirm an iron deficient state not amenable to oral iron therapy.
A risk of carcinogenesis may attend the i.m. injection of iron-carbohydrate complexes. Under experimental conditions iron dextran has been found to produce sarcomata when large doses were given to rodents, or when smaller doses were injected repeatedly into the same site in rodents and rabbits.
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 i.m. injections of iron dextran.
Large i.v. doses, such as those used with Total Dose Infusions (TDI), have been associated with an increased incidence of adverse effects. The adverse effects frequently are delayed (1 to 2 days) reactions typified by 1 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 to 48 hours after administration and symptoms generally subside within 3 to 4 days. These symptoms have also been reported following i.m. injection and generally subside within 3 to 7 days. The etiology of these reactions is unknown. The potential for a delayed reaction must be considered when estimating the risks/benefits of treatment. The TDI method of administration is not currently recommended.
The maximum daily dose should not exceed 2 mL undiluted iron dextran injection.
Iron dextran should be used with extreme care in patients with serious impairment of liver function.
Iron dextran should not be used during the acute phase of infectious kidney disease.
Adverse reactions experienced following administration of iron dextran injection may exacerbate cardiovascular complications in patients with pre-existing cardiovascular disease.
Precautions: Unwarranted therapy with parenteral iron will cause excess storage of iron with the consequent possibility of iatrogenic hemosiderosis. Such iron overload is particularly apt to occur in patients with hemoglobinopathies and other refractory anemias that might be erroneously diagnosed as iron deficiency anemias.
Iron dextran should be used with caution in individuals with histories of significant allergies and/or asthma.
Anaphylaxis and other hypersensitivity reactions have been reported after uneventful test doses as well as therapeutic doses of iron dextran injection. Therefore, administration of subsequent test doses during therapy should be considered (see Dosage).
Epinephrine should be immediately available in the event of acute hypersensitivity reactions. The usual adult dose of epinephrine is 0.5 mL of a 1:1 000 solution, by s.c. or i.m. injection. Note: Patients using b-blocking agents may not respond adequately to epinephrine. Isoproterenol or similar b-agonist agents may be required in these patients.
Patients with rheumatoid arthritis may have an acute exacerbation of joint pain and swelling following the administration of iron dextran injection.
Reports in the literature from countries outside the United States (in particular, New Zealand) have suggested that the use of i.m. iron dextran in neonates has been associated with an increased incidence of Gram-negative sepsis, primarily due to E. coli.
Drug/Laboratory Test Interactions : Large doses of iron dextran injection (5 mL or more) have been reported to give a brown color to serum when blood samples are drawn 4 hours after administration. Iron dextran injection may cause falsely elevated serum bilirubin values and falsely decreased serum calcium values. Serum iron determinations (especially by colorimetric assays) may not be meaningful for 3 weeks following administration of iron dextran injection. Serum ferritin peaks approximately 7 to 9 days after an i.v. dose and slowly returns to baseline after about 3 weeks. Examination of bone marrow for iron stores may not be meaningful for prolonged periods following therapy with iron dextran injection because residual iron dextran may remain in reticuloendothelial cells. Bone scans involving 9mc-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 i.m. injections of iron dextran. In the presence of high serum ferritin levels or following iron dextran infusions, bone scans with 9mc-labeled bone seeking agents have been reported to show reduction of bony uptake, marked renal activity, and increased blood pool activity and soft tissue accumulation.
Carcinogenesis, Mutagenesis, Impairment of Fertility: See Warnings.
Pregnancy: Iron dextran has been shown to be teratogenic and embryocidal in nonanemic 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 have been reported in monkeys at a total i.v. dose of 90 mg iron/kg over a 14 day period. Similar effects were observed in mice and rats after 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. Iron dextran injection should be used in pregnant women only if the potential benefit justifies the potential risk to the fetus.
Placental Transfer: Various animal studies and studies in pregnant humans have been inconclusive with respect to the placental transfer of iron dextran. It appears that some iron does reach the fetus, but the form in which it crosses the placenta is not clear.
Lactation: Caution should be exercised when iron dextran injection is administered to nursing mothers. Traces of unmetabolized iron dextran are excreted in human milk.
Children: Not recommended for use in infants under 4 months of age (see Dosage).
Adverse Reactions: Severe/Fatal: Anaphylactic reactions have been reported with the use of iron dextran injection; on occasion these reactions have been fatal. Such reactions, which occur most often within the first several minutes of administration, are generally characterized by sudden onset of respiratory difficulty and/or cardiovascular collapse (see Warnings and Precautions pertaining to the immediate availability of epinephrine).
Cardiovascular: chest pain, chest tightness, shock, hypotension, hypertension, tachycardia, flushing, arrhythmias. (Flushing and hypotension may occur from too rapid injection by the i.v. route.)
Dermatologic: urticaria, pruritus, purpura, rash.
Gastrointestinal: abdominal pain, nausea, vomiting, diarrhea.
Hematologic/Lymphatic: leukocytosis, lymphadenopathy.
Musculoskeletal/Soft Tissue: arthralgia, myalgia, backache, arthritis (may represent reactivation in patients with quiescent rheumatoid arthritis, see Precautions); sterile abscess, atrophy/fibrosis, brown skin or underlying tissue discoloration or staining, soreness or pain at or near i.m. injection sites; cellulitis, swelling, inflammation, local phlebitis at or near i.v. injection sites.
Neurologic: convulsions, seizures, syncope, headache, weakness, unresponsiveness, paresthesia, febrile episodes, chills, dizziness, disorientation, numbness.
Respiratory: respiratory arrest, dyspnea, bronchospasm.
Urologic: hematuria.
Delayed Reactions: arthralgia, backache, chills, dizziness, fever, headache, malaise, myalgia, nausea, vomiting (see Warnings).
Miscellaneous: febrile episodes, sweating, shivering, chills, malaise, altered taste.
The administration of iron dextran injection has been reported to cause fever and exacerbation of joint pain and swelling in patients with rheumatoid arthritis, ankylosing spondylitis, and systemic lupus erythematosus (see Precautions).
Symptoms And Treatment Of Overdose: Symptoms and Treatment: Overdosage with iron dextran injection is unlikely to be associated with any acute manifestations. Excessive doses beyond the requirements for restoration of hemoglobin and replenishment of iron stores may lead to hemosiderosis. Periodic monitoring of serum ferritin levels may be helpful in recognizing a deleterious progressive accumulation of iron. This can occur when uptake of iron from the reticuloendothelial system is impaired, for example, in chronic renal failure, Hodgkin’s disease and rheumatoid arthritis.
Dosage And Administration: Oral iron should be discontinued prior to administration of iron dextran injection.
Iron Deficiency Anemia: Periodic determination of hemoglobin and hematocrit is a simple and accurate technique for monitoring hematological response, and should be used as a guide to therapy. It should be noted that iron storage may lag behind the appearance of normal blood morphology. Total iron binding capacity (TIBC), transferrin saturation and serum ferritin are other important tests for detecting and monitoring the iron deficient state. Serum ferritin is generally regarded as the most reliable marker of body iron stores; i.e., low serum ferritin correlates closely with low bone marrow iron stores, except in chronic renal dialysis patients who are receiving iron dextran. Serum iron is the least sensitive indicator of the response to iron dextran injection.
After administration of iron dextran injection, evidence of a therapeutic response can be seen in a few days as an increase in the reticulocyte count.
Although there are significant variations in body build and weight distribution among males and females, Table I and the formula below 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. Thus, therapy should aim at not only the restoration of hemoglobin but also the replenishment of iron stores.
Factors contributing to the formula include:
mg blood iron lb body weight = mL blood lb body weight ´ g hemoglobin mL blood ´ mg iron g hemoglobin a) Blood volume 65 mL/kg of body weight; b) Normal hemoglobin (males and females): over 15 kg (33 lbs) 14.8 g/100 mL, 15 kg (33 lbs) or less 12 g/100 mL; c) Iron content of hemoglobin 0.34%; d) Hemoglobin deficit; e) Weight. Based on these factors, individuals with normal hemoglobin levels will have approximately 33 mg of blood iron per kilogram of body weight (15 mg/lb).
Note: The formula and Table I 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.
The total amount of iron dextran in mL required to treat anemia and replenish iron stores may be approximated as follows: Adults and Children over 15 kg (33 lbs): See Table I. Alternatively the total dose may be calculated as follows:
Dose (mL) = 0.0442 (Desired Hb – Observed Hb) ´ LBW + (0.26 x LBW)
Where, Desired Hb = the target hemoglobin 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 used to determine the dose.
To convert the patient’s weight from pounds to kg:
patient’s weight in pounds 2.2 = weight in kg Males: LBW=50 kg+2.3 kg for each inch of patient’s height over 5 feet.
Females: LBW=45.5 kg+2.3 kg for each inch of patient’s height over 5 feet.
Children 5 to 15 kg (11 to 33 lbs): Iron dextran should not normally be given in the first 4 months of life (see Precautions). See Table I. Alternatively the total dose may be calculated as follows:
Dose (mL) = 0.0442 (Desired Hb – Observed Hb) ´ W + (0.26´W)
Where, Desired Hb = the target hemoglobin in g/dL. (Normal hemoglobin for children weighing 15 kg or less is 12 g/dL.) Observed Hb = the patient’s current hemoglobin in g/dL. W = weight in kg.
To convert the patient’s weight from pounds to kg:
patient’s weight in pounds 2.2 = weight in kg 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 dialysis.
Iron therapy in these patients should be directed toward replacement of the equivalent amount of iron represented in the blood loss. Table I and formula described under 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 calculating 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) ´ hematocrit
Example: Blood loss of 500 mL with 20% hematocrit
Replacement iron = 500 ´ 0.20=100 mg
DexIron dose = 100 mg = 2 mL
50 mg/mL Administration: The total amount of iron dextran required for the treatment of iron deficiency anemia or iron replacement for blood loss is determined from Table I or appropriate formula.
I.V. Injection: Prior to receiving their first iron dextran therapeutic dose, all patients should be given an i.v. test dose of 0.5 mL (see Precautions). The test dose should be administered at a gradual rate over at least 5 minutes.
Although anaphylactic reactions known to occur following administration of iron dextran injection are usually evident within a few minutes or sooner, it is recommended that a period of 1 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. Iron dextran is given undiluted at a slow gradual rate not to exceed 50 mg (1 mL)/minute.
I.M. Injection: Prior to receiving their first iron dextran therapeutic dose, all patients should be given an i.m. test dose of 0.5 mL gradually (see Precautions). 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 iron dextran administration are usually evident within a few minutes or sooner, it is recommended that a period of 1 hour or longer elapse before the remainder of the initial therapeutic dose is given.
If no adverse reactions are observed, iron dextran 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; 1 mL (50 mg of iron) for children under 10 kg; and 2 mL (100 mg of iron) for other patients.
Iron dextran 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 5 cm, 19 or 20 gauge needle. In an obese patient, a longer needle is usually necessary, and in children and frail adults a shorter and smaller needle will suffice. If the patient is standing, he/she should be bearing his/her weight on the leg opposite the injection site. If recumbent, he/she should be in the lateral position with the injection site uppermost. To avoid injection or leakage into the s.c. tissue, a Z-track technique (lateral displacement of the skin prior to injection) is recommended.
The i.m. route of administration is to be used unless there are valid reasons for i.v. administration.
Note: Do not mix DexIron with other medications or add to parenteral nutrition solutions for i.v. infusion. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit.
Availability And Storage: Each mL of dark brown, slightly viscous, sterile liquid contains: elemental iron as iron dextran 50 mg. Nonmedicinal ingredients: sodium chloride, sodium hydroxide and/or hydrochloric acid and water for injection. Single dose vials of 1 and 2 mL, cartons of 10. Store at controlled room temperature, 15 to 30°C. Protect from excessive heat. Do not freeze. Keep out of reach of children.
DEXIRON Genpharm Iron Dextran Hematinic – Iron Supplement
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