IRON DEXTRAN 50 mg/mL Injection, 2 mL — NDC 51662-1441-1 (Billing 51662-1441-01)

WARNINGS Risk for Anaphylactic-type Reactions: Anaphylactic-type reactions, including fatalities have followed the parenteral administration of iron dextran. Always have resuscitation equipment and personnel trained in the detection and treatment of anaphylactic-type reactions readily available during INFeD administration. Prior to the first therapeutic dose, administer a test INFeD dose of 0.5 mL.

(See DOSAGE AND ADMINISTRATION. ) Although reactions are usually evident within a few minutes, observe patients for at least one hour before administering the therapeutic dose. During all INFeD administrations, observe patients for signs or symptoms of anaphylactic-type reactions. Fatal reactions have followed the test dose of iron dextran and have also occurred in situations where the test dose was tolerated.

Use INFeD only in patients in whom clinical and laboratory investigations have established an iron deficient state not amenable to oral iron therapy. The factors that affect the risk for anaphylactic-type reactions to iron dextran products are not fully known but limited clinical data suggest the risk may be increased among patients with a history of drug allergy or multiple drug allergies. Additionally, concomitant use of angiotensin-converting enzyme inhibitor drugs may increase the risk for reactions to an iron dextran product.

The extent of risk for anaphylactic-type reactions following exposure to any specific iron dextran product is unknown and may vary among the products. Iron dextran products differ in chemical characteristics and may differ in clinical effects. Iron dextran products are not clinically interchangeable.

Delayed Reactions: 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.

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.

Risk in Patients with Underlying Conditions: INFeD 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 pre-existing cardiovascular disease.

Carcinogenesis: 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.

ADVERSE REACTIONS Severe/Fatal: Anaphylactic reactions have been reported with the use of iron dextran injection; on occasions these reactions have been fatal. Such reactions, which occur most often within the first several minutes of administration, have been generally characterized by sudden onset of respiratory difficulty and/or cardiovascular collapse. Because fatal anaphylactic reactions have been reported after administration of iron dextran injection, the drug should be given only when resuscitation techniques and treatment of anaphylactic and anaphylactoid shock are readily available.

(See BOXED WARNING and PRECAUTIONS : General, pertaining to immediate availability of epinephrine.) Cardiovascular: Chest pain, chest tightness, shock, cardiac arrest, hypotension, hypertension, tachycardia, bradycardia, flushing, arrhythmias. (Flushing and hypotension may occur from too rapid injections by the intravenous route.) Dermatologic: Urticaria, pruritus, purpura, rash, cyanosis. Gastrointestinal: Abdominal pain, nausea, vomiting, diarrhea.

Hematologic/lymphatic: Leucocytosis, lymphadenopathy. Musculoskeletal/soft tissue: Arthralgia, arthritis (may represent reactivation in patients with quiescent rheumatoid arthritis - See PRECAUTIONS : General), myalgia; backache; sterile abscess, atrophy/fibrosis (intramuscular injection site); brown skin and/or underlying tissue discoloration (staining), soreness or pain at or near intramuscular injection sites; cellulitis; swelling; inflammation; local phlebitis at or near intravenous injection site. Neurologic: Convulsions, seizures, syncope, headache, weakness, unresponsiveness, paresthesia, febrile episodes, chills, dizziness, disorientation, numbness, unconsciousness.

Respiratory: Respiratory arrest, dyspnea, bronchospasm, wheezing. 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.

PRECAUTIONS General: Unwarranted therapy with parenteral iron will cause excess storage of iron with the consequent possibility of exogenous 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. INFeD 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, administer a test dose prior to the first therapeutic dose of INFeD. (See BOXED WARNING and DOSAGE AND ADMINISTRATION: Administration.) Epinephrine should be immediately available in the event of acute hypersensitivity reactions.

(Usual adult dose: 0.5 mL of a 1:1000 solution, by subcutaneous or intramuscular injection.) Note: Patients using beta-blocking agents may not respond adequately to epinephrine. Isoproterenol or similar beta-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 INFeD.

Reports in the literature from countries outside the United States (in particular, New Zealand) have suggested that the use of intramuscular iron dextran in neonates has been associated with an increased incidence of gram-negative sepsis, primarily due to E. Coli. Information For Patients: Patients should be advised of the potential adverse reactions associated with the use of INFeD.

Drug/Laboratory Test Interactions: Large doses of iron dextran (5 mL or more) have been reported to give a brown color to serum from a blood sample drawn 4 hours after administration. The drug may cause falsely elevated values of serum bilirubin and falsely decreased values of serum calcium. Serum iron determinations (especially by colorimetric assays) may not be meaningful for 3 weeks following the administration of iron dextran.

Serum ferritin peaks approximately 7 to 9 days after an intravenous dose of INFeD and slowly returns to baseline after about 3 weeks. 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. 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 levels or following iron dextran infusions, have been reported to show reduction of bony uptake, marked renal activity, and excessive blood pool and soft tissue accumulation. Carcinogenesis, Mutagenesis, Impairment Of Fertility: See WARNINGS . Pregnancy: 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 of iron dextran as iron dextran. It appears that some iron do… [Excerpted — this section continues on DailyMed.]