Azathioprine Sodium

INDICATIONS AND USAGE Azathioprine Sodium for Injection, USP is indicated as an adjunct for the prevention of rejection in renal homotransplantation. It is also indicated for the management of active rheumatoid arthritis to reduce signs and symptoms. Renal Homotransplantation Azathioprine is indicated as an adjunct for the prevention of rejection in renal homotransplantation. Experience with over 16,000 transplants shows a five-year patient survival of 35% to 55%, but this is dependent on donor, match for HLA antigens, anti-donor or anti-B-cell alloantigen antibody and other variables. The effect of azathioprine on these variables has not been tested in controlled trials.

ADVERSE REACTIONS The principal and potentially serious toxic effects of azathioprine are hematologic and gastrointestinal. The risks of secondary infection and malignancy are also significant (see WARNINGS ). The frequency and severity of adverse reactions depend on the dose and duration of azathioprine as well as on the patient’s underlying disease or concomitant therapies. The incidence of hematologic toxicities and neoplasia encountered in groups of renal homograft recipients is significantly higher than that in studies employing azathioprine for rheumatoid arthritis.

Pregnancy: Azathioprine can cause fetal harm when administered to a pregnant woman. Azathioprine should not be given during pregnancy without careful weighing of risk versus benefit. Whenever possible, use of azathioprine in pregnant patients should be avoided. This drug should not be used for treating rheumatoid arthritis in pregnant women. 3 Azathioprine is teratogenic in rabbits and mice when given in doses equivalent to the human dose (5 mg/kg daily). Abnormalities included skeletal malformations and visceral anomalies.

WARNING - MALIGNANCY Chronic immunosuppression with azathioprine, a purine antimetabolite increases risk of malignancy in humans. Reports of malignancy include post-transplant lymphoma and hepatosplenic T-cell lymphoma (HSTCL) in patients with inflammatory bowel disease. Physicians using this drug should be very familiar with this risk as well as with the mutagenic potential to both men and women and with possible hematologic toxicities. WARNINGS Malignancy: Patients receiving immunosuppressants, including azathioprine, are at increased risk of developing lymphoma and other malignancies, particularly of the skin. Physicians should inform patients of the risk of malignancy with azathioprine. As usual for patients with increased risk for skin cancer, exposure to sunlight and ultraviolet light should be limited by wearing protective clothing and using a sunscreen with a high protection factor. Post-transplant: Renal transplant patients are known to have an increased risk of malignancy, predominantly skin cancer and reticulum cell or lymphomatous tumors. The risk of post-transplant lymphomas may be increased in patients who receive aggressive treatment with immunosuppressive drugs, including azathioprine. CONTRAINDICATIONS Azathioprine Sodium for Injection should not be given to patients who have shown hypersensitivity to the drug. Azathioprine should not be used for treating rheumatoid arthritis in pregnant women.