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Azathioprine

NEO PLASTIC DISORDERS

CYTOTOXIC IMMUNO SUPPRESSANTS - [ NEO PLASTIC DISORDERS ]

Azathioprine is a purine antimetabolite. Following exposure to nucleophiles such as glutathione, azathioprine is cleaved to 6-mercaptopurine, which in turn is converted to additional metabolites that inhibit de novo purine synthesis. 6-thio-IMP, is converted to 6-thio-GMP and finally to 6-thio-GTP and is incorporated into DNA. Thereby inhibiting cell proliferation and impairing a variety of lymphocyte functions. (1)

As an adjunct for the prevention of rejection in renal homotransplantation Management of active rheumatoid arthritis to reduce signs and symptoms. Inflammatory bowel disease Multiple sclerosis Autoimmune hepatitis Atopic dermatitis (AD) (2,3)

Hypersensitivity to the drug Rheumatoid arthritis in pregnant women Patients with rheumatoid arthritis previously treated with alkylating agents as they carry a risk of malignancy (2)

Lymphoma and other malignancies, particularly of the skin Post-transplant lymphomas Acute myelogenous leukemia as well as solid tumors have been reported in patients with rheumatoid arthritis who have received azathioprine Severe leukopenia, thrombocytopenia, anemias including macrocytic anemia, and/or pancytopenia Serious infections Nausea and vomiting Hepatotoxicity manifest by elevation of serum alkaline phosphatase, bilirubin, and/or serum transaminases is known to occur following azathioprine use, primarily in allograft recipients Additional side effects reported with low frequency include skin rashes, alopecia, fever, arthralgias, diarrhea, steatorrhea, negative nitrogen balance, reversible interstitial pneumonitis and hepatosplenic T cell lymphoma (2)

Allopurinol: Dose reduction of 1/3rd to 1/4th of usual dose for azathioprine as : One of the pathways for inactivation of azathioprine is inhibited by allopurinol Aminosalicylates: : There is in vitro evidence that aminosalicylate derivatives (e.g., sulphasalazine, mesalazine, or olsalazine) inhibit the thiopurine methyltransferase (TPMT) enzyme. Concomitant use of these agents with azathioprine should be done with caution Drugs which may affect leukocyte production, including co­trimoxazole, may lead to exaggerated leukopenia, especially in renal transplant recipients ACE inhibitors: The use of angiotensin-converting enzyme inhibitors to control hypertension in patients on azathioprine has been reported to induce anemia and severe leukopenia. Warfarin: Azathioprine may inhibit the anticoagulant effect of warfarin. Ribavarin: The use of ribavirin for hepatitis C in patients receiving azathioprine has been reported to induce severe pancytopenia and may increase the risk of azathioprine-related myelotoxicity (2)

Azathioprine can cause fetal harm when administered to a pregnant woman.This drug should not be used for treating rheumatoid arthritis in pregnant women Not recommended in nursing mothers Safety and efficacy of azathioprine in pediatric patients have not been established. Full blood counts necessary every week for patients of hepatic and renal impairment (2)

Oral Adult and child over 3 months-Renal transplantation: initially 5 mg/kg body weight daily. Maintenance 2 to 2.5 mg/kg daily. Atopic dermatitis (AD): 1 to 3 mg /kg/day once daily. (3)

1.Krensky AM, Bennett WM, Vincenti F. Immunosuppressants, Tolerogens and Immunostimulants. In: Brunton L, Chabner B, Knollmann B eds. Goodman & Gilman’s The Pharmacological basis of Therapeutics. 12th ed. China: McGraw Hill; 2011. P1005-31. 2. Imuran [Internet]. [cited 2013 October 6]. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/016324s034s035lbl.pdf 3. National Formulary of India. 4 th ed. Government of India, Ministry of Health and Family Welfare. India: Indian Pharmacopoeia Commission; 2011