Brands, Medical Use, Clinical Data
- Antimetabolites, Antineoplastic
- Antirheumatic Agents
- Immunosuppressive Agents
- Powder for solution and tablets for oral administration (25 mg, 75 mg and 100 mg)
Brands / Synonyms
ATP; Azamun; Azanin; Azasan; Azathioprin; Azathioprine Sodium; Azatioprin; Azothioprine; Ccucol; Imuran; Imurek; Imurel; Muran; Rorasul
For use as an adjunct in the prevention of rejection in renal homotransplantation. Also for the management of severe, active rheumatoid arthritis unresponsive to rest, aspirin or other nonsteroidal anti-inflammatory drugs, or to agents in the class of which gold is an example.
Azathioprine is a chemotherapy drug, now rarely used for chemotherapy but more for immunosuppression in organ transplantation and autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease or Crohn's disease. It is a pro-drug, converted in the body to the active metabolite 6-mercaptopurine. Azathioprine acts to inhibit purine synthesis necessary for the proliferation of cells, especially leukocytes and lymphocytes. It is a safe and effective drug used alone in certain autoimmune diseases, or in combination with other immunosuppressants in organ transplantation. Its most severe side effect is bone marrow suppression, and it should not be given in conjunction with purine analogues such as allopurinol. The enzyme thiopurine S-methyltransferase (TPMT) deactivates 6-mercaptopurine. Genetic polymorphisms of TPMT can lead to excessive drug toxicity, thus assay of serum TPMT may be useful to prevent this complication.
Mechanism of Action
Azathioprine antagonizes purine metabolism and may inhibit synthesis of DNA, RNA, and proteins. It may also interfere with cellular metabolism and inhibit mitosis. The mechanism of action of azathioprine in rheumatoid arthritis is not known but is most likely related to its immunosuppresive action.
Well absorbed following oral administration.
The oral LD50 for single doses of azathioprine in mice and rats are 2500 mg/kg and 400 mg/kg, respectively. Very large doses of this antimetabolite may lead to marrow hypoplasia, bleeding, infection, and death.
Biotrnasformation / Drug Metabolism
Primarily converted to the active metabolites 6-mercaptopurine and 6-thioinosinic acid.
Azathioprine should not be given to patients who have shown hypersensitivity to the drug.
Azathioprine should not be used to treat rheumatoid arthritis in pregnant women. Patients with rheumatoid
arthritis previously treated with alkylating agents (cyclophosphamide, chlorambucil, melphalan or others) may have a
prohibitive risk of neoplasia if treated with azathioprine.
Use with Allopurinol: The principal pathway for detoxification of azathioprine is inhibited by
allopurinol. Patients receiving azathioprine and allopurinol concomitantly should have a dose reduction of
azathioprine, to approximately 1/3 to 1/4 the usual dose.
Use with Other Agents Affecting Myelopoesis: Drugs which may affect leukocyte production, including
co-trimoxazole, may lead to exaggerated leukopenia, especially in renal transplant recipients.
Use with Angiotensln Converting Enzyme Inhibitors: The use of angiotensin converting enzyme
inhibitors to control hypertension in patients on azathioprine has been reported to induce severe leukopenia.