Azathioprine is a potent immunosuppressive purine antimetabolite prodrug, widely used in India for the management of autoimmune disorders and to prevent organ transplant rejection. It is a cornerstone therapy in rheumatology, gastroenterology, and nephrology. Its use requires careful hematological monitoring due to significant myelosuppressive effects.
Adult: Initial: 1-3 mg/kg/day orally, usually as a single daily dose. Maintenance: Dose is titrated to response and tolerability, often aiming for the lowest effective dose. Typical range: 50-150 mg/day. In RA: Start at 1 mg/kg/day (50-100 mg), increase by 0.5 mg/kg every 4-6 weeks to max 2.5 mg/kg/day.
Note: Administer orally, with or immediately after food to reduce gastrointestinal upset. Tablets should be swallowed whole with a full glass of water. Dose should be taken at the same time each day. Do not crush or break tablets (cytotoxic precaution).
Azathioprine is a prodrug that is cleaved in vivo to 6-mercaptopurine (6-MP). 6-MP is then converted into active thioguanine nucleotide (TGN) metabolites. These TGNs are incorporated into DNA and RNA, substituting for natural purines (guanine and hypoxanthine). This incorporation inhibits de novo purine synthesis and disrupts nucleic acid metabolism, leading to cytotoxicity. The effect is most pronounced on rapidly dividing cells, particularly lymphocytes, resulting in suppression of cell-mediated immunity and humoral antibody production.
Pregnancy: FDA Pregnancy Category D. There is positive evidence of human fetal risk (teratogenicity, intrauterine growth retardation). Use only if the potential benefit justifies the potential risk to the fetus (e.g., life-threatening maternal autoimmune disease). Women of childbearing potential must use effective contraception during and for at least 3 months after therapy.
Driving: Azathioprine itself does not impair driving ability. However, patients should be cautioned that severe side effects like dizziness, fever, or malaise could affect their ability to drive or operate machinery safely.
| Allopurinol, Febuxostat | Potentiates azathioprine toxicity by inhibiting xanthine oxidase, leading to dangerous accumulation of active metabolites. Dose of azathioprine must be reduced to 25-33% of usual. | High |
| Warfarin | Azathioprine may reduce anticoagulant effect; monitor INR closely. | Moderate |
| Angiotensin-Converting Enzyme (ACE) Inhibitors (e.g., Enalapril) | Concurrent use may increase risk of severe leukopenia. | Moderate |
| Live Vaccines (MMR, Varicella, OPV, Yellow Fever) | Risk of disseminated vaccine-induced infection. Contraindicated. | High |
| Other Myelosuppressants (Methotrexate, Cyclophosphamide) | Additive bone marrow toxicity; monitor blood counts intensively. | High |
| Aminosalicylates (e.g., Sulfasalazine, Mesalamine) | May inhibit TPMT, increasing azathioprine toxicity. Monitor for myelosuppression. | Moderate |
| Ribavirin | Additive myelotoxicity; avoid combination. | High |