Azathioprine
IMURAN
What it isPurine-synthesis-inhibiting prodrug; transplant immunosuppression and autoimmune disease.
Why this oneLong clinical experience and pregnancy compatibility distinguish it from mycophenolate.
What limits it⚑ TPMT or NUDT15 deficiency can cause profound myelosuppression; allopurinol or febuxostat can make standard exposure dangerously high.
FDA-approved for
- immunosuppression (~1968)
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Prevention of rejection in renal homotransplantation | Adults | 3–5 mg/kg/day QD (beginning at transplant) | maintenance 1–3 mg/kg/day | 5 mg/kg/day |
| Rheumatoid arthritis | Adults | 1.0 mg/kg/day (50–100 mg) QD or ÷BID | increase by 0.5 mg/kg/day at intervals; up to 2.5 mg/kg/day | 2.5 mg/kg/day |
Titration RA: increase beginning at 6–8 weeks, then by steps at 4-week intervals; minimum 12-week trial before deeming refractory
Renal Oliguric patients (e.g., tubular necrosis in immediate post-transplant period) may have delayed clearance — give lower doses
Hepatic Undefined
Instructions
- Consider TPMT and NUDT15 testing; reduce dose or use alternative therapy in deficiency
- Give in divided doses and/or after meals to reduce GI upset
- Handle and dispose of as a cytotoxic antimetabolite
Contraindications
- Treatment of rheumatoid arthritis in pregnant women
- Rheumatoid arthritis previously treated with alkylating agents (cyclophosphamide, chlorambucil, melphalan) — prohibitive malignancy risk
Cautions
- Malignancy (boxed)
- Severe, dose-dependent myelosuppression (leukopenia, thrombocytopenia); higher risk with TPMT/NUDT15 deficiency
- Serious/secondary infections
- Hepatotoxicity, including rare hepatic veno-occlusive disease
- GI toxicity, nausea/vomiting, hypersensitivity pancreatitis
- Mutagenic potential
Adverse reactions
- Leukopenia
- Thrombocytopenia
- Infections
- Nausea/vomiting
- Hepatotoxicity
- Malignancy/lymphoma
- Rash
- Alopecia
- Fever
- Arthralgias
- Pancreatitis
Pregnancy Should not be used for rheumatoid arthritis in pregnancy; teratogenic effects noted; intrahepatic cholestasis of pregnancy reported postmarketing
Lactation Undefined
⚠ BOXED WARNING
- Malignancy risk, including lymphoma
Cost, est. cash$10–$500/month
Generic entry1996
Classes and tags
Clinical profile
Legacy pregnancy categoryC
Defining liabilityMyelosuppression, hepatotoxicity, malignancy risk and dangerous interaction with xanthine oxidase inhibitors.
Mechanism of action: Azathioprine ballicule
