AZASAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AZASAN (AZASAN).
Azathioprine is a purine analog that inhibits purine synthesis, thereby interfering with DNA and RNA synthesis. It is metabolized to 6-mercaptopurine, which inhibits T-cell activation and proliferation, leading to immunosuppression.
| Metabolism | Metabolized via xanthine oxidase and thiopurine methyltransferase (TPMT) to active and inactive metabolites. Co-administration with allopurinol inhibits xanthine oxidase, requiring dose reduction of azathioprine. |
| Excretion | Renal: 88% as 6-mercaptopurine and metabolites; biliary: <10% |
| Half-life | Terminal elimination half-life of azathioprine is approximately 4.5 hours (range 2–6 h), while its active metabolite 6-mercaptopurine has a half-life of 0.5–2 hours. Clinical context: Renal impairment prolongs half-life. |
| Protein binding | 30% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.8–1.0 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Oral: 41–47% (azathioprine); 100% for IV administration. |
| Onset of Action | Oral: 3–6 months for full therapeutic effect in autoimmune diseases; IV: within 24 hours for immunosuppression in transplantation. |
| Duration of Action | Duration: 8–12 hours for immunosuppressive effect; clinical note: maximal effect on lymphocyte counts occurs after 3–6 months of continuous therapy. |
1-3 mg/kg/day orally once daily or divided twice daily; maximum dose 2.5 mg/kg/day for rheumatoid arthritis; usual dose 50-150 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR >50 mL/min: no adjustment; GFR 10-50 mL/min: 75% of normal dose; GFR <10 mL/min: 50% of normal dose. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: contraindicated. |
| Pediatric use | 2-3 mg/kg/day orally once daily; initial dose 1 mg/kg/day in divided doses; not recommended in children <1 year. |
| Geriatric use | Start at low end of dosing range (50 mg once daily); monitor renal function and adjust accordingly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AZASAN (AZASAN).
| Breastfeeding | Azathioprine is excreted into breast milk in small amounts; milk-to-plasma ratio approximately 0.1. Infant exposure is low, but theoretical risk of immunosuppression. Weigh benefits against risks; consider monitoring infant for leukopenia and infections. |
| Teratogenic Risk | Azathioprine is FDA Pregnancy Category D. First trimester: Associated with congenital anomalies (e.g., atrial septal defect, limb defects) in case reports, but risk may be lower than with other immunosuppressants. Second and third trimesters: Risk of fetal growth restriction, preterm delivery, and neonatal immunosuppression. Avoid unless benefit outweighs risk. |
■ FDA Black Box Warning
Chronic immunosuppression increases the risk of malignancy, particularly lymphoma and skin cancer. Patients should be monitored for neoplasia. The drug should be used only if potential benefits outweigh risks.
| Serious Effects |
Hypersensitivity to azathioprine or 6-mercaptopurine. Pregnancy (category D) unless potential benefit justifies risk. Lactation. Severe hepatic impairment. Myelosuppression or active infection. Concurrent use with allopurinol without dose adjustment.
| Precautions | Hematologic toxicity (leukopenia, thrombocytopenia, anemia) - monitor blood counts. Hepatotoxicity. Increased infection risk. Hypersensitivity reactions. TPMT deficiency increases toxicity risk. Monitor for pancreatitis, especially in Crohn's patients. Avoid live vaccines. Photosensitivity and skin cancer risk. |
| Food/Dietary | No significant food interactions. May be taken with food to reduce gastrointestinal upset. Avoid concurrent use with raw or undercooked meats to reduce risk of infection due to immunosuppression. |
Loading safety data…
| Fetal Monitoring | Maternal: CBC with differential, liver function tests every 1-2 months; thyroid function tests if indicated. Fetal: Serial ultrasound for growth and anatomy; consider fetal echocardiogram. Neonatal: Monitor for neutropenia, lymphopenia, and infection in first weeks. |
| Fertility Effects | Azathioprine may cause reversible oligospermia or azoospermia in males; no significant impact on female fertility. Data limited. |
| Clinical Pearls | Azasan (azathioprine) is a prodrug of 6-mercaptopurine. Screen for TPMT deficiency before initiation to avoid severe myelosuppression. Monitor CBC and liver function weekly for first month, then monthly. Corticosteroid-sparing agent in autoimmune conditions. Avoid live vaccines during therapy. |
| Patient Advice | Take exactly as prescribed; do not change dose without consulting your doctor. · Report any signs of infection, unusual bruising/bleeding, or fatigue immediately. · Avoid exposure to individuals with infections; maintain good hand hygiene. · Use effective contraception during treatment and for at least 3 months after stopping. · Do not receive live vaccines (e.g., MMR, varicella) while taking this medication. · Limit sun exposure; use sunscreen and protective clothing due to increased skin cancer risk. |