IMURAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IMURAN (IMURAN).
Imuran (azathioprine) is a purine antimetabolite that inhibits DNA synthesis by interfering with purine metabolism. It is converted in vivo to 6-mercaptopurine (6-MP), which is further metabolized to thioinosinic acid and thioguanine nucleotides. These metabolites inhibit de novo purine synthesis and incorporation of purines into nucleic acids, thereby suppressing T-cell proliferation and antibody production.
| Metabolism | Azathioprine is rapidly metabolized in the liver and erythrocytes by xanthine oxidase (XO) and thiopurine S-methyltransferase (TPMT) to its active metabolite 6-mercaptopurine (6-MP). 6-MP is further metabolized by TPMT and XO to inactive metabolites (6-thiouric acid, 6-methylmercaptopurine). |
| Excretion | Primarily renal excretion of inactive metabolites; 50% as 6-thiouric acid and other metabolites; <2% unchanged. Minor biliary/fecal elimination (<10% total). |
| Half-life | Azathioprine: 0.16–0.75 h; 6-mercaptopurine: 1.5–4.7 h (terminal). Extended up to 5 h in renal impairment. Context: short half-life allows daily dosing; clinical effect persists due to active metabolites. |
| Protein binding | Azathioprine: ~30% bound to albumin; 6-mercaptopurine: ~20% bound to albumin. |
| Volume of Distribution | Azathioprine: Vd ~0.8–1.0 L/kg (extensive distribution); 6-mercaptopurine: Vd ~0.6 L/kg. Clinical meaning: distributes into total body water and tissues. |
| Bioavailability | Oral: 41–44% (range 27–60%) due to first-pass metabolism. IV: 100%. |
| Onset of Action | Oral: 3–6 months for full clinical effect in autoimmune conditions; IV: days to weeks for immunosuppression. Immediate T-cell suppression not seen. |
| Duration of Action | Duration: 24–48 h after single dose; sustained effect with chronic dosing (weeks to months for therapeutic response). Clinical notes: myelosuppression may occur weeks after dose adjustment. |
| Action Class | Immunosuppressant- Purine analogs |
| Brand Substitutes | Transimune 50mg Tablet, Azap 50 Tablet, Zesoris-AZ 50mg Tablet, Autorin 50mg Tablet, Azawan Tablet |
Initially 3-5 mg/kg/day orally once daily; maintenance dose 1-3 mg/kg/day orally once daily. IV dose equivalent to oral.
| Dosage form | TABLET |
| Renal impairment | GFR >50 mL/min: no adjustment. GFR 10-50 mL/min: administer 75% of normal dose. GFR <10 mL/min: administer 50% of normal dose. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: avoid use. |
| Pediatric use | 2-5 mg/kg/day orally once daily; titrate to response. Monitoring of blood counts required. |
| Geriatric use | Initiate at lower end of dosing range (e.g., 1-2 mg/kg/day) due to increased risk of myelosuppression; monitor renal function and CBC closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for IMURAN (IMURAN).
| Breastfeeding | Azathioprine is excreted into breast milk in low concentrations (M/P ratio approximately 1.0 – 2.0 based on limited data). The American Academy of Pediatrics considers it compatible with breastfeeding, but caution is advised. Monitor infant for signs of immunosuppression or infections. Weigh benefits of therapy against potential risks. |
| Teratogenic Risk | First trimester: Increased risk of congenital malformations, particularly craniofacial, cardiac, and skeletal defects (based on animal data and limited human reports). Second and third trimesters: Risks include intrauterine growth restriction, preterm birth, and neonatal immunosuppression or pancytopenia due to transfer across placenta. Use only if maternal benefit outweighs fetal risk; avoid in first trimester if possible. |
■ FDA Black Box Warning
Warning: Malignancy. Patients receiving azathioprine have an increased risk of developing lymphoma and other malignancies, particularly of the skin (non-melanoma). This risk may be related to the immunosuppressive effect. Exposure to sunlight and UV light should be minimized. Chronic immunosuppression increases the risk of lymphoproliferative disorders and other malignancies.
| Serious Effects |
["Hypersensitivity to azathioprine or any component of the formulation","Hypersensitivity to 6-mercaptopurine","Pregnancy (unless potential benefit justifies risk, category D)","Lactation (avoid use)","Severe immunosuppression or active infection (relative contraindication)","Malignancy (except for non-melanoma skin cancer) (relative contraindication)"]
| Precautions | ["Myelosuppression: Monitor CBC regularly; dose reductions may be needed for severe leukopenia or thrombocytopenia.","Hepatotoxicity: Can cause dose-related hepatotoxicity; monitor liver function tests.","Increased risk of infection: Due to immunosuppression; avoid live vaccines.","TPMT deficiency: Patients with low TPMT activity are at increased risk for severe myelosuppression; consider TPMT testing before therapy.","Pancreatitis: Rare but serious; discontinue if pancreatitis develops.","Hypersensitivity reactions: Including Stevens-Johnson syndrome.","Teratogenicity: Use effective contraception in women of childbearing potential.","Increased risk of skin cancer: Use protective measures against UV exposure."] |
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| Fetal Monitoring | Maternal: Complete blood counts (CBC) with differential, liver function tests (LFTs), and renal function at baseline and regularly (e.g., monthly) during therapy. Monitor for signs of infection, myelosuppression, and hepatotoxicity. Fetal: Serial ultrasound for growth restriction and anomalies; consider fetal echocardiogram if exposed in first trimester. Neonatal: CBC at birth and monitoring for infections. |
| Fertility Effects | Azathioprine does not appear to significantly impair fertility in males or females based on clinical data. However, in animal studies, high doses have caused reduced spermatogenesis and ovarian dysfunction. In humans, no consistent evidence of infertility; but disease activity (e.g., inflammatory bowel disease) may affect fertility secondarily. |