⚠️ Important: Screen for thiopurine methyltransferase (TPMT) deficiency before starting therapy. TPMT is an enzyme that metabolises azathioprine - about 1 in 300 patients have very low activity, predisposing to severe toxicity. Patients should be warned to report immediately any signs of bone marrow suppression (e.g. unexplained bruising, bleeding, sore throat, infection).

📖 About

Azathioprine is an immunosuppressive drug that inhibits purine metabolism, thereby suppressing DNA synthesis in proliferating cells.
Used in autoimmune diseases (e.g. IBD, lupus, myasthenia gravis) and in transplant medicine to prevent rejection.
Prodrug converted to 6-mercaptopurine (6-MP).

⚙️ Mechanism

Azathioprine → 6-MP → active metabolites (e.g. 6-thioguanine nucleotides).
Incorporated into DNA → inhibits lymphocyte proliferation (mainly T cells).
Blocks cell-mediated immunity and reduces antibody responses.

💊 Indications & Dosing – Azathioprine (verify with BNF/datasheet & local guidance)

Indication	Details
🩺 Transplant rejection prophylaxis	• 1–2.5 mg/kg/day PO • Adjust to response/tolerability
🧬 Autoimmune diseases	• 1–3 mg/kg/day PO • Withdraw if no response after 3 months
💩 Inflammatory bowel disease (IBD)	• 2–2.5 mg/kg/day PO (normal TPMT activity) • ⚠️ Start at ~50% target dose for first week to reduce side effects
💉 IV Azathioprine	• Strongly irritant • Only if oral route not feasible

⚠️ Side Effects

Bone marrow suppression: leukopenia, anaemia, thrombocytopenia.
Hypersensitivity: malaise, arthralgia, rash, fever, dizziness.
GI/hepatobiliary: nausea, pancreatitis, hepatitis, cholestasis.
Renal/hepatic toxicity: requires regular monitoring.
High-dose/IV use → severe local irritation if extravasation.
Long-term: ↑ risk of non-melanoma skin cancer and lymphoma (especially with other immunosuppressants).

⚠️ Cautions & Monitoring

FBC: weekly for 4–8 weeks, then every 1–3 months once stable.
LFTs & U&E: baseline and regular during treatment.
TPMT deficiency:
- Complete deficiency = contraindication.
- Intermediate deficiency = reduce dose and monitor closely (specialist input required).
Infection risk: avoid live vaccines; screen for hepatitis B/C, HIV, varicella, TB if clinically indicated.

🔄 Interactions

Allopurinol/febuxostat: potent xanthine oxidase inhibitors → dangerously ↑ azathioprine levels → must reduce azathioprine dose to 25–33% if unavoidable.
ACE inhibitors & ARBs: risk of severe haematological toxicity.
Trimethoprim/co-trimoxazole: risk of additive bone marrow suppression.
Rifampicin: ↓ efficacy by ↑ metabolism of 6-MP.

🚫 Contraindications

Complete TPMT deficiency.
Hypersensitivity to azathioprine or 6-MP.
Severe uncontrolled infections (bacterial, viral, e.g. varicella, HSV, shingles).
Pregnancy: may be used with caution in some cases under specialist advice (risk vs benefit in transplant/IBD).

📚 References

BNF: Azathioprine
UK Specialist Pharmacy Service (SPS) monitoring guidance

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Azathioprine 💊