Azathioprine 💊

⚠️ 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)

⚠️ 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