Mercaptopurine 💊
📖 About
Always refer to the British National Formulary (BNF) for up-to-date information on mercaptopurine.
Check the BNF link here.
⚡ Mode of Action
- Mercaptopurine is a purine analogue → inhibits purine synthesis, disrupting DNA/RNA replication.
- It suppresses the immune system by targeting rapidly dividing cells such as lymphocytes.
- Classed as an antimetabolite and cytotoxic immunosuppressant.
💊 Indications & Dose
- Ulcerative Colitis / Crohn’s Disease: used as a steroid-sparing agent in IBD.
- Dosing:
- Normal TPMT: 1–1.5 mg/kg once daily orally.
- Start at ~50% target dose for 1 week to reduce early toxicity.
- Low TPMT: ⚠️ much lower dose needed - discuss with specialist due to high risk of myelosuppression.
- Absent TPMT activity: ❌ contraindicated (severe, life-threatening marrow toxicity risk).
🤝 Interactions
- Allopurinol/febuxostat: markedly increase mercaptopurine levels → severe myelosuppression; dose must be reduced if co-prescribed.
- Other immunosuppressants (e.g. azathioprine, cyclophosphamide): additive marrow suppression.
- Refer to the BNF for the full list.
⚠️ Cautions
- Increased infection risk due to immunosuppression (counsel patients re: fever, sore throat, bruising).
- Monitor closely for bone marrow suppression and hepatotoxicity.
- Adjust dose in renal or hepatic impairment.
- Vaccination advice: avoid live vaccines during treatment.
🚫 Contraindications
- Known hypersensitivity to mercaptopurine.
- Pregnancy & breastfeeding - specialist advice required (teratogenic potential).
- Absent TPMT activity.
- Refer to the BNF for full details.
💥 Side Effects
- Haematological: Bone marrow suppression (leucopenia, thrombocytopenia, anaemia).
- Hepatic: Hepatotoxicity (elevated LFTs, hepatic necrosis, cholestasis).
- GI: Nausea, anorexia, vomiting, oral ulcers; rarely GI ulceration.
- Hypersensitivity: Fever, rash, arthralgia, rigors.
- Other: Pancreatitis (idiosyncratic), alopecia, CNS effects (headache, drowsiness, blurred vision).
📊 Monitoring (UK Practice)
- Baseline: FBC, LFTs, U&E, TPMT assay.
- Then: FBC & LFTs weekly for 4 weeks, then every 2–3 months (shared care in IBD/RA).
- Stop if significant leucopenia, neutropenia, or hepatotoxicity develops.
📚 References
