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Conventional DMARD — Purine Antimetabolite Pregnancy: D — evidence of fetal risk; use only if clearly needed. Compatible with breastfeeding per specialist guidance

Azathioprine (Rheumatology)

Brand names: Imuran, Azapress

Adult dose

Dose: 1–3 mg/kg/day
Route: Oral
Frequency: Once daily
Max: 3 mg/kg/day
Start at 1 mg/kg/day and titrate up over 4–8 weeks. Used as steroid-sparing agent in SLE, myositis, vasculitis, inflammatory arthritis. TPMT testing mandatory before initiation.

Paediatric dose

Dose: 1–3 mg/kg
Route: Oral
Frequency: Once daily
Max: 3 mg/kg/day
Used in paediatric SLE and inflammatory conditions under specialist guidance

Dose adjustments

Renal

Reduce dose in renal impairment — metabolites accumulate; consider 50% dose reduction if eGFR <10 mL/min

Hepatic

Use with caution; reduce dose in severe hepatic impairment; hepatotoxicity can occur

Paediatric weight-based calculator

Used in paediatric SLE and inflammatory conditions under specialist guidance

Clinical pearls

  • MHRA: TPMT (thiopurine methyltransferase) testing required before initiation — patients with absent TPMT activity (1 in 300) are at risk of life-threatening myelosuppression at standard doses
  • Hypersensitivity syndrome (flu-like illness, rash, hepatitis) occurs in ~5% within 4 weeks — do NOT rechallenge
  • Allopurinol interaction is one of the most clinically dangerous drug interactions in rheumatology — must not be co-prescribed without azathioprine dose reduction to 25%
  • TPMT heterozygotes (11%) — intermediate activity; reduce starting dose
  • Used as preferred maintenance therapy in SLE nephritis after cyclophosphamide induction (Houssiau protocol)

Contraindications

  • Absent TPMT activity (homozygous deficiency)
  • Concurrent allopurinol without dose reduction
  • Previous hypersensitivity to azathioprine or 6-mercaptopurine
  • Active severe infection
  • Pregnancy (relative — risk vs benefit)

Side effects

  • Myelosuppression — dose-dependent; TPMT-dependent
  • Nausea and vomiting (most common early)
  • Hepatotoxicity — elevated LFTs
  • Increased infection risk
  • Hypersensitivity syndrome (fever, rash, hepatitis) — usually within first 4 weeks
  • Long-term: increased risk of lymphoma and skin cancers

Interactions

  • Allopurinol — CRITICAL: inhibits xanthine oxidase, reduces azathioprine metabolism → 4-fold increase in toxicity. Reduce azathioprine to 25% dose or use alternative
  • Febuxostat — same mechanism as allopurinol; AVOID combination
  • Warfarin — azathioprine reduces anticoagulant effect
  • ACE inhibitors — enhanced leucopenia

Monitoring

  • TPMT activity before initiation
  • FBC weekly for first 8 weeks, then monthly
  • LFTs monthly for first 3 months, then 3-monthly
  • Signs of infection

Reference: BNFc; BNF 90; MHRA Drug Safety Update (TPMT testing); BSR/BHPR SLE Guidelines; Houssiau Protocol (ELNT Study). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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