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Thiopurine Immunosuppressant

Azathioprine 1–3mg/kg/day

Brand names: Imuran, Azapress

Adult dose

Dose: Renal transplant maintenance: 1–3 mg/kg once daily. Nephrotic syndrome/GN: 1–2 mg/kg/day. Autoimmune conditions: 50mg OD initially, titrate to 1–3 mg/kg/day.
Route: Oral
Frequency: Once daily
Max: 3 mg/kg/day (transplant); 2.5 mg/kg/day (autoimmune conditions)
Prodrug — converted to 6-mercaptopurine (6-MP) then active thioguanine nucleotides. TPMT enzyme activity determines dose tolerance — check before starting. Largely replaced by mycophenolate mofetil in renal transplantation but remains used in second-line for GN/vasculitis.

Paediatric dose

Dose: 1 mg/kg
Route: Oral
Frequency: Once daily
Max: 3 mg/kg/day
Concentration: 25 mg, 50 mg tablets; 50 mg/mL oral suspension (unlicensed) mg/ml
Paediatric renal transplant maintenance and nephrotic syndrome: 1–3 mg/kg OD. TPMT testing mandatory before starting. Specialist paediatric nephrology.

Dose adjustments

Renal

Reduce dose in renal impairment — metabolites accumulate; eGFR 10–50: 75% of dose; eGFR <10: 50% of dose

Hepatic

Caution in severe hepatic impairment — hepatotoxicity and impaired metabolism; monitor LFTs closely

Paediatric weight-based calculator

Paediatric renal transplant maintenance and nephrotic syndrome: 1–3 mg/kg OD. TPMT testing mandatory before starting. Specialist paediatric nephrology.

Clinical pearls

  • TPMT genotyping or phenotyping MANDATORY before starting — homozygous TPMT-deficient patients have life-threatening myelosuppression at normal doses; heterozygotes require dose reduction
  • Allopurinol interaction is potentially fatal — one of the most important drug interactions in clinical practice; if patient starts allopurinol, reduce azathioprine by 75% immediately
  • Nausea management: take with food or switch to divided doses; splitting to BD can improve tolerability
  • Monitoring frequency: FBC weekly for first 8 weeks, then monthly — neutropenia is the main dose-limiting toxicity
  • Pregnancy: classified as Pregnancy Prevention Programme drug by MHRA in some indications — seek specialist guidance; generally continues in renal transplant (benefit outweighs risk)

Contraindications

  • TPMT deficiency (homozygous — very high myelosuppression risk; avoid or use very low dose with specialist guidance)
  • Concurrent allopurinol without dose reduction (CRITICAL — allopurinol inhibits xanthine oxidase → azathioprine toxicity at normal doses; reduce azathioprine by 75% if combination essential)
  • Hypersensitivity

Side effects

  • Myelosuppression (leucopenia, thrombocytopenia, anaemia — dose-dependent and TPMT-dependent)
  • Hepatotoxicity (cholestasis, hepatitis — monitor LFTs)
  • Increased infection risk (opportunistic infections)
  • GI intolerance (nausea, vomiting — take with food)
  • Pancreatitis (rare)
  • Lymphoma risk (long-term)

Interactions

  • Allopurinol — MAJOR INTERACTION: allopurinol inhibits xanthine oxidase → azathioprine cannot be catabolised → myelosuppression (fatal cases reported; reduce azathioprine dose by 75% or avoid combination)
  • Warfarin — azathioprine reduces anticoagulant effect
  • Trimethoprim — additive myelosuppression
  • ACEi — additive leucopenia risk

Monitoring

  • FBC (weekly × 8 weeks; then every 3 months when stable)
  • LFTs (monthly)
  • TPMT activity (before starting)
  • Renal function
  • Signs of infection

Reference: BNFc; BNF; KDIGO Transplant Guidelines 2009; UK Renal Association; MHRA Drug Safety Update (azathioprine-allopurinol interaction). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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