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Drug Reference

azathioprine

immunosuppressant· Brands: Imuran, AzasanIVPO

Mechanism of action
Azathioprine is a prodrug that is converted to 6-mercaptopurine, which inhibits DNA synthesis by interfering with purine metabolism. This results in suppression of lymphocyte proliferation, particularly T cells, and reduces immune responses.
Pharmacokinetics
Azathioprine is well absorbed after oral administration and undergoes extensive hepatic metabolism to the active metabolite. It is metabolised by xanthine oxidase and thiopurine methyltransferase, and is excreted mainly in the urine. The half-life is approximately 2 to 3 hours, but active metabolites persist longer.
Indications & dosing

Prevention of organ transplant rejection

Start at 1-2 mg/kg/day, titrate to 3 mg/kg/day based on renal function and toxicity. Dose adjusted to maintain therapeutic effect.

  • adult · PO: 1–3 mg/kg/day Once daily · Start at 1-2 mg/kg/day, titrate to 3 mg/kg/day based on renal function and toxicity. Dose adjusted to maintain therapeutic effect.

Rheumatoid arthritis

Slowly titrate; monitor for myelosuppression. May take up to 3 months for full effect.

  • adult · PO: 1–2.5 mg/kg/day Once daily · Slowly titrate; monitor for myelosuppression. May take up to 3 months for full effect.

Crohn's disease

Used for maintenance of remission. Consider TPMT genotyping before starting.

  • adult · PO: 2–2.5 mg/kg/day Once daily · Used for maintenance of remission. Consider TPMT genotyping before starting.

Ulcerative colitis

Used as steroid-sparing agent for maintenance. Monitor blood counts regularly.

  • adult · PO: 2–2.5 mg/kg/day Once daily · Used as steroid-sparing agent for maintenance. Monitor blood counts regularly.

Systemic lupus erythematosus (lupus nephritis)off-label

Off-label use; often as adjunct to corticosteroids. Monitor for cytopenias.

  • adult · PO: 1–2.5 mg/kg/day Once daily · Off-label use; often as adjunct to corticosteroids. Monitor for cytopenias.
Contraindications & precautions
  • Hypersensitivity to azathioprine or mercaptopurine
  • Severe active infection
  • Severe bone marrow suppression
  • Live vaccines · Avoid live vaccines during immunosuppression.
  • Pregnancy · Only if benefit outweighs risk; consider alternative therapy.
  • Concurrent allopurinol without dose adjustment · Dose reduction required, usually to 25% of standard dose.
  • Monitor full blood count weekly during initial treatment, then every 1 to 3 months.
  • Check thiopurine methyltransferase (TPMT) status before starting therapy to assess risk of myelotoxicity.
  • Reduce azathioprine dose by 75% when given with allopurinol, or avoid the combination.
  • Avoid live vaccines (e.g. BCG, MMR) during immunosuppressive therapy.
  • Advise effective contraception for men and women of childbearing potential.
  • Monitor liver function tests; discontinue if evidence of hepatotoxicity.
Adverse effects
  • Myelosuppression (leucopenia, thrombocytopenia, anaemia)serious
  • Infections (bacterial, fungal, viral)serious
  • Nausea, vomiting, diarrhoea
  • Hepatotoxicity (raised transaminases, cholestatic jaundice)serious
  • Pancreatitisserious
  • Lymphoma and other malignancies (especially skin cancer)serious
  • Alopecia
  • Hypersensitivity reactions (fever, rash, arthralgia)
Interactions
  • trimethoprimmajorAvoid concurrent use unless absolutely necessary. If co-prescribed, consider alternative antibiotics with a more favourable profile. If no alternative is feasible, reduce the azathioprine dose, monitor full blood count closely (weekly for the first month, then at least twice monthly), and advise patients to report symptoms of infection or bleeding. Consider TPMT genotyping if not already done.
  • allopurinolmajorAvoid co-prescription. If unavoidable, reduce the azathioprine dose to approximately one quarter of the usual dose and monitor full blood count closely, especially during the first few weeks of therapy. Consider alternative agents or use of allopurinol with a different immunosuppressant.
  • febuxostatcontraindicatedThe combination is contraindicated. Do not prescribe febuxostat with azathioprine. If no alternative urate-lowering therapy is suitable, consider referral to a specialist for management. If combination is deemed absolutely necessary despite the contraindication, extreme caution is required, with substantial dose reduction of azathioprine and frequent monitoring of full blood counts; however, this is rarely acceptable clinical practice.
Renal & hepatic adjustment
  • Hepatic impairment (mild): No dose adjustment required; monitor liver function.
  • Hepatic impairment (moderate): Use with caution; consider reducing the dose.
  • Hepatic impairment (severe): Avoid use; consider alternative immunosuppressant. (avoid)
Monitoring, pregnancy & toxicity
  • Full blood count (FBC) · Weekly for the first 8 weeks, then monthly
  • Liver function tests (LFTs) · At baseline, then periodically (e.g., 3-monthly)
  • TPMT genotype or enzyme activity · Before starting treatment
  • Signs of infection or bleeding · At each visit
  • Pregnancy: Azathioprine may be used in pregnancy when clearly indicated, with the lowest effective dose. There is a small risk of fetal anomalies; specialist advice should be sought. Uncontrolled disease also carries risk.
  • Toxicity: Myelosuppression (leukopenia, thrombocytopenia, anaemia) · Stop or reduce dose, monitor FBC, manage infections, consider granulocyte colony-stimulating factor (G-CSF) in severe neutropenia.
  • Toxicity: Hepatotoxicity (elevated transaminases, cholestasis) · Stop or reduce dose, monitor LFTs, exclude other causes.
  • Toxicity: Pancreatitis · Withdraw azathioprine, provide supportive care, monitor serum lipase.
  • Toxicity: Malignancy (especially skin cancer and lymphoma) · Regular skin examination, sun protection, monitor for lymphadenopathy.
Clinical notes
Use is indicated for organ transplant maintenance and autoimmune conditions such as rheumatoid arthritis and inflammatory bowel disease. Monitor blood counts and liver function regularly, as myelosuppression and hepatotoxicity can occur. Check thiopurine methyltransferase (TPMT) status before starting, and reduce dose if allopurinol is co-prescribed, because it inhibits xanthine oxidase and increases toxicity.

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BNF; local formulary