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Pharmacology · Antiproliferative immunosuppressants

Azathioprine !

An older immunosuppressant tablet that becomes 6-mercaptopurine and stops immune cells multiplying. Blood counts are checked; allopurinol is a dangerous mix.

Updated 2026-11-01

Mechanism of action

Azathioprine is a prodrug of 6-mercaptopurine. It is converted to thioguanine nucleotides, which inhibit purine synthesis and are incorporated into DNA, so rapidly dividing lymphocytes cannot proliferate. 6-Mercaptopurine is inactivated by TPMT (methylation) and by xanthine oxidase (oxidation); low TPMT or NUDT15 activity, or blocking xanthine oxidase, lets active metabolites build up.

  1. Converted to 6-mercaptopurine
  2. Then to thioguanine nucleotides (active)
  3. Purine synthesis falls and the nucleotides enter DNA
  4. Lymphocytes cannot proliferate

Pharmacokinetics

Absorption
Well absorbed by mouth
Metabolism
Converted to 6-mercaptopurine; inactivated by TPMT and xanthine oxidase; toxicity is more likely with kidney impairment

Indications

Adverse effects

Common

  • Nausea and vomiting
  • Leukopenia
  • Raised liver enzymes
  • Rash

Contraindications

  • Hypersensitivity to azathioprine
  • Rheumatoid arthritis in pregnancy
  • Rheumatoid arthritis previously treated with alkylating agents (high risk of malignancy)

Key interactions

Allopurinol and febuxostat
Block xanthine oxidase: active metabolites accumulate and marrow toxicity can be severe; febuxostat is not used with it.
Aminosalicylates (sulfasalazine, mesalazine)
Inhibit TPMT; used with caution.
Warfarin
May weaken its anticoagulant effect.
Ribavirin and other marrow-suppressing drugs
Severe pancytopenia.

What is monitored

  • Complete blood count with platelets, often at first and then regularly
  • TPMT and NUDT15 testing before starting
  • Liver tests
  • Skin checks for cancer

Administration and safety

  • Oral tablet, usually after meals; taking it after meals or in divided doses can lessen nausea.
  • Taken at about the same times every day.

Nursing care

  • Ask about allopurinol or febuxostat before the first dose.
  • Check that TPMT and NUDT15 results are available.
  • Teach the signs of infection and bleeding: fever, sore throat, bruising.
  • Teach sun protection and skin checks.
  • Report severe nausea, vomiting, fever or abdominal pain soon after starting.

Pregnancy and breastfeeding

Can harm the fetus; it is contraindicated for rheumatoid arthritis in pregnancy, and in transplant recipients the treating team weighs it case by case.

Test yourself

Think of the answer, then tap the question to see it.

Which enzyme test is done before azathioprine, and why?

TPMT (and NUDT15) activity or genotype: deficient patients build up thioguanine nucleotides and develop severe myelotoxicity at usual doses.

A patient on azathioprine is given allopurinol for gout. What is the risk?

Allopurinol blocks xanthine oxidase, one of the routes that inactivate 6-mercaptopurine, so active metabolites accumulate and bone marrow suppression can be severe.

Which lymphoma is linked to azathioprine in young patients with inflammatory bowel disease?

Hepatosplenic T-cell lymphoma, a rare and aggressive lymphoma reported with azathioprine, some cases in patients who also received a TNF blocker.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Azathioprine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2023); DailyMed - AZATHIOPRINE tablet (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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