Drug Action
Azathioprine is metabolised to mercaptopurine.
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Drug reference
Azathioprine is metabolised to mercaptopurine.
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Severe acute Crohn’s disease | Maintenance of remission of Crohn’s disease | Maintenance of remission of acute ulcerative colitis ▶BY MOUTH ▶Adult: 2–2.5 mg/kg daily, some patients may respond to lower doses Rheumatoid arthritis that has not responded to other disease-modifying drugs | Severe systemic lupus erythematosus and other connective tissue disorders | Polymyositis in cases of corticosteroid resistance ▶BY MOUTH ▶Adult: Initially up to 2.5 mg/kg daily in divided doses, adjusted according to response, rarely more than 3 mg/kg daily; maintenance 1–3 mg/kg daily, consider withdrawal if no improvement within 3 months Autoimmune conditions ▶BY MOUTH, OR BY INTRAVENOUS INJECTION, OR BY INTRAVENOUS INFUSION ▶Adult: 1–3 mg/kg daily, adjusted according to response, consider withdrawal if no improvement within 3 months, oral administration preferable, if not possible then can be given by intravenous injection (intravenous solution very irritant) or by intravenous infusion Suppression of transplant rejection ▶BY MOUTH, OR BY INTRAVENOUS INJECTION, OR BY INTRAVENOUS INFUSION ▶Adult: 1–2.5 mg/kg daily, adjusted according to response, oral administration preferable, if not possible then can be given by intravenous injection (intravenous solution very irritant) or by intravenous infusion Severe refractory eczema, normal or high TPMT activity ▶BY MOUTH continued → ▶Adult: 1–3 mg/kg daily Severe refractory eczema, intermediate TPMT activity ▶BY MOUTH ▶Adult: 0.5–1.5 mg/kg daily Generalised myasthenia gravis ▶BY MOUTH, OR BY INTRAVENOUS INJECTION, OR BY INTRAVENOUS INFUSION ▶Adult: Initially 0.5–1 mg/kg daily, then increased to 2–2.5 mg/kg daily, dose is increased over 3–4 weeks, azathioprine is usually started at the same time as the corticosteroid and allows a lower maintenance dose of the corticosteroid to be used, oral administration preferable, if not possible then can be given by Immune system and malignant disease intravenous injection (intravenous solution very irritant) or by intravenous infusion
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DUE TO INTERACTIONS ▶Manufacturer advises reduce dose to one-quarter of the usual dose with concurrent use of allopurinol. l UNLICENSED USE Azathioprine doses given in BNF for suppression of transplant rejection and autoimmune conditions may differ from those in product literature. Use for severe refractory eczema is unlicensed.
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▶When used for severe refractory eczema absent thiopurine methyltransferase (TPMT) activity. very low thiopurine methyltransferase (TPMT) activity
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Reduce dose in elderly. reduced thiopurine methyltransferase activity
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Contra-indicated in hypersensitivity to mercaptopurine.
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Thiopurine methyltransferase The enzyme thiopurine methyltransferase (TPMT) metabolises thiopurine drugs (azathioprine, mercaptopurine, tioguanine); the risk of myelosuppression is increased in patients with reduced activity of the enzyme, particularly for the few individuals in whom TPMT activity is undetectable. Consider measuring TPMT activity before starting azathioprine, mercaptopurine, or tioguanine therapy. Patients with absent TPMT activity should not receive thiopurine drugs; those with reduced TPMT activity may be treated under specialist supervision.
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→Appendix 1: azathioprine
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GENERAL SIDE-EFFECTS ▶Common or very common Bone marrow depression (dose- related). increased risk of infection. leucopenia. pancreatitis. thrombocytopenia ▶Uncommon Anaemia. hepatic disorders. hypersensitivity ▶Rare or very rare Agranulocytosis. alopecia. bone marrow disorders. diarrhoea. gastrointestinal disorders. neoplasms. photosensitivity reaction. pneumonitis. severe cutaneous adverse reactions (SCARs) ▶Frequency not known Nodular regenerative hyperplasia. sinusoidal obstruction syndrome SPECIFIC SIDE-EFFECTS ▶With oral use Nausea SIDE-EFFECTS, FURTHER INFORMATION Side-effects may require drug withdrawal. Hypersensitivity reactions Hypersensitivity reactions (including malaise, dizziness, vomiting, diarrhoea, fever, rigors, myalgia, arthralgia, rash, hypotension and renal dysfunction) call for immediate withdrawal. Neutropenia and thrombocytopenia Neutropenia is dose-dependent. Management of neutropenia and thrombocytopenia requires careful monitoring and dose adjustment. Nausea Nausea is common early in the course of treatment and usually resolves after a few weeks without an alteration in dose. Moderate nausea can be managed by using divided daily doses, taking doses after food, prescribing concurrent antiemetics or temporarily reducing the dose.
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Transplant patients immunosuppressed with azathioprine should not discontinue it on becoming pregnant. However, there have been reports of premature birth and low birth-weight following exposure to azathioprine, particularly in combination with corticosteroids. Spontaneous abortion has been reported following maternal or paternal exposure. Azathioprine is teratogenic in animal studies. The use of azathioprine during pregnancy needs to be supervised in specialist units. Treatment should not generally be initiated during pregnancy.
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Present in milk in low concentration. No evidence of harm in small studies—use if potential benefit outweighs risk.
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Manufacturer advises caution (impaired metabolism)—monitor liver function and complete blood count more frequently in those with severe impairment. Dose adjustments Manufacturer advises use doses at lower end of the dose range in hepatic failure; reduce dose if hepatic or haematological toxicity occur.
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Dose adjustments Reduce dose.
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▶Monitor for toxicity throughout treatment. ▶Monitor full blood count weekly (more frequently with higher doses or if severe renal impairment) for first 4 weeks (manufacturer advises weekly monitoring for 8 weeks but evidence of practical value unsatisfactory), thereafter reduce frequency of monitoring to at least every 3 months. ▶Blood tests and monitoring for signs of myelosuppression are essential in long-term treatment.
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▶With intravenous use For intravenous injection, give over at least 1 minute (followed by 50 mL sodium chloride intravenous infusion). For intravenous infusion (Imuran ®), give intermittently in Glucose 5% or Sodium Chloride 0.9%. Reconstitute 50 mg with 5–15 mL Water for Injections; dilute requisite dose to a volume of 20–200 mL with infusion fluid. Intravenous injection is alkaline and very irritant, intravenous route should therefore be used only if oral route not feasible.
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There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: capsule, oral suspension, oral solution Tablet CAUTIONARY AND ADVISORY LABELS 21 ▶Azathioprine (Non-proprietary) Azathioprine 25 mg Azathioprine 25mg tablets | 28 tablet P £6.64 DT = £1.89 | 100 tablet P £8.98–£33.26 Azathioprine 50 mg Azathioprine 50mg tablets | 56 tablet P £7.28 DT = £2.57 | 100 tablet P £4.65–£16.55 ▶Azapress (Ennogen Pharma Ltd) Azathioprine 50 mg Azapress 50mg tablets | 56 tablet P £2.83 DT = £2.57 ▶Imuran (Aspen Pharma Trading Ltd) Azathioprine 25 mg Imuran 25mg tablets | 100 tablet P £10.99 Azathioprine 50 mg Imuran 50mg tablets | 100 tablet P £7.99 Powder for solution for injection ▶Imuran (Aspen Pharma Trading Ltd) Azathioprine 50 mg Imuran 50mg powder for solution for injection vials | 1 vial P £15.38 IMMUNOSUPPRESSANTS › CALCINEURIN INHIBITORS AND RELATED DRUGS
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Bone marrow suppression Patients and their carers should be warned to report immediately any signs or symptoms of bone marrow suppression e.g. inexplicable bruising or bleeding, infection.
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2–2.5 mg/kg daily, some patients may respond
First-line fragment. Read the complete Indications and Dose section above.
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Initially up to 2.5 mg/kg daily in divided doses,
First-line fragment. Read the complete Indications and Dose section above.
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1–3 mg/kg daily, adjusted according to response,
First-line fragment. Read the complete Indications and Dose section above.
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1–2.5 mg/kg daily, adjusted according to
First-line fragment. Read the complete Indications and Dose section above.
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1–3 mg/kg daily
First-line fragment. Read the complete Indications and Dose section above.
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0.5–1.5 mg/kg daily
First-line fragment. Read the complete Indications and Dose section above.
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Initially 0.5–1 mg/kg daily, then increased to
First-line fragment. Read the complete Indications and Dose section above.
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