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Optimising use of thiopurines in inflammatory bowel disease
  1. Lawrence Sunder Raj,
  2. A Barney Hawthorne
  1. Department of Gastroenterology, University Hospital of Wales, Heath Park, Cardiff, UK
  1. Correspondence to Dr B Hawthorne, Department of Medicine, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, UK; barney.hawthorne{at}cardiffandvale.wales.nhs.uk

Abstract

Azathioprine (AZA) and 6-mercaptopurine (6-MP) are the most widely used immunosuppressive therapies in inflammatory bowel disease. Pretreatment measurement of thiopurine methyltransferase (TPMT) activity is recommended and although conventional practice is to use a dose of 2 mg/kg AZA (1 mg/kg 6-MP), higher doses of 2.5 mg/kg AZA or more may be required in some patients, particularly if TPMT activity is high. Dose raising is limited by toxicity, and a robust monitoring system is mandatory. Patients with side effects to AZA may tolerate 6-MP but pancreatitis is a contraindication to switching. Metabolite monitoring is not widely available but may be useful, particularly if non-compliance is possible or where metabolite shunting to 6-methylmercaptopurine is suspected, on the basis of non-response or toxicity. It may allow dose optimisation before switching to alternative immunosuppressants. The drug appears safe in pregnancy and breast feeding. Long term duration of therapy is a balance between benefits in relation to the underlying disease extent, activity and aggressiveness, and the risk of neoplasia, particularly lymphoma.

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Footnotes

  • Competing interest None.

  • Provenance and peer review Commissioned; externally peer reviewed.