Use of thiopurines in inflammatory bowel disease: Safety issues

Abstract

Thiopurines are widely used for maintenance treatment of inflammatory bowel disease. Inter-individual variability in clinical response to thiopurines may be attributed to several factors including genetic polymorphisms, severity and chronicity of disease, comorbidities, duration of administration, compliance issues and use of concomitant medication, environmental factors and clinician and patient preferences. The purpose of this review is to summarise the current evidence on thiopurine safety and toxicity, to describe adverse drug events and emphasise the significance of drug interactions, and to discuss the relative safety of thiopurine use in adults, elderly patients, children and pregnant women. Thiopurines are safe to use and well tolerated, however dose adjustment or discontinuation of treatment must be considered in cases of non-response, poor compliance or toxicity. Drug safety, clinical response to treatment and short to long term risks and benefits must be balanced throughout treatment duration for different categories of patients. Treatment should be individualised and stratified according to patient requirements. Enzymatic testing prior to treatment commencement is advised. Surveillance with regular clinic follow-up and monitoring of laboratory markers is important. Data on long term efficacy, safety of thiopurine use and interaction with other disease modifying drugs are lacking, especially in paediatric inflammatory bowel disease. High quality, collaborative clinical research is required so as to inform clinical practice in the future.

Keywords: Thiopurines; Azathioprine; Mercaptopurine; Inflammatory bowel disease; Adult; Children; Therapeutic drug monitoring

Core tip: This review summarises the safety issues around thiopurine use in adult and paediatric inflammatory bowel disease. Adverse drug effects, toxicity and malignancy risks, interactions with concomitant medications, clinical and laboratory drug surveillance and value of pharmacogenetics in therapeutic drug monitoring are discussed.