Safety of Thiopurine Use in Paediatric Gastrointestinal Disease

Abstract

Thiopurines, alone or in combination with other agents, have a pivotal role in the treatment of specific gastrointestinal and hepatological disorders. In inflammatory bowel disease and autoimmune hepatitis thiopurines have proven their value as steroid sparing agents for the maintenance of remission and may be considered for preventing postoperative Crohn's disease recurrence where there is moderate risk of this occuring. Their use with infliximab therapy reduces antibody formation and increases biologic drug levels. However, the routine clinical use of thiopurines has been questioned due to a number of potential adverse effects.The aim of this paper is to provide information regarding the use, and in particular, safety of these agents in clinical practice in the light of such potentially severe, albeit rare, effects.

Drug‐Related Adverse Reactions in Pediatric Inflammatory Bowel Disease

“…ARs included hepatitis (including cholestatic hepatitis), pancreatitis, myelosuppression, and gastrointestinal intolerance; there was also 1 case of reported nephrotoxicity, which resolved after dose reduction. These results mirror the existing literature, except in the case of nephrotoxicity, which, so far, has not been described in patients with IBD being treated with azathioprine 26,28 . In all cases the drug had to be discontinued.…”

“…They are generally well tolerated by children but may cause dose‐dependent (bone marrow suppression and hepatotoxicity) or dose‐independent (nausea, pancreatitis, infection, malignancy) toxicities. Therefore, patients treated with these drugs require frequent monitoring 26,27 . Twelve ARs to azathioprine were identified in our study, corresponding to 16.0% of patients that were using immunomodulators and 75.0% of the total number of ARs.…”

“…Therefore, patients treated with these drugs require frequent monitoring. 26,27 Twelve ARs to azathioprine were identified in our study, corresponding to 16.0% of patients that were using immunomodulators and 75.0% of the total number of ARs. ARs included hepatitis (including cholestatic hepatitis), pancreatitis, myelosuppression, and gastrointestinal intolerance; there was also 1 case of reported nephrotoxicity, which resolved after dose reduction.…”

“…These results mirror the existing literature, except in the case of nephrotoxicity, which, so far, has not been described in patients with IBD being treated with azathioprine. 26,28 In all cases the drug had to be discontinued. These results differ from a single-center study of children with IBD (n = 233), in which 21.5% of patients discontinued thiopurine treatment because of ARs.…”