Thiopurine hepatotoxicity in inflammatory bowel disease: the role for adding allopurinol

Expert Opin Drug Saf. 2008 Sep;7(5):607-16. doi: 10.1517/14740338.7.5.607.

Abstract

Background: Immunomodulator therapy with the thiopurine analogues azathioprine or 6-mercaptopurine is commonly prescribed for the treatment of inflammatory bowel disease (IBD). Drug adverse effects and the lack of efficacy, however, commonly require withdrawal of therapy. Allopurinol, a xanthine oxidase inhibitor, was recently evaluated in its role in modifying thiopurine metabolism and improving drug efficacy in IBD.

Objective: This article reviews the role and safety of allopurinol co-therapy in the setting of thiopurine hepatotoxicity and/or non-responsiveness in IBD.

Methods: Published articles on thiopurines in the treatment of IBD were examined.

Conclusion: The addition of low dose allopurinol to dose-reduced thiopurine analogue seems safe but careful monitoring for adverse effects and profiling of thiopurine metabolites is essential. There is evidence of improved immunomodulator efficacy and reduced hepatotoxicity clinically but further confirmatory studies are required before more definitive treatment recommendations can be given.

Publication types

  • Review

MeSH terms

  • Allopurinol / administration & dosage
  • Allopurinol / pharmacology*
  • Azathioprine / administration & dosage
  • Azathioprine / adverse effects
  • Azathioprine / pharmacokinetics
  • Chemical and Drug Induced Liver Injury
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Monitoring / methods
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Inflammatory Bowel Diseases / drug therapy*
  • Liver Diseases / prevention & control
  • Mercaptopurine / administration & dosage
  • Mercaptopurine / adverse effects
  • Mercaptopurine / pharmacokinetics

Substances

  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • Allopurinol
  • Mercaptopurine
  • Azathioprine