Azathioprine and allopurinol: A two‐edged interaction

The thiopurines, azathioprine and 6-mercaptopurine (6-MP), are immunosuppressive drugs used in a number of clinical settings, such as following transplantation and for the management of inflammatory conditions like inflammatory bowel disease (IBD). Allopurinol, a xanthine oxidase inhibitor used in the treatment of gout, is not infrequently coincidentally co-prescribed with the thiopurines. A recent safety report from the New South Wales Department of Health (NSW, Australia) highlights the potential risk with the co-administration of these two drugs. This commentary reviews the interaction of these drugs and highlights important precautions that should be taken by clinicians when using them together.

[1]  M. Schwartz,et al.  Long term efficacy and safety of allopurinol and azathioprine or 6-mercaptopurine in patients with inflammatory bowel disease. , 2009, Journal of Crohn's & colitis.

[2]  D. Collier,et al.  The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations. , 1999, Pharmacogenetics.

[3]  R. Gearry,et al.  Azathioprine and 6‐mercaptopurine pharmacogenetics and metabolite monitoring in inflammatory bowel disease , 2005, Journal of gastroenterology and hepatology.

[4]  J. Berg,et al.  Ethnic variation of thiopurine S-methyltransferase activity: a large, prospective population study. , 2008, Pharmacogenomics.

[5]  W. Bishop,et al.  Initial clinical experience with allopurinol‐thiopurine combination therapy in pediatric inflammatory bowel disease , 2008, Inflammatory bowel diseases.

[6]  A. Ginsberg,et al.  Use of allopurinol with low-dose 6-mercaptopurine in inflammatory bowel disease to achieve optimal active metabolite levels: a review of four cases and the literature. , 2008, Canadian journal of gastroenterology = Journal canadien de gastroenterologie.

[7]  S. Targan,et al.  6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. , 2002, Gastroenterology.

[8]  E. Sprecher,et al.  Distribution of TPMT risk alleles for thioupurine toxicity in the Israeli population , 2009, European Journal of Clinical Pharmacology.

[9]  J. Sanderson,et al.  Long‐term outcome of using allopurinol co‐therapy as a strategy for overcoming thiopurine hepatotoxicity in treating inflammatory bowel disease , 2008, Alimentary pharmacology & therapeutics.

[10]  S. Hanauer,et al.  Allopurinol safely and effectively optimizes tioguanine metabolites in inflammatory bowel disease patients not responding to azathioprine and mercaptopurine , 2005, Alimentary pharmacology & therapeutics.

[11]  R. Gearry,et al.  Severe hepatotoxicity with high 6-methylmercaptopurine nucleotide concentrations after thiopurine dose escalation due to low 6-thioguanine nucleotides. , 2008, European journal of gastroenterology & hepatology.

[12]  S. Hanauer,et al.  Effect of allopurinol on clinical outcomes in inflammatory bowel disease nonresponders to azathioprine or 6-mercaptopurine. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[13]  H. Simmonds,et al.  Low-dose allopurinol plus azathioprine/ cyclosporin/prednisolone, a novel immunosuppressive regimen , 1993, The Lancet.

[14]  M. Hiratsuka,et al.  Functional characterization of human xanthine oxidase allelic variants , 2008, Pharmacogenetics and genomics.

[15]  R. Gearry,et al.  Thiopurine hepatotoxicity in inflammatory bowel disease: the role for adding allopurinol. , 2008, Expert opinion on drug safety.