Allopurinol enhanced thiopurine treatment for inflammatory bowel disease: Safety considerations and guidelines for use

Summary What is known and objective The thiopurine medications are standard inflammatory bowel disease treatments. Therapeutic failure is observed, however, often because of variable drug metabolism. Allopurinol can enhance the potency of thiopurine treatment. Our objective is to review the relevant literature, and our own experience, to determine if allopurinol enhancement of thiopurine treatment is a reasonable therapeutic strategy. Comment Published reports of, and our own experience using, allopurinol-thiopurine combination therapy indicate that the addition of allopurinol will enhance thiopurine treatment in up to 60% of patients. There are risks to this approach, but with appropriate monitoring, these risks should approximate those observed with thiopurine therapy alone. What is new and conclusion Combination therapy with allopurinol and a thiopurine is a reasonable alternative for inflammatory bowel disease patients not responding to thiopurine monotherapy. Physicians experienced in thiopurine treatment, who have familiarity with thiopurine metabolism, and are willing to engage in appropriate therapeutic monitoring, should consider this strategy. The thiopurines, 6-mercaptopurine (6-MP) and, its pro-drug, azathioprine (AZA), first described in the early 1950s, are purine analogues that are now important treatment options in the management of inflammatory bowel disease (IBD). First described as a treatment for ulcerative colitis in 1962, they have been shown to be effective in reducing steroid dependence and maintaining remission. Unfortunately, approximately 50-60% of patients on thiopurines eventually discontinue treatment due to adverse effects or lack of efficacy. Our objective is to review the efficacy and safety of allopurinol enhancement of thiopurine IBD treatment