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Allopurinol, a xanthine oxidase inhibitor, is a urate-lowering medication that is FDA approved for managing gout, preventing tumor lysis syndrome, and preventing recurrent calcium nephrolithiasis in patients with hyperuricosuria. Other non-FDA-approved indications include Lesch-Nyhan syndrome-associated hyperuricemia and the prevention of recurrent uric acid nephrolithiasis. It is important to note that asymptomatic hyperuricemia is not an indication of allopurinol or any urate-lowering therapy. This activity outlines the indications, mechanism, pharmacology, contraindications, and adverse events associated with allopurinol drug therapy. Objectives: Identify the various indications, both approved and off-label, for allopurinol therapy. Describe the potential adverse effects of allopurinol. Summarize the mechanism of action of allopurinol. Review the importance of coordinating and collaborating among various disciplines in an interprofessional health team to coordinate care and management to enhance outcomes for patients receiving allopurinol therapy. Access free multiple choice questions on this topic.

Allopurinol is a relatively safe drug that has been used for over half a century. Still, recent studies in gout have shown significant underutilization of this agent and suboptimal dose use, insufficient to reach target serum uric acid concentrations in a considerable proportion of gout patients. A problem with allopurinol treatment for gout is therapy adherence. Emad Y. et al. found that the most common reason for lack of patient adherence to pharmacotherapy is: "patients wanting to lead a normal life."[17] This is an opportunity for healthcare professionals to improve pharmacotherapy adherence. Contrary to the common belief, recent studies have shown that allopurinol is safe in severe chronic kidney disease and can impede the progression of renal disease in patients with gout and chronic kidney disease.[18][19] Using allopurinol in patients with gout is also associated with lower all-cause mortality and other adverse cardiovascular events, including readmissions due to congestive heart failure.[19][20][21][22] American College of Rheumatology recommends allopurinol as one of the first-line agents of urate-lowering therapy for gout management. Several studies report that allopurinol reduced cardiovascular events. However, research by Suissa S. et al. concludes that these studies contained time-related biases and, thus, allopurinol does not provide cardiovascular protection.[23]

Contrary to the common belief, recent studies have shown that allopurinol is safe in severe chronic kidney disease and can impede the progression of renal disease in patients with gout and chronic kidney disease.[18][19] Using allopurinol in patients with gout is also associated with lower all-cause mortality and other adverse cardiovascular events, including readmissions due to congestive heart failure.[19][20][21][22] American College of Rheumatology recommends allopurinol as one of the first-line agents of urate-lowering therapy for gout management. Several studies report that allopurinol reduced cardiovascular events. However, research by Suissa S. et al. concludes that these studies contained time-related biases and, thus, allopurinol does not provide cardiovascular protection.[23] There are, however, potential rare though severe adverse effects associated with allopurinol. The use of allopurinol requires management by an interprofessional healthcare team that includes clinicians (MDs, DOs, NPs, PAs), nurses, and pharmacists. Clinicians initiating allopurinol therapy should ensure no drug interactions and that xanthine oxidase inhibitor therapy is the optimal choice; if necessary, a pharmacist consult can assist in this evaluation. Pharmacists can also verify dosing and provide additional patient counsel regarding how to take the drug. The nursing team shall assist with verifying patient adherence and helping to monitor for adverse events and therapeutic effectiveness. All team members should document their observations in the patient's permanent health record, and be prepared to reach out to other team members when necessary, so alterations to the therapeutic regimen can be made. The best chance for allopurinol to have therapeutic success with minimal adverse events is via an interprofessional team approach. [Level 5]