A Comprehensive Clinical and Pharmacological Monograph of Allopurinol (DB00437)

Executive Summary

Allopurinol is a cornerstone therapeutic agent in the long-term management of disorders caused by hyperuricemia. As a first-line xanthine oxidase inhibitor, its primary function is to decrease the production of uric acid in the body. The therapeutic efficacy of allopurinol is predominantly mediated by its principal active metabolite, oxipurinol, which possesses a significantly longer half-life and provides sustained inhibition of the terminal enzymatic steps in purine catabolism.

The United States Food and Drug Administration (FDA) has approved allopurinol for three primary clinical indications: the management of chronic gout, including gouty arthritis and tophaceous disease; the prevention of acute uric acid nephropathy and severe hyperuricemia associated with tumor lysis syndrome (TLS) during cancer chemotherapy; and the management of recurrent calcium oxalate kidney stones in patients with hyperuricosuria.

Despite its widespread use and established efficacy, the safety profile of allopurinol requires careful clinical consideration. The most critical safety concern is the risk of rare but potentially fatal Severe Cutaneous Adverse Reactions (SCARs), including Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). A strong pharmacogenomic association has been established between the risk of these reactions and the presence of the Human Leukocyte Antigen (HLA)-B*58:01 allele, which is found with higher prevalence in individuals of certain Asian and African ancestries.