Rasburicase (DB00049): A Comprehensive Monograph on its Pharmacology, Clinical Efficacy, and Safety in the Management of Hyperuricemia

Executive Summary

Rasburicase is a potent, recombinant urate oxidase enzyme that represents a cornerstone in the modern management of hyperuricemia, particularly in the context of Tumor Lysis Syndrome (TLS) secondary to chemotherapy. As a biotech therapeutic, it addresses a critical unmet need created by the limitations of traditional uricostatic agents. Its unique uricolytic mechanism of action—the direct enzymatic degradation of existing uric acid into the highly soluble metabolite allantoin—confers a significant therapeutic advantage, characterized by a remarkably rapid onset of action and profound efficacy. This allows for the swift resolution of life-threatening hyperuricemia, mitigating the risk of acute kidney injury and enabling the timely administration of aggressive anticancer regimens.

The clinical utility of Rasburicase is, however, balanced by a distinct and serious safety profile, underscored by several U.S. Food and Drug Administration (FDA) Black Box Warnings. The most critical of these is the absolute contraindication in patients with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, a pharmacogenomic consideration rooted directly in the drug's mechanism of action. The production of hydrogen peroxide as a byproduct of uric acid catalysis can precipitate severe hemolysis and methemoglobinemia in these susceptible individuals. Furthermore, its nature as a foreign protein carries an inherent risk of hypersensitivity and anaphylaxis.