Rasburicase is used in tumour lysis syndrome to lower uric acid. It is absolutely contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency because:

• A It competitively inhibits G6PD, worsening enzyme deficiency
• B Rasburicase undergoes N-hydroxylation by G6PD into a haemolytic intermediate
• C Hydrogen peroxide generated as a by-product of urate oxidation causes oxidative haemolysis in G6PD-deficient erythrocytes ✓
• D G6PD deficiency impairs hepatic glucuronidation of rasburicase causing drug accumulation

Explanation

Rasburicase (recombinant urate oxidase) converts uric acid to allantoin, simultaneously generating hydrogen peroxide (H2O2). In normal red cells, glutathione peroxidase (dependent on NADPH from G6PD) neutralises H2O2. In G6PD-deficient erythrocytes, NADPH is unavailable, H2O2 accumulates, causing oxidative haemolysis and methaemoglobinaemia. Therefore, G6PD status must be checked before rasburicase administration.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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