Rasburicase is planned for a patient with tumour lysis syndrome and a urate of 18 mg/dL. Screening must be done before the first dose because rasburicase is absolutely contraindicated in:

• A Methaemoglobin reductase deficiency, due to ferricytochrome accumulation
• B Glucose-6-phosphate dehydrogenase deficiency, due to hydrogen peroxide generated during urate oxidation ✓
• C Hereditary xanthinuria, due to absent xanthine oxidase substrate
• D Lesch-Nyhan syndrome, due to complete HGPRT deficiency

Explanation

Rasburicase is a recombinant urate oxidase that converts uric acid to allantoin via an intermediate step that generates hydrogen peroxide. In G6PD deficiency, erythrocytes cannot reduce oxidised glutathione, so the peroxide causes severe haemolysis and methaemoglobinaemia. Testing for G6PD status before administration is mandatory, particularly in populations of African, Mediterranean or South Asian ancestry. Lesch-Nyhan syndrome and hereditary xanthinuria are not contraindications, and methaemoglobin reductase deficiency plays no role here.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.