New CPIC Guideline: G6PD & Rasburicase

CPIC has published therapeutic guidelines for rasburicase based on G6PD genotype.

Rasburicase is a drug that lowers uric acid levels and is used to treat or prevent hyperuricemia in cancer patients undergoing chemotherapy, and in newborns to prevent kidney damage. It is contraindicated for use in patients with G6PD deficiency due to an increased risk of acute hemolytic anemia and possibly also methemoglobinemia. Reduced G6PD enzyme activity is caused by underlying genetic variants in the G6PD gene. There are more than 180 G6PD variants, each categorized class I to V depending on the level of deficiency in red blood cells conferred and the associated resulting clinical manifestations.  

To our knowledge, this is the first published guideline to fully address therapeutic recommendations for patients who have pre-emptive G6PD genotyping or sequencing results in both men and women, for a large collection of variants.

CPIC contraindicate the use of rasburicase in males or females who are hemi/homozygous for class I-III G6PD variants, respectively. For females heterozygous for class I-III G6PD variants, phenotype is variable due to X-linked mosaicism and thus an enzyme test is recommended prior to rasburicase use. An enzyme test to determine G6PD phenotype is also the recommendation for patients who have negative or inconclusive genetic results.

> View the CPIC guidelines for G6PD variants & rasburicase.

> Read the accepted article preview of the guideline manuscript:
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Rasburicase Therapy in the context of G6PD Deficiency Genotype.
Relling MV, McDonagh EM, Chang T, Caudle KE, McLeod HL, Haidar CE, Klein T, Luzzatto L.
Clin Pharmacol Ther. Accepted article preview online 02 May 2014 doi:10.1038/clpt.2014.97.

> Learn more about G6PD and drug response.

> Learn more about the mechanism underlying rasburicase-induced hemolytic anemia.