New antifungal guidelines highlight CYP2C19 testing for voriconazole
Voriconazole is an azole antifungal used to treat serious fungal infections. It is metabolized primarily by the CYP2C19 enzyme and genetic polymorphisms in the CYP2C19 gene account for a large portion of variability in voriconazole exposure.
Consensus guidelines for optimizing antifungal therapy in patients treated for cancer were recently released by the Royal Australasian College of Physicians. In addition to other clinical guidance, these recommendations address the use of pharmacogenomic data with voriconazole.
Guideline authors performed a literature review using PubMed and Medline to identify papers published since 2007 that addressed questions regarding antifungal drug interactions, toxicities, therapeutic drug monitoring, and pharmacogenomics. Authors wrote that availability of point-of-care CYP2C19 testing with voriconazole use may inform clinicians’ ability to:
- Predict risk of voriconazole toxicity;
- Estimate the impact of potential drug interactions between voriconazole and chemotherapy agents, specifically in CYP2C19 poor metabolizers;
- Investigate strategies for patients with subtherapeutic voriconazole levels (i.e., in CYP2C19 ultrarapid and extensive metabolizers); and
- Develop voriconazole dose-titration algorithms.
“These potential applications should inform future research exploring the clinical utility and relevance of CYP2C19 genotyping,” guideline authors wrote.
Dosing guidelines for voriconazole and CYP2C19 have previously been published by the Dutch Pharmacogenetics Working Group. The Clinical Pharmacogenetics Implementation Consortium identifies this gene-drug pair as Level A (i.e., preponderance of evidence is high or moderate in favor of changing prescribing) and supporting evidence is categorized by the Pharmacogenomics KnowledgeBase (PharmGKB) as Level 2A.
Chau MM et al. Consensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy, 2014. Internal Medicine Journal. 2014;44:1364-88.