Applying Pharmacogenomics to Antifungal Selection and Dosing: Are We There Yet?

Abstract

This review summarizes recent literature for applying pharmacogenomics to antifungal selection and dosing, providing an approach to implementing antifungal pharmacogenomics in clinical practice. The Clinical Pharmacogenetics Implementation Consortium published guidelines on CYP2C19 and voriconazole, with recommendations to use alternative antifungals or adjust voriconazole dose with close therapeutic drug monitoring (TDM). Recent studies demonstrate an association between CYP2C19 phenotype and voriconazole levels, clinical outcomes, and adverse events. Additionally, CYP2C19-guided preemptive dose adjustment demonstrated benefit in two prospective studies for prophylaxis. Pharmacokinetic-pharmacodynamic modeling studies have generated proposed voriconazole treatment doses based on CYP2C19 phenotypes, with further validation studies needed. Sufficient evidence is available for implementing CYP2C19-guided voriconazole selection and dosing among select patients at risk for invasive fungal infections. The institution needs appropriate infrastructure for pharmacogenomic testing, integration of results in the clinical decision process, with TDM confirmation of goal trough achievement, to integrate antifungal pharmacogenomics into routine clinical care.