CPIC Guideline Links CYP2C19 Genotype to Voriconazole Dosing
This Clinical Pharmacogenetics Implementation Consortium guideline provides evidence-based recommendations for adjusting voriconazole therapy according to CYP2C19 metaboliser status. Ultrarapid metabolisers achieve subtherapeutic trough levels, risking treatment failure, while poor metabolisers accumulate drug and face increased toxicity. For clinical laboratories, the guideline defines a clear actionable gene-drug pair that supports implementation of CYP2C19 genotyping as part of antifungal stewardship.
The original study
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C19 and Voriconazole Therapy.
- Authors
- Moriyama B, Obeng AO, Barbarino J, Penzak SR, Henning SA, Scott SA, et al.
- Journal
- Clinical pharmacology and therapeutics
- Type
- Journal Article, Practice Guideline, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't
- PMID
- 27981572
Original abstract
Voriconazole, a triazole antifungal agent, demonstrates wide interpatient variability in serum concentrations, due in part to variant CYP2C19 alleles. Individuals who are CYP2C19 ultrarapid metabolizers have decreased trough voriconazole concentrations, delaying achievement of target blood concentrations; whereas poor metabolizers have increased trough concentrations and are at increased risk of adverse drug events. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of voriconazole for treatment based on CYP2C19 genotype (updates at https://cpicpgx.org/guidelines/ and www.pharmgkb.org).