Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C19 and Voriconazole Therapy

B Moriyama; A Owusu Obeng; J Barbarino; S R Penzak; S A Henning; S A Scott; Jag Agúndez; J R Wingard; H L McLeod; T E Klein; S J Cross; K E Caudle; T J Walsh

doi:10.1002/cpt.583

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C19 and Voriconazole Therapy

Clin Pharmacol Ther. 2017 Jul;102(1):45-51. doi: 10.1002/cpt.583. Epub 2017 Apr 18.

Authors

B Moriyama¹, A Owusu Obeng^{2

3

4}, J Barbarino⁵, S R Penzak⁶, S A Henning¹, S A Scott^{2

7}, Jag Agúndez⁸, J R Wingard⁹, H L McLeod¹⁰, T E Klein⁵, S J Cross^{11

12}, K E Caudle¹¹, T J Walsh¹³

Affiliations

¹ National Institutes of Health Clinical Center Pharmacy Department, Bethesda, Maryland, USA.
² The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
³ Department of Pharmacy, The Mount Sinai Hospital, New York, New York, USA.
⁴ Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁵ Department of Genetics, Stanford University, Stanford, California, USA.
⁶ Department of Pharmacotherapy, University of North Texas, System College of Pharmacy, Fort Worth, Texas, USA.
⁷ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁸ Department of Pharmacology, University of Extremadura, Cáceres, Spain.
⁹ University of Florida College of Medicine, Gainesville, Florida, USA.
¹⁰ DeBartolo Family Personalized Medicine Institute, Division of Population Sciences, Moffitt Cancer Center, Tampa, Florida, USA.
¹¹ Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
¹² Department of Clinical Pharmacy, University of Tennessee College of Pharmacy, Memphis, Tennessee, USA.
¹³ Transplantation-Oncology Infectious Diseases Program, Departments of Medicine, Pediatrics, and Microbiology and Infectious Diseases, Weill Cornell Medical Center of Cornell University, New York, New York, USA.

PMID: 27981572
PMCID: PMC5474211
DOI: 10.1002/cpt.583

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).

Publication types

Practice Guideline
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Antifungal Agents / pharmacokinetics
Antifungal Agents / therapeutic use
Cytochrome P-450 CYP2C19 / genetics*
Dose-Response Relationship, Drug
Drug-Related Side Effects and Adverse Reactions* / metabolism
Drug-Related Side Effects and Adverse Reactions* / prevention & control
Genotyping Techniques / methods*
Humans
Metabolic Clearance Rate / physiology*
Patient Selection
Pharmacogenomic Variants / genetics
Risk Assessment / methods
Voriconazole* / pharmacokinetics
Voriconazole* / therapeutic use

Substances

Antifungal Agents
CYP2C19 protein, human
Cytochrome P-450 CYP2C19
Voriconazole

Abstract

Publication types

MeSH terms

Substances

Grants and funding