Table 3.

Dosing recommendations for voriconazole treatment based on CYP2C19 phenotype for pediatric patients (children and adolescents <18 years old)

CYP2C19 phenotype	Implications for voriconazole pharmacologic measures	Therapeutic recommendations	Classification of Recommendationsa
CYP2C19 Ultrarapid Metabolizer (*17/*17)	In patients for whom an ultrarapid metabolizer genotype (*17/*17) is identified, the probability of attainment of therapeutic concentrations is small.	Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole. Such agents include liposomal amphotericin B, and posaconazole.b,c	Moderate
Rapid Metabolizer (*1/*17)	In patients for whom a rapid metabolizer genotype (*1/*17) is identified, the probability of attainment of therapeutic concentrations is variable.	Initiate therapy with recommended standard of care dosing.b Use therapeutic drug monitoring to titrate dose to therapeutic trough concentrations.c,d	Moderate
CYP2C19 Normal Metabolizer	Normal voriconazole metabolism	Initiate therapy with recommended standard of care dosing.b	Strong
CYP2C19 Intermediate Metabolizer	Higher dose-adjusted trough concentrations of voriconazole compared to normal metabolizers.	Initiate therapy with recommended standard of care dosing.b	Moderate
CYP2C19 Poor Metabolizer	Higher dose-adjusted trough concentrations of voriconazole and may increase probability of adverse events.	Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole. Such agents include liposomal amphotericin B and posaconazole.b, e In the event that voriconazole is considered to be the most appropriate agent, based on clinical advise, for a patient with poor metabolizer genotype, voriconazole should be administered at a preferably lower than standard dosage with careful therapeutic drug monitoring.	Moderatee

^aRating scheme is described in Supplementary Data online.

^bFurther dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, TDM, and comorbidities.

^cAchieving voriconazole therapeutic concentrations in the pediatric population with ultrarapid and rapid metabolizer phenotypes in a timely manner is difficult. As critical time may be lost in achieving therapeutic concentrations, an alternative antifungal agent is recommended in order that the child receives effective antifungal therapy as soon as possible.

^dMeticulous therapeutic drug monitoring is critical for rapid metabolizers. There is insufficient evidence to distinguish a CYP2C19*1/*17 and *1/*1 pediatric patient due to large variability in trough concentrations.

^eRecommendation based upon data extrapolated from adults.