CYP2C19 gene linked to voriconazole-related adverse reactions in children

Carriers of the CYP2C19 allele are at greater risk of voriconazole-induced thrombocytopenia and cholestasis, reports a Japan study.

Sixty paediatric patients were recruited between 2020 and 2022 for this study and received voriconazole. The authors then examined the occurrence of cholestasis and thrombocytopenia as adverse reactions of the study drug. They modelled voriconazole plasma levels in a previous study using a population pharmacokinetics approach. A Bayesian method was used to estimate missing values.

Furthermore, the authors obtained clinical and laboratory data before and after treatment with voriconazole, as well as analysed the CYP2C19*2, CYP2C19*3, and CYP2C19*17 alleles.

Of the patients (mean age 6.5 years, 53.3 percent male), 38 had haematological malignancies, 18 inborn errors of immunity, two solid tumours, and two other diseases. Twelve patients had adverse reactions.

The voriconazole plasma concentrations were significantly higher among patients with adverse reactions (mean normalized concentrations: 0.66 in cases vs ‒0.16 in controls; p=0.025). A trend towards higher concentrations was seen in carriers of the CYP2C19*2 or CYP2C19*3 alleles (mean normalized concentrations: 0.98 in carriers vs 0.016 in noncarriers; p=0.14).

A predictive model for voriconazole concentrations that included carriership of CYP2C19*2, CYP2C19*3, C-reactive protein levels, and platelet counts demonstrated 23.6-percent summed variance explained, with the variance attributable to CYP2C19*2 or CYP2C19*3 carrier status alone being 2.6 percent.

“Including carrier status improved the area under the receiver operating characteristic curve for predicting adverse reactions to 0.70,” the authors said.