Efficacy, safety, and pharmacokinetics of oral valganciclovir in patients with congenital cytomegalovirus infection.

ABSTRACT

OBJECTIVES: Valganciclovir (VGCV) has been shown to improve sensorineural hearing loss (SNHL) and neurological outcomes in patients with neonatal symptomatic congenital cytomegalovirus (cCMV) infection. However, reports on the pharmacokinetics, efficacy and safety of oral VGCV are limited. The aim of this study is to evaluate the pharmacokinetics of VGCV for use in the treatment of cCMV. METHODS: This was a single-center, retrospective observational study conducted at Saitama Children's Medical Center in Japan between 2012 and 2017. CMV DNA copy number, maximum plasma VGCV concentration (Cmax), and adverse events (ADEs) during treatment were evaluated. RESULTS: A total of 26 patients with cCMV who received VGCV were included in this study. The median age at VGCV initiation was 9.5 months (range 0-46). Twenty-one patients (81%) had SNHL at baseline. Of these, five patients (19%) presented with improved SNHL, and none experienced worsened SNHL during treatment. The mean VGCV Cmax was 3.5 µg/mL (range 2-5.3), with no significant variation among individual values, and the values were maintained during treatment. Furthermore, there were no correlations between the Cmax values and age, sex, SNHL improvement or ADEs. Neutropenia (<1000/mm3) was observed in six patients (23%); however, no serious ADEs occurred. CONCLUSIONS: VGCV prevented the progression of SNHL without serious ADEs due to its stable pharmacokinetics. This study provides safety and tolerability of VGCV for the treatment of cCMV patients.