Dosing, Toxicity and Drug Concentrations for Ganciclovir/Valganciclovir in Preterm and Low Birthweight Infants Treated for Cytomegalovirus.

Background: There is a lack of data regarding suitable dosage when administering intravenous ganciclovir (GCV) or oral valganciclovir (valGCV) to preterm and low birthweight infants with cytomegalovirus (CMV) disease.

Methods: Data were collected for infants born before 32 weeks gestation and/or weighing less than 1.8 kg treated for CMV disease with GCV or valGCV between 2016 and 2023.

Results: Twenty-four infants (58% males and 48% Asian ethnicity) with a median gestation of 31 weeks [interquartile range (IQR): 26.6-36.1], median weight of 950 g (IQR: 470-1692) and median age of 45 days (IQR: 6-84) at initiation of treatment were included. Seventeen infants were treated for symptomatic postnatal CMV and 7 for symptomatic congenital CMV. Most infants receiving GCV had 6 mg/kg twice daily dosing and most receiving valGCV had 16 mg/kg twice daily dosing. Fourteen infants had drug concentrations measured with combined geometric mean minimum blood plasma concentration (Cmin) of 2.44 mg/L and maximum blood plasma concentration of 7.98 mg/L for doses of 6 mg/kg GCV and 16 mg/kg valGCV, which is higher compared with term infants. The estimated area under the curve at 12 hours (AUC0-12h) was 54.34 mg × h/L, which doubled the value for term infants in a previous study. Notably, AUC0-12h had an inverse relationship with gestational age and weight. Infants with lower gestation and higher Cmin showed a higher tendency for more than 1 adverse effect.

Conclusions: GCV and valGCV use among preterm and very low birthweight infants with CMV disease resulted in a higher incidence of adverse events, increased AUC0-12h and elevated Cmin compared with term infants. Further pharmacokinetic studies are necessary to determine the ideal dosage in this population.