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.