Ganciclovir/valganciclovir tied to adverse effects in preterm infants with CMV

03 Apr 2025 byStephen Padilla
Ganciclovir/valganciclovir tied to adverse effects in preterm infants with CMV

Preterm and very low birthweight (VLBW) infants who have been treated with ganciclovir (GCV) or oral valganciclovir (valGCV) for cytomegalovirus (CMV) disease are more likely to experience adverse events than term infants, a study has shown.

In addition, the use of GCV and valGCV in this population results in higher area under the curve at 12 hours (AUC0–12h) and minimum blood plasma concentration (Cmin).

“The pharmacokinetic (PK) data and toxicity profile suggest that the 6-mg/kg GCV and 16-mg/kg valGCV twice daily dosing regime is too high for preterm and VLBW infants,” the investigators said. “Given the heterogeneity in PK, we anticipate that multiple-dose brackets with increasing gestational age and weight may be necessary.”

This study obtained data for infants born before 32 weeks gestation and/or weighing <1.8 kg treated for CMV disease with either GCV or valGCV between 2016 and 2023. Twenty-four infants (median age 45 days) with a median gestation of 31 weeks and a median weight of 950 g at initiation of treatment were included in the analysis.

Of these, 17 received treatment for symptomatic postnatal CMV and seven for symptomatic congenital CMV. Most infants receiving GCV and valGCV had 6- and 16-mg/kg twice daily dosing, respectively. [Pediatr Infec Dis J 2025;44:319-325]

“Fourteen infants had drug concentrations measured with combined geometric mean Cmin of 2.44 mg/L and maximum blood plasma concentration (Cmax) 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 investigators said.

“The estimated AUC0–12h was 54.34 mg × h/L, which doubled the value for term infants in a previous study,” they added.

AUC0–12h was inversely associated with gestational age and weight. Notably, infants who had lower gestation and higher Cmin were more likely to experience more than one adverse effect.

“Future research should focus on developing and validating dosing regimens through PK modelling and simulation, followed by prospective PK studies to confirm these findings,” the investigators said.

Recommended dose

Information regarding the association PK and pharmacodynamics for preterm and VLBW infants on either GCV or valGCV remains limited, according to the investigators.

In an earlier study, there was a proposal to use the adult GCV target AUC0–12h of 40–60 mg × h/L for symptomatic CMV treatment in paediatric patients. Children, however, fail to achieve this target when using the registered paediatric dosages of GCV and valGCV. [Expert Opin Drug Metab Toxicol 2015;11:205-219; The J Pediatr Pharmacol Ther 2023;28:93-101]

Another study suggested the adult Cmin (0.5–1.0 mg/L) and Cmax (7–9 mg/L) GCV therapeutic drug concentration ranges, but these ranges show no association with efficacy and toxicity in infants. [Int J Antimicrob Agents 2011;37:445-448]

“While some studies suggest dosing of GCV and valGCV based on estimated glomerular filtration rate (eGFR) and body surface area for children, the currently recommended GCV and valGCV dose is based on mg/kg body weight in infants due to unreliability of eGFR in infants,” the investigators said. “Nevertheless, these dose recommendations have not been validated for preterm and VLBW infants.”