Dosing, toxicity and drug concentrations for ganciclovir/valganciclovir in preterm and low birthweight Infants treated for cytomegalovirus

• Main Authors: Abu Bakar, Asrar, Helen, Payne, Neil, Tickner, Muhd Helmi, Muhd Alwi, Jacobs, Tom G, Hermione, Lyall
• Format: Article
• Language: English
• Published: Wolters Kluwer Health, Inc. 2024
• Subjects: RJ251 Newborn infants. Neonatology; RJ254 Disease and abnormalities; RJ370 Disease of children; RM300 Drugs and their action
• Online Access: http://irep.iium.edu.my/115860/7/115860_Dosing%2C%20toxicity%20and%20drug%20concentrations%20for%20GanciclovirValganciclovir.pdf; http://irep.iium.edu.my/115860/; https://journals.lww.com/pidj/fulltext/9900/dosing,_toxicity_and_drug_concentrations_for.1087.aspx

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.