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Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients: A Prospective
Orit Peled1, Matitiahu Berkovitch, Eran Rom
1From the *Department of Pharmacy, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; †Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; ‡Clinical Pharmacology and Toxicology Unit, Assaf Harofeh Medical Center, Zriffin, Israel; §Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; ¶Department of Epidemiology and Preventive Medicine, School of Public Health, Tel Aviv University, Tel Aviv, Israel; and ‖Biochemistry Laboratory, Assaf Harofeh Medical Center, Zriffin, Israel.
Insights
Valganciclovir dosing for pediatric transplant patients showed lower ganciclovir exposure, especially in younger children. This weight-based regimen proved effective for cytomegalovirus (CMV) prophylaxis, suggesting current manufacturer recommendations may be too high.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Transplant Medicine
Background:
- Valganciclovir is crucial for cytomegalovirus (CMV) management in pediatric solid-organ transplant recipients.
- Limited pharmacokinetic data exists for pediatric dosing, creating uncertainty.
Purpose of the Study:
- To prospectively assess valganciclovir pharmacokinetics, efficacy, and safety in pediatric transplant patients.
- To compare different dosing regimens for CMV prophylaxis.
Main Methods:
- A cohort of pediatric solid-organ transplant recipients received weight-based oral valganciclovir (17 mg/kg/day).
- Ganciclovir concentrations and area under the curve (AUC0-24) were measured.
Main Results:
- Median ganciclovir AUC0-24 was 21.0 mcg·h/mL; 77% achieved AUC0-24 <40 mcg·h/mL.
- Ganciclovir exposure was significantly lower in younger children (<9 years) and those with low body surface area (BSA <0.7 m²).
- The weight-based protocol yielded lower doses than manufacturer recommendations, particularly in infants.
Conclusions:
- The 17 mg/kg weight-based valganciclovir regimen provides adequate CMV prophylaxis in pediatric transplant recipients, despite lower ganciclovir exposure in younger/smaller children.
- Manufacturer dosing recommendations may lead to excessive ganciclovir concentrations.
- Further research is needed to optimize valganciclovir dosing for pediatric CMV prophylaxis.
Background:
Valganciclovir is extensively used for prophylaxis and treatment of cytomegalovirus (CMV) infection in solid-organ transplant recipients. However, pharmacokinetic data in children are scarce, and the pediatric dosing regimen is uncertain. This study sought to prospectively evaluate the pharmacokinetic profile, the clinical efficacy and safety of oral valganciclovir in pediatric transplant recipients and compare different dosing regimens.
Methods:
The cohort included solid-organ transplant recipients treated with valganciclovir for CMV prophylaxis in 2014-2015 at a tertiary pediatric medical center. All received a weight-based once-daily oral dose of 17 mg/kg. Ganciclovir concentrations were measured and the area under the curve (AUC0-24) was calculated.
Results:
Thirteen children of median age 7.3 years (interquartile range, 2.2-11.6) were included. Median ganciclovir AUC0-24 was 21.0 mcg·h/mL (interquartile range, 17.1-39.8); 10 patients (77%) attained AUC0-24 <40 mcg·h/mL. Exposure to ganciclovir was about 2-fold lower in young children (<9 years old; P = 0.01) and children with low body surface area (BSA; <0.7 m; P = 0.006) than in their counterparts. Significantly lower doses were recommended with our weight-based protocol than with the manufacturer-recommended BSA- and glomerular filtration rate-based protocol (P = 0.002), reaching a 3-fold difference in infants. No evidence of CMV viremia or disease was observed while prophylaxis was given.
Conclusions:
The weight-based regimen of 17 mg/kg/dose oral valganciclovir results in relatively low ganciclovir exposure, especially in young children with low BSA, yet showed satisfactory clinical efficacy for CMV prophylaxis. The manufacturer's dosing recommendation appears to result in supratherapeutic ganciclovir concentrations. Further studies are needed to establish target AUCs and valganciclovir dosing for CMV prophylaxis in pediatric transplant recipients.