Valganciclovir dosing using area under the curve calculations in pediatric solid organ transplant recipients

Abstract

Pediatric valganciclovir dosing recommendations have not been extensively validated for prevention or treatment for CMV infection. As such, we performed a pharmacokinetic study to compare different valganciclovir dosing regimens and the potential benefits of individualized dose adjustments in children following organ transplantation. Ganciclovir AUCs were calculated from four plasma drug levels in pediatric SOT recipients aged six months through three yr receiving valganciclovir suspension by mouth. Of the 28 ganciclovir AUC calculations performed, 11 (39%) were outside the therapeutic target range of 40-60 mcg h/L leading to a valganciclovir dose adjustment. Current manufacturer-recommended dosing based on BSA and CrCl was estimated to result in therapeutic AUCs in fewer patients than the simple weight-based formula used in our institution (4 vs. 13; p = 0.017). An AUC calculation using only the two- and five-h measurements was strongly correlated with the AUC using all four time measurements (R(2) = 0.846; p < 0.001). A simple weight-based dosing approach gives a higher probability for therapeutic AUCs compared to the manufacturer-recommended dosing in pediatric transplant patients aged six months through three yr with normal renal function. An AUC calculated using two sample times might allow for fewer blood draws in the future.

Viral surveillance and subclinical viral infection in pediatric kidney transplantation

“…Use of the valganciclovir dosing algorithm that is adjusted for BSA and creatinine clearance is recommended by the Transplantation Society International CMV Consensus Group [43]. Other centers have employed a weight based approach [45]. Due to the challenges particularly in infants and young children, ganciclovir levels may be helpful to guide therapy.Leukopenia is a common side effect of valganciclovir therapy.…”

Pediatric Dosing of Ganciclovir and Valganciclovir: How Model‐Based Simulations Can Prevent Underexposure and Potential Treatment Failure

“…Clinical efficacy data of ganciclovir and valganciclovir are limited in pediatric patients, and although consensus exists that i.v. ganciclovir and oral valganciclovir are effective in prevention and treatment of pediatric CMV infection, the appropriate pediatric dosing strategy is a topic of broad debate …”

Pediatric transplantation case conference: Update on cytomegalovirus

“…Refinement of CMV risk stratification is being explored through research on viral genetic diversity, host genetic susceptibility, and the related virus‐host interactions . In this context, polymorphisms in specific genes associated with immune responses have been reported to be associated with an increased risk of CMV disease .…”

“…The advent of effective oral antiviral medications and highly sensitive molecular diagnostic tests has significantly impacted CMV management in pediatric SOT recipients . Cumulative pediatric pharmacokinetic data inform more precise valganciclovir dosing for infants and young children, and wider access to quantitative CMV DNA PCR assays with rapid turnaround time makes the preemptive treatment of children more feasible. Assays to monitor CMV‐specific cellular immune function, adoptive immunotherapy, and novel antiviral medications, such as maribavir and letermovir, promise further advances but require extensive study in children.…”