Efficacy and Safety of a Weight-based Dosing Regimen of Valganciclovir for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients

Abstract

Background. Valganciclovir has been widely used for cytomegalovirus (CMV) prophylaxis in solid-organ transplant recipients. However, the optimal dosing protocol and target exposure in children are still unclear. Specific data as to the efficacy and safety of low-dose/low-exposure regimens are lacking and urgently needed. Methods. During 2010 to 2015, the clinical efficacy and safety of a weight-based regimen of valganciclovir of 17 mg/kg/day, with a stratified dose reduction for impaired creatinine clearance, given as a CMV prophylaxis for 3 to 6 months, was retrospectively evaluated among pediatric kidney and liver transplant recipients, 12 months posttransplantation. Incidence of CMV infection was assessed by periodic measurements of viral load; adverse events were evaluated. Results. Eighty-three children who had undergone 86 transplantations and were treated with 17 mg/kg of valganciclovir were included. Median age was 9.77 years (range, 0.6 to 18.9). Twelve (14%) developed CMV infection: 1 during prophylaxis and 11 during follow-up. These events comprised 6 cases of asymptomatic viremia and 6 cases of a clinically significant disease without occurrences of tissue-invasive disease. Treatment-related adverse effects occurred in 7 patients (8%), mostly hematological, resulting in premature drug cessation. Conclusions. Our results support the use of 17 mg/kg of valganciclovir for CMV prophylaxis in liver and kidney transplanted children as it showed satisfactory long-term efficacy and a good safety profile.

“Weight‐ing” for an answer on optimal valganciclovir prophylaxis dosing in pediatric solid organ transplantation recipients

“…As only 8 of these breakthrough events occurred after dose reduction for presumed valGCV-associated adverse events (VAAE), one possible conclusion from this study may be that weight-based dosing leads to an unacceptably high level of breakthrough CMV DNAemia. Breakthrough rates of CMV DNAemia in published pSOT cohort studies using weight-based valGCV dosing range from 10% to 16%, [21][22][23][24] whereas breakthrough rates in BSA-based dosing cohorts range between 0% and 6%, [25][26][27][28][29] with one study having an outlier breakthrough rate of 15%. 30 Comparative studies that evaluate the impact of both dosing strategies on virologic and clinical outcomes are needed to answer this question.…”

Cytomegalovirus infection in liver-transplanted children

“…The efficacy of the pre-emptive protocol has been studied in some trials. In the study by Pappo et al [ 72 ], liver-transplanted children were given oral valganciclovir 17 mg/kg/d for 3-6 mo, leading to a decrease in the incidence of CMV infection. A study by Ueno et al [ 73 ], reported that the incidence of CMV infection in patients with 1 year prophylaxis decreased by more than 80.5% compared with a regimen of less than 1 year.…”

Clinical practice guidelines standardisation of immunosuppressive and anti-infective drug regimens in UK paediatric renal transplantation: the harmonisation programme

“…Limited evidence suggests that 6 months of prophylaxis may be associated with a lower rate of late-onset disease than 3 month regimens in CYP receiving valganciclovir [7], however, the committee agreed to propose a recommendation for 'at least 3 months' of valganciclovir due to concerns about its significant side effect profile (infection, diarrhoea, leukopenia, neutropenia) [8].…”