Body surface area compared to body weight dosing of valganciclovir is associated with increased toxicity in pediatric solid organ transplantation recipients

Demirhan, Salih; Valencia-Deray, Kristen; Bocchini, Claire; Danziger‐Isakov, Lara; Blum, Samantha; Sharma, Tanvi S.; Sherman, Gilad; Boguniewicz, Juri; Bacon, Samantha; Ardura, Monica I.; Maron, Gabriela; Ferrolino, Jose; Foca, Marc; Herold, Betsy C.

doi:10.1016/j.ajt.2023.07.013

Cited by 4 publications

(4 citation statements)

References 28 publications

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“…Patel et al. [13] confirmed other authors' findings that solid organ transplant recipients receiving valganciclovir doses based on body surface area and creatinine clearance have a higher incidence of neutropenia than those who are dosed by weight [12]. It has become clear that the Pescovitz formula may over‐expose patients with low BSA, although in the Patel et al.…”

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confidence: 78%

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Valganciclovir and Risk for Neutropenia: When the Friend Becomes the Foe

Nalli,

Teoh,

Allen

2024

Pediatric Transplantation

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confidence: 78%

“…FDA warnings and safety concerns have been expressed, urging the need for capped creatinine clearance (150 mL/min/1.73 m 2 ) and a maximum dose of 900 mg daily, regardless of calculation [8]. Innovative dosing algorithms have emerged to enhance safety and efficacy in pediatric solid organ transplant recipients [9–12].…”

mentioning

confidence: 99%

Valganciclovir and Risk for Neutropenia: When the Friend Becomes the Foe

Nalli,

Teoh,

Allen

2024

Pediatric Transplantation

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“…The need to adjust the dose for presumed drug-associated adverse events is mitigated, in part, when weight-based rather than manufacturer-recommended body surface area (BSA) dosing is used. In a recently published study involving a subset of the current cohort, we found that CMV DNAemia (breakthrough or at any time in the first year) occurred no more often with weight-based dosing whereas neutropenia and lymphopenia leading to dosing modifications were documented more frequently in those receiving BSA-based dosing [ 13 ]. A single-center study also found an increased risk of neutropenia with BSA-based dosing [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…The VGCV duration and dosing were based on internal protocols at each center as previously described ( Supplementary Table 2 ) [ 13 ]. Similarly, the induction and maintenance immunosuppressive agents and the use of trimethoprim-sulfamethoxazole for PJP prophylaxis were at the discretion of each center and individual transplant program.…”

Section: Methodsmentioning

confidence: 99%

Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients

Foca,

Demirhan,

Munoz

et al. 2024

Open Forum Infectious Diseases

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Background Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes. Methods A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models. Results Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (P = .002); liver transplants, specifically, had increased rejection if CMV DNAemia occurred in the first year (P = .004). These associations may be bidirectional as rejection may contribute to infection risk. Conclusions CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted.

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