Evaluation of valganciclovir's neutropenia risk in pediatric solid organ transplant recipients utilizing two dosing regimens.

BACKGROUND: Valganciclovir is approved for cytomegalovirus prophylaxis in pediatrics using the Pescovitz algorithm. There are reports of valganciclovir overdoses in children with low body surface area and overestimated creatinine clearance utilizing this algorithm. This study compared the incidence of neutropenia and cytomegalovirus infection between the Pescovitz and weight-based dosing algorithms. METHODS: A single-center retrospective chart review from January 2010 to September 2018 was performed on pediatric heart, liver, and kidney transplant recipients, who received valganciclovir. Data were collected from the initiation of valganciclovir prophylaxis to 30 days after discontinuation. The primary objective was the incidence of neutropenia in patients receiving valganciclovir dosed by the Pescovitz versus weight-based dosing algorithms. RESULTS: This study included 187 pediatric transplant recipients who received valganciclovir dosed via the Pescovitz (62 recipients) or weight-based dosing algorithms (125 recipients). The incidence of neutropenia was higher in the Pescovitz (69.4%) compared to the weight-based dosing group (53.6%; p = .04) including moderate and severe neutropenia. Cytomegalovirus viremia was not significantly different between the two groups and occurred in 4.8% of the Pescovitz group compared to 2.4% of the weight-based group (p = .4). CONCLUSIONS: The incidence of neutropenia was greater in recipients receiving valganciclovir dosed via the Pescovitz algorithm compared to the weight-based dosing. There were no significant differences in regard to cytomegalovirus viremia or disease between the two groups.

A randomized, open-label pharmacokinetic trial of tacrolimus extended-release dosing in obese de novo kidney transplant recipients.

PURPOSE: Tacrolimus extended-release (TAC-ER; Astagraf XL® ) is utilized in many immunosuppressive regimens post-renal transplantation. Current dosing recommendation for the TAC-ER in renal transplant is 0.15-0.2 mg/kg/day administered once daily. The purpose of this study was to determine the best method of dosing TAC-ER in obese renal transplant recipients. METHODS: De novo obese kidney transplant recipients were randomized to receive TAC-ER 0.15 mg/kg/day based on either adjusted body weight (aBW) or ideal body weight (IBW). Post-transplant patients underwent three pharmacokinetic assessments over 14 days. The primary endpoint was the difference in TAC-ER exposure (AUC0-24) in obese patients dosed using aBW compared with IBW. RESULTS: A total of 20 obese renal transplant recipients were randomized to participate in the study (10 aBW and 10 IBW). Results of the primary outcome (AUC0-24) on Study Day 1, 7, and 14 were not statistically different between the two groups. There was no difference in the number of days to therapeutic trough concentration between the two dosing weights (aBW = 5.1, IBW = 4.9, days; P = 0.90). CONCLUSION: In a population of obese renal transplant recipients, comparable trough concentrations and overall exposure in both groups indicate that IBW may be preferred, as less initial drug was needed to attain adequate exposure.

A national survey of valganciclovir dosing strategies in pediatric organ transplant recipients.

PURPOSE: Data remain limited on the most appropriate valganciclovir (VGCV) dosing strategy for cytomegalovirus (CMV) prophylaxis and treatment in pediatric organ transplant recipients. Therefore, the objective of this study was to describe methods used to calculate VGCV dosing among pediatric transplant centers. METHODS: A survey of pharmacists was conducted to assess VGCV dosing strategies for CMV prophylaxis and treatment among pediatric organ transplant centers in the U.S. FINDINGS: Of 54 centers that perform pediatric organ transplants, 22 (40.7%) centers responded to the survey. Fourteen centers (53.8%) utilize the Food and Drug Administration (FDA) recommended VGCV dosing strategy of 7 × body surface area (BSA) × creatinine clearance (CrCl) for CMV prophylaxis. Other dosing strategies reported included weight based and 520 mg/m2  × BSA per day. Dosing strategies of VGCV for the treatment of CMV also differed across centers, with a majority (43.5%) using 7 × BSA × CrCl twice daily. CONCLUSION: Less than two-thirds of centers utilize the FDA-approved daily dosing regimen with various methods of CrCl calculation and serum creatinine assay measurements used. More retrospective and prospective studies with clinical outcomes associated with VCGV dosing strategies are warranted to determine the most appropriate prophylaxis and treatment strategies for CMV.