Adi Pappo1, Orit Peled2, Matitiahu Berkovitch3,4, Efraim Bilavsky1,4, Eran Rom1,4, Jacob Amir1,4, Irit Krause1,4, Havatzelet Yarden-Bilavsky4,5, Oded Scheuerman4,6,7, Liat Ashkenazi-Hoffnung4,6,7. 1. Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel. 2. Department of Pharmacy, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel. 3. Clinical Pharmacology and Toxicology Unit, Assaf Harofeh Medical Center, Zriffin, Israel. 4. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 5. Department of Pediatrics A, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel. 6. Department of Pediatrics B, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel. 7. Infectious Diseases Unit, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel.
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.
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.
Authors: Jan Dudley; Martin Christian; Alice Andrews; Nicola Andrews; Julie Baker; Sheila Boyle; Mairead Convery; Fiona Gamston; Martin Garcia; Shuman Haq; Shivaram Hegde; Richard Holt; Helen Jones; Shakeeb Khan; Jennifer McCaughan; David Milford; Charlie Pickles; Ben Reynolds; Vijaya Sathyanarayana; Jelena Stojanovic; Yincent Tse; Dean Wallace; Grainne Walsh; Nick Ware; Alun Williams; Pallavi Yadav; Stephen Marks Journal: BMC Nephrol Date: 2021-09-16 Impact factor: 2.388