Pediatric Transplantaton 2016; 1–11 wileyonlinelibrary.com/journal/petr | 1 © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Accepted: 21 September 2016 DOI: 10.1111/petr.12833 Abstract This multcenter, open-label study evaluated the tolerability of extended prophylaxis with valganciclovir in pediatric kidney transplant recipients at risk of CMV disease. Fify-six patents aged 4 months to 16 years received once-daily valganciclovir oral soluton and/or tablets, dosed by BSA and renal functon, for up to 200 days. The most common AEs on treatment were upper respiratory tract infecton (33.9%), urinary tract infecton (33.9%), diarrhea (32.1%), leukopenia (25.0%), neutropenia (23.2%), and headache (21.4%). There were fewer AEs during days 101-228 vs days 1-100. Twenty- seven patents (48.2%) had treatment-related AEs during valganciclovir treatment, most commonly leukopenia (21.4%), neutropenia (19.6%), anemia (7.1%), and tremor (5.4%). Treatment-related serious AEs were reported for nine patents (16.1%) and six withdrew due to AEs. Viremia was centrally confrmed in 10 patents; there was no confrmed CMV disease. One patent tested positve for a resistance mutaton (UL97 L595F). Biopsy-proven acute rejecton occurred in six patents (10.7%), but no graf loss or deaths occurred. In conclusion, up to 200 days of valganciclovir prophylaxis in pediatric kidney allograf recipients showed a safety profle consistent with that estab- lished in adult transplant patents. KEYWORDS cytomegalovirus, extended prophylaxis, safety, valganciclovir 1 Department of Transplantaton, Hospital Infantl de México Federico Gómez, Mexico City, Mexico 2 Department of Pediatrics, Mount Sinai Medical Center, New York, NY, USA 3 Department of Transplantaton, Hospital de Especialidades Miguel Hidalgo, Aguascalientes, Mexico 4 PDS Safety Risk Management, F. Hofmann-La Roche Ltd, Basel, Switzerland 5 PD Clinical Science, Roche Products Ltd, Welwyn Garden City, UK 6 Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil Correspondence Gustavo Varela-Fascineto, Jefe del Depto. de Trasplantes y Director del Programa de Trasplante Hepátco, Hospital Infantl de México Federico Gómez, México, D.F., Mexico. Email: varelafas@aol.com Funding informaton F. Hofmann-La Roche Ltd, Basel, Switzerland. ORIGINAL ARTICLE Tolerability of up to 200 days of prophylaxis with valganciclovir oral soluton and/or flm-coated tablets in pediatric kidney transplant recipients at risk of cytomegalovirus disease G. Varela-Fascineto 1 | C. Benchimol 2 | R. Reyes-Acevedo 3 | M. Genevray 4 | D. Bradley 5 | J. Ives 5 | H. T. Silva Jr. 6 1 | INTRODUCTION Human CMV remains the most common opportunistc pathogen in- fectng solid organ transplant recipients following immunosuppres- sion and leads to substantal morbidity and mortality. 1–4 Clinically, symptomatc CMV disease manifests either as a viral syndrome characterized by fever, malaise, leukopenia, and/or thrombocytope- nia, or as tssue-invasive disease associated with hepatts, gastrits, pneumonits, or other end-organ involvement. 1,2,5 In additon to these direct efects, immune modulaton by the virus is believed to contrib- ute to the increased risk of other opportunistc infectons, reduced graf survival, and increased mortality. 2,6–8 The risk of CMV disease is greatest among seronegatve recipients (R−) of organs from seroposi- tve donors (D+). 1,5 To prevent CMV disease in high-risk solid organ transplant re- cipients, clinical practce guidelines recommend antviral therapy, with prophylaxis favored over preemptve therapy for seronegatve patents with a seropositve donor (D+/R− patents) receiving kid- ney, heart, liver, or pancreas transplants. 5 The preferred prophylactc agent for adults is valganciclovir, 5 a valyl ester prodrug of ganciclovir, which has 10-fold greater absolute oral bioavailability compared with Abbreviatons: AE, adverse event; ANC, absolute neutrophil count; BPAR, biopsy-proven acute rejecton; BSA, body surface area; CMV, cytomegalovirus; CrCLS, creatnine clearance calculated using the modifed Schwartz equaton; D−, donor seronegatve; D+, donor sero- positve; EBV, Epstein-Barr virus; ITT, intent to treat; R−, recipient seronegatve; R+, recipient seropositve; SAE, serious adverse event.