Abstract :
on behalf of the (1) Keywords Acyclovir; Herpes; Herpes simplex virus; Infant; Exposure Highlights * Linking acyclovir exposure to safety in infants has not been previously reported. * Although AEs were common with high-dose acyclovir use, severe AEs were rare. * Acyclovir exposure was not associated with the incidence of AEs. Abstract Background Neonatal herpes simplex virus (HSV) disease has been treated with high-dose (20 mg/kg/dose) acyclovir since 1991. Aims Determine the safety of acyclovir in infants with neonatal HSV treated with high-dose acyclovir; examine the association between acyclovir dose and exposure with adverse events (AEs). Study design We obtained demographic information and acyclovir dosing via medical records. Acyclovir exposure was calculated using an established pharmacokinetic model. Subjects Infants Outcome measures We identified clinical and laboratory adverse events (AEs). Results and conclusions We identified 49 infants with neonatal HSV treated with acyclovir; 42 infants had complete 21-day dosing information. Median mean daily dose was 59 mg/kg/day. Clinical AEs were common among all gestational and postnatal age groups. Rash was the most common clinical AE (37 %). Mild laboratory AEs occurred in 2--37 % of infants. The median maximum doses (mg/kg/day) were higher among infants with hypokalemia, elevated blood urea nitrogen, and thrombocytosis. For all other laboratory AEs, the median maximum doses for infants without events were higher or equal to the median maximum dose of infants with the AE. The odds of experiencing any clinical or laboratory AE did not differ by predicted acyclovir exposure for either area under the curve (AUC) or maximum concentration (Cmax) (odds ratio [OR] = 1.00 [0.98, 1.03] and OR = 1.01 [0.93, 1.12], respectively). Although AEs were common with high-dose acyclovir exposure, severe AEs were rare. Acyclovir exposure was not associated with AEs. Author Affiliation: (a) Department of Pediatrics, Penn State College of Medicine, Hershey, PA, United States of America (b) Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, United States of America (c) Department of Pediatrics, Duke University School of Medicine, Durham, NC, United States of America (d) Children's Hospital of Orange County, Orange, CA, United States of America (e) The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America (f) Cincinnati Children's Hospital, Cincinnati, OH, United States of America (g) The Emmes Corporation, Rockville, MD, United States of America * Corresponding author at: Duke Clinical Research Institute, Box 179769, Durham, NC 27715, United States of America. Article History: Received 4 November 2021; Accepted 16 June 2022 (footnote)1 Please see Acknowledgments. Byline: Jessica E. Ericson (a), Daniel K. Benjamin Jr (b,c), Felix Boakye-Agyeman (b), Stephen J. Balevic (b,c), C. Michael Cotten (b,c), Felice Adler-Shohet (d), Matthew Laughon (e), Brenda Poindexter (f), Barrie Harper (b), Elizabeth H. Payne (g), Kim Kaneshige (g), P. Brian Smith [brian.smith@duke.edu] (c,*)