PMID- 35763957
OWN - NLM
STAT- MEDLINE
DCOM- 20220707
LR  - 20230703
IS  - 1872-6232 (Electronic)
IS  - 0378-3782 (Print)
IS  - 0378-3782 (Linking)
VI  - 170
DP  - 2022 Jul
TI  - Exposure-safety relationship for acyclovir in the treatment of neonatal herpes 
      simplex virus disease.
PG  - 105616
LID - S0378-3782(22)00079-2 [pii]
LID - 10.1016/j.earlhumdev.2022.105616 [doi]
AB  - 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 <120 days of age with neonatal HSV 
      discharged from four academic children's hospitals. 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.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Ericson, Jessica E
AU  - Ericson JE
AD  - Department of Pediatrics, Penn State College of Medicine, Hershey, PA, United 
      States of America.
FAU - Benjamin, Daniel K Jr
AU  - Benjamin DK Jr
AD  - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, 
      United States of America; Department of Pediatrics, Duke University School of 
      Medicine, Durham, NC, United States of America.
FAU - Boakye-Agyeman, Felix
AU  - Boakye-Agyeman F
AD  - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, 
      United States of America.
FAU - Balevic, Stephen J
AU  - Balevic SJ
AD  - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, 
      United States of America; Department of Pediatrics, Duke University School of 
      Medicine, Durham, NC, United States of America.
FAU - Cotten, C Michael
AU  - Cotten CM
AD  - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, 
      United States of America; Department of Pediatrics, Duke University School of 
      Medicine, Durham, NC, United States of America.
FAU - Adler-Shohet, Felice
AU  - Adler-Shohet F
AD  - Children's Hospital of Orange County, Orange, CA, United States of America.
FAU - Laughon, Matthew
AU  - Laughon M
AD  - The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States 
      of America.
FAU - Poindexter, Brenda
AU  - Poindexter B
AD  - Cincinnati Children's Hospital, Cincinnati, OH, United States of America.
FAU - Harper, Barrie
AU  - Harper B
AD  - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, 
      United States of America.
FAU - Payne, Elizabeth H
AU  - Payne EH
AD  - The Emmes Corporation, Rockville, MD, United States of America.
FAU - Kaneshige, Kim
AU  - Kaneshige K
AD  - The Emmes Corporation, Rockville, MD, United States of America.
FAU - Smith, P Brian
AU  - Smith PB
AD  - Department of Pediatrics, Duke University School of Medicine, Durham, NC, United 
      States of America. Electronic address: brian.smith@duke.edu.
CN  - Best Pharmaceuticals for Children Act - Pediatric Trials Network
LA  - eng
GR  - HHSN267200700051C/HD/NICHD NIH HHS/United States
GR  - HHSN275201000003I/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20220622
PL  - Ireland
TA  - Early Hum Dev
JT  - Early human development
JID - 7708381
RN  - 0 (Antiviral Agents)
RN  - X4HES1O11F (Acyclovir)
RN  - Neonatal herpes
SB  - IM
MH  - *Acyclovir/adverse effects
MH  - Antiviral Agents/adverse effects
MH  - Child
MH  - Female
MH  - *Herpes Simplex/chemically induced/drug therapy
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Pregnancy Complications, Infectious
MH  - Simplexvirus
PMC - PMC9645023
MID - NIHMS1841395
OTO - NOTNLM
OT  - Acyclovir
OT  - Exposure
OT  - Herpes
OT  - Herpes simplex virus
OT  - Infant
EDAT- 2022/06/29 06:00
MHDA- 2022/07/08 06:00
PMCR- 2023/07/01
CRDT- 2022/06/28 18:20
PHST- 2021/11/04 00:00 [received]
PHST- 2022/06/16 00:00 [accepted]
PHST- 2022/06/29 06:00 [pubmed]
PHST- 2022/07/08 06:00 [medline]
PHST- 2022/06/28 18:20 [entrez]
PHST- 2023/07/01 00:00 [pmc-release]
AID - S0378-3782(22)00079-2 [pii]
AID - 10.1016/j.earlhumdev.2022.105616 [doi]
PST - ppublish
SO  - Early Hum Dev. 2022 Jul;170:105616. doi: 10.1016/j.earlhumdev.2022.105616. Epub 
      2022 Jun 22.