Exposure-safety relationship for acyclovir in the treatment of neonatal herpes simplex virus disease.
Acyclovir
Exposure
Herpes
Herpes simplex virus
Infant
Journal
Early human development
ISSN: 1872-6232
Titre abrégé: Early Hum Dev
Pays: Ireland
ID NLM: 7708381
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
04
11
2021
accepted:
16
06
2022
pubmed:
29
6
2022
medline:
8
7
2022
entrez:
28
6
2022
Statut:
ppublish
Résumé
Neonatal herpes simplex virus (HSV) disease has been treated with high-dose (20 mg/kg/dose) acyclovir since 1991. 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). We obtained demographic information and acyclovir dosing via medical records. Acyclovir exposure was calculated using an established pharmacokinetic model. Infants <120 days of age with neonatal HSV discharged from four academic children's hospitals. We identified clinical and laboratory adverse events (AEs). 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.
Sections du résumé
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.
Identifiants
pubmed: 35763957
pii: S0378-3782(22)00079-2
doi: 10.1016/j.earlhumdev.2022.105616
pmc: PMC9645023
mid: NIHMS1841395
pii:
doi:
Substances chimiques
Antiviral Agents
0
Acyclovir
X4HES1O11F
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
105616Subventions
Organisme : NICHD NIH HHS
ID : HHSN267200700051C
Pays : United States
Organisme : NICHD NIH HHS
ID : HHSN275201000003I
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier B.V. All rights reserved.
Références
Pediatr Clin North Am. 2013 Apr;60(2):351-65
pubmed: 23481105
J Pediatr. 2015 Jun;166(6):1462-8.e1-4
pubmed: 25708691
J Perinatol. 2005 Mar;25(3):156-61
pubmed: 15605069
Pediatr Transplant. 2006 Aug;10(5):632-4
pubmed: 16857003
N Engl J Med. 2011 Oct 6;365(14):1284-92
pubmed: 21991950
Pediatrics. 2010 Feb;125(2):e214-24
pubmed: 20100760
Clin Perinatol. 2015 Mar;42(1):47-59, viii
pubmed: 25677996
Contemp Clin Trials. 2016 Mar;47:376-82
pubmed: 26968616
N Engl J Med. 1991 Feb 14;324(7):444-9
pubmed: 1988829
Paediatr Drugs. 2014 Jun;16(3):229-34
pubmed: 24497110
JAMA. 2006 Aug 23;296(8):964-73
pubmed: 16926356
Pediatrics. 2011 Dec;128(6):1153-60
pubmed: 22123868
Pediatrics. 2001 Aug;108(2):230-8
pubmed: 11483782
Pediatrics. 2001 Aug;108(2):223-9
pubmed: 11483781
Am J Med. 2015 Jul;128(7):692-4
pubmed: 25784625
Turk J Pediatr. 1989 Oct-Dec;31(4):317-21
pubmed: 2486432
Pediatr Nephrol. 1997 Dec;11(6):741-3
pubmed: 9438656
Expert Opin Drug Saf. 2008 Mar;7(2):147-58
pubmed: 18324877
Pediatr Infect Dis J. 2017 Apr;36(4):369-373
pubmed: 27977557
Clin Pharmacokinet. 2006;45(11):1077-97
pubmed: 17048973
No To Hattatsu. 1998 Jul;30(4):334-8
pubmed: 9695630
Clin Infect Dis. 1995 Jun;20(6):1557-9
pubmed: 7548511
Paediatr Drugs. 2008;10(2):135-9
pubmed: 18345723
Pediatr Infect Dis J. 2014 Jan;33(1):42-9
pubmed: 24346595