Safety of High-dose Acyclovir in Infants With Suspected and Confirmed Neonatal Herpes Simplex Virus Infections

Pediatr Infect Dis J. 2017 Apr;36(4):369-373. doi: 10.1097/INF.0000000000001451.

Abstract

Background: Acyclovir is used to treat herpes simplex virus disease in infants. Treatment with high-dose acyclovir, 60 mg/kg/d, is recommended; however, the safety of this dosage has not been assessed in the past 15 years, and this dosage is not currently approved for infants by the US Food and Drug Administration.

Methods: We included infants with neonatal herpes simplex virus disease treated with ≥14 days of intravenous acyclovir starting in the first 120 days of life admitted to 1 of 42 neonatal intensive care units managed by the Pediatrix Medical Group between 2002 and 2012. We determined the frequency and proportion of infants with clinical and laboratory adverse events (AEs) as well as the number and proportion of infant days with laboratory AEs occurring during acyclovir exposure.

Results: We identified 89 infants during the study period with 1658 days of acyclovir exposure. Almost all received high-dose acyclovir therapy (79/89, 89%). The most common clinical AEs were hypotension and seizure, both occurring in 9% of infants. Thrombocytopenia was the most common laboratory AE occurring in 25% of infants and on 9% of infant-days. Elevated creatinine occurred in 2% of infants and 0.2% of infant-days and no infants developed renal failure requiring dialysis. Overall, 45% of infants had ≥1 AE.

Conclusions: In this cohort of infants treated during the high-dose acyclovir era, AEs were common but usually not severe. Many of the AEs reported in this cohort may be related to the underlying infection rather than due to acyclovir exposure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acyclovir / administration & dosage
  • Acyclovir / adverse effects*
  • Acyclovir / therapeutic use
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects*
  • Antiviral Agents / therapeutic use
  • Female
  • Herpes Simplex / drug therapy*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Pregnancy Complications, Infectious / drug therapy*
  • Retrospective Studies
  • Simplexvirus*
  • Thrombocytopenia

Substances

  • Antiviral Agents
  • Acyclovir

Supplementary concepts

  • Neonatal herpes