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Published on: September 20, 2021
Exposure-safety relationship for acyclovir in the treatment of neonatal herpes simplex virus disease
Jessica E Ericson1, Daniel K Benjamin2, Felix Boakye-Agyeman3
1Department of Pediatrics, Penn State College of Medicine, Hershey, PA, United States of America.
Insights
High-dose acyclovir is commonly used for neonatal herpes simplex virus (HSV) but can cause adverse events (AEs). This study found that while AEs were frequent, acyclovir exposure was not linked to their occurrence, suggesting it is generally safe.
Area of Science:
- Neonatal Medicine
- Pediatric Infectious Diseases
- Pharmacology
Background:
- Neonatal herpes simplex virus (HSV) disease management relies on high-dose acyclovir therapy.
- Established treatment protocols since 1991 utilize high-dose (20 mg/kg/dose) acyclovir.
- Understanding the safety profile of this treatment in infants is crucial.
Purpose of the Study:
- To assess the safety of high-dose acyclovir in infants diagnosed with neonatal HSV.
- To investigate the relationship between acyclovir dosage, exposure levels, and the incidence of adverse events (AEs).
Main Methods:
- Retrospective analysis of medical records from four academic children's hospitals.
- Inclusion criteria: infants <120 days old with neonatal HSV.
- Acyclovir exposure was quantified using a pharmacokinetic model; clinical and laboratory AEs were identified.
Main Results:
- 49 infants with neonatal HSV received acyclovir; 42 had complete dosing data (median daily dose 59 mg/kg/day).
- Clinical AEs, primarily rash (37%), were common across age groups. Mild laboratory AEs occurred in 2-37% of infants.
- No significant association was found between acyclovir exposure (AUC or Cmax) and the likelihood of experiencing clinical or laboratory AEs (OR=1.00 [0.98, 1.03] and OR=1.01 [0.93, 1.12]).
Conclusions:
- High-dose acyclovir treatment for neonatal HSV is associated with common, though generally mild, adverse events.
- Severe adverse events were rare in this cohort.
- Acyclovir exposure levels were not found to be predictive of adverse events, indicating a favorable safety profile within the studied dosage range.
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.
