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

The Pediatric Infectious Disease Journal • December 2016.

Ericson JE, Gostelow M, Autmizguine J, Hornik CP, Clark RH, Benjamin DK Jr, Smith PB; Pediatric Trials Network Executive Committee and Investigators.

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. 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.

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Population pharmacokinetics of intravenous acyclovir in preterm and term infants

The Pediatric Infectious Disease Journal • December 2013.

Sampson MR, Bloom BT, Lenfestey RW, Harper B, Kashuba AD, Anand R, Benjamin DK Jr, Capparelli E, Cohen-Wolkowiez M, Smith PB; Best Pharmaceuticals for Children Act–Pediatric Trials Network.

Acyclovir is used to treat herpes infections in preterm and term infants; however, the influence of maturation on drug disposition and dosing requirements is poorly characterized in this population. We administered intravenous acyclovir to preterm and term infants <31 days postnatal age and collected plasma samples. We performed a population pharmacokinetic analysis.

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Acyclovir PK study is complete

The PTN open-label study to describe the pharmacokinetics (PK) of acyclovir in premature infants has concluded, with results recently published in the Pediatric Infectious Diseases Journal.

Acyclovir is a drug used to treat herpes simplex virus (HSV) infections in infants. HSV is a very serious infection in those <6 months of age, often resulting in death or profound mental retardation. Appropriate dosing of acyclovir is known for adults and children but has not been adequately studied in full-term or premature neonates.

This study examined acyclovir levels in the blood of premature and term infants who were placed on the drug to treat a suspected HSV infection, thereby determining the appropriate dose in this vulnerable population. Investigators found that infant maturity as measured by post-menstrual age* is associated with the infant body’s ability to clear the drug; in short, they determined that less frequent dosing is needed in younger infants to achieve optimal therapeutic benefit.

The study was conducted at two sites — Duke University Medical Center in Durham, North Carolina, and Wesley Medical Center in Wichita, Kansas. Site teams headed by Robert Lenfestey (Duke) and Paula Delmore (Wesley) enrolled 32 patients over the 9-month study. Next steps will involve a retrospective analysis of data from infants who received high-dose acyclovir; this information will support proposed label changes submitted to the Food and Drug Administration for use of acyclovir in infants.

* Post-menstrual age is the time elapsed between the first day of the mother’s last menstrual period and the infant’s birth, plus the time elapsed since birth.