Pharmacokinetics and safety of famciclovir in children with herpes simplex or varicella-zoster virus infection

X. Sáez-Llorens, R. Yogev, A. Arguedas, A. Rodriguez, M. G. Spigarelli, T. De León Castrejón, L. Bomgaars, M. Roberts, B. Abrams, W. Zhou, M. Looby, G. Kaiser, K. Hamed*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Two multicenter, open-label, single-arm, two-phase studies evaluated single-dose pharmacokinetics and single- and multiple-dose safety of a pediatric oral famciclovir formulation (prodrug of penciclovir) in children aged 1 to 12 years with suspicion or evidence of herpes simplex virus (HSV) or varicella-zoster virus (VZV) infection. Pooled pharmacokinetic data were generated after single doses in 51 participants (∼12.5 mg/kg of body weight [BW] for children weighing <40 kg and 500 mg for children weighing ≥40 kg). The average systemic exposure to penciclovir was similar (6- to 12-year-olds) or slightly lower (1- to <6-year-olds) than that in adults receiving a 500-mg dose of famciclovir (historical data). The apparent clearance of penciclovir increased with BW in a nonlinear manner, proportional to BW 0.696. An eight-step weight-based dosing regimen was developed to optimize exposure in smaller children and was used in the 7-day multiple-dose safety phases of both studies, which enrolled 100 patients with confirmed/suspected viral infections. Twenty-six of 47 (55.3%) HSV-infected patients who received famciclovir twice a day and 24 of 53 (45.3%) VZV-infected patients who received famciclovir three times a day experienced at least one adverse event. Most adverse events were gastrointestinal in nature. Exploratory analysis following 7-day famciclovir dosing regimen showed resolution of symptoms in most children with active HSV (19/21 [90.5%]) or VZV disease (49/53 [92.5%]). Famciclovir formulation (sprinkle capsules in OraSweet) was acceptable to participants/caregivers. In summary, we present a weight-adjusted dosing schedule for children that achieves systemic exposures similar to those for adults given the 500-mg dose.

Original languageEnglish (US)
Pages (from-to)1912-1920
Number of pages9
JournalAntimicrobial agents and chemotherapy
Volume53
Issue number5
DOIs
StatePublished - May 2009

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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