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

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 (approximately 12.5 mg/kg of body weight [BW] for children weighing < 40 kg and 500 mg for children weighing > or = 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.

• Authors: 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
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 53 Issue 5 Pg. 1912-20 (May 2009) ISSN: 1098-6596 [Electronic] United States
• PMID: 19273678 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• 2-Aminopurine
• Famciclovir
• Acyclovir

Topics

• 2-Aminopurine (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Acyclovir (administration & dosage)
• Antiviral Agents (administration & dosage, adverse effects, pharmacokinetics)
• Chickenpox (drug therapy, virology)
• Child
• Child, Preschool
• Drug Administration Schedule
• Drug Therapy, Combination
• Famciclovir
• Female
• Herpes Simplex (drug therapy, virology)
• Herpesvirus 3, Human (drug effects)
• Humans
• Infant
• Male
• Simplexvirus (drug effects)
• Treatment Outcome