Pharmacokinetics and safety of famciclovir in children with herpes simplex or varicella-zoster virus infection.
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Sáez-Llorens, X, Yogev, R, Arguedas, A, Rodriguez, A, Spigarelli, M G, De León Castrejón, T, Bomgaars, L, Roberts, Maria, Abrams, Beatrice, Zhou, Wenchun, Looby, Michael, Kaiser, Guenther and Hamed, Kamal (2009) Pharmacokinetics and safety of famciclovir in children with herpes simplex or varicella-zoster virus infection. Antimicrobial Agents and Chemotherapy, 53 (5). pp. 1912-1920. ISSN 1098-6596
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.
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| Date Deposited: | 22 Jan 2011 00:45 |
| Last Modified: | 01 Feb 2013 00:47 |
| URI: | https://oak.novartis.com/id/eprint/4281 |