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Antimicrobial Agents and Chemotherapy, May 2009, p. 1912-1920, Vol. 53, No. 5
0066-4804/09/$08.00+0 doi:10.1128/AAC.01054-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Pharmacokinetics and Safety of Famciclovir in Children with Herpes Simplex or Varicella-Zoster Virus Infection
X. Sáez-Llorens,1
R. Yogev,2
A. Arguedas,3
A. Rodriguez,4
M. G. Spigarelli,5
T. De León Castrejón,6
L. Bomgaars,7
M. Roberts,8
B. Abrams,8
W. Zhou,8
M. Looby,9
G. Kaiser,9 and
K. Hamed8*
Hospital del Niño, Panama City, Panama,1 Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois 60614,2 Instituto de Atención Pediátrica and Universidad de Ciéncias Médicas, San José, Costa Rica,3 Hospital Infantil de Infectologia y Rehabilitación, Guatemala City, Guatemala,4 Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229,5 Hospital Materno Infantil Jose Domingo de Obaldia, Chiriqui, Panama,6 Texas Children's Hospital, Houston, Texas 77030,7 Novartis, East Hanover, New Jersey 07936,8 Novartis Pharma AG, Basel CH 4002, Switzerland9
Received 5 August 2008/ Returned for modification 26 January 2009/ Accepted 3 March 2009
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 BW0.696. 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.
* Corresponding author. Mailing address: Novartis, One Health Plaza, East Hanover, NJ 07936. Phone: (862) 778-4780. Fax: (973) 781-6042. E-mail: kamal.hamed{at}novartis.com
Published ahead of print on 9 March 2009.
Antimicrobial Agents and Chemotherapy, May 2009, p. 1912-1920, Vol. 53, No. 5
0066-4804/09/$08.00+0 doi:10.1128/AAC.01054-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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