Pharmacokinetics and safety of famciclovir in children with herpes simplex or varicella-zoster virus infection.
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.
Sáez-Llorens
X
X
Hospital del Niño, Panama City, Panama.
Yogev
R
R
Arguedas
A
A
Rodriguez
A
A
Spigarelli
M G
MG
De León Castrejón
T
T
Bomgaars
L
L
Roberts
M
M
Abrams
B
B
Zhou
W
W
Looby
M
M
Kaiser
G
G
Hamed
K
K
D015075:2-Aminopurine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000212:Acyclovir / Q000008:administration & dosage; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002644:Chickenpox / Q000188:drug therapy* / Q000821:virology; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000077595:Famciclovir; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy* / Q000821:virology; D014645:Herpesvirus 3, Human / Q000187:drug effects*; D006801:Humans; D007223:Infant; D008297:Male; D018139:Simplexvirus / Q000187:drug effects*; D016896:Treatment Outcome
D000998:Antiviral Agents; D015075:2-Aminopurine; D000077595:Famciclovir; D000212:Acyclovir