ished in pediatric patients 2 months to 17 years of age. Use of XEPI in pediatric patients (2 months to 17 years of age) is supported by evidence from adequate and well-controlled studies of XEPI in which 251 pediatric patients received at least one dose of XEPI. The median age of the patients enrolled in the clinical trials was 10 years; 3 % of patients were 2 months to less than 2 years of age, 55 % of patients were 2 to less than 12 years of age, 11 % of patients were 12 to less than 18 years of age, and 31 % of patients were 18 years of age or older. In these studies, the maximum dose applied was approximately 0.5 g of XEPI applied twice daily for up to 5 days (i.e., up to 10 applications total) [see Clinical Studies (14)].
The safety profile of XEPI in pediatric patients 2 months and older was similar to that of adults [see Adverse Reactions (6.1)].
The safety and effectiveness of XEPI in pediatric patients younger than 2 months of age have not been established [see Clinical Studies (14)].
8.5 Geriatric Use
Clinical studies of XEPI did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
10 OVERDOSAGE
Any sign or symptom of overdose, either topically or by accidental ingestion, should be treated symptomatically. No specific antidote is known.
11 DESCRIPTION
XEPI contains ozenoxacin, a quinolone antimicrobial. It is intended for topical use only.
The chemical name of ozenoxacin is 1-Cyclopropyl-8-methyl-7-(5-methyl-6-methylamino-pyridin-3-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid. Ozenoxacin, a white to pale-yellow crystalline solid, has a molecular formula of C21H21N3O3, and a molecular weight of 363.41. The chemical structure is:
Chemical Structure
Each gram of cream contains 10 mg of ozenoxacin (1% w/w) and the following inactive ingredients: benzoic acid, octyldodecanol, peglicol 5 oleate, pegoxol 7 stearate, propylene glycol, purified water, stearyl alcohol.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
XEPI is an antimicrobial drug [see Microbiology (12.4)].
12.2 Pharmacodynamics
Exposure-Response Relationship
The exposure response relationship for ozenoxacin following topical application has not been studied, however; a relationship is unlikely because systemic exposure following topical application is negligible [see Clinical Pharmacology (12.3)].
12.3 Pharmacokinetics
Absorption
Four pharmacokinetic studies were conducted in 110 patients utilizing varying strengths of ozenoxacin cream, up to 2% (twice the concentration of the marketed formulation). Three of these studies assessed systemic absorption in healthy subjects and in subjects with impetigo. These studies were conducted with either single or repeated application of up to 1 g ozenoxacin cream to intact or abraded skin (up to 200 cm2 surface area). No systemic absorption was observed in 84 of 86 subjects, and negligible systemic absorption was observed at the level of detection (0.489 ng/mL) in 2 subjects.
Distribution
Plasma protein binding of [14C]-ozenoxacin was moderate (~80 to 85%) and did not appear to be dependent on concentration. Since negligible systemic absorption was observed in clinical studies, tissue distri
