Included as part of the PRECAUTIONS section.
Systemic absorption of clindamycin has been demonstrated
following topical use of clindamycin. Diarrhea, bloody diarrhea, and colitis
(including pseudomembranous colitis) have been reported with the use of topical
and systemic clindamycin. If significant diarrhea occurs, ONEXTON Gel should be
Severe colitis has occurred following oral and parenteral
administration of clindamycin with an onset of up to several weeks following
cessation of therapy. Antiperistaltic agents such as opiates and diphenoxylate
with atropine may prolong and/or worsen severe colitis. Severe colitis may
result in death.
Studies indicate toxin(s) produced by Clostridia is one
primary cause of antibiotic-associated colitis. The colitis is usually
characterized by severe persistent diarrhea and severe abdominal cramps and may
be associated with the passage of blood and mucus. Stool cultures for Clostridium
difficile and stool assay for C. difficile toxin may be helpful diagnostically.
Ultraviolet Light And Environmental Exposure
Minimize sun exposure (including use of tanning beds or
sun lamps) following drug application [see Nonclinical Toxicology].
Patient Counseling Information
See FDA-Approved Patient Labeling (PATIENT INFORMATION).
- Patients who develop allergic reactions such as severe
swelling or shortness of breath should discontinue use and contact their
- ONEXTON Gel may cause irritation such as erythema,
scaling, itching, or burning, especially when used in combination with other
topical acne therapies.
- Patients should limit excessive or prolonged exposure to
sunlight. To minimize exposure to sunlight, a hat or other clothing should be
worn. Sunscreen may also be used.
- ONEXTON Gel may bleach hair or colored fabric.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Carcinogenicity, mutagenicity and impairment of fertility
testing of ONEXTON Gel have not been performed.
Benzoyl peroxide has been shown to be a tumor promoter
and progression agent in a number of animal studies. Benzoyl peroxide in
acetone at doses of 5 and 10 mg administered topically twice per week for 20
weeks induced skin tumors in transgenic Tg.AC mice. The clinical significance
of this is unknown.
Carcinogenicity studies have been conducted with a gel
formulation containing 1% clindamycin and 5% benzoyl peroxide. In a 2-year
dermal carcinogenicity study in mice, treatment with the gel formulation at
doses of 900, 2700, and 15000 mg/kg/day (1.8, 5.4, and 30 times amount of
clindamycin and 2.4, 7.2, and 40 times amount of benzoyl peroxide in the highest
recommended adult human dose of 2.5 g ONEXTON Gel based on mg/m²,
respectively) did not cause any increase in tumors. However, topical treatment
with a different gel formulation containing 1% clindamycin and 5% benzoyl
peroxide at doses of 100, 500, and 2000 mg/kg/day caused a dose-dependent
increase in the incidence of keratoacanthoma at the treated skin site of male
rats in a 2-year dermal carcinogenicity study in rats. In an oral (gavage)
carcinogenicity study in rats, treatment with the gel formulation at doses of
300, 900 and 3000 mg/kg/day (1.2, 3.6, and 12 times amount of clindamycin and
1.6, 4.8, and 16 times amount of benzoyl peroxide in the highest recommended
adult human dose of 2.5 g ONEXTON Gel based on mg/m², respectively)
for up to 97 weeks did not cause any increase in tumors. In a 52-week dermal
photocarcinogenicity study in hairless mice, (40 weeks of treatment followed by
12 weeks of observation), the median time to onset of skin tumor formation
decreased and the number of tumors per mouse increased relative to controls
following chronic concurrent topical administration of the higher concentration
benzoyl peroxide formulation (5000 and 10000 mg/kg/day, 5 days/week) and
exposure to ultraviolet radiation.
Clindamycin phosphate was not genotoxic in the human
lymphocyte chromosome aberration assay. Benzoyl peroxide has been found to
cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic
in S. typhimurium tests by some but not all investigators, and to cause sister
chromatid exchanges in Chinese hamster ovary cells.
Fertility studies have not been performed with ONEXTON
Gel or benzoyl peroxide, but fertility and mating ability have been studied
with clindamycin. Fertility studies in rats treated orally with up to 300 mg/kg/day
of clindamycin (approximately 120 times the amount of clindamycin in the
highest recommended adult human dose of 2.5 g ONEXTON Gel, based on mg/m²)
revealed no effects on fertility or mating ability.
Use In Specific Populations
Pregnancy Category C
There are no adequate and well-controlled studies in
pregnant women treated with ONEXTON Gel. ONEXTON Gel should be used during
pregnancy only if the potential benefit justifies the potential risk to the
Animal reproductive/developmental toxicity studies have
not been conducted with ONEXTON Gel or benzoyl peroxide. Developmental toxicity
studies of clindamycin performed in rats and mice using oral doses of up to 600
mg/kg/day (240 and 120 times amount of clindamycin in the highest recommended
adult human dose based on mg/m², respectively) or subcutaneous doses
of up to 200 mg/kg/day (80 and 40 times the amount of clindamycin in the
highest recommended adult human dose based on mg/m², respectively)
revealed no evidence of teratogenicity.
It is not known whether clindamycin is excreted in human
milk after topical application of ONEXTON Gel. However, orally and parenterally
administered clindamycin has been reported to appear in breast milk. Because of
the potential for serious adverse reactions in nursing infants, a decision should
be made whether to use ONEXTON Gel while nursing, taking into account the
importance of the drug to the mother.
Safety and effectiveness of ONEXTON Gel in pediatric
patients under the age of 12 years have not been evaluated.
Clinical trials of ONEXTON Gel did not include sufficient
numbers of subjects age 65 years and older to determine whether they respond
differently from younger subjects.