Clindagel

Clindagel® containing clindamycin phosphate equivalent to 10 mg clindamycin per gram, is available in the following size:

75 mL bottle - NDC 16781-462-75

Store under controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Do not store in direct sunlight.

Manufactured for: Valeant Pharmaceuticals North America LLC, Bridgewater, NJ 08807 USA. by: DPT Laboratories, Ltd., San Antonio, Texas 78215 USA. Revised: Nov 2015

Clindagel® is indicated for topical application in the treatment of acne vulgaris. In view of the potential for diarrhea, bloody diarrhea and pseudomembranous colitis, the physician should consider whether other agents are more appropriate. (See CONTRAINDICATIONS, WARNINGS, and ADVERSE REACTIONS).

Apply a thin film of Clindagel® once daily to the skin where acne lesions appear. Use enough to cover the entire affected area lightly.

Keep container tightly closed.

Clindagel® is contraindicated in individuals with a history of hypersensitivity to preparations containing clindamycin or lincomycin, a history of regional enteritis or ulcerative colitis, or a history of antibioticassociated colitis.

WARNINGS

Orally and parenterally administered clindamycin has been associated with severe colitis , which may result in patient death. Use of the topical formulation of clindamycin results in absorption of the antibiotic from the skin surface. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis ) have been reported with the use of topical and systemic clindamycin.

Studies indicate a 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. Endoscopic examination may reveal pseudomembranous colitis. Stool culture for Clostridium difficile and stoolassay for C. difficile toxin may be helpful diagnostically.

When significant diarrhea occurs, the drug should be discontinued. Large bowel endoscopy should be considered to establish a definitive diagnosis in cases of severe diarrhea. Antiperistaltic agents, such as opiates and diphenoxylate with atropine, may prolong and/or worsen the condition.

Diarrhea, colitis , and pseudomembranous colitis have been observed to begin up to several weeks following cessation of oral and parenteral therapy with clindamycin.

PRECAUTIONS

General

Clindagel® should be prescribed with caution in atopic individuals.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

The carcinogenicity of a 1% clindamycin phosphate gel similar to Clindagel® was evaluated by daily application to mice for two years. The daily doses used in this study were approximately 3 and 15 times higher than the human dose of clindamycin phosphate from 5 milliliters of Clindagel® , assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals.

A 1% clindamycin phosphate gel similar to Clindagel® caused a statistically significant shortening of the median time to tumor onset in a study in hairless mice in which tumors were induced by exposure to simulated sunlight.

Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative. Reproduction studies in rats using oral doses of clindamycin hydrochloride and clindamycin palmitate hydrochloride have revealed no evidence of impaired fertility.

Pregnancy

Teratogenic Effects

Pregnancy Category B

Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of clindamycin phosphate, clindamycin hydrochloride and clindamycin palmitate hydrochloride. These studies revealed no evidence of fetal harm. The highest dose used in the rat and mouse teratogenicity studies was equivalent to a clindamycin phosphate dose of 432 mg/kg. For a rat, this dose is 84 fold higher and for a mouse 42 fold higher, than the anticipated human dose of clindamycin phosphate from Clindagel® based on a mg/m comparison. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether clindamycin is excreted in human milk following use of Clindagel®. 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 discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in children under the age of 12 have not been established.

Geriatric Use

The clinical study with Clindagel® did not include sufficient numbers of patients aged 65 and over to determine if they respond differently than younger patients.

SIDE EFFECTS

In the one well-controlled clinical study comparing Clindagel® and its vehicle, the incidence of skin and appendages adverse events occurring in ≥ 1% of the patients in either group is presented below:

Orally and parenterally administered clindamycin has been associated with severe colitis, which may end fatally.

Cases of diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported as adverse reactions in patients treated with oral and parenteral formulations of clindamycin and rarely with topical clindamycin (see WARNINGS). Abdominal pain and gastrointestinal disturbances, as well as gram-negative folliculitis, have also been reported in association with the use of topical formulations of clindamycin.

To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC at 1-800-321-4576 and/or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

DRUG INTERACTIONS

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents.

Teratogenic Effects

Pregnancy Category B

Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of clindamycin phosphate, clindamycin hydrochloride and clindamycin palmitate hydrochloride. These studies revealed no evidence of fetal harm. The highest dose used in the rat and mouse teratogenicity studies was equivalent to a clindamycin phosphate dose of 432 mg/kg. For a rat, this dose is 84 fold higher and for a mouse 42 fold higher, than the anticipated human dose of clindamycin phosphate from Clindagel® based on a mg/m comparison. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

In the one well-controlled clinical study comparing Clindagel® and its vehicle, the incidence of skin and appendages adverse events occurring in ≥ 1% of the patients in either group is presented below:

Orally and parenterally administered clindamycin has been associated with severe colitis, which may end fatally.

Cases of diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported as adverse reactions in patients treated with oral and parenteral formulations of clindamycin and rarely with topical clindamycin (see WARNINGS). Abdominal pain and gastrointestinal disturbances, as well as gram-negative folliculitis, have also been reported in association with the use of topical formulations of clindamycin.

To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC at 1-800-321-4576 and/or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Topically applied Clindagel® may be absorbed in sufficient amounts to produce systemic effects (see WARNINGS).

In an open label, parallel group study of 24 patients with acne vulgaris, once-daily topical administration of approximately 3-12 grams/day of Clindagel® for five days resulted in peak plasma clindamycin concentrations that were less than 5.5 ng/mL.

Following multiple applications of Clindagel® less than 0.04% of the total dose was excreted in the urine.