EVOCLIN 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 BELOW)

Contraindications

EVOCLIN is contraindicated in individuals with a history of:

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 stool assay 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.

Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective against C. difficile colitis.

Avoid contact of EVOCLIN with eyes. If contact occurs, rinse eyes thoroughly with water.

PRECAUTIONS

General: EVOCLIN should be prescribed with caution in atopic individuals.

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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenicity of a 1% clindamycin phosphate gel similar to EVOCLIN 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 EVOCLIN, 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 EVOCLIN 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 EVOCLIN based on a mg/m2 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 EVOCLIN. 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 of EVOCLIN in children under the age of 12 have not been studied.

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

ADVERSE REACTIONS

The incidence of adverse events occurring in greater than or equal to 1% of the patients in clinical studies comparing EVOCLIN and its vehicle is presented below:

Clinical trial-derived data show that EVOCLIN patients experienced minimal dryness, application-site burning or systemic exposure. Although EVOCLIN Foam is ethanol-based, application-site dryness was not one of the most commonly reported adverse events. A summary of the adverse events reported shows that:

• The most commonly reported adverse events were mild or moderate application-site burning (6%) and headache(3%)².
• Only 1% of subjects experienced application-site dryness or pruritus².
• Only 2 out of 439 subjects (0.46%) discontinued due to adverse events³.
• Incidence of systemic exposure was not significantly different than clindamycin gel².