Evoclin

Dosage Forms And Strengths

White to off-white thermolabile foam. Each gram of EVOCLIN Foam contains, as dispensed, 12 mg (1.2%) of clindamycin phosphate, equivalent to 10 mg (1%) of clindamycin.

EVOCLIN Foam containing clindamycin phosphate equivalent to 10 mg clindamycin per gram, is white to off-white in color and thermolabile. It is available in the following sizes:

100 gram aerosol can - NDC 0145-0061-00
50 gram aerosol can - NDC 0145-0061-50

Storage and Handling

Store at controlled room temperature between 68°F to 77°F (20°C to 25°C).

Flammable. Avoid fire, flame or smoking during and immediately following application.

Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperature above 120°F (49°C).

Keep out of reach of children.

Manufactured for: Stiefel Laboratories, Inc. Research Triangle Park, NC 27709. Revised: 1/2012

EVOCLIN Foam is indicated for topical application in the treatment of acne vulgaris in patients 12 years and older.

EVOCLIN Foam is for topical use only, and not for oral, ophthalmic, or intravaginal use.

Apply EVOCLIN Foam once daily to affected areas after the skin is washed with mild soap and allowed to fully dry. Use enough to cover the entire affected area.

If there has been no improvement after 6 to 8 weeks or if the condition becomes worse, treatment should be discontinued.

The contents of EVOCLIN Foam are flammable; avoid fire, flame and/or smoking during and immediately following application.

EVOCLIN Foam is contraindicated in individuals with a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis (including pseudomembranous colitis).

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Colitis

Systemic absorption of clindamycin has been demonstrated following topical use of this product. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical clindamycin. If significant diarrhea occurs, EVOCLIN Foam should be discontinued.

Severe colitis has occurred following oral or 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 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. Stool cultures for Clostridium difficile and stool assay for C. difficile toxin may be helpful diagnostically.

Irritation

EVOCLIN Foam can cause irritation. Concomitant topical acne therapy should be used with caution since a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. If irritation or dermatitis occurs, clindamycin should be discontinued.

Avoid contact of EVOCLIN Foam with eyes, mouth, lips, other mucous membranes or areas of broken skin. If contact occurs, rinse thoroughly with water.

EVOCLIN Foam should be prescribed with caution in atopic individuals.

Patient Counseling Information

See FDA-Approved patient labeling (PATIENT INFORMATION).

Instructions for Use

• Patients should be advised to wash their skin with mild soap and allow it to dry before applying EVOCLIN Foam.
• Patients should use enough EVOCLIN Foam to cover the face and to apply once daily.
• Patients should dispense EVOCLIN Foam directly into the cap or onto a cool surface.
• Patients should wash their hands after applying EVOCLIN Foam.

Skin Irritation

EVOCLIN Foam may cause irritation such as erythema, scaling, itching, burning, or stinging. Patients should be advised to discontinue use if excessive irritancy or dermatitis occur.

Colitis

In the event a patient treated with EVOCLIN Foam experiences severe diarrhea or gastrointestinal discomfort, EVOCLIN Foam should be discontinued and a physician should be contacted.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenicity of a 1.2% clindamycin phosphate gel similar to EVOCLIN Foam 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 Foam, assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals.

A 1.2% clindamycin phosphate gel similar to EVOCLIN Foam 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.

Use In Specific Populations

Pregnancy

Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women treated with EVOCLIN Foam. EVOCLIN Foam should be used during pregnancy only if the potential benefit clearly outweighs the potential risk to the fetus.

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 Foam based on a mg/m² comparison.

Nursing Mothers

It is not known whether clindamycin is excreted in human milk following use of EVOCLIN Foam. 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.

If used during lactation and EVOCLIN Foam is applied to the chest, care should be taken to avoid accidental ingestion by the infant.

Pediatric Use

Safety and effectiveness of EVOCLIN Foam in children under the age of 12 have not been studied.

Geriatric Use

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

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

A total of 439 subjects with mild to moderate acne vulgaris were treated once daily for 12 weeks with EVOCLIN Foam.

The incidence of adverse reactions occurring in ≥1% of the subjects in clinical trials comparing EVOCLIN Foam and its vehicle is presented in Table 1.

Table 1: Adverse Reactions Occurring in ≥1% of Subjects

In a contact sensitization study, none of the 203 subjects developed evidence of allergic contact sensitization to EVOCLIN Foam.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of EVOCLIN Foam: application site pain, application site erythema, diarrhea, urticaria, abdominal pain, hypersensitivity, rash, abdominal discomfort, nausea, seborrhea, application site rash, dizziness, pain of skin, colitis (including pseudomembranous colitis), and hemorrhagic diarrhea. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

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

DRUG INTERACTIONS

Erythromycin

EVOCLIN Foam should not be used in combination with topical or oral erythromycin-containing products due to possible antagonism to its clindamycin component. In vitro studies have shown antagonism between these two antimicrobials. The clinical significance of this in vitro antagonism is not known.

Neuromuscular Blocking Agents

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

Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women treated with EVOCLIN Foam. EVOCLIN Foam should be used during pregnancy only if the potential benefit clearly outweighs the potential risk to the fetus.

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 Foam based on a mg/m² comparison.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

A total of 439 subjects with mild to moderate acne vulgaris were treated once daily for 12 weeks with EVOCLIN Foam.

The incidence of adverse reactions occurring in ≥1% of the subjects in clinical trials comparing EVOCLIN Foam and its vehicle is presented in Table 1.

Table 1: Adverse Reactions Occurring in ≥1% of Subjects

In a contact sensitization study, none of the 203 subjects developed evidence of allergic contact sensitization to EVOCLIN Foam.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of EVOCLIN Foam: application site pain, application site erythema, diarrhea, urticaria, abdominal pain, hypersensitivity, rash, abdominal discomfort, nausea, seborrhea, application site rash, dizziness, pain of skin, colitis (including pseudomembranous colitis), and hemorrhagic diarrhea. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

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

No information provided.

Pharmacodynamics of EVOCLIN Foam is unknown.

In an open label, parallel group study in 24 subjects with acne vulgaris, 12 subjects (3 male and 9 female) applied 4 grams of EVOCLIN Foam once-daily for five days, and 12 subjects (7 male and 5 female) applied 4 grams of a clindamycin gel, 1%, once daily for five days. On Day 5, the mean Cmax and AUC(0-12) were 23% and 9% lower, respectively, for EVOCLIN Foam than for the clindamycin gel, 1%.

Following multiple applications of EVOCLIN Foam, less than 0.024% of the total dose was excreted unchanged in the urine over 12 hours on Day 5.