1.1 Indication

Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 5% is indicated for the topical treatment of inflammatory acne vulgaris in patients 12 years and older.

1.2 Limitations of Use

Clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% has not been demonstrated to have any additional benefit when compared with benzoyl peroxide alone in the same vehicle when used for the treatment of non-inflammatory acne.

4.1 Hypersensitivity

Clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% is contraindicated in those individuals who have shown hypersensitivity to clindamycin, benzoyl peroxide, any components of the formulation, or lincomycin. Anaphylaxis, as well as allergic reactions leading to hospitalization, has been reported in postmarketing use with clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5%. [See Adverse Reactions (6.2).]

4.2 Colitis/Enteritis

Clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% is contraindicated in those individuals with a history of regional enteritis, ulcerative colitis, pseudomembranous colitis, or antibiotic-associated colitis [see Warnings and Precautions (5.1)].

5.1 Colitis

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, clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% should be discontinued.

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 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.

5.2 Ultraviolet Light and Environmental Exposure

Benzoyl peroxide, a component of clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5%, may cause increased sensitivity to sunlight. Minimize sun exposure (including use of tanning beds or sun lamps) following drug application. [See Nonclinical Toxicology (13.1).] Patients who may be required to have considerable sun exposure due to occupation and those with inherent sensitivity to the sun should exercise particular caution.

6.1 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

During clinical trials, 397 subjects used clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% once daily for 11 weeks for the treatment of moderate to moderately severe facial acne vulgaris. All subjects were graded for facial local skin reactions (erythema, peeling, burning, and dryness) on the following scale: 0 = absent, 1 = mild, 2 = moderate, and 3 = severe. The percentage of subjects that had symptoms present before treatment (at baseline) and during treatment is presented in Table 1.

Table 1. Local Skin Reactions with Use of Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 5% Combined Results from Five Trials (n = 397)

(Percentages derived by number of subjects receiving clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% with symptom score/number of enrolled subjects receiving clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5%).

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5%. 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.

Anaphylaxis, as well as allergic reactions leading to hospitalization, has been reported in postmarketing use with clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5%.

Urticaria, application site reactions, including discoloration have been reported.

7.1 Erythromycin

Avoid using clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% in combination with erythromycin-containing products due to its clindamycin component. In vitro studies have shown antagonism between erythromycin and clindamycin. The clinical significance of this in vitro antagonism is not known.

7.2 Concomitant Topical Medications

 Concomitant topical acne therapies should be used with caution since a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. If irritancy or dermatitis occurs, reduce frequency of application or temporarily interrupt treatment and resume once the irritation subsides. Treatment should be discontinued if the irritation persists.

7.3 Neuromuscular Blocking Agents

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% should be used with caution in patients receiving such agents.

7.4 Topical Sulfone Products

Use of topical benzoyl-peroxide-containing preparations with topical sulfone products may cause skin and facial hair to temporarily change color (yellow/orange).

8.1 Pregnancy

Pregnancy Category C.

There are no adequate and well-controlled studies in pregnant women treated with clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5%. Clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Developmental toxicity studies performed in rats and mice using oral doses of clindamycin up to 600 mg per kg per day (240 and 120 times the amount of clindamycin in the highest recommended adult human dose based on mg per m2, respectively) or subcutaneous doses of clindamycin up to 250 mg per kg per day (100 and 50 times the amount of clindamycin in the highest recommended adult human dose based on mg per m2, respectively) revealed no evidence of teratogenicity.

8.3 Nursing Mothers

It is not known whether clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% is excreted into human milk after topical application. 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. Because many drugs are excreted in human milk, caution should be exercised when clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% in pediatric patients below the age of 12 have not been established.

8.5 Geriatric Use

Clinical studies of clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% did not include sufficient numbers of subjects ages 65 and over to determine whether they respond differently from younger subjects.

12.1 Mechanism of Action

Clindamycin

Clindamycin is a lincosamide antibacterial [see Clinical Pharmacology (12.4)].

Benzoyl Peroxide

Benzoyl peroxide is an oxidizing agent with bacteriocidal and keratolytic effects, but the precise mechanism of action is unknown.

12.3 Pharmacokinetics

A comparative trial of the pharmacokinetics of clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% and 1% clindamycin solution alone in 78 subjects indicated that mean plasma clindamycin levels during the 4-week dosing period were less than 0.5 ng/mL for both treatment groups.

Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid. Less than 2% of the dose enters systemic circulation as benzoic acid.

12.4 Microbiology

Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis.

In Vivo Activity

No microbiology studies were conducted in the clinical trials with this product.

In Vitro Activity

The clindamycin and benzoyl peroxide components individually have been shown to have in vitro activity against Propionibacterium acnes, an organism which has been associated with acne vulgaris; however, the clinical significance of this in vitro activity is not known.

Drug Resistance

There are reports of an increase of P. acnes resistance to clindamycin in the treatment of acne. In patients with P. acnes resistant to clindamycin, the clindamycin component may provide no additional benefit beyond benzoyl peroxide alone.

13.1 Carcinogenesis and Mutagenesis and Impairment of Fertility

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 twice per week induced squamous cell skin tumors in transgenic TgAC mice in a study using 20 weeks of topical treatment. The clinical significance of this is unknown.

In a 2-year dermal carcinogenicity study in mice, treatment with clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% at doses up to 8,000 mg per kg per day (16 times the highest recommended adult human dose of 2.5 g clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5%, based on mg per m2) did not cause an increase in skin tumors. However, topical treatment with another formulation containing 1% clindamycin and 5% benzoyl peroxide at doses of 100, 500, or 2,000 mg per kg per 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 a 52-week 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 treatment with clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5% and exposure to ultraviolet radiation.

Genotoxicity studies were not conducted with clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5%. Clindamycin phosphate was not genotoxic in Salmonella typhimurium or in a rat micronucleus test. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in Salmonella typhimurium tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells.

Studies have not been performed with clindamycin phosphate and benzoyl peroxide gel,

1.2% / 5% or benzoyl peroxide to evaluate the effect on fertility. Fertility studies in rats treated orally with up to 300 mg per kg per day of clindamycin (approximately 120 times the amount of clindamycin in the highest recommended adult human dose of 2.5 g clindamycin phosphate and benzoyl peroxide gel, 1.2% / 5%, based on mg per m2) revealed no effects on fertility or mating ability.

16.1  How Supplied

Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 5% is a white to slightly yellow, opaque gel. It is supplied as follows:

• 45 gram tube NDC 0781-7161-19

16.2 Storage and Handling

 Pharmacist:

• Prior to Dispensing: Store in a cold place, preferably in a refrigerator, between 2°C and 8°C (36°F and 46°F). Do not freeze.

16.3 Dispensing Instructions for the Pharmacist

• Dispense Clindamycin Phosphate and Benzoyl Peroxide Gel, 1.2% / 5% with a 60-day expiration date.
• Specify “Store at room temperature up to 25°C (77°F). Do not freeze.”
• Keep tube tightly closed.
• Keep out of the reach of small children.