General Information
Benzoyl peroxide has been shown to be a tumor promoter and progression agent in a number of animal studies. The clinical significance of this is unknown. 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. Genotoxicity studies were not conducted with benzoyl peroxide; clindamycin. 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 benzoyl peroxide; clindamycin or benzoyl peroxide to evaluate the effect on fertility. 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 benzoyl peroxide; clindamycin, based on mg/m2) revealed no effects on fertility or mating ability.
Benzoic acid hypersensitivity, clindamycin hypersensitivity, lincomycin hypersensitivity
The risk versus benefit should be considered prior to using a benzoyl peroxide; clindamycin combination in patient with benzoic acid hypersensitivity. Cross-sensitivity may occur in patients sensitive to benzoic acid derivatives (e.g., cinnamon and certain topical anesthetics). Benzoyl peroxide; clindamycin products are contraindicated in patients with clindamycin hypersensitivity or lincomycin hypersensitivity or hypersensitivity to any other components of the product.
Eczema, ocular exposure, skin abrasion, skin disease, sunburn, sunlight (UV) exposure
Avoid accidental exposure of benzoyl peroxide; clindamycin products to the eyes, lips, mucus membranes and inflamed or raw skin due to severe irritation. If unintended mucus membrane or ocular exposure occurs, thoroughly rinse affected areas with water. Use of these products in patients with skin disease such as dermatitis, seborrhea, and eczema or with skin abrasion or inflammation, denuded skin including sunburn or windburn may increase the risk of skin irritation. The drug should be discontinued until skin sensitivity resolves. Patients should limit their sunlight (UV) exposure while using this drug product to decrease the risk for skin irritation. If mild to moderate itching, redness, swelling or dryness occurs, apply a moisturizer daily. If severe itching, redness, swelling or undue dryness occurs, consult health care provider and discontinue use.
Children, infants, neonates
Safe and effective use of benzoyl peroxide; clindamycin in neonates, infants, and children younger than 12 years of age has not been established. Avoid use in this patient population.
Colitis, Crohn's disease, diarrhea, GI disease, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis
Benzoyl peroxide; clindamycin combination products are contraindicated in patients with a history of regional enteritis (Crohn's disease), antibiotic-associated colitis, ulcerative colitis, or pseudomembranous colitis. Orally and parenterally administered clindamycin has been associated with severe colitis which may result in patient death. Use of topical clindamycin results in some (< 1% of the topical dose) systemic absorption from the skin surface. Almost all antibacterial agents have been associated with pseudomembranous colitis (antibiotic-associated colitis) which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may exist when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. It is known that systemic use of antibiotics predisposes patients to development of pseudomembranous colitis. Consideration should be given to the diagnosis of pseudomembranous colitis in patients presenting with diarrhea following antibacterial administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. In milder cases, the colitis may respond to discontinuation of the offending agent. In moderate to severe cases, fluids and electrolytes, protein supplementation, and treatment with an antibacterial effective against Clostridium difficile may be warranted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over two months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken.
Pregnancy
There are no well-controlled studies of benzoyl peroxide; clindamycin combination products in pregnant women and it is unknown if they can cause fetal harm when administered during pregnancy. Animal reproduction studies have not been conducted with topical application of these combinations. Developmental toxicity studies performed in rats and mice using oral doses of clindamycin up to 600 mg/kg/day (240 and 120 times the amount of clindamycin in the highest recommended adult human dose based on mg/m2, respectively) or subcutaneous doses of clindamycin up to 250 mg/kg/day (100 and 50 times the amount of clindamycin in the highest recommended adult human dose based on mg/m2, respectively) revealed no evidence of teratogenicity.
Breast-feeding
It is not known whether benzoyl peroxide; clindamycin is secreted into human milk after topical application; however, little systemic exposure occurs after topical application of these products. Orally and parenterally administered clindamycin has been reported to appear in breast milk. The American Academy of Pediatrics generally considers the use of clindamycin to be compatible with breast-feeding. Only water-miscible cream products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.