Prescription Drugs

CLINICAL PHARMACOLOGY The exact method of action of benzoyl peroxide In acne vulgaris is not known. Benzoyl peroxide is an antibacterial agent with demonstrated activity against Propionibacterium acnes. This action, combined with the mild keratolytic effect of benzoyl peroxide is believed to be responsible for its usefulness in acne. Benzoyl peroxide is absorbed by the skin where it is metabolized to benzoic acid and excreted as benzoate in the urine.

CLINICAL PHARMACOLOGY Benzoyl peroxide is an antibacterial agent which has been shown to be effective against Propionibacterium acnes. This action is believed to be responsible for its usefulness in acne. One study in the rhesus monkey demonstrated a percutaneous absorption of about 1.8 µg per cm2 of benzoyl peroxide or 45% of the applied dose in a 24-hour period. The absorbed benzoyl peroxide was completely converted in the skin to benzoic acid.

Brevoxyl-4 Gel (benzoyl peroxide 4%) Brevoxyl-8 Gel (benzoyl peroxide 8%) AQUEOUS BASE ACNE GEL FOR TOPICAL USE DESCRIPTION Brevoxyl-4 Gel (benzoyl peroxide gel) and Brevoxyl-8 Gel are topical preparations containing benzoyl peroxide 4% and 8%, respectively, as the active Ingredient In a gel vehicle containing purified water, cetyl alcohol, dimethyl Isosorblde, fragrance, simethicone, stearyl alcohol and ceteareth-20. The structural formula of benzoyl peroxide is:

5 Benzagel (benzoyl peroxide gel) ® & 10 Benzagel® Acne Gel (benzoyl peroxide) Gel DESCRIPTION Each gram of 5 Benzagel (benzoyl peroxide gel) and 10 Benzagel contains 50 mg and 100 mg respectively, of benzoyl peroxide in a gel vehicle of purified water, carbomer 940, 14% alcohol, sodium hydroxide, docusate sodium and fragrances. Benzoyl peroxide is an antibacterial and keratolytic agent. The structural formula is: Hydrous Benzoyl Peroxide

INDICATIONS Brevoxyl-4 Gel (benzoyl peroxide gel) and Brevoxyl-8 Gel are indicated for use in the topical treatment of mild to moderate acne vulgaris. Brevoxyl-4 Gel (benzoyl peroxide gel) or Brevoxyl-8 Gel may be used as an adjunct in acne treatment regimens including antibiotics, retinoic acid products, and sulfur/salicylic acid containing preparations. DOSAGE AND ADMINISTRATION Therapy may be initiated with either Brevoxyl-4 Gel (benzoyl peroxide gel) or Brevoxyl-8 Gel. The medication should be applied once or twice daily to the affected areas. Frequency of use should be adjusted to obtain the desired clinical response. Gentle cleansing of the affected areas prior to application of Brevoxyl-4 Gel (benzoyl peroxide gel) or Brevoxyl-8 Gel may be beneficial. Clinically visible improvement will normally occur by the third week of therapy. Maximum lesion reduction may be expected after approximately eight to twelve weeks of drug use. Continuing use of the drug is normally required to maintain a satisfactory clinical response. HOW SUPPLIED Brevoxyl®-4 Gel is supplied in 42.5 g (1.5 oz) tubes NDC 0145-2374-06. Brevoxyl®-8 Gel is supplied in 42.5 g (1.5 oz) tubes NDC 0145-2384-06. Store at controlled room temperature 15°-30°C (59°- 86°F). Stiefel Laboratories, Inc. Coral Gables, FL 33134. Rev. 1007

INDICATIONS 5 & 10 Benzagel (benzoyl peroxide gel) may be used alone topically for mild to moderate acne and as an adjunct in acne treatment regimens which might include retinoic acid products, systemic antibiotics, and/or sulfur and salicylic acid containing preparations. The active ingredient, benzoyl peroxide, exerts a desquamative and antibacterial action. It provides mild peeling and keratolytic activity. DOSAGE AND ADMINISTRATION Wash and dry affected areas prior to application. Apply sparingly one or more times daily. HOW SUPPLIED 5 Benzagel (benzoyl peroxide gel) is available in 1.5 oz. (42.5g) (NDC 0066-0430-15) plastic tubes; 10 Benzagel (benzoyl peroxide gel) is available in 1.5 oz. (42.5 g) (NDC 0066-0431-15) plastic tubes. 5 Benzagel contains 50 mg of benzoyl peroxide per gram and 10 Benzagel contains 100 mg of benzoyl peroxide per gram. Store at Controlled Room Temperature 20 to 25°C (68 to 77°F) [See USP]. Revised October 2006. Mfd for: Dermik Laboratories, a business of sanofi-aventis U.S. LLC., Bridgewater, NJ 08807.

PATIENT INFORMATION No information provided. Please refer to the PRECAUTIONS section.

PATIENT INFORMATION No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

OVERDOSE No information provided. CONTRAINDICATIONS Brevoxyl-4 Gel (benzoyl peroxide gel) and Brevoxyl-8 Gel should not be used in patients who have shown hypersensitivity to benzoyl peroxide or to any of the other ingredients in the product.

OVERDOSE No information provided. CONTRAINDICATIONS Benzagel (benzoyl peroxide gel) should not be used by patients having known sensitivity to benzoyl peroxide or any of its components.

SIDE EFFECTS Contact sensitization reactions are associated with the use of topical benzoyl peroxide products and may be expected to occur in 10 to 25 of 1000 patients. The most frequent adverse reactions associated with benzoyl peroxide use are excessive erythema and peeling which may be expected to occur in 5 of 100 patients. Excessive erythema and peeling most frequently appear during the initial phase of drug use and may normally be controlled by reducing frequency of use. DRUG INTERACTIONS No information provided.

SIDE EFFECTS Irritation and contact dermatitis are the most frequent side reactions to benzoyl peroxide. DRUG INTERACTIONS No information provided.

WARNINGS No information provided. PRECAUTIONS General - For external use only. Avoid contact with eyes and mucous membranes. AVOID CONTACT WITH HAIR, FABRICS OR CARPETING AS BENZOYL PEROXIDE WILL CAUSE BLEACHING. Carcinogenesis, Mutagenesis, Impairment of Fertility Based upon all available evidence, benzoyl peroxide is not considered to be a carcinogen. However, data from a study using mice known to be highly susceptible to cancer suggest that benzoyl peroxide acts as a tumor promoter. The clinical significance of the findings is not known. Pregnancy Category C - Animal reproduction studies have not been conducted with benzoyl peroxide. It is also not known whether benzoyl peroxide can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Benzoyl peroxide should be used by a pregnant woman only if clearly needed. Nursing Mothers It is not known whetherthis drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when benzoyl peroxide is administered to a nursing woman. Pediatric Use Safety and effectiveness in children below the age of 12 have not been established.

WARNINGS If itching, redness, burning, swelling or undue dryness occurs, discontinue use. PRECAUTIONS For external use only. Not for ophthalmic use. Keep away from eyes and mucosae. Very fair individuals should begin with a single application at bedtime allowing overnight medication. May bleach colored fabrics. Keep this and all medications out of the reach of children. Carcinogenesis, Mutagenesis and Impairment of Fertility Long-term studies in animals have not been performed to evaluate carcinogenic potential. Pregnancy Category C Animal reproduction studies have not been conducted with benzoyl peroxide. It is also not known whether benzoyl peroxide can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Benzoyl peroxide should be given to a pregnant woman only if clearly needed. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when benzoyl peroxide is administered to a nursing woman. Pediatric Use Safety and effectiveness in pediatric patients under the age of 12 have not been established.