Erythromycin-Benzoyl Peroxide

Physicians Total Care, Inc.

FULL PRESCRIBING INFORMATION: CONTENTS*

• ERYTHROMYCIN-BENZOYL PEROXIDE DESCRIPTION
• CLINICAL PHARMACOLOGY
• MICROBIOLOGY
• ERYTHROMYCIN-BENZOYL PEROXIDE INDICATIONS AND USAGE
• ERYTHROMYCIN-BENZOYL PEROXIDE CONTRAINDICATIONS
• WARNINGS
• PRECAUTIONS
• ERYTHROMYCIN-BENZOYL PEROXIDE ADVERSE REACTIONS
• ERYTHROMYCIN-BENZOYL PEROXIDE DOSAGE AND ADMINISTRATION
• HOW SUPPLIED AND COMPOUNDING DIRECTIONS
• PRINCIPAL DISPLAY PANEL

FULL PRESCRIBING INFORMATION

Topical Gel: erythromycin (3%), benzoyl peroxide (5%)
For Dermatological Use Only – Not for Ophthalmic Use
Reconstitute Before Dispensing

ERYTHROMYCIN-BENZOYL PEROXIDE DESCRIPTION

Erythromycin-Benzoyl Peroxide Topical Gel contains erythromycin [(3R*, 4S*, 5S*, 6R*, 7R*, 9R*, 11R*, 12R*, 13S*, 14R*)-4-[(2,6-Dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-14-ethyl-7,12,13-trihydroxy-3,5,7,9,11,13-hexa-methyl-6-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione]. Erythromycin is a macrolide antibiotic produced from a strain of Saccharopolyspora erythraea (formerly Streptomyces erythreus). It is a base and readily forms salts with acids.

Chemically, erythromycin is (C₃₇H₆₇NO₁₃). It has the following structural formula:

Erythromycin has the molecular weight of 733.94. It is a white crystalline powder and has a solubility of approximately 1 mg/mL in water and is soluble in alcohol at 25°C.

Erythromycin-Benzoyl Peroxide Topical Gel also contains benzoyl peroxide for topical use. Benzoyl peroxide is an antibacterial and keratolytic agent.

Chemically, benzoyl peroxide is (C₁₄H₁₀O₄). It has the following structural formula:

Benzoyl peroxide has the molecular weight of 242.23. It is a white granular powder and is sparingly soluble in water and alcohol and soluble in acetone, chloroform and ether.

Each gram of Erythromycin-Benzoyl Peroxide Topical Gel contains, as dispensed, 30 mg (3%) of erythromycin and 50 mg (5%) of benzoyl peroxide in a base of purified water USP, carbomer, alcohol 20%, sodium hydroxide NF, docusate sodium and fragrance.

CLINICAL PHARMACOLOGY

The exact mechanism by which erythromycin reduces lesions of acne vulgaris is not fully known; however, the effect appears to be due in part to the antibacterial activity of the drug.

Benzoyl peroxide has a keratolytic and desquamative effect which may also contribute to its efficacy. Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid.

MICROBIOLOGY

Erythromycin acts by inhibition of protein synthesis in susceptible organisms by reversibly binding to 50 S ribosomal subunits, thereby inhibiting translocation of aminoacyl transfer-RNA and inhibiting polypeptide synthesis. Antagonism has been demonstrated in vitro between erythromycin, lincomycin, chloramphenicol and clindamycin.

Benzoyl peroxide is an antibacterial agent which has been shown to be effective against Propionibacterium acnes, an anaerobe found in sebaceous follicles and comedones. The antibacterial action of benzoyl peroxide is believed to be due to the release of active oxygen.

ERYTHROMYCIN-BENZOYL PEROXIDE INDICATIONS AND USAGE

Erythromycin-Benzoyl Peroxide Topical Gel is indicated for the topical treatment of acne vulgaris.

ERYTHROMYCIN-BENZOYL PEROXIDE CONTRAINDICATIONS

Erythromycin-Benzoyl Peroxide Topical Gel is contraindicated in those individuals who have shown hypersensitivity to any of its components.

WARNINGS

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including erythromycin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of "antibiotic-associated colitis."

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. 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.

PRECAUTIONS

For topical use only; not for ophthalmic use. Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating or abrasive agents. If severe irritation develops, discontinue use and institute appropriate therapy.

The use of antibiotic agents may be associated with the overgrowth of nonsusceptible organisms including fungi. If this occurs, discontinue use and take appropriate measures.

Avoid contact with eyes and all mucous membranes.

Patients using Erythromycin-Benzoyl Peroxide Topical Gel should receive the following information and instructions:

• This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes, nose, mouth, and all mucous membranes.
• This medication should not be used for any disorder other than that for which it was prescribed.
• Patients should not use any other topical acne preparation unless otherwise directed by physician.
• Patients should report to their physician any signs of local adverse reactions.
• Erythromycin-Benzoyl Peroxide Topical Gel may bleach hair or colored fabric.
• Keep product refrigerated and discard after 3 months.

Data from a study using mice known to be highly susceptible to cancer suggests that benzoyl peroxide acts as a tumor promoter. The clinical significance of this is unknown.

No animal studies have been performed to evaluate the carcinogenic and mutagenic potential or effects on fertility of topical erythromycin. However, long-term (2-year) oral studies in rats with erythromycin ethylsuccinate and erythromycin base did not provide evidence of tumorigenicity. There was no apparent effect on male or female fertility in rats fed erythromycin (base) at levels up to 0.25% of diet.

Animal reproduction studies have not been conducted with Erythromycin-Benzoyl Peroxide Topical Gel or benzoyl peroxide.

There was no evidence of teratogenicity or any other adverse effect on reproduction in female rats fed erythromycin base (up to 0.25% diet) prior to and during mating, during gestation and through weaning of two successive litters.

There are no well-controlled trials in pregnant women with Erythromycin-Benzoyl Peroxide Topical Gel. It also is not known whether Erythromycin-Benzoyl Peroxide Topical Gel can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Erythromycin-Benzoyl Peroxide Topical Gel should be given to a pregnant woman only if clearly needed.

It is not known whether Erythromycin-Benzoyl Peroxide Topical Gel is excreted in human milk after topical application. However, erythromycin is excreted in human milk following oral and parenteral erythromycin administration. Therefore, caution should be exercised when erythromycin is administered to a nursing woman.

Safety and effectiveness of this product in pediatric patients below the age of 12 have not been established.

ERYTHROMYCIN-BENZOYL PEROXIDE ADVERSE REACTIONS

In controlled clinical trials, the incidence of adverse reactions associated with the use of Erythromycin-Benzoyl Peroxide Topical Gel was approximately 3%. These were dryness and urticarial reaction.

The following additional local adverse reactions have been reported occasionally: irritation of the skin including peeling, itching, burning sensation, erythema, inflammation of the face, eyes and nose, and irritation of the eyes. Skin discoloration, oiliness and tenderness of the skin have also been reported.

ERYTHROMYCIN-BENZOYL PEROXIDE DOSAGE AND ADMINISTRATION

Erythromycin-Benzoyl Peroxide Topical Gel should be applied twice daily, morning and evening, or as directed by a physician, to affected areas after the skin is thoroughly washed, rinsed with warm water and gently patted dry.

HOW SUPPLIED AND COMPOUNDING DIRECTIONS

Prior to dispensing, tap vial until all powder flows freely. Add indicated amount of room temperature 70% ethyl alcohol to vial (to the mark) and immediately shake to completely dissolve erythromycin. Add this solution to gel and stir until homogeneous in appearance (1 to 1½ minutes). Erythromycin-Benzoyl Peroxide Topical Gel should then be stored under refrigeration. Do not freeze. Place a 3-month expiration date on the label.

NOTE: Prior to reconstitution, store at room temperature between 15° and 30°C (59° – 86°F).

After reconstitution, store under refrigeration between 2° and 8°C (36° – 46°F).

Do not freeze. Keep tightly closed. Keep out of the reach of children.

Prescribing Information as of March 2006.

Manufactured by:
sanofi-aventis Canada Inc.,
Laval, Quebec, Canada H7L 4A8

Distributed by:
Perrigo^®
Allegan, MI 49010

Country of Origin: Canada

Relabeling of "Additional Barcode Label" by:
Physicians Total Care, Inc.
Tulsa, OK     74146

Erythromycin-Benzoyl Peroxide Topical Gel

PRINCIPAL DISPLAY PANEL

Erythromycin-Benzoyl Peroxide Topical Gel

23.3 grams (as dispensed)