Benzamycin® Pak
(erythromycin 3%-benzoyl peroxide 5% topical gel)
For Dermatological Use Only – Not for Ophthalmic Use
DESCRIPTION
Benzamycin® Pak contains erythromycin [(3R*,4S*,5S*,6R*,7R*,9R*,11R*,12R*,13S*,14R*)-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-a-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)-b-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.
Benzamycin ® Pak also contains benzoyl peroxide for topical use. Benzoyl peroxide is an oxidizing agent demonstrating antibacterial activity.
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 product, as dispensed, contains 30 mg of erythromycin and 50 mg of benzoyl peroxide in a base of SD Alcohol 40B, purified water, hydroxypropyl cellulose, carbomer 934, sodium hydroxide, dioctyl sodium sulfosuccinate 75%. Each Benzamycin ® Pak contains 0.8 grams of product.
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CLINICAL PHARMACOLOGY
Pharmacokinetics
Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid. A single dose pharmacokinetic study, involving the application of either one or three units of Benzamycin ® Pak, was performed in 16 adult acne patients to determine systemic absorption of erythromycin. Erythromycin (with a plasma lower limit of quantitation of 2 ng/ml) was not detectable, except in one patient who was in the one unit application group.
Pharmacodynamics
The exact mechanism by which erythromycin and benzoyl peroxide reduce lesions of acne vulgaris is not fully known.
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CLINICAL STUDIES
In two adequate and well controlled clinical studies 228 patients used Benzamycin® Pak, 113 patients used the currently marketed Benzamycin® Topical Gel, and 183 patients used vehicle. Benzamycin® Pak applied twice daily for 8 weeks was significantly more effective than vehicle and comparable to Benzamycin® Topical Gel in the treatment of moderate to moderately severe facial acne vulgaris. Patients entering the study had a minimum of 15 and a maximum of 80 facial inflammatory lesions (papules and pustules) and a minimum of 20 and a maximum of 140 facial non-inflammatory lesions (open and closed comedones). The primary efficacy measures evaluated at week 8 were the lesion counts and the investigator's global assessment.
Patients were instructed to wash their face twice daily (morning and evening) with warm water and a mild cleanser provided by sponsor. No abrasive cloths or sponges, alcoholic toners, astringents or medicated solutions were used. The medication was to be applied 15 minutes after washing, in a thin film over the entire facial area. A moisturizer (supplied by the sponsor) or non-medicated make-up could be applied one hour after application, as needed. All medications were to be kept away from the eyes. Sun exposure to the face was to be limited.
Outcomes for mean percent reductions in lesion counts and investigators global assessment after 8 weeks of treatment are shown below:
| Study 1 | Benzamycin® Pak
N = 119 | Benzamycin®
Topical Gel
N = 113 | Benzamycin® Pak
Vehicle
N = 38 | Benzamycin®
Topical Gel
Vehicle
N = 37 |
|---|
| Mean % Lesion Counts Reduction | | | |
| Inflammatory
| 49% | 45% | 17% | 28% |
| Non Inflammatory | 46% | 43% | 24% | 20% |
| Total | 48% | 44% | 22% | 26% |
| Investigator's Global | | | |
| Global Success | 28% | 27% | 3% | 11% |
| Study 2 | Benzamycin Pak
N = 109 | Benzamycin Pak
Vehicle
N = 108 |
|---|
| Mean % Lesion Counts Reduction | |
| Inflammatory
| 57% | 34% |
| Non Inflammatory | 36% | 30% |
| Total | 45% | 31% |
| Investigator's Global | |
| Global Success | 36% | 12% |
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 has been shown to be effective in vitro against Propionibacterium acnes, an anaerobe found in sebaceous follicles and comedones. Benzoyl peroxide is believed to act by releasing active oxygen.
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