Benzamycin Pak

• Tell all of your health care providers that you take Benzamycin Pak. This includes your doctors, nurses, pharmacists, and dentists.
• Certain acne products that contain benzoyl peroxide or salicylic acid can rarely cause very bad and sometimes life-threatening allergic reactions or very bad irritation. Before first use, you may need to follow certain steps to make sure you do not have an allergic reaction. Use this medicine as you were told by the doctor or read the package label. Talk with the doctor.
• Do not use longer than you have been told by the doctor.
• Use of other skin products while using Benzamycin Pak may cause more irritation.
• Talk with your doctor before you use other drugs or products on your skin.
• Use care when putting on. It may bleach hair or colored fabric.
• You may get sunburned more easily. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
• Diarrhea, bloody diarrhea, and a certain bowel problem (colitis) have happened with this medicine. Very bad colitis may lead to death. Call your doctor right away if you have stomach pain or cramps, very bad or watery diarrhea, or bloody diarrhea. Do not try to treat diarrhea without first checking with your doctor.
• This medicine may catch on fire. Do not use near an open flame or while smoking.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Benzamycin Pak while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Do not take Benzamycin Pak by mouth. Use on your skin only. Keep out of your mouth, nose, and eyes (may burn).
• Wash your hands before and after use.
• Wash and rinse affected skin with warm water, then pat dry.
• Mix in the palm of your hand.
• Use right away after mixing.
• Put a thin layer on the affected skin and rub in gently.
• Do not put on irritated skin.
• Put on gel at the same time of day.

What do I do if I miss a dose?

• Put on a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not put on 2 doses at the same time or extra doses.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very bad skin irritation.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

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 (formerlyStreptomyces 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 Homopolymer Type B, sodium hydroxide, dioctyl sodium sulfosuccinate 75%. Each Benzamycin Pak contains 0.8 grams of product.

Benzamycin Pak is indicated for the topical treatment of acne vulgaris.

General

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. If this occurs, discontinue use and take appropriate measures.

Avoid contact with eyes and all mucous membranes.

Information for Patients

Patients using Benzamycin Pak should receive the following information and instructions:

1. Patients should be informed that they will need to mix this medication prior to use. The medication will be dispensed in one foil pouch which contains medication in two separated compartments. 2. The contents must be mixed thoroughly by the patient (in the palm of the hand), prior to application. 3. Patients should apply the product immediately after mixing, then the hands should be washed. 4. Do not mix or apply near an open flame. 5. Benzamycin Pak may bleach hair or colored fabric. 6. Excessive or prolonged exposure to sunlight should be limited. To minimize exposure to sunlight, a hat or other clothing should be worn. 7. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes, mouth, and all mucous membranes as this product may be irritating. 8. Patients should report to their physician any signs of local adverse reactions. 9. This medication should not be used for any disorder other than that for which it was prescribed. 10. Patients should not use any other topical acne preparation unless otherwise directed by physician. 11. Patients should be instructed to review the instructions for use on the product carton. 12. This medication should be stored at room temperature away from heat and any open flame.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

The combination of benzoyl peroxide and erythromycin in Benzamycin Pak has not been evaluated for its carcinogenic or mutagenic potential or for its effects on fertility.

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 skin tumors in transgenic Tg.AC mice in a study using 20 weeks of topical treatment.

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.

No animal studies have been performed to evaluate the carcinogenic potential or effects on fertility of topical erythromycin. However, long-term (2-year) oral studies in rats with erythromycin base and erythromycin ethylsuccinate and in rats and mice with erythromycin stearate did not provide evidence of tumorigenicity.

The genotoxicity of erythromycin stearate has been evaluated in the Salmonella typhimurium reverse mutation assay, the mouse L5178Y lymphoma cell assay, and for sister chromatid exchanges and chromosomal aberrations in CHO cells. These studies indicated that erythromycin stearate was not genotoxic.

There was no apparent effect on male or female fertility in rats fed erythromycin base at levels up to 0.25% of diet.

Pregnancy

Teratogenic Effects: Pregnancy CATEGORY C

Animal reproduction studies have not been conducted with Benzamycin Pak 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 Benzamycin Pak. It also is not known whether Benzamycin Pak can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Benzamycin Pak should be given to a pregnant woman only if clearly needed.

Nursing Women

It is not known whether the ingredients of Benzamycin Pak are 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.

Pediatric Use

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

During clinical trials, 550 acne patients were studied. Of these patients, 236 were treated with Benzamycin Pak. The most frequently reported adverse event considered at least possibly related was dry skin (7.6%) as compared to Vehicle (3.9%). Application site reactions (stinging, burning sensation, tingling, erythema) were reported in 2.5% of patients versus 1.3% for Vehicle patients. Blepharitis, pruritus and photosensitivity reactions were reported in <2% of patients who used the dual pouch product.

	Treatment Group Summaries Number of Patients (%)
COSTART Term	Benzamycin Pak N = 236	Benzamycin Pak Vehicle N = 153	Benzamycin Topical Gel N = 121	Benzamycin Topical Gel Vehicle N = 40
DRY SKIN	18 (7.6%)	6 (3.9%)	6 (5.0%)	0
APPLICATION SITE REACTION (stinging, erythema, and burning)	6 (2.5%)	2 (1.3%)	1 (0.8%)	0
BLEPHARITIS	4 (1.7%)	1 (0.7%)	0	1 (2.5%)
PRURITUS	4 (1.7%)	2 (1.3%)	3 (2.5%)	0
PHOTOSENSITIVITY REACTION (Sunburn, stinging with sun exposure)	3 (1.3%)	0	0	0
PEELING	1 (0.5%)	1 (0.7%)	0	0

Benzamycin Pak requires thorough mixing by the patient immediately prior to each use. The medication 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.