Bactroban (Mupirocin) CREAM (mupirocin calcium cream, 2%) contains the dihydrate crystalline calcium hemi-salt of the antibiotic mupirocin. Chemically, it is (α,2,3,4,5)-5-[(2,3,4,5)-2,3-Epoxy-5-hydroxy-4-methylhexyl]tetrahydro-3,4-dihydroxy-β-methyl-2-pyran-2-crotonic acid, ester with 9-hydroxynonanoic acid, calcium salt (2:1), dihydrate.

The molecular formula of mupirocin calcium is (CHO)Ca•2HO, and the molecular weight is 1075.3. The molecular weight of mupirocin free acid is 500.6. The structural formula of mupirocin calcium is:

Bactroban (Mupirocin) CREAM is a white cream that contains 2.15% w/w mupirocin calcium (equivalent to 2.0% mupirocin free acid) in an oil and water-based emulsion. The inactive ingredients are benzyl alcohol, cetomacrogol 1000, cetyl alcohol, mineral oil, phenoxyethanol, purified water, stearyl alcohol, and xanthan gum.

Mupirocin is an antibacterial agent produced by fermentation using the organism . It is active against a wide range of gram-positive bacteria including methicillin-resistant (MRSA). It is also active against certain gram-negative bacteria. Mupirocin inhibits bacterial protein synthesis by reversibly and specifically binding to bacterial isoleucyl transfer-RNA synthetase. Due to this unique mode of action, mupirocin demonstrates no in vitro cross-resistance with other classes of antimicrobial agents.

Resistance occurs rarely; however, when mupirocin resistance does occur, it appears to result from the production of a modified isoleucyl-tRNA synthetase. High-level plasmid-mediated resistance (MIC >1024 mcg/mL) has been reported in some strains of and coagulase-negative staphylococci.

Mupirocin is bactericidal at concentrations achieved by topical application. The minimum bactericidal concentration (MBC) against relevant pathogens is generally 8-fold to 30-fold higher than the minimum inhibitory concentration (MIC). In addition, mupirocin is highly protein bound (>97%), and the effect of wound secretions on the MICs of mupirocin has not been determined.

Mupirocin has been shown to be active against most strains of and , both in vitro and in clinical studies. (See INDICATIONS AND USAGE.) The following in vitro data are available, BUT THEIR CLINICAL SIGNIFICANCE IS UNKNOWN. Mupirocin is active against most strains of and .

Bactroban (Mupirocin) CREAM is indicated for the treatment of secondarily infected traumatic skin lesions (up to 10 cm in length or 100 cm in area) due to susceptible strains of and .

Bactroban (Mupirocin) CREAM is contraindicated in patients with known hypersensitivity to any of the constituents of the product.

Avoid contact with the eyes.

In the event of a sensitization or severe local irritation from Bactroban (Mupirocin) CREAM, usage should be discontinued, and appropriate alternative therapy for the infection instituted.

As with other antibacterial products, prolonged use may result in overgrowth of nonsusceptible microorganisms, including fungi. (See DOSAGE AND ADMINISTRATION.)

Bactroban (Mupirocin) CREAM is not formulated for use on mucosal surfaces.

• Use this medication only as directed by your healthcare provider. It is for external use only. Avoid contact with the eyes.

• The treated area may be covered by gauze dressing if desired.

• Report to your healthcare provider any signs of local adverse reactions. The medication should be stopped and your healthcare provider contacted if irritation, severe itching, or rash occurs.

• If no improvement is seen in 3 to 5 days, contact your healthcare provider.

Long-term studies in animals to evaluate carcinogenic potential of mupirocin calcium have not been conducted.

Results of the following studies performed with mupirocin calcium or mupirocin sodium in vitro and in vivo did not indicate a potential for mutagenicity: Rat primary hepatocyte unscheduled DNA synthesis, sediment analysis for DNA strand breaks, reversion test (Ames), mutation assay, metaphase analysis of human lymphocytes, mouse lymphoma assay, and bone marrow micronuclei assay in mice.

Fertility studies were performed in rats with mupirocin administered subcutaneously at doses up to 49 times a human topical dose of 1 gram/day (approximately 20 mg mupirocin per day) on a mg/m basis and revealed no evidence of impaired fertility from mupirocin sodium.

In 2 randomized, double-blind, double-dummy trials, 339 patients were treated with topical Bactroban (Mupirocin) CREAM plus oral placebo. Adverse events thought to be possibly or probably drug-related occurred in 28 (8.3%) patients. The incidence of those events that were reported in at least 1% of patients enrolled in these trials were: Headache (1.7%), rash, and nausea (1.1% each).

Other adverse events thought to be possibly or probably drug-related which occurred in less than 1% of patients were: Abdominal pain, burning at application site, cellulitis, dermatitis, dizziness, pruritus, secondary wound infection, and ulcerative stomatitis.

In a supportive study in the treatment of secondarily infected eczema, 82 patients were treated with Bactroban (Mupirocin) CREAM. The incidence of adverse events thought to be possibly or probably drug-related was as follows: Nausea (4.9%), headache, and burning at application site (3.6% each), pruritus (2.4%) and 1 report each of abdominal pain, bleeding secondary to eczema, pain secondary to eczema, hives, dry skin, and rash.

Intravenous infusions of 252 mg, as well as single oral doses of 500 mg of mupirocin, have been well tolerated in healthy adult subjects. There is no information regarding overdose of Bactroban (Mupirocin) CREAM.

A small amount of Bactroban (Mupirocin) CREAM should be applied to the affected area 3 times daily for 10 days. The area treated may be covered with gauze dressing if desired. Patients not showing a clinical response within 3 to 5 days should be re-evaluated.

The efficacy of topical Bactroban (Mupirocin) CREAM for the treatment of secondarily infected traumatic skin lesions (e.g., lacerations, sutured wounds, and abrasions not more than 10 cm in length or 100 cm in total area) was compared to that of oral cephalexin in 2 randomized, double-blind, double-dummy clinical trials. Clinical efficacy rates at follow-up in the per protocol populations (adults and pediatric patients included) were 96.1% for Bactroban (Mupirocin) CREAM (n = 231) and 93.1% for oral cephalexin (n = 219). Pathogen eradication rates at follow-up in the per protocol populations were 100% for both Bactroban (Mupirocin) CREAM and oral cephalexin.

Bactroban (Mupirocin) CREAM is supplied in 15-gram and 30-gram tubes.

NDC 0029-1527-22 (15-gram tube)

NDC 0029-1527-25 (30-gram tube)

Store at or below 25°C (77°F). Do not freeze.

GlaxoSmithKline

Research Triangle Park, NC 27709

Bactroban (Mupirocin) CREAM is a registered trademark of GlaxoSmithKline.

©2005, GlaxoSmithKline. All rights reserved.

May 2005 BB:L7B