PEDIATRIC USE SECTION.

Pediatric Use. The safety and effectiveness of BACTROBAN CREAM have been established in the age groups months to 16 years. Use of BACTROBAN CREAM in these age groups is supported by evidence from adequate and well-controlled studies of BACTROBAN CREAM in adults with additional data from 93 pediatric patients studied as part of the pivotal trials in adults. (See CLINICAL STUDIES.).

PRECAUTIONS SECTION.

PRECAUTIONS. General. As with other antibacterial products, prolonged use may result in overgrowth of nonsusceptible microorganisms, including fungi. (See DOSAGE AND ADMINISTRATION.) BACTROBAN CREAM is not formulated for use on mucosal surfaces.. Information for Patients. Use this medication only as directed by your healthcare provider. It is for external use only. Avoid contact with the eyes.o The treated area may be covered by gauze dressing if desired.o 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.o If no improvement is seen in to days, contact your healthcare provider.. Drug Interactions. The effect of the concurrent application of topical mupirocin calcium cream and other topical products has not been studied.. Carcinogenesis, Mutagenesis, Impairment of Fertility. 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 potential for mutagenicity: Rat primary hepatocyte unscheduled DNA synthesis, sediment analysis for DNA strand breaks, Salmonella reversion test (Ames), Escherichia coli 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 human topical dose of gram/day (approximately 20 mg mupirocin per day) on mg/m2 basis and revealed no evidence of impaired fertility from mupirocin sodium.. Pregnancy. Teratogenic Effects: Pregnancy Category B. Teratology studies have been performed in rats and rabbits with mupirocin administered subcutaneously at doses up to 78 and 154 times, respectively, human topical dose of gram/day (approximately 20 mg mupirocin per day) on mg/m2 basis and revealed no evidence of harm to the fetus due to mupirocin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy 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 BACTROBAN CREAM is administered to nursing woman.. Pediatric Use. The safety and effectiveness of BACTROBAN CREAM have been established in the age groups months to 16 years. Use of BACTROBAN CREAM in these age groups is supported by evidence from adequate and well-controlled studies of BACTROBAN CREAM in adults with additional data from 93 pediatric patients studied as part of the pivotal trials in adults. (See CLINICAL STUDIES.). Geriatric Use. In well-controlled studies, 30 patients older than 65 years were treated with BACTROBAN CREAM. No overall difference in the efficacy or safety of BACTROBAN CREAM was observed in this patient population when compared to that observed in younger patients.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, Mutagenesis, Impairment of Fertility. 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 potential for mutagenicity: Rat primary hepatocyte unscheduled DNA synthesis, sediment analysis for DNA strand breaks, Salmonella reversion test (Ames), Escherichia coli 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 human topical dose of gram/day (approximately 20 mg mupirocin per day) on mg/m2 basis and revealed no evidence of impaired fertility from mupirocin sodium.

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS. In randomized, double-blind, double-dummy trials, 339 patients were treated with topical BACTROBAN 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 supportive study in the treatment of secondarily infected eczema, 82 patients were treated with BACTROBAN 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 report each of abdominal pain, bleeding secondary to eczema, pain secondary to eczema, hives, dry skin, and rash.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

BACTROBAN CREAM(R) MUPIROCIN CALCIUM CREAM 2% PACKAGE LABEL. Label Structure.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. Pharmacokinetics. Systemic absorption of mupirocin through intact human skin is minimal. The systemic absorption of mupirocin was studied following application of BACTROBAN CREAM times daily for days to various skin lesions (>10 cm in length or 100 cm2 in area) in 16 adults (aged 29 to 60 years) and 10 children (aged to 12 years). Some systemic absorption was observed as evidenced by the detection of the metabolite, monic acid, in urine. Data from this study indicated more frequent occurrence of percutaneous absorption in children (90% of patients) compared to adults (44% of patients); however, the observed urinary concentrations in children (0.07 1.3 mcg/mL [1 pediatric patient had no detectable level]) are within the observed range (0.08 10.03 mcg/mL [9 adults had no detectable level]) in the adult population. In general, the degree of percutaneous absorption following multiple dosing appears to be minimal in adults and children. Any mupirocin reaching the systemic circulation is rapidly metabolized, predominantly to inactive monic acid, which is eliminated by renal excretion.. Microbiology. Mupirocin is an antibacterial agent produced by fermentation using the organism Pseudomonas fluorescens. It is active against wide range of gram-positive bacteria including methicillin-resistant Staphylococcus aureus (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 modified isoleucyl-tRNA synthetase. High-level plasmid-mediated resistance (MIC >1024 mcg/mL) has been reported in some strains of Staphylococcus aureus 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 S. aureus and Streptococcus pyogenes, 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 Staphylococcus epidermidis and Staphylococcus saprophyticus.

CLINICAL STUDIES SECTION.

CLINICAL STUDIES. The efficacy of topical BACTROBAN 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 cm2 in total area) was compared to that of oral cephalexin in 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 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 CREAM and oral cephalexin.Pediatrics: There were 93 pediatric patients aged weeks to 16 years enrolled per protocol in the secondarily infected skin lesion studies, although only were less than years of age in the population treated with BACTROBAN CREAM. Patients were randomized to either 10 days of topical BACTROBAN CREAM times daily or 10 days of oral cephalexin (250 mg times daily for patients >40 kg or 25 mg/kg/day oral suspension in divided doses for patients <=40 kg). Clinical efficacy at follow-up (7 to 12 days post-therapy) in the per protocol populations was 97.7% (43/44) for BACTROBAN CREAM and 93.9% (46/49) for cephalexin. Only adverse event (headache) was thought to be possibly or probably related to drug therapy with BACTROBAN CREAM in the intent-to-treat pediatric population of 70 children (1.4%).

CONTRAINDICATIONS SECTION.

CONTRAINDICATIONS. BACTROBAN CREAM is contraindicated in patients with known hypersensitivity to any of the constituents of the product.

DESCRIPTION SECTION.

DESCRIPTION. BACTROBAN CREAM (mupirocin calcium cream, 2%) contains the dihydrate crystalline calcium hemi-salt of the antibiotic mupirocin. Chemically, it is (E,2S,3R,4R,5S)-5-[(2S,3S,4S,5S)-2,3-Epoxy-5-hydroxy-4-methylhexyl]tetrahydro-3,4-dihydroxy--methyl-2H-pyran-2-crotonic acid, ester with 9-hydroxynonanoic acid, calcium salt (2:1), dihydrate. The molecular formula of mupirocin calcium is (C26H43O9)2Cao2H2O, 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 CREAM is 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.. chemical structure.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. small amount of BACTROBAN CREAM should be applied to the affected area times daily for 10 days. The area treated may be covered with gauze dressing if desired. Patients not showing clinical response within to days should be re-evaluated.

DRUG INTERACTIONS SECTION.

Drug Interactions. The effect of the concurrent application of topical mupirocin calcium cream and other topical products has not been studied.

GENERAL PRECAUTIONS SECTION.

General. As with other antibacterial products, prolonged use may result in overgrowth of nonsusceptible microorganisms, including fungi. (See DOSAGE AND ADMINISTRATION.) BACTROBAN CREAM is not formulated for use on mucosal surfaces.

GERIATRIC USE SECTION.

Geriatric Use. In well-controlled studies, 30 patients older than 65 years were treated with BACTROBAN CREAM. No overall difference in the efficacy or safety of BACTROBAN CREAM was observed in this patient population when compared to that observed in younger patients.

HOW SUPPLIED SECTION.

HOW SUPPLIED. BACTROBAN 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 25C (77F). Do not freeze.GlaxoSmithKlineResearch Triangle Park, NC 27709BACTROBAN CREAM is registered trademark of GlaxoSmithKline.(C)2005, GlaxoSmithKline. All rights reserved.May 2005 BB:L7B.

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE. BACTROBAN CREAM is indicated for the treatment of secondarily infected traumatic skin lesions (up to 10 cm in length or 100 cm2 in area) due to susceptible strains of S. aureus and S. pyogenes.

INFORMATION FOR PATIENTS SECTION.

Information for Patients. Use this medication only as directed by your healthcare provider. It is for external use only. Avoid contact with the eyes.o The treated area may be covered by gauze dressing if desired.o 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.o If no improvement is seen in to days, contact your healthcare provider.

NURSING MOTHERS SECTION.

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 BACTROBAN CREAM is administered to nursing woman.

OVERDOSAGE SECTION.

OVERDOSAGE. 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 CREAM.

PREGNANCY SECTION.

Pregnancy. Teratogenic Effects: Pregnancy Category B. Teratology studies have been performed in rats and rabbits with mupirocin administered subcutaneously at doses up to 78 and 154 times, respectively, human topical dose of gram/day (approximately 20 mg mupirocin per day) on mg/m2 basis and revealed no evidence of harm to the fetus due to mupirocin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

SPL UNCLASSIFIED SECTION.

Pharmacokinetics. Systemic absorption of mupirocin through intact human skin is minimal. The systemic absorption of mupirocin was studied following application of BACTROBAN CREAM times daily for days to various skin lesions (>10 cm in length or 100 cm2 in area) in 16 adults (aged 29 to 60 years) and 10 children (aged to 12 years). Some systemic absorption was observed as evidenced by the detection of the metabolite, monic acid, in urine. Data from this study indicated more frequent occurrence of percutaneous absorption in children (90% of patients) compared to adults (44% of patients); however, the observed urinary concentrations in children (0.07 1.3 mcg/mL [1 pediatric patient had no detectable level]) are within the observed range (0.08 10.03 mcg/mL [9 adults had no detectable level]) in the adult population. In general, the degree of percutaneous absorption following multiple dosing appears to be minimal in adults and children. Any mupirocin reaching the systemic circulation is rapidly metabolized, predominantly to inactive monic acid, which is eliminated by renal excretion.

TERATOGENIC EFFECTS SECTION.

Teratogenic Effects: Pregnancy Category B. Teratology studies have been performed in rats and rabbits with mupirocin administered subcutaneously at doses up to 78 and 154 times, respectively, human topical dose of gram/day (approximately 20 mg mupirocin per day) on mg/m2 basis and revealed no evidence of harm to the fetus due to mupirocin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

WARNINGS SECTION.

WARNINGS. Avoid contact with the eyes. In the event of sensitization or severe local irritation from BACTROBAN CREAM, usage should be discontinued, and appropriate alternative therapy for the infection instituted.