MUPIROCIN- mupirocin calcium cream 
Glenmark Generics Inc., USA

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Mupirocin Cream USP, 2%

For Dermatologic Use

Rx Only

DESCRIPTION

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

The molecular formula of mupirocin calcium USP is (C26H43O9)2Ca•2H2O, and the molecular weight is 1075.3. The molecular weight of mupirocin free acid is 500.6. The structural formula of mupirocin calcium USP is:

Structural Formula of Mupirocin Calcium USP

Mupirocin cream USP, 2% is a white cream that contains 2.15% w/w mupirocin calcium USP (equivalent to 2.0% mupirocin free acid) in an oil and water-based emulsion. The inactive ingredients are benzyl alcohol, glycerol monostearate, mineral oil, phenoxyethanol, polyoxyl 20 cetostearyl ether, purified water and xanthan gum.

CLINICAL PHARMACOLOGY

Pharmacokinetics:

Systemic absorption of mupirocin through intact human skin is minimal. The systemic absorption of mupirocin was studied following application of mupirocin cream three times daily for 5 days to various skin lesions (greater than 10 cm in length or 100 cm2 in area) in 16 adults (aged 29 to 60 years) and 10 children (aged 3 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 a 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 a 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.

INDICATIONS AND USAGE

Mupirocin cream USP, 2 % 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.

CONTRAINDICATIONS

Mupirocin cream is contraindicated in patients with known hypersensitivity to any of the constituents of the product.

WARNINGS

Avoid contact with the eyes.

In the event of a sensitization or severe local irritation from mupirocin cream, usage should be discontinued, and appropriate alternative therapy for the infection instituted.

PRECAUTIONS

General

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

Mupirocin 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.
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.

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 a 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 a human topical dose of 1 gram/day (approximately 20 mg mupirocin per day) on a 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, a human topical dose of 1 gram/day (approximately 20 mg mupirocin per day) on a 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 mupirocin cream is administered to a nursing woman.

Pediatric use

The safety and effectiveness of mupirocin cream have been established in the age groups 3 months to 16 years. Use of mupirocin cream in these age groups is supported by evidence from adequate and well-controlled studies of mupirocin 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 2 well-controlled studies, 30 patients older than 65 years were treated with mupirocin cream. No overall difference in the efficacy or safety of mupirocin cream was observed in this patient population when compared to that observed in younger patients.

ADVERSE REACTIONS

In 2 randomized, double-blind, double-dummy trials, 339 patients were treated with topical 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 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.

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 mupirocin cream.

DOSAGE AND ADMINISTRATION

A small amount of mupirocin cream USP should be applied to the affected area three 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.

CLINICAL STUDIES

The efficacy of topical 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 cm2 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 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 mupirocin cream and oral cephalexin.

Pediatrics:

There were 93 pediatric patients aged 2 weeks to 16 years enrolled per protocol in the secondarily infected skin lesion studies, although only 3 were less than 2 years of age in the population treated with mupirocin cream. Patients were randomized to either 10 days of topical mupirocin cream three times daily or 10 days of oral cephalexin (250 mg four times daily for patients >40 kg or 25 mg/kg/day oral suspension in 4 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 mupirocin cream and 93.9% (46/49) for cephalexin. Only 1 adverse event (headache) was thought to be possibly or probably related to drug therapy with mupirocin cream in the intent-to-treat pediatric population of 70 children (1.4%).

HOW SUPPLIED

Mupirocin cream USP, 2% is supplied in 15 gram and 30 gram tubes.

NDC 68462-564-17 (15 gram tube)

NDC 68462-564-35 (30 gram tube)

Store at 20o to 25oC (68o to 77oF) [see USP Controlled Room Temperature]. Do not freeze.

Manufactured by:

Glenmark Generics Ltd.
Colvale-Bardez, Goa 403 513, India

Manufactured for:
Glenmark Logo

Glenmark Generics Inc., USA
Mahwah, NJ 07430

Questions? 1 (888)721-7115
www.glenmarkgenerics.com

January 2012

Mupirocin Cream USP, 2% - Tube Label - 15 gm

Mupirocin Cream USP , 2 % - 15 gram tube label
MUPIROCIN 
mupirocin cream
Product Information
Product TypeHUMAN PRESCRIPTION DRUG LABELItem Code (Source)NDC:68462-564
Route of AdministrationTOPICALDEA Schedule    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
MUPIROCIN CALCIUM (MUPIROCIN) MUPIROCIN2 g  in 100 g
Inactive Ingredients
Ingredient NameStrength
MINERAL OIL 
PHENOXYETHANOL 
WATER 
XANTHAN GUM 
BENZYL ALCOHOL 
POLYOXYL 20 CETOSTEARYL ETHER 
GLYCERYL MONOSTEARATE 
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:68462-564-1715 g in 1 TUBE
2NDC:68462-564-3530 g in 1 TUBE
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA20158701/24/2013
Labeler - Glenmark Generics Inc., USA (130597813)
Establishment
NameAddressID/FEIBusiness Operations
Glenmark Generics Limited677318665ANALYSIS(68462-564), MANUFACTURE(68462-564)

Revised: 1/2013
Document Id: acd6e23e-d83f-4ed8-9c50-467ed422a8c4
Set id: acd6e23e-d83f-4ed8-9c50-467ed422a8c4
Version: 2
Effective Time: 20130125
 
Glenmark Generics Inc., USA