Mupirocin

1 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 cm 2 in area) due to susceptible isolates of Staphylococcus aureus (S. aureus) and Streptococcus pyogenes (S. pyogenes) . Mupirocin cream is an RNA synthetase inhibitor antibacterial indicated for the treatment of secondarily infected traumatic skin lesions (up to 10 cm in length or 100 cm 2 in area) due to susceptible isolates of Staphylococcus aureus and Streptococcus pyogenes . ( 1 )

2 DOSAGE AND ADMINISTRATION • For Topical Use Only. • Apply a small amount of mupirocin cream, with a cotton swab or gauze pad, to the affected area 3 times daily for 10 days. • Cover the treated area with gauze dressing if desired. • Re-evaluate patients not showing a clinical response within 3 to 5 days. • Mupirocin cream is not for intranasal, ophthalmic, or other mucosal use [see Warnings and Precautions ( 5.2 , 5.6 )] . • Do not apply mupirocin cream concurrently with any other lotions, creams, or ointments [see Clinical Pharmacology ( 12.3 )]. • For Topical Use Only. ( 2 ) • Apply a small amount of mupirocin cream, with a cotton swab or gauze pad, to the affected area 3 times daily for 10 days. ( 2 ) • Re-evaluate patients not showing a clinical response within 3 to 5 days. ( 2 ) • Not for intranasal, ophthalmic, or other mucosal use. ( 2 )

3 DOSAGE FORMS AND STRENGTHS Mupirocin Cream USP is a white cream that contains 20 mg (2% w/w) of mupirocin per gram (equivalent to 21.5 mg (2.15% w/w) of mupirocin calcium, USP) in an oil- and water-based emulsion, supplied in 15-gram and 30-gram tubes. Cream: 20 mg (2% w/w) of mupirocin per gram (equivalent to 21.5 mg (2.15% w/w) of mupirocin calcium, USP) in 15-gram and 30-gram tubes. ( 3 )

4 CONTRAINDICATIONS Mupirocin cream is contraindicated in patients with known hypersensitivity to mupirocin or any of the excipients of mupirocin cream. Known hypersensitivity to mupirocin or any of the excipients of mupirocin cream. ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: • Severe Allergic Reactions [see Warnings and Precautions ( 5.1 )] • Eye Irritation [see Warnings and Precautions ( 5.2 )] • Local Irritation [see Warnings and Precautions ( 5.3 )] • Clostridium difficile -Associated Diarrhea [see Warnings and Precautions ( 5.4 )] • The most frequent adverse reactions (at least 1%) were headache, rash, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Glenmark Pharmaceuticals Inc., USA at 1(888)721-7115 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. In 2 randomized, double-blind, double-dummy trials, 339 subjects were treated with topical mupirocin cream plus oral placebo. Adverse reactions occurred in 28 (8.3%) subjects. The following adverse reactions were reported by at least 1% of subjects in connection with the use of mupirocin cream in clinical trials: headache (1.7%), rash (1.1%), and nausea (1.1%). Other adverse reactions which occurred in less than 1% of subjects were: abdominal pain, burning at application site, cellulitis, dermatitis, dizziness, pruritus, secondary wound infection, and ulcerative stomatitis. In a supportive trial in the treatment of secondarily infected eczema, 82 subjects were treated with mupirocin cream. The incidence of adverse reactions 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. 6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following reactions have been identified during postmarketing use of mupirocin cream. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal relationship to mupirocin cream. Immune System Disorders Systemic allergic reactions, including anaphylaxis, urticaria, angioedema, and generalized rash [see Warnings and Precautions ( 5.1 )] .

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are insufficient human data to establish whether there is a drug-associated risk with mupirocin cream in pregnant women. Systemic absorption of mupirocin through intact human skin is minimal following topical administration of mupirocin cream [see Clinical Pharmacology ( 12.3 )] . No developmental toxicity was observed in rats or rabbits treated with mupirocin subcutaneously during organogenesis at doses of 160 or 40 mg per kg per day, respectively (22 and 11 times the human topical dose based on calculations of dose divided by the entire body surface area). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. The estimated background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data: Developmental toxicity studies have been performed with mupirocin administered subcutaneously to rats and rabbits at doses up to 160 mg per kg per day during organogenesis. This dose is 22 and 43 times, respectively, the human topical dose (approximately 60 mg mupirocin per day) based on calculations of dose divided by the entire body surface area. Maternal toxicity was observed (body weight loss/decreased body weight gain and reduced feeding) in both species with no evidence of developmental toxicity in rats. In rabbits, excessive maternal toxicity at the high dose precluded the evaluation of fetal outcomes. There was no developmental toxicity in rabbits at 40 mg per kg per day, 11 times the human topical dose based on calculations of dose divided by the entire body surface area. Mupirocin administered subcutaneously to rats in a prenatal and postnatal development study (dosed during late gestation through lactation) was associated with reduced offspring viability in the early postnatal period at a dose of 106.7 mg per kg, in the presence of injection site irritation and/or subcutaneous hemorrhaging. This dose is 14 times the human topical dose based on calculations of dose divided by the entire body surface area. The no-observed adverse effect level in this study was 44.2 mg per kg per day, which is 6 times the human topical dose. 8.2 Lactation Risk Summary It is not known whether mupirocin is present in human milk, has effects on the breastfed child, or has effects on milk production. However, breastfeeding is not expected to result in exposure of the child to the drug due to the minimal systemic absorption of mupirocin in humans following topical administration of mupirocin cream [see Clinical Pharmacology ( 12.3 )] . The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for mupirocin cream and any potential adverse effects on the breastfed child from mupirocin cream or from the underlying maternal condition. Clinical Considerations To minimize oral exposure of the drug to children, a breast and/or nipple being treated with mupirocin cream should be thoroughly washed prior to breastfeeding. 8.4 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 trials of mupirocin cream in adults with additional data from 93 pediatric subjects studied as part of the pivotal trials in adults [see Clinical Studies ( 14 )] . 8.5 Geriatric Use In 2 adequate and well‐controlled trials, 30 subjects 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 with that observed in younger patients.

12.1 Mechanism of Action Mupirocin is an RNA synthetase inhibitor antibacterial [see Microbiology ( 12.4 )].

11 DESCRIPTION Mupirocin Cream USP, 2% contains the dihydrate crystalline calcium hemi-salt of the RNA synthetase inhibitor antibacterial, mupirocin. Chemically, it is (α E, 2 S ,3 R ,4 R ,5 S )-5-[(2 S ,3 S ,4 S ,5 S )-2,3-epoxy-5-hydroxy-4-methylhexyl]tetrahydro-3,4-dihydroxy-β-methyl-2 H -pyran-2-crotonic acid, ester with 9-hydroxynonanoic acid, calcium salt (2:1), dihydrate. The molecular formula of mupirocin calcium, USP is (C 26 H 43 O 9 ) 2 Ca•2H 2 O, and the molecular weight is 1075.3 g/mol. The molecular weight of mupirocin free acid is 500.6 g/mol. The structural formula of mupirocin calcium, USP is: Figure 1. Structure of Mupirocin Cream, USP Mupirocin Cream USP is a white cream that contains 20 mg (2% w/w) of mupirocin equivalent to 21.5 mg (2.15% w/w) of mupirocin calcium, USP 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. Structure

16 HOW SUPPLIED Mupirocin cream, USP is a white to off-white homogeneous cream free from foreign particles that contains 20 mg (2% w/w) of mupirocin, USP per gram in an oil- and water-based emulsion. Mupirocin cream, USP is supplied in 15-gram and 30-gram tubes. NDC 69238-2029-5 (15-gram tube) NDC 69238-2029-3 (30-gram tube) Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Do not freeze.