Mupirocin

1 INDICATIONS AND USAGE Mupirocin Ointment USP, 2% is indicated for the topical treatment of impetigo due to susceptible isolates of Staphylococcus aureus (S. aureus) and Streptococcus pyogenes (S. pyogenes) . Mupirocin Ointment USP, 2% is an RNA synthetase inhibitor antibacterial indicated for the topical treatment of impetigo 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 Ointment USP, 2%, with a cotton swab or gauze pad, to the affected area 3 times daily for up to 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 Ointment USP, 2% is not for intranasal, ophthalmic, or other mucosal use [ see Warnings and Precautions (5.2, 5.6) ]. • Do not apply Mupirocin Ointment USP, 2% concurrently with any other lotions, creams, or ointments [ see Clinical Pharmacology (12.3) ]. • For Topical Use Only. ( 2 ) • Apply a small amount of Mupirocin Ointment USP, 2%, with a cotton swab or gauze pad, to the affected area 3 times daily for up to 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 Each gram of Mupirocin Ointment USP, 2% contains 20 mg mupirocin, USP in a water-miscible ointment base supplied in 15-gram, 22-gram and 30-gram tubes. • Ointment: Each gram contains 20 mg mupirocin, USP in a water-miscible ointment base supplied in 15-gram, 22-gram and 30-gram tubes. ( 3 )

4 CONTRAINDICATIONS Mupirocin Ointment USP, 2% is contraindicated in patients with known hypersensitivity to mupirocin or any of the excipients of Mupirocin Ointment USP, 2%. • Known hypersensitivity to mupirocin or any of the excipients of Mupirocin Ointment USP, 2%. ( 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 burning, stinging or pain, and itching. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993 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. The following local adverse reactions were reported by at least 1% of subjects in connection with the use of mupirocin ointment in clinical trials: burning, stinging, or pain in 1.5% of subjects; itching in 1% of subjects. Rash, nausea, erythema, dry skin, tenderness, swelling, contact dermatitis, and increased exudate were reported in less than 1% of subjects. 6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following reactions have been identified during postmarketing use of mupirocin ointment. 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 ointment. Immune System Disorders Systemic allergic reactions, including anaphylaxis, urticaria, angioedema, and generalized rash [see Warnings and Precautions (5.1) ] . To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions - The effect of the concurrent application of Mupirocin Ointment USP, 2% and other drug products has not been studied.

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 ointment in pregnant women. Systemic absorption of mupirocin through intact human skin is minimal following topical administration of mupirocin ointment [see Clinical Pharmacology (12.3) ] . No developmental toxicity was observed in rats or rabbits treated with mupirocin subcutaneously during organogenesis at doses of 160 mg per kg per day 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 miscarriages 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 pre- 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 ointment [see Clinical Pharmacology (12.3) ] . The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for mupirocin ointment and any potential adverse effects on the breastfed child from mupirocin ointment 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 ointment should be thoroughly washed prior to breastfeeding. 8.4 Pediatric Use The safety and effectiveness of mupirocin ointment have been established in the age range of 2 months to 16 years. Use of mupirocin ointment in these age-groups is supported by evidence from adequate and well-controlled trials of mupirocin ointment in impetigo in pediatric subjects studied as a part of the pivotal clinical trials in adults [see Clinical Studies (14) ] .

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

11 DESCRIPTION Mupirocin Ointment USP, 2% contains the RNA synthetase inhibitor antibacterial, mupirocin, USP. The chemical name is ( 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-3,4dihydroxy-β-methyl-2 H -pyran-2-crotonic acid, ester with 9-hydroxynonanoic acid. The molecular formula of mupirocin, USP is C 26 H 44 O 9 , and the molecular weight is 500.6 g/mol. The structural formula of mupirocin, USP is: Figure 1. Structure of Mupirocin, USP Each gram of Mupirocin Ointment USP, 2% contains 20 mg mupirocin, USP in a water-miscible ointment base (polyethylene glycol ointment, N.F.) consisting of polyethylene glycol 400 and polyethylene glycol 3350. Structure

HOW SUPPLIED Mupirocin ointment USP, 2% is supplied in 22 gram tubes. NDC 63187-015-22 (22-gram tube) Store at 20 o to 25 o C (68 o to 77 o F) [see USP Controlled Room Temperature]. *Bactroban ® Nasal is a registered trademark of GlaxoSmithKline. Manufactured by: Glenmark Generics Ltd. Colvale-Bardez, Goa 403 513, India Manufactured for: Glenmark Generics Inc., USA Mahwah, NJ 07430 Questions? 1 (888)721-7115 www.glenmarkgenerics.com Relabeled by: Proficient Rx LP Thousand Oaks, CA 91320 June 2011 Glenmark logo