MUPIROCIN OINTMENT USP, 2% 1010 For Dermatologic Use Rx only

Each gram of Mupirocin Ointment USP, 2% contains 20 mg mupirocin in a bland water miscible ointment base (polyethylene glycol ointment, N.F.) consisting of polyethylene glycol 400 and polyethylene glycol 3350. Mupirocin is a naturally occurring antibiotic. 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-3,4-dihydroxy-β- methyl-2 H-pyran-2-crotonic acid, ester with 9-hydroxynonanoic acid. The chemical structure is:

C ₂₆H ₄₄O ₉ M.W. 500.63

Application of ¹⁴C-labeled mupirocin ointment to the lower arm of normal male subjects followed by occlusion for 24 hours showed no measurable systemic absorption (< 1.1 nanogram mupirocin per milliliter of whole blood). Measurable radioactivity was present in the stratum corneum of these subjects 72 hours after application.

Following intravenous or oral administration, mupirocin is rapidly metabolized. The principal metabolite, monic acid, is eliminated by renal excretion, and demonstrates no antibacterial activity. In a trial conducted in 7 healthy adult male subjects, the elimination half-life after intravenous administration of mupirocin was 20 to 40 minutes for mupirocin and 30 to 80 minutes for monic acid. The pharmacokinetics of mupirocin has not been studied in individuals with renal insufficiency.

Mupirocin ointment USP, 2% is indicated for the topical treatment of impetigo due to: S. aureus and S. pyogenes.

This drug is contraindicated in patients with known hypersensitivity to any of the constituents of the product.

Avoid contact with the eyes. In case of accidental contact, rinse well with water.

In the event of sensitization or severe local irritation from mupirocin ointment, usage should be discontinued.

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including mupirocin ointment, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin- producing isolates of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

As with other antibacterial products, prolonged use may result in overgrowth of nonsusceptible organisms, including fungi.

Mupirocin ointment is not formulated for use on mucosal surfaces. Intranasal use has been associated with isolated reports of stinging and drying. A paraffin-based formulation – Bactroban ^® Nasal (mupirocin calcium ointment) – is available for intranasal use.

Polyethylene glycol can be absorbed from open wounds and damaged skin and is excreted by the kidneys. In common with other polyethylene glycol-based ointments, mupirocin ointment should not be used in conditions where absorption of large quantities of polyethylene glycol is possible, especially if there is evidence of moderate or severe renal impairment.

Mupirocin ointment should not be used with intravenous cannulae or at central intravenous sites because of the potential to promote fungal infections and antimicrobial resistance.

The following local adverse reactions have been reported in connection with the use of mupirocin ointment: 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 in less than 1% of subjects.

Systemic allergic reactions, including anaphylaxis, urticaria, angioedema, and generalized rash have been reported in patients treated with formulations of mupirocin.

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

The efficacy of topical mupirocin ointment in impetigo was tested in 2 trials. In the first, subjects with impetigo were randomized to receive either mupirocin ointment or vehicle placebo 3 times daily for 8 to 12 days. Clinical efficacy rates at end of therapy in the evaluable populations (adults and pediatric subjects included) were 71% for mupirocin ointment (n = 49) and 35% for vehicle placebo (n = 51). Pathogen eradication rates in the evaluable populations were 94% for mupirocin ointment and 62% for vehicle placebo. There were no side effects reported in the group receiving mupirocin ointment.

In the second trial, subjects with impetigo were randomized to receive either mupirocin ointment 3 times daily or 30 to 40 mg/kg oral erythromycin ethylsuccinate per day (this was an unblinded trial) for 8 days. There was a follow-up visit 1 week after treatment ended. Clinical efficacy rates at the follow-up visit in the evaluable populations (adults and pediatric subjects included) were 93% for mupirocin ointment (n = 29) and 78.5% for erythromycin (n = 28). Pathogen eradication rates in the evaluable populations were 100% for both test groups. There were no side effects reported in the group receiving mupirocin ointment.

Mupirocin Ointment USP, 2% is supplied in 22 gram tubes (NDC 0093-1010-42).

Store at 20 ^o to 25 ^oC (68 ^o to 77 ^oF) [See USP Controlled Room Temperature].

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility
Tests for Bacteria that Grow Aerobically; Approved Standard -Tenth Edition. CLSI document M07-
A10 [2015], Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne,
Pennsylvania 19087, USA.

2. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk
Diffusion Susceptibility Tests; Approved Standard – Twelfth Edition. CLSI document M02-A12
[2015], Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne,
Pennsylvania 19087, USA.

3. Finlay JE, Miller LA, Poupard JA. Interpretive criteria for testing susceptibility of staphylococci to
mupirocin. Antimicrob Agents Chemother 1997;41(5):1137-1139.

All brand names listed are the registered trademarks of their respective owners and are not trademarks of Teva Pharmaceuticals USA, Inc.

Manufactured In Croatia By:

PLIVA HRVATSKA d.o.o.

Zagreb, Croatia

Manufactured For:

TEVA PHARMACEUTICALS USA, INC.

North Wales, PA 19454

Rev. I 3/2015

pdp