Mupirocin

CLINICAL PHARMACOLOGY

Application of C-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. ¹⁴

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 study conducted in seven 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 is an antibacterial agent produced by fermentation using the organism It is active against a wide range of gram-positive bacteria including methicillin-resistant (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 cross-resistance with other classes of antimicrobial agents. Microbiology: Pseudomonas fluorescens. Staphylococcus aureus in vitro

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 and coagulase-negative staphylococci. S. aureus

Mupirocin is bactericidal at concentrations achieved by topical administration. However, the minimum bactericidal concentration (MBC) against relevant pathogens is generally eight-fold to thirty-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 and , both and in clinical studies. (See ) The following data are available, BUT THEIR CLINICAL SIGNIFICANCE IS UNKNOWN. Mupirocin is active against most strains of and Staphylococcus aureus Streptococcus pyogenes in vitro . INDICATIONS AND USAGE in vitro Staphylococcus epidermidis Staphylococcus saprophyticus.

MUPIROCIN INDICATIONS AND USAGE

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

MUPIROCIN CONTRAINDICATIONS

This drug is contraindicated in individuals with a history of sensitivity reactions to any of its components.

WARNINGS

Mupirocin ointment is not for ophthalmic use.

PRECAUTIONS

If a reaction suggesting sensitivity or chemical irritation should occur with the use of mupirocin ointment 2%, treatment should be discontinued and appropriate alternative therapy for the infection instituted. 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.

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. A paraffin-based formulation- *Bactroban Nasal (mupirocin calcium ointment) - is available for intranasal use. ^®

Use this medication only as directed by your healthcare practitioner. It is for external use only. Avoid contact with the eyes. The medication should be stopped and your healthcare practitioner contacted if irritation, severe itching, or rash occurs. If impetigo has not improved in 3 to 5 days, contact your healthcare practitioner. Information for Patients:

The effect of the concurrent application of mupirocin ointment and other drug products has not been studied. Drug Interactions:

Long-term studies in animals to evaluate carcinogenic potential of mupirocin have not been conducted. Results of the following studies performed with mupirocin calcium or mupirocin sodium and did not indicate a potential for genotoxicity: rat primary hepatocyte unscheduled DNA synthesis, sediment analysis for DNA strand breaks, reversion test (Ames), mutation assay, metaphase analysis of human lymphocytes, mouse lymphoma assay, and bone marrow micronuclei assay in mice. Reproduction studies were performed in male and female rats with mupirocin administered subcutaneously at doses up to 14 times a human topical dose (approximately 60 mg mupirocin per day) on a mg/m basis and revealed no evidence of impaired fertility and reproductive performance from mupirocin. Carcinogenesis, Mutagenesis, Impairment of Fertility: in vitro in vivo Salmonella Escherichia coli ²

Reproduction studies have been performed in rats and rabbits with mupirocin administered subcutaneously at doses up to 22 and 43 times, respectively, the human topical dose (approximately 60 mg mupirocin per day) on a mg/m 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 studies are not always predictive of human response, this drug should be used during opregnancy only if clearly needed. Pregnancy Teratogenic Effects.Pregnancy Category B: ²

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 is administered to a nursing woman. Nursing Mothers: mupirocin ointment

The safety and effectiveness of have been established in the age range of 2 months to 16 years. Use of in these age groups is supported by evidence from adequate and well-controlled studies of in impetigo in pediatric patients studied as a part of the pivotal clinical trials. (See .) Pediatric Use: mupirocin ointment mupirocin ointment mupirocin ointment CLINICAL STUDIES

MUPIROCIN ADVERSE REACTIONS

The following local adverse reactions have been reported in connection with the use of : burning, stinging, or pain in 1.5% of patients; itching in 1% of patients; rash, nausea, erythema, dry skin, tenderness, swelling, contact dermatitis, and increased exudate in less than 1% of patients. mupirocin ointment

MUPIROCIN DOSAGE AND ADMINISTRATION

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

CLINICAL STUDIES

The efficacy of topical in impetigo was tested in two studies. In the first, patients with impetigo were randomized to receive either or vehicle placebo t.i.d. for 8 to 12 days. Clinical efficacy rates at end of therapy in the evaluable populations (adults and pediatric patients included) were 71% for (n=49) and 35% for vehicle placebo (n=51). Pathogen eradication rates in the evaluable populations were 94% for and 62% for vehicle placebo. There were no side effects reported in the group receiving In the second study, patients with impetigo were randomized to receive either t.i.d. or 30 to 40 mg/kg oral erythromycin ethylsuccinate per day (this was an unblinded study) for 8 days. There was a follow-up visit 1 week after treatment ended. mupirocin ointment mupirocin ointment mupirocin ointment mupirocin ointment mupirocin ointment. mupirocin ointment

Clinical efficacy rates at the follow-up visit in the evaluable populations (adults and pediatric patients included) were 93% for (n=29) and 78.5% for erythromycin (n=28). Pathogen eradication rates in the evaluable patient populations were 100% for both test groups. There were no side effects reported in the group. mupirocin ointment mupirocin ointment

Pediatrics

There were 91 pediatric patients aged 2 months to 15 years in the first study described above. Clinical efficacy rates at end of therapy in the evaluable populations were 78% for (n=42) and 36% for vehicle placebo (n=49). In the second study described above, all patients were pediatric except two adults in the group receiving . The age range of the pediatric patients was 7 months to 13 years. mupirocin ointment mupirocin ointment

The clinical efficacy rate for (n=27) was 96%, and for erythromycin it was unchanged (78.5%). mupirocin ointment

MUPIROCIN OINTMENT