Mupirocin

BACTROBAN® cream 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 isolates of Staphylococcus aureus (S. aureus) and Streptococcus pyogenes (S. pyogenes).

Bactroban is a topical antibacterial agent, active against those organisms responsible for the majority of skin infections, e.g. Staphylococcus aureus, including methicillin-resistant strains, other staphylococci, streptococci. It is also active against Gram-negative organisms such as Escherichia coli and Haemophilus influenzae. Mupirocin is used for skin infections, e.g. impetigo, folliculitis, furunculosis.

• For Topical Use Only.
• Apply a small amount of Mupirocin, 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 is not for intranasal, ophthalmic, or other mucosal use.
• Do not apply Mupirocin concurrently with any other lotions, creams or ointments.

Posology

Adults (including elderly/hepatically impaired) and children

Two to three times a day for up to ten days, depending on the response.

Renally impaired

Method of administration

For topical administration.

A small quantity of Mupirocin should be applied to cover the affected area. The treated area may be covered by a dressing.

Any product remaining at the end of treatment should be discarded.

Do not mix with other preparations as there is a risk of dilution, resulting in a reduction of the antibacterial activity and potential loss of stability of the mupirocin in the ointment.

Mupirocin is contraindicated in patients with known hypersensitivity to mupirocin or any of the excipients of Mupirocin.

This Mupirocin formulation is not suitable for ophthalmic or intranasal use.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Severe Allergic Reactions

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

Eye Irritation

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

Local Irritation

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

Clostridium Difficile-Associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents 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 strains 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 2 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.

Potential For Microbial Overgrowth

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

Risk Associated With Mucosal Use

Mupirocin is not formulated for use on mucosal surfaces. A separate formulation, BACTROBAN® (mupirocin calcium) nasal ointment, is available for intranasal use.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).

Advise the patient to administer Mupirocin as follows:

• Use Mupirocin only as directed by the healthcare provider. It is for external use only. Avoid contact of Mupirocin with the eyes. If Mupirocin gets in the eyes, rinse thoroughly with water.
• Do not use Mupirocin in the nose.
• Wash your hands before and after applying BACTROBAN cream.
• Use a gauze pad or cotton swab to apply a small amount of Mupirocin to the affected area. The treated area may be covered by gauze dressing if desired.
• Report to the healthcare provider any signs of local adverse reactions. Mupirocin should be stopped and the healthcare provider contacted if irritation, severe itching, or rash occurs.
• Report to the healthcare provider or go to the nearest emergency room if severe allergic reactions, such as swelling of the lips, face, or tongue, or wheezing occur.
• If no improvement is seen in 3 to 5 days, contact the healthcare provider.

Nonclinical Toxicology

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 genotoxicity: 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.

Reproduction studies were performed with mupirocin administered subcutaneously to male and female rats at doses up to 100 mg per kg per day which is 14 times the human topical dose (approximately 60 mg mupirocin per day) based on body surface area. Neither evidence of impaired fertility nor impaired reproductive performance attributable to mupirocin was observed.

Use In Specific Populations

Pregnancy

Pregnancy Category B

There are no adequate and well-controlled studies of Mupirocin (contains equivalent of 2% mupirocin free acid) 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.

Developmental toxicity studies have been performed with mupirocin administered subcutaneously to rats and rabbits at doses up to 160 mg per kg per day in both species. This dose is 22 and 43 times, respectively, the human topical dose (approximately 60 mg mupirocin per day) based on body surface area. There was no evidence of fetal harm due to mupirocin.

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 is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of Mupirocin have been established in the age-groups 3 months to 16 years. Use of Mupirocin in these age-groups is supported by evidence from adequate and well-controlled trials of Mupirocin in adults with additional data from 93 pediatric subjects studied as part of the pivotal trials in adults.

Geriatric Use

In 2 adequate and well-controlled trials, 30 subjects older than 65 years were treated with Mupirocin. No overall difference in the efficacy or safety of Mupirocin was observed in this patient population when compared with that observed in younger patients.

Should a possible sensitisation reaction or severe local irritation occur with the use of Mupirocin, treatment should be discontinued, the product should be washed off and appropriate therapy instituted.

As with other antibacterial products, prolonged use may result in overgrowth of non-susceptible organisms.

Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea during or after antibiotic use. Although this is less likely to occur with topically applied mupirocin, if prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further.

Renal impairment

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 is not suitable for:

- ophthalmic use

- intranasal use

- use in conjunction with cannulae and

- at the site of central venous cannulation.

Avoid contact with the eyes. If contaminated, the eyes should be thoroughly irrigated with water until the ointment residues have been removed.

The following adverse reactions are discussed in more detail in other sections of the labeling:

• Severe Allergic Reactions
• Eye Irritation
• Local Irritation
• Clostridium difficile-Associated Diarrhea

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 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 BACTROBAN 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. 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.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following reactions have been identified during postmarketing use of Mupirocin. 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.

Immune System Disorders

Systemic allergic reactions, including anaphylaxis, urticaria, angioedema, and generalized rash.

Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10,000, <1/1000), very rare (<1/10,000), including isolated reports.

Common and uncommon adverse reactions were determined from pooled safety data from a clinical trial population of 1573 treated patients encompassing 12 clinical studies. Very rare adverse reactions were primarily determined from post-marketing experience data and therefore refer to reporting rate rather than true frequency.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report andy suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

No information provided.

Symptoms and signs

There is currently limited experience with overdosage of mupirocin.

Treatment

There is no specific treatment for an overdose of mupirocin. In the event of overdose, the patient should be treated supportively with appropriate monitoring as necessary. Further management should be as clinically indicated or as recommended by the national poisons centre, where available.

Absorption

Systemic absorption of mupirocin through intact human skin is minimal. The systemic absorption of mupirocin was studied following application of Mupirocin 3 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 trial indicated more frequent occurrence of percutaneous absorption in children (90% of subjects) compared with adults (44% of subjects); however, the observed urinary concentrations in children (0.07 to 1.3 mcg per mL [1 pediatric subject had no detectable level]) are within the observed range (0.08 to 10.03 mcg per 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.

The effect of the concurrent application of BACTROBAN cream with other topical products has not been studied.

Elimination

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.

Metabolism: Following intravenous or oral administration, mupirocin is rapidly metabolized. The principal metabolite, monic acid, demonstrates no antibacterial activity.

Excretion: Monic acid is predominantly eliminated by renal excretion.

After topical application of Mupirocin, mupirocin is only very minimally absorbed systemically and that which is absorbed is rapidly metabolised to the antimicrobially inactive metabolite, monic acid. Penetration of mupirocin into the deeper epidermal and dermal layers of the skin is enhanced in traumatised skin and under occlusive dressings.

Elderly patients

No restrictions unless there is evidence of moderate or severe renal impairment.