Бактробан

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).

Бактробан Cream is indicated for the topical treatment of secondarily infected traumatic lesions such as small lacerations, sutured wounds or abrasions (up to 10 cm in length or 100 cm² in area), due to susceptible strains of Staphylococcus aureus and Streptococcus 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. Бактробан is used for skin infections, e.g. impetigo, folliculitis, furunculosis.

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

Dosage

Adults/children > 1 year/elderly

3 times a day for up to 10 days, depending on the response.

Patients not showing a clinical response within 3 to 5 days should be re-evaluated.

The duration of treatment should not exceed 10 days.

Children < 1 year

Бактробан Cream has not been studied in infants under 1 year old and therefore it should not be used in these patients until further data become available.

Patients with hepatic impairment: No dosage adjustment is necessary.

Patients with renal impairment: No dosage adjustment is necessary.

Method of administration

A thin layer of cream should be applied to the affected area with a piece of clean cotton wool or gauze swab.

The treated area may be covered by a dressing.

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

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 Бактробан 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.

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

Hypersensitivity to mupirocin or any of the excipients.

This Бактробан 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 Бактробан.

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 Бактробан, 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 Бактробан may result in overgrowth of nonsusceptible microorganisms, including fungi.

Risk Associated With Mucosal Use

Бактробан 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 Бактробан as follows:

• Use Бактробан only as directed by the healthcare provider. It is for external use only. Avoid contact of Бактробан with the eyes. If Бактробан gets in the eyes, rinse thoroughly with water.
• Do not use Бактробан 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 Бактробан 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. Бактробан 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 Бактробан (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 Бактробан is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of Бактробан have been established in the age-groups 3 months to 16 years. Use of Бактробан in these age-groups is supported by evidence from adequate and well-controlled trials of Бактробан 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 Бактробан. No overall difference in the efficacy or safety of Бактробан 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 Бактробан Cream, 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.

Бактробан Cream formulation is not suitable for ophthalmic use and intranasal use.

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

Бактробан Cream contains cetyl alcohol and stearyl alcohol. These inactive ingredients may cause local skin reactions (e.g. contact dermatitis).

Should a possible sensitisation reaction or severe local irritation occur with the use of Бактробан, 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.

Бактробан 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 Бактробан 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 Бактробан. 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 Бактробан. 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 Бактробан.

Immune System Disorders

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

Data from clinical trials was used to determine the frequency of very common to rare undesirable effects. Very rare adverse reactions were primarily determined from post-marketing experience data and therefore refer to reporting rate rather than true frequency.

The following convention has been used for the classification of frequency:-

very common >1/10, common >1/100 and <1/10 , uncommon >1/1000 and <1/100, rare >1/10,000 and <1/1000 , very rare <1/10,000.

Skin dryness and erythema have been reported in irritancy studies in volunteers.

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 any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk.yellowcard

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:

There is currently limited experience with overdosage of Бактробан Cream.

Management:

There is no specific treatment for an overdose of Бактробан Cream. 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.

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.

Pharmacotherapeutic group: Dermatologicals ATC code: D06AX09, Antibiotics and chemotherapeutics for dermatological use

Mode of Action

Mupirocin is a novel antibiotic produced through fermentation by Pseudomonas fluorescens. Mupirocin inhibits isoleucyl transfer-RNA synthetase, thereby arresting bacterial protein synthesis.

Mupirocin has bacteriostatic properties at minimum inhibitory concentrations and bactericidal properties at the higher concentrations reached when applied locally.

Mechanism of Resistance

Low-level resistance in staphylococci is thought to result from point mutations within the usual staphylococcal chromosomal gene (ileS) for the target isoleucyl tRNA synthetase enzyme. High-level resistance in staphylococci has been shown to be due to a distinct, plasmid encoded isoleucyl tRNA synthetase enzyme.

Intrinsic resistance in Gram negative organisms such as the Enterobacteriaceae could be due to poor penetration of the outer membrane of the Gram-negative bacterial cell wall.

Due to its particular mode of action, and its unique chemical structure, mupirocin does not show any cross-resistance with other clinically available antibiotics.

Microbiological Susceptibility

The prevalence of acquired resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infection is questionable.

* Activity has been satisfactorily demonstrated in clinical studies

Pharmacotherapeutic group: Antibiotics and chemotherapeutics for dermatological use.

ATC code: D06AX09

Mode of Action

Mupirocin is a novel antibiotic produced through fermentation by Pseudomonas fluorescens. Mupirocin inhibits isoleucyl transfer-RNA synthetase, thereby arresting bacterial protein synthesis.

Mupirocin has bacteriostatic properties at minimum inhibitory concentrations and bactericidal properties at the higher concentrations reached when applied locally.

Mechanism of Resistance

Low-level resistance in staphylococci is thought to result from point mutations within the usual staphylococcal chromosomal gene (ileS) for the target isoleucyl tRNA synthetase enzyme. High-level resistance in staphylococci has been shown to be due to a distinct, plasmid encoded isoleucyl tRNA synthetase enzyme.

Intrinsic resistance in Gram negative organisms such as the Enterobacteriaceae could be due to poor penetration of the outer membrane of the Gram-negative bacterial cell wall.

Due to its particular mode of action, and its unique chemical structure, mupirocin does not show any cross-resistance with other clinically available antibiotics.

Microbiological Susceptibility

The prevalence of acquired resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infection is questionable.

* Activity has been satisfactorily demonstrated in clinical studies

Absorption

Systemic absorption of mupirocin through intact human skin is minimal. The systemic absorption of mupirocin was studied following application of Бактробан 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.

Absorption

Systemic absorption of mupirocin through intact human skin is low although it may occur through broken/diseased skin. However, clinical trials have shown that when given systemically, it is metabolised to the microbiologically inactive metabolite monic acid and rapidly excreted.

Excretion

Mupirocin is rapidly eliminated from the body by metabolism to its inactive metabolite monic acid which is rapidly excreted by the kidney.

After topical application of Бактробан, 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.

Pre-clinical effects were seen only at exposures which are extremely unlikely to cause concern for humans under normal conditions of clinical use. Mutagenicity studies revealed no risks to man.

Pre-clinical effects were seen only at exposures which are extremely unlikely to cause concern for humans under normal conditions of use. Mutagenicity studies revealed no risks to man.

None known

None stated.

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

Wash your hands after application.

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

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Wash your hands after application.