Bactroban Cream

DESCRIPTION

BACTROBAN (mupirocin calcium) cream, 2% contains the dihydrate crystalline calciumhemi-salt of the RNA synthetase inhibitorantibacterial, mupirocin. Chemically, it is (αE,2S,3R,4R,5S)-5-[(2S,3S,4S,5S)-2,3-epoxy-5-hydroxy-4-methylhexyl]tetrahydro-3,4-dihydroxy-β-methyl-2H-pyran-2-crotonic acid, ester with 9-hydroxynonanoic acid, calcium salt (2:1), dihydrate.

The molecular formula of mupirocin calcium is (C₂₆H₄₃O₉)₂Ca•2H₂O, and the molecular weight is 1075.3. The molecular weight of mupirocin free acid is 500.6. The structural formula of mupirocin calcium is:

Figure 1: Structure of Mupirocin Calcium

BACTROBAN cream is a white cream that contains 2.15% w/w mupirocin calcium (equivalent to 2% mupirocin free acid) in an oil- and water-based emulsion. The inactive ingredients are benzyl alcohol, cetomacrogol 1000, cetyl alcohol, mineral oil, phenoxyethanol, purified water, stearyl alcohol, and xanthan gum.

INDICATIONS

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 ofStaphylococcus aureus (S. aureus)andStreptococcus pyogenes (S. pyogenes).

DOSAGE AND ADMINISTRATION

• For Topical Use Only.
• Apply a small amount of BACTROBAN cream, with acottonswab 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.
• BACTROBAN cream is not for intranasal,ophthalmic, or other mucosal use [see警告ANDPRECAUTIONS].
• Do not apply BACTROBAN cream concurrently with any other lotions, creams or ointments [seeCLINICAL PHARMACOLOGY].

HOW SUPPLIED

Dosage Forms And Strengths

BACTROBAN cream is a white cream that contains 2.15% w/w mupirocin calcium (equivalent to 2% mupirocin free acid) in an oil- and water-based emulsion supplied in 15-gramand 30-gramtubes.

Storage And Handling

BACTROBAN cream, 2% is supplied in 15-gram and 30-gram tubes.

BACTROBANcream is a white cream that contains 2.15% w/w mupirocin calcium (equivalent to 2% mupirocin free acid) in an oil- and water-based emulsion.

NDC0029-1527-22 (15-gram tube)
NDC0029-1527-25 (30-gram tube)

Store at or below 25°C (77°F). Do not freeze.

GlaxoSmithKline, Research Triangle Park, NC 27709. Revised: December 2015

SIDE EFFECTS

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

• Severe Allergic Reactions [see警告ANDPRECAUTIONS]
• Eye Irritation [see警告ANDPRECAUTIONS]
• Local Irritation [see警告ANDPRECAUTIONS]
• Clostridium difficile-Associated Diarrhea [see警告ANDPRECAUTIONS]

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 BACTROBAN cream 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 infectedeczema, 82 subjects were treated with BACTROBAN cream. 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 BACTROBAN cream. 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 BACTROBAN cream.

Immune System Disorders

Systemic allergic reactions, includinganaphylaxis,urticaria,angioedema, and generalized rash [see警告ANDPRECAUTIONS].

药物国际米兰ACTIONS

No information provided.

警告

Included as part of thePRECAUTIONSsection.

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 BACTROBAN cream [seeADVERSE REACTIONS].

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 BACTROBAN cream, 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 fatalcolitis. Treatment with antibacterial agents alters the normalfloraof thecolonleading to overgrowth ofC. difficile.

C. difficileproduces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains ofC. difficilecause increased morbidity and mortality, as these infections can berefractorytoantimicrobialtherapy and may requirecolectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Carefulmedical historyis 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 againstC. difficilemay need to be discontinued. Appropriate fluid andelectrolytemanagement, protein supplementation, antibacterial treatment ofC. difficile, and surgical evaluation should be instituted as clinically indicated.

Potential For Microbial Overgrowth

As with other antibacterial products, prolonged use of BACTROBAN cream may result in overgrowth of nonsusceptible microorganisms, including fungi [seeDOSAGE AND ADMINISTRATION].

与粘膜使用有关的风险

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

Patient Counseling Information

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

建议病人管理BACTROBAN奶油s follows:

• Use BACTROBAN cream only as directed by the healthcare provider. It is for external use only. Avoid contact of BACTROBAN cream with the eyes. If BACTROBAN cream gets in the eyes, rinse thoroughly with water.
• Do not use BACTROBAN cream 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 BACTROBAN cream 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. BACTROBAN cream 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, orwheezingoccur [see警告AND PRECAUTIONS].
• 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 evaluatecarcinogenicpotential of mupirocin calcium have not been conducted.

Results of the following studies performed with mupirocin calcium or mupirocin sodiumin vitroandin vivodid not indicate a potential for genotoxicity: rat primary hepatocyte unscheduled DNA synthesis, sediment analysis for DNA strand breaks,Salmonellareversion test (Ames),Escherichia colimutation assay,metaphaseanalysis of human lymphocytes, mouselymphomaassay, andbone marrowmicronuclei 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 BACTROBAN cream (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 BACTROBAN cream is administered to a nursing woman.

Pediatric Use

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

老年使用

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

OVERDOSE

No information provided.

CONTRAINDICATIONS

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

CLINICAL PHARMACOLOGY

Mechanism Of Action

Mupirocin is an RNA synthetase inhibitor antibacterial [seeMicrobiology].

Pharmacokinetics

Absorption

Systemic absorption of mupirocin through intact human skin is minimal. The systemic absorption of mupirocin was studied following application of BACTROBAN cream 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 ofpercutaneousabsorption 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 [seeDOSAGE AND ADMINISTRATION].

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.

Special Populations

Renal Impairment:The pharmacokinetics of mupirocin have not been studied in individuals with renal insufficiency.

Microbiology

Mupirocin is an RNA synthetase inhibitor antibacterial produced by fermentation using the organismPseudomonas fluorescens.

Mechanism of Action

Mupirocin inhibits bacterial protein synthesis by reversibly and specifically binding to bacterial isoleucyl-transfer RNA(tRNA) synthetase.

Mupirocin is bactericidal at concentrations achieved by topical administration. Mupirocin is highly protein bound (greater than 97%) and the effect of wound secretions on the minimum inhibitory concentrations (MICs) of mupirocin has not been determined.

Mechanism of Resistance

When mupirocin resistance occurs, it results from the production of a modified isoleucyl-tRNA synthetase, or the acquisition of, by genetic transfer, aplasmidmediating a new isoleucyl-tRNA synthetase. High-level plasmid-mediated resistance (MIC ≥ 512 mcg/mL) has been reported in increasing numbers of isolates ofS. aureusand with higher frequency in coagulase-negative staphylococci. Mupirocin resistance occurs with greater frequency inmethicillin-resistant than methicillin-susceptible staphylococci.

Cross Resistance

Due to its mode of action, mupirocin does not demonstrate cross resistance with other classes of antimicrobial agents.

Antimicrobial Activity

Mupirocin has been shown to be active against susceptible isolates ofS. aureusand链球菌, bothin vitroand in clinical trials [seeINDICATIONS AND USAGE]. The followingin vitrodata are available, but their clinical significance is unknown. Mupirocin is active against most isolates ofStaphylococcus epidermidis.

Susceptibility Testing

High-level mupirocin resistance ( ≥ 512 mcg/mL) may be determined using standard disk diffusion or broth microdilution tests.^1,2Because of the occurrence of mupirocin resistance in methicillin-resistantS. aureus(MRSA), it is appropriate to test MRSA populations for mupirocin susceptibility prior to the use of mupirocin using a standardized method.^3,4,5

Clinical Studies

局部BACTROBAN cr的功效eam for the treatment of secondarily infected traumatic skin lesions (e.g., lacerations, sutured wounds, and abrasions not more than 10 cm in length or 100 cm² in total area) was compared with that of oral cephalexin in 2 randomized, double-blind, double-dummy clinical trials. Clinical efficacy rates at follow-up in the per-protocol populations (adults and pediatric subjects included) were 96.1% for BACTROBAN cream (n = 231) and 93.1% for oral cephalexin (n = 219).Pathogeneradication rates at follow-up in the per-protocol populations were 100% for both BACTROBAN cream and oral cephalexin.

Pediatrics

There were 93 pediatric subjects aged 2 weeks to 16 years enrolled per protocol in the secondarily infected skinlesion试验,尽管只有3都未满2年of age in the population treated with BACTROBAN cream. Subjects were randomized to either 10 days of topical BACTROBAN cream 3 times daily or 10 days of oral cephalexin (250 mg 4 times daily for subjects greater than 40 kg or 25 mg per kg per day oral suspension in 4 divided doses for subjects less than or equal to 40 kg). Clinical efficacy at follow-up (7 to 12 days post-therapy) in the per-protocol populations was 97.7% (43 of 44) for BACTROBAN cream and 93.9% (46 of 49) for cephalexin.

REFERENCES

1. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fifth Informational Supplement. CLSI document M100-S25. Clinical and Laboratory Standards Institute, 950 West Valley Rd., Suite 2500, Wayne, PA 19087, USA, 2015.

2. Patel J, Gorwitz RJ, et al. Mupirocin Resistance. Clinical Infectious Diseases. 2009; 49(6): 935-41.

3.临床和实验室标准协会(CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – Tenth Edition. CLSI document M07-A10. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.

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

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

PATIENT INFORMATION

BACTROBAN®
(BACK-troh-ban)
(mupirocin calcium) Cream

What is BACTROBAN cream?

BACTROBAN cream is a prescription medicine used on the skin (topical use) to treat certain skin infections caused by bacteria calledStaphylococcusaureus andStreptococcuspyogenes.

It is not known if BACTROBAN cream is safe and effective in children under 3 months of age.

Who should not use BACTROBAN cream?

Do not use BACTROBAN cream if:

• you are allergic to mupirocin or any of the ingredients in BACTROBAN cream. See the end of this Patient Information leaflet for a complete list of the ingredients in BACTROBAN cream.

What should I tell my healthcare provider before using BACTROBAN cream?

Before using BACTROBAN cream, tell your healthcare provider about all of your medical conditions including if you:

• are pregnant or plan to become pregnant. It is not known if BACTROBAN cream will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if BACTROBAN cream passes into your breast milk. You and your healthcare provider should decide if you can use BACTROBAN cream while breastfeeding.

Tell your healthcare provider about all of the medicines you take,including prescription and over-the-counter medicines, vitamins, and herbal supplements. Do not mix BACTROBAN cream with other lotions, creams, or ointments.

How should I use BACTROBAN cream?

• BACTROBAN cream is for use on the skin (topical).Do not get BACTROBAN cream in your eyes, nose, mouth, orvagina(mucosal surfaces).
• Use BACTROBAN cream exactly as your healthcare provider tells you to use it.
• Apply a small amount of BACTROBAN cream, with a cotton swab or gauze pad, to the affected area 3 times each day. Apply BACTROBAN cream for 10 days.
• It is important that you take the full course of BACTROBAN cream. Do not stop early because your symptoms may disappear before the infection is fully cleared.
• Wash your handsbefore and afterapplying BACTROBAN cream.
• After applying BACTROBAN cream, you may cover the treated area with a clean gauze pad, unless your healthcare provider has told you to leave it uncovered.
• Talk to your healthcare provider if your skin does not improve after 3 to 5 days of treatment with BACTROBAN cream.

What are the possible side effects of BACTROBAN cream?

BACTROBAN cream may cause serious side effects, including:

• severe allergic reactions.Stop using BACTROBAN cream and call your healthcare provider or go to the nearest emergency room right away if you have any of the following signs or symptoms of a severe allergic reaction:
  • hives
  • swelling of your face, lips, mouth, or tongue
  • a rash over your whole body
  • trouble breathing or wheezing
  • dizziness, fast heartbeat, or pounding in your chest
• eye irritation.Do not get BACTROBAN cream in your eyes. If BACTROBAN cream gets in your eyes, rinse your eyes well with water.
• irritation in the area BACTROBAN cream is used.A rash may occur after using BACTROBAN cream and can be severe. Stop using BACTROBAN cream and call your healthcare provider if you develop an irritation, severe itching, or a rash while using BACTROBAN cream.
• a type of diarrhea calledclostridium difficile-associated diarrhea (CDAD).CDAD may happen in people who use or have used medicine to treat bacterial infections. The severity of CDAD can range from mild diarrhea to severe diarrhea that may cause death (fatal colitis). Call your healthcare provider or go to the nearest emergency room right away if you have diarrhea while using or after you stop using BACTROBAN cream.

The most common side effects of BACTROBAN cream include:

• headache
• rash
• nausea

These are not all the possible side effects of BACTROBAN cream. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store BACTROBAN cream?

• Store BACTROBAN cream at room temperature between 68°F to 77°F (20°C to 25°C).
• Do not freeze BACTROBAN cream.
• Keep BACTROBAN cream and all medicines out of the reach of children.

General information about the safe and effective use of BACTROBAN cream.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use BACTROBAN cream for a condition for which it was not prescribed. Do not give BACTROBAN cream to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about BACTROBAN cream that is written for health professionals.

What are the ingredients in BACTROBAN cream?

Active Ingredient:mupirocin calcium

Inactive Ingredients:benzyl alcohol, cetomacrogol 1000, cetyl alcohol, mineral oil, phenoxyethanol, purified water, stearyl alcohol, andxanthan gum