SPL PATIENT PACKAGE INSERT SECTION.


Bactroban(R)CreamReadall of this leaflet carefully before you start using this medicine.oKeepthis leaflet. You may need to read it again.o Ifyou have any further questions, ask your doctor, nurse or pharmacist.oThismedicine has been prescribed for you. Do not pass it on to others. Itmay harm them, even if their symptoms are the same as yours.o Ifany of the side effects get serious, or if you notice any sideeffects not listed in this leaflet, please tell your doctor, nurse orpharmacist.Inthis leaflet:1WhatBactroban is and what it is used for2Beforeyou use Bactroban3Howto use Bactroban4Possibleside effects5Howto store Bactroban6Furtherinformation1What Bactroban is and what it is used forBactrobanCream (called Bactroban in this leaflet) contains medicinecalled mupirocin calcium. Bactroban is an antibiotic cream.Itis used:o totreat infections on your skin in small cuts, wounds or on scrapedskin.o tokill bacteria causing infections on your skin called Staphylococcusaureus and Streptococcuspyogensothiscream is for external use on your skin only.2Before you use BactrobanDonot use Bactroban if:oyouare allergic (hypersensitive) to mupirocin calcium, mupirocin or anyof the other ingredients of Bactroban (listed in Section 6)othepatient is less than year old.Ifyou are not sure if this applies to you, do not use this medicine.Talk to your doctor, nurse or pharmacist before using Bactroban.Usingother medicinesPleasetell your doctor, nurse or pharmacist if you are taking or haverecently taken any other medicines. This includes medicines obtainedwithout prescription, including herbal medicines.Pregnancyand breast-feedingDonot use Bactroban if you are pregnant, might become pregnant or arebreast-feeding. Talk to your doctor, nurse or pharmacist for advicebefore using any medicine, if you are pregnant or breastfeeding.Importantinformation about some of the ingredients of BactrobanBactrobancontains cetyl alcohol and stearyl alcohol. These ingredients maycause skin reactions where you apply the cream. See also Section 4.3How to use BactrobanAlwaysuse Bactroban exactly as your doctor has told you. You should checkwith your doctor, nurse or pharmacist if you are not sure.Takespecial care with Bactrobano Donot use Bactroban in your eyes. If you are using Bactroban on yourface, be careful not to use it in or near your eyes or nose.o Donot put Bactroban into your mouth or swallow it.o Ifa cracked nipple is being treated, the cream must be thoroughlywashed off prior to breast-feeding.Usingthis medicineDonot mix Bactroban with any other external cream or ointment medicineson the infected area of your skin as this may reduce theeffectiveness of Bactroban.Youusually apply Bactroban on your skin up to times day.1.Wash and dry your hands.2.Place small amount of Bactroban on clean cotton wool pad or gauzeswab.3.Apply the cream to the infected area of your skin.4.You can cover the treated area with plaster or other suitabledressing, unless your doctor has told you to leave it uncovered.5.Replace the cap on the tube and wash your hands.Howlong should you use Bactroban forUseBactroban for as long as your doctor has told you. If you are notsure, ask your doctor, nurse or pharmacist. The bacteria are normallycleared from your skin within 10daysof starting treatment. Do not use for more than 10 days.Ifyour skin condition does not improve within to days, see yourdoctor.Ayeast infection of moist areas of the body may develop if Bactrobanis used for long time. On the skin this looks like bright red spotswhich may be very itchy. On occasion small pustules may be present inthe middle.Ifthis occurs, tell your doctor, pharmacist or nurse.Ifyou use more Bactroban than you shouldo Ifyou use more Bactroban than you should, speak to your doctor, nurseor pharmacist for advice.o Ifyou swallow Bactroban, contact your doctor immediately and indicatewhat and how much you have swallowed.Ifyou forget to use Bactrobano Ifyou forget to apply Bactroban, apply it as soon as you remember.o Ifyour next dose is due within an hour, skip the missed dose.o Donot use double dose to make up for forgotten dose.Ifyou stop using Bactroban too early, not all the bacteria may havebeen killed or they may continue to grow. Ask your doctor, nurse orpharmacist when to stop using thecream.Ifyou have any further questions on the use of this product, ask yourdoctor, nurse or pharmacist.4Possible side effectsLikeall medicines, Bactroban can cause side effects, not everybody getsthem. The following side effects may happen with this medicine:Common(these mayaffect between and 100 people)oItching,redness, burning, rash, swelling, pain on your skin where Bactrobanis applied.Drynessand redness of the skin can also occur on other parts of your body.Ifyou develop severe skin reaction or allergy:owipeoff the creamostopusing it andotellyour doctor as soon as possible.Ifany of the side effects gets serious, or if you noticeany side effects not listed in this leaflet,please tell your doctor, nurse or pharmacist.5How to store Bactroban\oKeepout of the reach and sight of children.o Donot store above 25C. Do not freeze.o Donot use Bactroban after the expiry date which is stated on the tube.The expiry date refers to the last day of that month.o Donot use Bactroban if it looks different to normal.oMedicinesshould not be disposed of via wastewater or household waste. Ask yourpharmacist how to dispose of medicines no longer required. Thesemeasures willhelpto protect the environment.6Further information6Further informationWhatBactroban containso 1g of cream contains 21.5 mg mupirocin calcium equivalent to 20 mgmupirocin.oTheother ingredients are xanthan gum, liquid paraffin, cetomacrogol1000, stearyl alcohol, cetyl alcohol, phenoxyethanol, benzyl alcoholand purified water. See also section 2.WhatBactroban looks like and contents of the packoBactrobanis smooth white cream.oBactrobanis available in 15 tube.Eachtube comes in carton.MarketingAuthorisation Holder and ManufacturerMarketingauthorisation holderBeechamGroup plcTradingas GlaxoSmithKline UKStockleyPark WestUxbridgeMiddlesexUB111BTManufacturerGlaxoWellcome OperationsHarmireRoadBarnardCastleCoDurhamDL128DTOtherformatsTolisten to or request copy of this leaflet in Braille, large printor audio please call, free of charge:0800198 5000 (UK Only)Pleasebe ready to give the following information: Productname Bactroban Cream Referencenumber 00038/0372Thisis service provided by the RoyalNationalInstitute for the Blind.Leafletdate: October 2007 Bactrobanis registered trademark of the GlaxoSmithKlinegroup of companies(C)2007 GlaxoSmithKline group of companies.

ADVERSE REACTIONS SECTION.


ADVERSE REACTIONS. In randomized, double-blind, double-dummy trials, 339 patients were treated with topical BACTROBAN CREAM plus oral placebo. Adverse events thought to be possibly or probably drug-related occurred in 28 (8.3%) patients. The incidence of those events that were reported in at least 1% of patients enrolled in these trials were: Headache (1.7%), rash, and nausea (1.1% each). Other adverse events thought to be possibly or probably drug-related which occurred in less than 1% of patients were: Abdominal pain, burning at application site, cellulitis, dermatitis, dizziness, pruritus, secondary wound infection, and ulcerative stomatitis. In supportive study in the treatment of secondarily infected eczema, 82 patients were treated with BACTROBAN CREAM. The incidence of adverse events thought to be possibly or probably drug-related was as follows: Nausea (4.9%), headache, and burning at application site (3.6% each), pruritus (2.4%) and report each of abdominal pain, bleeding secondary to eczema, pain secondary to eczema, hives, dry skin, and rash.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.


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 potential for mutagenicity: 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. Fertility studies were performed in rats with mupirocin administered subcutaneously at doses up to 49 times human topical dose of gram/day (approximately 20 mg mupirocin per day) on mg/m2 basis and revealed no evidence of impaired fertility from mupirocin sodium.

CLINICAL PHARMACOLOGY SECTION.


CLINICAL PHARMACOLOGY. Pharmacokinetics. Systemic absorption of mupirocin through intact human skin is minimal. The systemic absorption of mupirocin was studied following application of BACTROBAN CREAM times daily for days to various skin lesions (>10 cm in length or 100 cm2 in area) in 16 adults (aged 29 to 60 years) and 10 children (aged to 12 years). Some systemic absorption was observed as evidenced by the detection of the metabolite, monic acid, in urine. Data from this study indicated more frequent occurrence of percutaneous absorption in children (90% of patients) compared to adults (44% of patients); however, the observed urinary concentrations in children (0.07 1.3 mcg/mL [1 pediatric patient had no detectable level]) are within the observed range (0.08 10.03 mcg/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. Any mupirocin reaching the systemic circulation is rapidly metabolized, predominantly to inactive monic acid, which is eliminated by renal excretion.. Microbiology. Mupirocin is an antibacterial agent produced by fermentation using the organism Pseudomonas fluorescens. It is active against wide range of gram-positive bacteria including methicillin-resistant Staphylococcus aureus (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 in vitro cross-resistance with other classes of antimicrobial agents. Resistance occurs rarely; however, when mupirocin resistance does occur, it appears to result from the production of modified isoleucyl-tRNA synthetase. High-level plasmid-mediated resistance (MIC >1024 mcg/mL) has been reported in some strains of Staphylococcus aureus and coagulase-negative staphylococci. Mupirocin is bactericidal at concentrations achieved by topical application. The minimum bactericidal concentration (MBC) against relevant pathogens is generally 8-fold to 30-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 S. aureus and Streptococcus pyogenes, both in vitro and in clinical studies. (See INDICATIONS AND USAGE.) The following in vitro data are available, BUT THEIR CLINICAL SIGNIFICANCE IS UNKNOWN. Mupirocin is active against most strains of Staphylococcus epidermidis and Staphylococcus saprophyticus.

CLINICAL STUDIES SECTION.


CLINICAL STUDIES. The efficacy of topical BACTROBAN CREAM 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 to that of oral cephalexin in randomized, double-blind, double-dummy clinical trials. Clinical efficacy rates at follow-up in the per protocol populations (adults and pediatric patients included) were 96.1% for BACTROBAN CREAM (n 231) and 93.1% for oral cephalexin (n 219). Pathogen eradication rates at follow-up in the per protocol populations were 100% for both BACTROBAN CREAM and oral cephalexin.Pediatrics: There were 93 pediatric patients aged weeks to 16 years enrolled per protocol in the secondarily infected skin lesion studies, although only were less than years of age in the population treated with BACTROBAN CREAM. Patients were randomized to either 10 days of topical BACTROBAN CREAM times daily or 10 days of oral cephalexin (250 mg times daily for patients >40 kg or 25 mg/kg/day oral suspension in divided doses for patients <=40 kg). Clinical efficacy at follow-up (7 to 12 days post-therapy) in the per protocol populations was 97.7% (43/44) for BACTROBAN CREAM and 93.9% (46/49) for cephalexin. Only adverse event (headache) was thought to be possibly or probably related to drug therapy with BACTROBAN CREAM in the intent-to-treat pediatric population of 70 children (1.4%).

CONTRAINDICATIONS SECTION.


CONTRAINDICATIONS. BACTROBAN CREAM is contraindicated in patients with known hypersensitivity to any of the constituents of the product.

DESCRIPTION SECTION.


DESCRIPTION. BACTROBAN CREAM (mupirocin calcium cream, 2%) contains the dihydrate crystalline calcium hemi-salt of the antibiotic mupirocin. Chemically, it is (E,2S,3R,4R,5S)-5-[(2S,3S,4S,5S)-2,3-Epoxy-5-hydroxy-4-methylhexyl]tetrahydro-3,4-dihydroxy--methyl-2H-pyran-2-crotonic acid, ester with 9-hydroxynonanoic acid, calcium salt (2:1), dihydrate. The molecular formula of mupirocin calcium is (C26H43O9)2Cao2H2O, and the molecular weight is 1075.3. The molecular weight of mupirocin free acid is 500.6. The structural formula of mupirocin calcium is: BACTROBAN CREAM is white cream that contains 2.15% w/w mupirocin calcium (equivalent to 2.0% 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.. chemical structure.

DOSAGE & ADMINISTRATION SECTION.


DOSAGE AND ADMINISTRATION. small amount of BACTROBAN CREAM should be applied to the affected area times daily for 10 days. The area treated may be covered with gauze dressing if desired. Patients not showing clinical response within to days should be re-evaluated.

DRUG INTERACTIONS SECTION.


Drug Interactions. The effect of the concurrent application of topical mupirocin calcium cream and other topical products has not been studied.

GENERAL PRECAUTIONS SECTION.


General. As with other antibacterial products, prolonged use may result in overgrowth of nonsusceptible microorganisms, including fungi. (See DOSAGE AND ADMINISTRATION.) BACTROBAN CREAM is not formulated for use on mucosal surfaces.

GERIATRIC USE SECTION.


Geriatric Use. In well-controlled studies, 30 patients 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 to that observed in younger patients.

HOW SUPPLIED SECTION.


HOW SUPPLIED. BACTROBAN CREAM is supplied in 15-gram and 30-gram tubes.NDC 54868-4642-1 (15-gram tube)NDC 54868-4642-0 (30-gram tube) Store at or below 25C (77F). Do not freeze.GlaxoSmithKlineResearch Triangle Park, NC 27709BACTROBAN CREAM is registered trademark of GlaxoSmithKline.(C)2005, GlaxoSmithKline. All rights reserved.May 2005 BB:L7B Relabeling of Additional Barcode Label by:Physicians Total Care, Inc.Tulsa, OK 74146.

INDICATIONS & USAGE SECTION.


INDICATIONS AND USAGE. 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 strains of S. aureus and S. pyogenes.

INFORMATION FOR PATIENTS SECTION.


Information for Patients. Use this medication only as directed by your healthcare provider. It is for external use only. Avoid contact with the eyes.o The treated area may be covered by gauze dressing if desired.o Report to your healthcare provider any signs of local adverse reactions. The medication should be stopped and your healthcare provider contacted if irritation, severe itching, or rash occurs.o If no improvement is seen in to days, contact your healthcare provider.

NURSING MOTHERS SECTION.


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 nursing woman.

OVERDOSAGE SECTION.


OVERDOSAGE. Intravenous infusions of 252 mg, as well as single oral doses of 500 mg of mupirocin, have been well tolerated in healthy adult subjects. There is no information regarding overdose of BACTROBAN CREAM.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.


Principal Display PanelBACTROBAN CREAM(R) MUPIROCIN CALCIUM CREAM 2%15 grams (Net Wt.)Rx onlyStore at or below 25oC (77oF). Do not freeze. Each gram contains 21.5 mg mupirocin calcium in mineral oil cream base. Dosage: For dermatologic use only. Apply small amount of cream to the affected area three times daily for 10 days. Patients not showing clinical response within to days should be re-evaluated.See accompanying prescribing information.. 15 gram tube.

PEDIATRIC USE SECTION.


Pediatric Use. The safety and effectiveness of BACTROBAN CREAM have been established in the age groups months to 16 years. Use of BACTROBAN CREAM in these age groups is supported by evidence from adequate and well-controlled studies of BACTROBAN CREAM in adults with additional data from 93 pediatric patients studied as part of the pivotal trials in adults. (See CLINICAL STUDIES.).

PRECAUTIONS SECTION.


PRECAUTIONS. General. As with other antibacterial products, prolonged use may result in overgrowth of nonsusceptible microorganisms, including fungi. (See DOSAGE AND ADMINISTRATION.) BACTROBAN CREAM is not formulated for use on mucosal surfaces.. Information for Patients. Use this medication only as directed by your healthcare provider. It is for external use only. Avoid contact with the eyes.o The treated area may be covered by gauze dressing if desired.o Report to your healthcare provider any signs of local adverse reactions. The medication should be stopped and your healthcare provider contacted if irritation, severe itching, or rash occurs.o If no improvement is seen in to days, contact your healthcare provider.. Drug Interactions. The effect of the concurrent application of topical mupirocin calcium cream and other topical products has not been studied.. 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 potential for mutagenicity: 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. Fertility studies were performed in rats with mupirocin administered subcutaneously at doses up to 49 times human topical dose of gram/day (approximately 20 mg mupirocin per day) on mg/m2 basis and revealed no evidence of impaired fertility from mupirocin sodium.. Pregnancy. Teratogenic Effects: Pregnancy Category B. Teratology studies have been performed in rats and rabbits with mupirocin administered subcutaneously at doses up to 78 and 154 times, respectively, human topical dose of gram/day (approximately 20 mg mupirocin per day) on mg/m2 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 reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.. 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 nursing woman.. Pediatric Use. The safety and effectiveness of BACTROBAN CREAM have been established in the age groups months to 16 years. Use of BACTROBAN CREAM in these age groups is supported by evidence from adequate and well-controlled studies of BACTROBAN CREAM in adults with additional data from 93 pediatric patients studied as part of the pivotal trials in adults. (See CLINICAL STUDIES.). Geriatric Use. In well-controlled studies, 30 patients 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 to that observed in younger patients.

PREGNANCY SECTION.


Pregnancy. Teratogenic Effects: Pregnancy Category B. Teratology studies have been performed in rats and rabbits with mupirocin administered subcutaneously at doses up to 78 and 154 times, respectively, human topical dose of gram/day (approximately 20 mg mupirocin per day) on mg/m2 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 reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

SPL UNCLASSIFIED SECTION.


Pharmacokinetics. Systemic absorption of mupirocin through intact human skin is minimal. The systemic absorption of mupirocin was studied following application of BACTROBAN CREAM times daily for days to various skin lesions (>10 cm in length or 100 cm2 in area) in 16 adults (aged 29 to 60 years) and 10 children (aged to 12 years). Some systemic absorption was observed as evidenced by the detection of the metabolite, monic acid, in urine. Data from this study indicated more frequent occurrence of percutaneous absorption in children (90% of patients) compared to adults (44% of patients); however, the observed urinary concentrations in children (0.07 1.3 mcg/mL [1 pediatric patient had no detectable level]) are within the observed range (0.08 10.03 mcg/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. Any mupirocin reaching the systemic circulation is rapidly metabolized, predominantly to inactive monic acid, which is eliminated by renal excretion.

TERATOGENIC EFFECTS SECTION.


Teratogenic Effects: Pregnancy Category B. Teratology studies have been performed in rats and rabbits with mupirocin administered subcutaneously at doses up to 78 and 154 times, respectively, human topical dose of gram/day (approximately 20 mg mupirocin per day) on mg/m2 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 reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

WARNINGS SECTION.


WARNINGS. Avoid contact with the eyes. In the event of sensitization or severe local irritation from BACTROBAN CREAM, usage should be discontinued, and appropriate alternative therapy for the infection instituted.