CATEGORIES: Impetigo; Infection, skin lesions; Infection, prophylaxis; Pregnancy Category B; FDA Approved December 1987
Drug Classes: Anti-infectives, topical; Dermatologics
BRAND NAMES: Bactroban; Centany
FOREIGN BRAND AVAILABILITY:
Bactoderm (Indonesia, Israel);
Eismycin (Germany);
Mupiderm (France)
COST OF THERAPY:
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For Dermatologic Use.
Bactroban Calcium Cream, 2%
Bactroban Cream (mupirocin calcium cream), 2% contains the dihydrate crystalline calcium hemi-salt of the antibiotic 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-crotonicacid, 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.
Bactroban Cream is a 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 xanthangum.
Bactroban Ointment, 2%
Each gram of Bactroban Ointment (mupirocin ointment), 2% contains 20 mg mupirocin in a bland water miscible ointment base (polyethylene glycol ointment) consisting of polyethylene glycol 400 and polyethylene glycol 3350. Mupirocin is a naturally occurring antibiotic. The chemical name is (E)-(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. The molecular formula of mupirocin is C26H44O9and the molecular weight is 500.63.
Mupirocin Calcium Cream, 2%
Pharmacokinetics
Systemic absorption of mupirocin through intact human skin is minimal. The systemic absorption of mupirocin was studied following application of mupirocin calcium cream, 2% three times a day for 5 days to various skin lesions (greater than 10 cm in length or 100 cm2 in area)in 16 adults (aged 29-60 years) and 10 children (aged 3-12 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 μg/ml (1 pediatric patient had no detectable level)] are within the observed range [0.08-10.03 μg/ml (9 adults had no detectable level)] in the adult population. In general, the degree of percutaneous absorptionfollowing 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 Psuedomonas fluorescens. It is active against a wide range of gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). It is also active against certaingram-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 antimicrobialagents.
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 μg/ml) has been reported in some strains of S. aureus and coagulase-negativestaphylococci.
Mupirocin is bactericidal at concentrations achieved by topical application. However, the minimum bactericidal concentration (MBC) against relevant pathogens is generally 8- to 30-fold higher than the minimum inhibitory concentration (MIC). In addition, mupirocin is highly protein bound (>97%), andthe effect of wound secretions on the MICs of mupirocin has not been determined.
Mupirocin has been shown to be active against most strains of Staphylococcus 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.
Mupirocin Ointment, 2%
Application of 14C-labeled mupirocin ointment to the lower arm of normal male subjects followed by occlusion for 24 hours showed no measurable systemic absorption (<1.1 ng mupirocin per ml of whole blood). Measurable radioactivity was present in the stratum corneum of thesesubjects 72 hours after application.
Following intravenous (IV) 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 7 healthy adult male subjects, the elimination half-life after IV administrationof mupirocin was 20-40 mins for mupirocin and 30-80 mins for monic acid. The pharmacokinetics of mupirocin has not been studied in individuals with renal insufficiency.
Microbiology
Mupirocin is an antibacterial agent produced by fermentation using the organism Pseudomonas fluorescens. It is active against a wide range of gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). It is also active against certaingram-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 antimicrobialagents.
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 μg/ml) has been reported in some strains of S. aureus and coagulase-negativestaphylococci.
Mupirocin is bactericidal at concentrations achieved by topical administration. However, the minimum bactericidal concentration (MBC) against relevant pathogens is generally 8- to 30-fold higher than the minimum inhibitory concentration (MIC). In addition, mupirocin is highly protein bound (>97%), andthe effect of wound secretions on the MICs of mupirocin has not been determined.
Mupirocin has been shown to be active against most strains of Staphylococcus 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.
Mupirocin Calcium Cream, 2%
The efficacy of topical mupirocin calcium cream, 2% 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 tothat of oral cephalexin in two 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 mupirocin calcium cream, 2% (n=231) and 93.1% for oral cephalexin (n=219). Pathogen eradicationrates at follow-up in the per protocol populations were 100% for both mupirocin calcium cream, 2% and oral cephalexin.
Pediatric
There were 93 pediatric patients aged 2 weeks to 16 years enrolled per protocol in the secondarily infected skin lesion studies, although only 3 were less than 2 years of age in the mupirocin calcium cream, 2% treated population. Patients were randomized to either 10 days of topical mupirocin calciumcream, 2% tid or 10 days of oral cephalexin (250 mg qid for patients >40 kg or 25 mg/kg/day oral suspension in 4 divided doses for patients ≤40 kg). Clinical efficacy at follow-up (7-12 days post-therapy) in the per protocol populations was 97.7% (43/44) for mupirocin calcium cream, 2% and 93.9% (46/49)for cephalexin. Only 1 adverse event (headache) was thought to be possibly or probably related to drug therapy in the mupirocin calcium cream, 2% intent-to-treat pediatric population of 70 children (1.4%).
Mupirocin Ointment, 2%
The efficacy of topical mupirocin ointment, 2% in impetigo was tested in two studies. In the first, patients with impetigo were randomized to receive either mupirocin ointment, 2% or vehicle placebo tid for 8-12 days. Clinical efficacy rates at end of therapy in the evaluable populations (adults andpediatric patients included) were 71% for mupirocin ointment, 2% (n=49) and 35% for vehicle placebo (n=51). Pathogen eradication rates in the evaluable populations were 94% for mupirocin ointment, 2% and 62% for vehicle placebo. There were no side effects reported in the group receiving mupirocin ointment,2%.
In the second study, patients with impetigo were randomized to receive either mupirocin ointment, 2% tid or 30-40 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. Clinical efficacy rates at the follow-upvisit in the evaluable populations (adults and pediatric patients included) were 93% for mupirocin ointment, 2% (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 mupirocin ointment,2% group.
Pediatric
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 mupirocin ointment, 2% (n=42) and 36% for vehicle placebo (n=49). In the second study described above, all patients werepediatric except 2 adults in the group receiving mupirocin ointment, 2%. The age range of the pediatric patients was 7 months to 13 years. The clinical efficacy rate for mupirocin ointment, 2% (n=27) was 96%, and for erythromycin it was unchanged (78.5%).
Mupirocin calcium cream, 2% 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 Staphylococcus aureus and Streptococcus pyogenes.
Mupirocin ointment, 2% is indicated for the topical treatment of impetigo due to: Staphylococcus aureus and Streptococcus pyogenes.
Mupirocin calcium cream, 2% and mupirocin ointment, 2% are contraindicated in individuals with a history of sensitivity reactons to any of its components.
Avoid contact with the eyes.
In the event of a sensitization or severe local irritation from mupirocin calcium cream, 2%, usage should be discontinued, and appropriate alternative therapy for the infection instituted.
Mupirocin ointment is not for ophthalmic use.
Mupirocin Calcium Cream, 2%
General
As with other antibacterial products, prolonged use may result in overgrowth of nonsusceptible microorganisms, including fungi. (See DOSAGE AND ADMINISTRATION.)
Mupirocin calcium cream, 2% is not formulated for use on mucosal surfaces.
Information for the Patient
Carcinogenesis, Mutagenesis, and 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 mutagenicity: Rat primary hepatocyte unscheduled DNA synthesis, sediment analysisfor 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 a human topical dose of 1 g/day (approximately 20 mg mupirocin per day) on a 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, a human topical dose of 1 g/day (approximately 20 mg mupirocin per day) on a mg/m2 basis and revealed no evidence of harm tothe 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 mupirocin calcium cream, 2% is administered to a nursing woman.
Pediatric Use
The safety and effectiveness of mupirocin calcium cream, 2% have been established in the age groups 3 months to 16 years. Use of mupirocin calcium cream, 2% in these age groups is supported by evidence from adequate and well-controlled studies of mupirocin calcium cream, 2% in adults with additionaldata from 93 pediatric patients studied as part of the pivotal trials in adults. (See CLINICAL STUDIES.)
Geriatric Use
In two well-controlled studies, 30 patients over 65 years old were treated with mupirocin calcium cream, 2%. No overall difference in the efficacy or safety of mupirocin calcium cream, 2% was observed in this patient population when compared to that observed in younger patients.
Mupirocin Ointment, 2%
If a reaction suggesting sensitivity of 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, 2% is not formulated for use on mucosal surfaces. Intranasal use has been associated with isolated reports of stinging and drying. A paraffin-based formulation — mupirocin calcium ointment, 2% — is available for intranasal use.
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, 2% should not be used in conditions where absorption of large quantities of polyethylene glycol is possible, especiallyif there is evidence of moderate or severe renal impairment.
Information for the Patient
Use this medication only as directed by your healthcare provider. 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 3-5 days, contact your healthcare practitioner.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
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 in vitro and in vivo did not indicate a potential for genotoxicity: Rat primary hepatocyte unscheduled DNA synthesis, sediment analysisfor 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 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/m2 basis and revealed no evidence of impaired fertility and reproductive performancefrom mupirocin.
Pregnancy, Teratogenic Effects, Pregnancy Category B
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/m2 basis and revealed no evidence of harm to the fetusdue 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 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 mupirocin ointment, 2% is administered to a nursing woman.
Pediatric Use
The safety and effectiveness of mupirocin ointment, 2% have been established in the age range of 2 months to 16 years. Use of mupirocin ointment, 2% in these age groups is supported by evidence from adequate and well-controlled studies of mupirocin ointment, 2% in impetigo in pediatric patients studiedas a part of the pivotal clinical trials. (See CLINICAL STUDIES.)
The effect of the concurrent application of topical mupirocin calcium cream, mupirocin ointment, and other drug products has not been studied.
Mupirocin Calcium Cream, 2%
In two randomized, double-blind, double-dummy trials, 339 patients were treated with topical mupirocin calcium cream, 2% 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 atleast 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 a supportive study in the treatment of secondarily infected eczema, 82 patients were treated with mupirocin calcium cream, 2%. 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 1 report each of abdominal pain, bleeding secondary to eczema, pain secondary to eczema, hives, dry skin, and rash.
Mupirocin Ointment, 2%
The following local adverse reactions have been reported in connection with the use of mupirocin ointment, 2%: 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 inless than 1% in patients. Systemic reactions to mupirocin oinment, 2% have occurred rarely.
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 mupirocin calcium cream, 2%.
A small amount of mupirocin calcium cream, 2% or mupirocin ointment, 2% should be applied to the affected area 3 times daily for 10 days. The area treated may be covered with a gauze dressing if desired. Patients not showing a clinical response within 3-5 days should be re-evaluated.
Bactroban Cream, 2%
Bactroban Cream, 2% is supplied in 15 and 30 g tubes.
Storage: Store at or below 25°C (77°F). Do not freeze.
Bactroban Ointment, 2%
Bactroban Ointment, 2% is supplied in 22 g tubes.
Storage: Store at controlled room temperature 20-25°C (68-77°F).
For Intranasal Use Only.
Bactroban Nasal (mupirocin calcium ointment), 2% contains the dihydrate crystalline calcium hemi-salt of the antibiotic mupirocin. Chemically, it is (αE,2S,3R,4R,5S)-5-[(2S,3S,4S,5S)-2,3-Epoxy-5-hydroxy-4-methylhexyl]tetra-hydro-3,4-dihydroxy-β-methyl-2H-pyran-2-crotonicacid, 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.
Bactroban Nasal is a white to off-white ointment that contains 2.15% w/w mupirocin calcium (equivalent to 2.0% pure mupirocin free acid) in a soft white ointment base. The inactive ingredients are paraffin and a mixture of glycerin esters.
Pharmacokinetics
Following single or repeated intranasal applications of 0.2 g of intranasal mupirocin calcium ointment, 2% tid for 3 days to 5 healthy adult male subjects, no evidence of systemic absorption of mupirocin was demonstrated. The dosage regimen use in this study was for pharmacokineticcharacterization only. (See DOSAGE AND ADMINISTRATION for proper clinical dosing information.)
In this study, the concentrations of mupirocin in urine and of monic acid in urine and serum were below the limit of determination of the assay for up to 72 hours after the applications. The lowest levels of determination of the assay used were 50 ng/ml of mupirocin in urine, 75 ng/ml of monic acidin urine, and 10 ng/ml of monic acid in serum. Based on the detectable limit of the urine assay for monic acid, one can extrapolate that a mean of 3.3% (range: 1.2-5.1%) of the applied dose could be systemically absorbed from the nasal mucosa of adults.
Data from a report of a pharmacokinetic study in neonates and premature infants indicate that, unlike in adults, significant systemic absorption occurred following intranasal administration of intranasal mupirocin calcium ointment, 2% in this population. At this time, the pharmacokinetic propertiesof mupirocin following intranasal application of intranasal mupirocin calcium ointment, 2% have not been adequately characterized in neonates or other children less than 12 years of age, and in addition, the safety of the product in children less than 12 years of age has not been established.
The effect of the concurrent application of intranasal mupirocin calcium ointment, 2% with other intranasal products has not been studied. (See DRUG INTERACTIONS.)
Following IV or oral administration, mupirocin is rapidly metabolized. The principal metabolite, monic acid, demonstrates no antibacterial activity. In a study conducted in 7 healthy adult male subjects, the elimination half-life after IV administration of mupirocin was 20-40 mins for mupirocin and30-80 mins for monic acid. Monic acid is predominantly eliminated by renal excretion. The pharmacokinetics of mupirocin has not been studied in individuals with renal insufficiency.
Microbiology
Mupirocin is an antibacterial agent produced by fermentation using the organism Pseudomonas fluorescens. Mupirocin inhibits bacterial protein synthesis by reversibly and specifically binding to bacterial isoleucyl transfer-RNA synthetsae. Due to this mode of action, mupirocindemonstrates no in vitro cross-resistance with other classes of antimicrobial agents.
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 μg/ml) has been reported in some strains of S. aureus and coagulase-negative staphylococci.
Mupirocin is bactericidal at concentrations achieved topically by intranasal administration. However, the minimum bactericidal concentration (MBC) against relevant intranasal pathogens is generally 8- to 30-fold higher than the minimum inhibitory concentration (MIC). In addition, mupirocin is highlyprotein bound (>97%), and the effect of nasal secretions on the MICs of intranasally applied mupirocin has not been determined.
Mupirocin has been shown to be active against most strains of methicillin-resistant S. aureus, both in vitro and in clinical studies of the eradication of nasal colonization. Intranasal mupirocin calcium ointment, 2% only has established clinicalutility in nasal eradication as part of a comprehensive program to curtail institutional outbreaks of infections with methicillin-resistant S. aureus. (See INDICATIONS AND USAGE.)
The following in vitro data are available, but their clinical significance is unknown. Mupirocin exhibits in vitro MICs of 1 μg/ml or less against most (>90%) strainsof methicillin-susceptible S. aureus; however, the safety and effectiveness of mupirocin calcium in eradicating nasal colonization of and preventing subsequent infections due to methicillin-susceptible S. aureus have not been established.
Intranasal mupirocin calcium ointment, 2% is indicated for the eradication of nasal colonization with methicillin-resistant Staphylococcus aureus in adult patients and health care workers as part of a comprehensive infection control program to reduce the risk of infection amongpatients at high risk of methicillin-resistant S. aureus infection during institutional outbreaks of infections with this pathogen.
Note:
All adequate and well-controlled trials of this product were vehicle-controlled; therefore, no data from direct, head-to-head comparisons with other products are available at this time.
Intranasal mupirocin calcium ointment, 2% is contraindicated in patients with known hypersensitivity to any of the constituents of the product.
AVOID CONTACT WITH THE EYES.
Application of intranasal mupirocin calcium ointment, 2% to the eye under testing conditions has caused severe symptoms such as burning and tearing. These symptoms resolved within days to weeks after discontinuation of the ointment.
In the event of a sensitization or severe local irritation from intranasal mupirocin calcium ointment, 2%, usage should be discontinued.
General
As with other antibacterial products, prolonged use may result in overgrowth of nonsusceptible microorganisms, including fungi. (See DOSAGE AND ADMINISTRATION.)
Information for the Patient
Patients should be given the following instructions:
Carcinogenesis, Mutagenesis, and 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 mutagenicity: Rat primary hepatocyte unscheduled DNA synthesis, sediment analysisfor 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 in rats with mupirocin administered subcutaneously at doses up to 40 times the human intranasal dose (approximately 20 mg mupirocin per day) on a mg/m2 basis and revealed no evidence of impaired fertility from mupirocinsodium.
Pregnancy, Teratogenic Effects, Pregnancy Category B
Reproduction studies have been performed in rats and rabbits with mupirocin administered subcutaneously at doses up to 65 and 130 times, respectively, the human intranasal dose (approximately 20 mg mupirocin per day) on a mg/m2 basis and revealed no evidence of harm to thefetus 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 intranasal mupirocin calcium ointment, 2% is administered to a nursing woman.
Pediatric Use
Safety in children under the age of 12 years has not been established. (See CLINICAL PHARMACOLOGY.)
The effect of the concurrent application of intranasal mupirocin calcium and other intranasal products has not been studied. Until further information is known, mupirocin calcium ointment, 2% should not be applied concurrently with any other intranasal products.
Clinical Trials
In clinical trials, 210 domestic and 2130 foreign adult subjects/patients received intranasal mupirocin calcium ointment, 2%. Less than 1% of domestic or foreign subjects and patients in clinical trials were withdrawn due to adverse events.
The most frequently reported adverse events in foreign clinical trials were as follows: Rhinitis (1.0%), taste perversion (0.8%), pharyngitis (0.5%).
In domestic clinical trials, 17% (36/210) of adults treated with intranasal mupirocin calcium ointment, 2% reported adverse events thought to be at least possibly drug-related. The incidence of adverse events that were reported in at least 1% of adults enrolled in domestic clinical trials is shown in TABLE 1.
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The following events thought possibly drug-related were reported in less than 1% of adults enrolled in domestic clinical trials: Blepharitis, diarrhea, dry mouth, ear pain, epistaxis, nausea, and rash.
All adequate and well-controlled clinical trials have been performed using intranasal mupirocin calcium ointment, 2% in one arm and the vehicle ointment in the other arm of the study. No adequate and well-controlled safety data are available from direct, head-to-head comparative studies of this productand other products for this indication.
Following single or repeated intranasal applications of intranasal mupirocin calcium ointment, 2% to adults, no evidence for systemic absorption of mupirocin was obtained. Intravenous infusions of 252 mg, as well as single oral doses of 500 mg of mupirocin, have been well tolerated in healthy adultsubjects. There is no information regarding local overdose of intranasal mupirocin calcium ointment, 2% or regarding oral ingestion of the nasal ointment formulation.
Adults (12 years of age and older)
Approximately one-half of the ointment from the single-use tube should be applied into 1 nostril and the other half into the other nostril twice daily (morning and evening) for 5 days.
After application, the nostrils should be closed by pressing together and releasing the sides of the nose repetitively for approximately 1 min. This will spread the ointment throughout the nares.
The single-use 1.0 g tube will deliver a total of approximately 0.5 g of the ointment (approximately 0.25 g/nostril).
The tube should be discarded after usage; it should not be re-used.
The safety and effectiveness of applications of this medication for greater than 5 days have not been established. There are no human clinical or pre-clinical animal data to support the use of this product in a chronic manner or in manners other than those described in this package insert.
Until further information is known, intranasal mupirocin calcium ointment, 2% should not be applied concurrently with any other intranasal products.
References
1.Bactroban Nasal, 2% is supplied in 1.0 g tubes.
Storage: Store at or below 25°C (77°F).
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