HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use BACTROBAN Nasal Ointment safely and effectively. See full prescribing information for BACTROBAN Nasal Ointment.
BACTROBAN (mupirocin calcium) nasal ointment
Initial U.S. Approval: 1995
INDICATIONS AND USAGE
BACTROBAN nasal ointment is an antibacterial drug indicated for the eradication of nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) in adult and pediatric patients (aged 12 years and older) and healthcare workers as part of a comprehensive infection control program to reduce the risk of infection among patients at high risk of MRSA infection during institutional outbreaks of infections with this microorganism. (1)
Limitations of Use (1)
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
WARNINGS AND PRECAUTIONS
To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
Limitations of Use
2 DOSAGE AND ADMINISTRATION
3 DOSAGE FORMS AND STRENGTHS
5 WARNINGS AND PRECAUTIONS
5.1 Severe Allergic Reactions
5.2 Eye Irritation
5.3 Local Irritation
5.4 Clostridium difficile-associated Diarrhea
5.5 Potential for Microbial Overgrowth
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
8 USE IN SPECIFIC POPULATIONS
8.3 Nursing Mothers
8.4 Pediatric Use
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
BACTROBAN® nasal ointment is indicated for the eradication of nasal colonization with methicillin‑resistant Staphylococcus aureus (MRSA) in adult and pediatric patients (aged 12 years and older) and healthcare workers as part of a comprehensive infection control program to reduce the risk of infection among patients at high risk of MRSA infection during institutional outbreaks of infections with this microorganism.
BACTROBAN nasal ointment is a white to off-white ointment that contains 2.15% w/w mupirocin calcium (equivalent to 2% mupirocin free acid) in a soft white ointment base supplied in single-use 1‑gram tubes.
BACTROBAN nasal ointment is contraindicated in patients with known hypersensitivity to mupirocin or any of the excipients of BACTROBAN nasal ointment.
Systemic allergic reactions, including anaphylaxis, urticaria, angioedema, and generalized rash have been reported in patients treated with formulations of BACTROBAN [see Adverse Reactions (6.2)].
Avoid contact with the eyes. In case of accidental contact, rinse well with water. Application of BACTROBAN nasal ointment 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 BACTROBAN nasal ointment, usage should be discontinued.
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including BACTROBAN nasal ointment, 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.
As with other antibacterial products, prolonged use of BACTROBAN nasal ointment may result in overgrowth of nonsusceptible microorganisms, including fungi [see Dosage and Administration (2)].
The following adverse reactions are discussed in more detail in other sections of the labeling:
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 clinical trials, 210 domestic (US) and 2,130 foreign adult subjects received BACTROBAN nasal ointment. Less than 1% of domestic or foreign subjects in clinical trials were withdrawn due to adverse reactions.
The most frequently reported adverse reactions in foreign clinical trials were rhinitis (1%), taste perversion (0.8%), and pharyngitis (0.5%).
In domestic clinical trials, 17% (36 of 210) of adults treated with BACTROBAN nasal ointment reported adverse reactions thought to be at least possibly drug related. Table 1 shows the incidence of adverse reactions that were reported in at least 1% of adults enrolled in clinical trials conducted in the US.
Table 1. Adverse Reactions (≥1% Incidence) – Adults in US Trials
% of Subjects Experiencing Reactions
BACTROBAN Nasal Ointment
(n = 210)
Respiratory disorder, including upper respiratory tract congestion
The following adverse reactions 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.
In addition to adverse reactions reported from clinical trials, the following reactions have been identified during postmarketing use of BACTROBAN nasal ointment. 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 nasal ointment.
Immune System Disorders
Systemic allergic reactions, including anaphylaxis, urticaria, angioedema, and generalized rash [see Warnings and Precautions (5.1)].
Pregnancy Category B.
There are no adequate and well-controlled studies of BACTROBAN nasal ointment (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 65 and 130 times, respectively, the human intranasal dose (approximately 20 mg mupirocin per day) based on body surface area. There was no evidence of fetal harm due to mupirocin.
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 nasal ointment is administered to a nursing woman.
Safety and efficacy in children younger than 12 years have not been established [see Clinical Pharmacology (12.3)].
Pharmacokinetic data in neonates and premature infants indicate that, unlike in adults, significant systemic absorption occurred following intranasal administration of BACTROBAN nasal ointment in this population.
Following single or repeated intranasal applications of BACTROBAN nasal ointment to adults, no evidence for systemic absorption of mupirocin was obtained. There is no information regarding local overdose of BACTROBAN nasal ointment or regarding oral ingestion of the nasal ointment formulation.
BACTROBAN (mupirocin calcium) nasal ointment, 2% contains the dihydrate crystalline calcium hemi‑salt of the antibacterial drug, 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:
BACTROBAN nasal ointment is a white to off‑white ointment that contains 2.15% w/w mupirocin calcium (equivalent to 2% mupirocin free acid) in a soft white ointment base. The inactive ingredients are paraffin and a mixture of glycerin esters (SOFTISAN® 649).
Mupirocin is an antibacterial drug [see Clinical Pharmacology (12.4)].
Following single or repeated intranasal applications of 0.2 grams of BACTROBAN nasal ointment 3 times daily for 3 days to 5 healthy adult male subjects, no evidence of systemic absorption of mupirocin was demonstrated. The dosage regimen used in this trial was for pharmacokinetic characterization only; see Dosage and Administration (2) for proper clinical dosing information.
In this trial, 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 acid in 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% to 5.1%) of the applied dose could be systemically absorbed from the nasal mucosa of adults.
The effect of concurrent application of BACTROBAN nasal ointment with other intranasal products has not been studied [see Dosage and Administration (2)].
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.
Pediatrics: The pharmacokinetic properties of mupirocin following intranasal application of BACTROBAN nasal ointment have not been adequately characterized in neonates or other children younger than 12 years, and in addition, the safety and efficacy of the product in children younger than 12 years have not been established.
Renal Impairment:The pharmacokinetics of mupirocin have not been studied in individuals with renal insufficiency.
Mupirocin is an antibacterial agent produced by fermentation using the organism Pseudomonas 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 intranasal administration. Mupirocin is highly protein bound (>97%), and the effect of nasal secretions on the minimum inhibitory concentrations (MICs) of intranasally applied 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, a plasmid mediating a new isoleucyl-tRNA synthetase. High‑level plasmid‑mediated resistance (MIC ≥512 mcg/mL) has been reported in increasing numbers of isolates of S. aureus and with higher frequency in coagulase‑negative staphylococci. Mupirocin resistance occurs with greater frequency in methicillin‑resistant than methicillin‑susceptible staphylococci.
Due to its mode of action, mupirocin does not demonstrate cross resistance with other classes of antimicrobial agents.
High-level mupirocin resistance (≥512 mcg/mL) may be determined using standard disk diffusion or broth microdilution tests1,2. The significance of these results, with regard to decolonization regimens, should be evaluated at each medical facility, in conjunction with laboratory, medical, and infection control staff.
Correlation of BACTROBAN nasal ointment in vitro activity and MRSA nasal decolonization has been demonstrated in clinical trials [see Clinical Studies (14)].
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 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 40 times the human intranasal dose (approximately 20 mg mupirocin per day) based on body surface area. Neither evidence of impaired fertility nor impaired reproductive performance attributable to mupirocin was observed.
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. 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 prescribing information.
In clinical trials, 210 domestic (US) and 2,130 foreign adult subjects received BACTROBAN nasal ointment. Greater than 90% of subjects in clinical trials had eradication of nasal colonization 2 to 4 days after therapy was completed. Approximately 30% recolonization was reported in 1 domestic trial within 4 weeks after completion of therapy. These eradication rates were clinically and statistically superior to those reported in subjects in the vehicle-treated arms of the adequate and well-controlled trials. Those treated with vehicle had eradication rates of 5% to 30% at 2 to 4 days post-therapy with 85% to 100% recolonization within 4 weeks.
BACTROBAN nasal ointment, 2% is supplied in single-use 1‑gram tubes.
BACTROBAN nasal ointment is a white to off-white ointment that contains mupirocin calcium (equivalent to 2% mupirocin free acid).
NDC 0029-1526-03 Single-use 1‑gram tube in Package of 10: NDC 0029-1526-11.
Store between 20°C and 25°C (68°F and 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not refrigerate.
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Advise the patient to administer BACTROBAN nasal ointment as follows:
BACTROBAN is a registered trademark of the GSK group of companies.
SOFTISAN is a trademark of its respective owner and is not a trademark of the GSK group of companies. The maker of this brand is not affiliated with and does not endorse the GSK group of companies or its products.
Research Triangle Park, NC 27709
©2015 the GSK group of companies. All rights reserved.
PHARMACIST‑DETACH HERE AND GIVE INSTRUCTIONS TO PATIENT
Patient Package Insert
(mupirocin calcium) nasal ointment
For intranasal use only
Read this Patient Information Leaflet before you start using BACTROBAN nasal ointment and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
What is BACTROBAN nasal ointment?
BACTROBAN nasal ointment is an antibiotic. It is used to reduce the amount of bacteria in your nose.
Who should not use BACTROBAN nasal ointment?
Do not use BACTROBAN nasal ointment if:
Before using BACTROBAN nasal ointment, tell your healthcare provider about your medical conditions and medicines you take including, if you:
How should I use BACTROBAN nasal ointment?
What are the possible side effects of BACTROBAN nasal ointment?
BACTROBAN nasal ointment may cause serious side effects, including:
Common side effects of BACTROBAN nasal ointment may include headache, runny nose, congestion, sore throat, distorted sense of taste, burning and/or stinging, cough and itching.
These are not all the possible side effects of BACTROBAN nasal ointment. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store BACTROBAN nasal ointment?
General information about the safe and effective use of BACTROBAN nasal ointment.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. You can ask your pharmacist or healthcare provider for information about BACTROBAN nasal ointment that is written for health professionals.
Do not use BACTROBAN nasal ointment for a condition for which it was not prescribed. Do not give BACTROBAN nasal ointment to other people, even if they have the same symptoms that you have. It may harm them.
What are the ingredients in BACTROBAN nasal ointment?
Active Ingredient: mupirocin calcium
Inactive Ingredients: paraffin and Softisan® 649
For more information call 1-888-825-5249.
This Patient Information has been approved by the U.S. Food and Drug Administration.
BACTROBAN is a registered trademark of the GSK group of companies.
SOFTISAN is a registered trademark of its respective owner and is not a trademark of the GSK group of companies. The maker of this brand is not affiliated with and does not endorse the GSK group of companies or its products.
©2015 the GSK group of companies. All rights reserved.
Research Triangle Park, NC 27709
Revised: September 2015