BACTROBAN Ointment 2% contains 20mg mupirocin per gram in a bland water soluble ointment base consisting of polyethylene glycol 400 and polyethylene glycol 3350 (polyethylene glycol ointment NF).
BACTROBAN Ointment is indicated for the topical treatment of the following primary and secondary skin infections due to susceptible pathogens: primary pyodermas such as impetigo, folliculitis, furunculosis, ecthyma; secondary infected dermatoses such as eczema, psoriasis, atopic dermatitis, herpes, epidermolysis bullosa, icthyosis, and infected traumatic lesions such as ulcers, minor burns, cuts, abrasions, lacerations, wounds, biopsy sites, surgical incisions and insect bites. Prophylactically, BACTROBAN Ointment may be used to prevent bacterial contamination in minor burns, biopsy sites, incisions and other clean lesions. For abrasions, minor cuts and wounds the prophylatic use of BACTROBAN may prevent the development of infection and permit wound healing.
A small amount of BACTROBAN Ointment should be applied to the affected area three times daily for up to 10 days, depending on the response. The area treated may be covered with a gauze dressing if required. Any product remaining at the end of treatment should be discarded. Do not mix with other preparations as there is a risk of dilution, resulting in a reduction in the antibacterial activity and potential loss of stability of the mupirocin in the ointment.
See Warnings and Precautions.
BACTROBAN ointment should not be given to patients with a history of hypersensitivity to mupirocin or any of the constituents of the preparation.
In the rare event of a possible sensitisation reaction or severe local irritation occurring with the use of the product, treatment should be discontinued, the product should be wiped off and appropriate alternative therapy for the infection instituted. As with other antibacterial products, prolonged use may result in overgrowth of non- susceptible organisms. Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea during or after antibiotic use. Although this is less likely to occur with topically applied mupirocin, if prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further. This mupirocin ointment formulation is not suitable for: ophthalmic use. intranasal use (in neonates or infants). use in conjunction with cannulae. at the site of central venous cannulation Avoid contact with eyes. If contaminated, the eyes should be thoroughly irrigated with water until the ointment residues have been removed. Polyethylene glycol can be absorbed from open wounds and damaged skin and is excreted by the kidneys. In common with other polyethylene glycol based ointments, mupirocin ointment should not be used in conditions where absorption of large quantities of polyethylene glycol is possible, especially if there is evidence of moderate or severe renal impairment.
Elderly patients: No restrictions unless the condition being treated could lead to absorption of polyethylene glycol and there is evidence of moderate or severe renal impairment.
There are no data on the effects of mupirocin on human fertility. Studies in rats showed no effects on fertility (see Preclinical Safety Data).
Adequate human data on use during pregnancy are not available. Studies in animals do not indicate reproductive toxicity (see Preclinical Safety Data).
Adequate human and animal data on use during lactation are not available. If a cracked nipple is to be treated, it should be thoroughly washed prior to breast feeding.
No adverse effects on the ability to drive or operate machinery have been observed.
Preclinical safety data
Carcinogenesis/Mutagenesis Carcinogenesis
Carcinogenicity studies with mupirocin have not been conducted.
Genotoxicity
Mupirocin was not mutagenic in Salmonella typhimurium or Escherichia coli (Ames assay). In a Yahagi assay, small increases in Salmonella typhimurium TA98 were observed at highly cytotoxic concentrations. In an in vitro mammalian gene mutation assay (MLA), no increase in mutation frequency was observed in the absence of metabolic activation. In the presence of metabolic activation, small increases in mutation frequency were observed at highly cytotoxic concentrations. However, no effects were observed in, yeast cell assays for gene conversion/mutation, an in vitro human lymphocyte assay or in an in vitro unscheduled DNA synthesis (UDS) assay. Furthermore, an in vivo mouse micronucleus assay (chromosome damage) and a rat Comet assay (DNA strand breakage) were negative, indicating the small increases observed at highly cytotoxic concentrations in vitro do not translate to the in vivo situation.
Reproductive Toxicology Fertility
Mupirocin administered subcutaneously to male rats 10 weeks prior to mating and to female rats 15 days prior to mating until 20 days post coitum at doses up to 100 mg/kg/day had no effect on fertility.
Pregnancy
In embryo-foetal development studies in rats there was no evidence of developmental toxicity at subcutaneous doses up to 375 mg/kg/day. In an embryo-foetal development study in rabbits at subcutaneous doses up to 160 mg/kg/day, maternal toxicity (impaired weight gain and severe injection site irritation) at the high dose resulted in abortion or poor litter performance. However, there was no evidence of developmental toxicity in foetuses of rabbits maintaining pregnancy to term.
Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as: very common (1/10), common (1/100, <1/10), uncommon (1/1000, <1/100), rare (1/10,000, <1/1000), very rare (<1/10,000), including isolated reports. Common and uncommon adverse reactions were determined from pooled safety data from a clinical trial population of 1573 treated patients encompassing 12 clinical studies. Very rare adverse reactions were primarily determined from post-marketing experience data and therefore refer to reporting rate rather than true frequency.
Immune system disorders:
Very rare:Systemic allergic reactions such as generalised rash, urticaria and angioedema have been reported with BACTROBAN ointment.
Skin and subcutaneous tissue disorders:
Common:Burning localised to the area of application. Uncommon:Itching, erythema, stinging and dryness localised to the area of application. Cutaneous sensitisation reactions to mupirocin or the ointment base.
No drug interactions have been reported.
Not applicable.
Mechanism of action
Mupirocin is a novel antibiotic produced through fermentation of Pseudomonas fluorescens. Mupirocin inhibits isoleucyl transfer-RNA synthetase, thereby arresting bacterial protein synthesis. Due to this particular mode of action and its unique chemical structure, mupirocin does not show any cross-resistance with other clinically available antibiotics. Mupirocin shows little risk of selection of resistant bacteria if used as prescribed. Mupirocin has bacteriostatic properties at minimum inhibitory concentrations and bactericidal properties at the higher concentrations reached when applied locally. Following intravenous or oral administration, mupirocin is rapidly metabolised to the inactive monic acid.
Pharmacodynamic Effects
Activity:
Mupirocin is a topical antibacterial agent showing in vivo activity against Staphylococcus aureus (including methicillin-resistant strains), S. epidermidis and beta-haemolytic Streptococcus species. The in vitro spectrum of activity includes the following bacteria: Aerobic Gram-positive:
Staphylococcus aureus
(including beta-lactamase producing strains and methicillin resistant strains)
Staphylococcus epidermidis
Other coagulase negative Staphylococci (including methicillin resistant strains)
Streptococcus
species Anaerobic Gram-negative:
Haemophilus influenzae
Neisseria gonorrheae
Neisseria meningitidis
Branhamella catarrhalis
Pasteurella multocida
Proteus mirabilis
Proteus vulgaris
Enterobacter cloacae
Enterobacter aerogenes
Citrobacter freundii
Bordetella pertussis
Susceptibility:
Susceptible:
Staphylococcus aureus *
Staphylococcus epidermidis *
Coagulase-negative staphylococci *
Streptococcus species *
Haemophilus influenzae
Neisseria gonorrhoeae
Neisseria meningitidis
Moraxella catarrhalis
Pasteurella multocida
Clinical efficacy has been demonstrated for susceptible isolates in approved clinical indications. Insusceptible
Corynebacterium
species
Enterobacteriaceae
Gram negative non-fermenting rods
Micrococcus
species
Anaerobes
Cross-resistance:
Mupirocin does not demonstrate cross-resistance with any other known antimicrobial.
Resistance mechanisms:
Low-level resistance in staphylococci (MICs 8-256 mcg/ml) has been shown to be due to changes in the native isoleucyl tRNA synthetase enzyme. High-level resistance in staphylococci (MICs 512 mcg/ml) has been shown to be due to a distinct, plasmid encoded isoleucyl tRNA synthetase enzyme. Intrinsic resistance in Gram negative organisms such as the Enterobacteriaceae could be due to poor penetration into the bacterial cell.
Absorption
Mupirocin is poorly absorbed through intact human skin. However, if it is absorbed (e.g. through broken/diseased skin) or it is given systemically, it is metabolised to the microbiologically inactive metabolite monic acid and rapidly excreted.
Excretion
Mupirocin is rapidly eliminated from the body by metabolism to its inactive metabolite monic acid which is excreted mainly by the kidney (90%).
Excipients
Bactroban Ointment contains the excipients: macrogol 400 macrogol 3350
Wash your hands after application.
None reported.
Two years when stored below 25degC.
BACTROBAN ointment may be stored at room temperature (below 25degC) up to the expiry date.
BACTROBAN Ointment 2% is supplied in 15 g tubes.
Prescription Medicine.
GlaxoSmithKline NZ Ltd Private Bag 106600 Downtown Auckland NEW ZEALAND Telephone: (09) 367 2900 Fax: (09) 367 2506
12 November 2013 Version: 3.0 BACTROBAN is a registered trade mark of the GlaxoSmithKline group of companies.