mupirocin 2% ointment generic centany

Uses

Skin Infections

Mupirocin is used topically as a dermatologic ointment for the treatment of impetigo caused by Staphylococcus aureus and Streptococcus pyogenes (group A β-hemolytic streptococci). Topical mupirocin is considered a drug of choice for treatment of impetigo, especially when limited numbers of lesions are present. If impetigo is extensive or has not responded to topical anti-infectives, an oral anti-infective active against S. aureus and S. pyogenes (e.g., dicloxacillin, cephalosporins, erythromycin, clindamycin, fixed combination of amoxicillin and clavulanate) should be used.

Mupirocin calcium is used topically as a dermatologic cream for the treatment of secondarily infected traumatic skin lesions (e.g., lacerations, sutured wounds, abrasions) that are not more than 10 cm in length or 100 cm in total area and are caused by susceptible S. aureus and S. pyogenes.

Topical mupirocin also has been effective when used in the treatment of other primary or secondary superficial skin infections, including ecthyma, eczema, folliculitis, furunculosis, atopic dermatitis, epidermolysis bullosa, and minor wounds, burns, and ulcers caused by susceptible bacteria.

Some clinicians suggest that topical mupirocin may be preferred over systemic anti-infective therapy for the treatment of impetigo and other superficial skin infections caused by susceptible bacteria since the drug appears to be as effective as and is associated with fewer adverse effects than systemic therapy. However, systemic anti-infectives generally are necessary for the treatment of serious or extensive skin infections.

Clinical Experience

In placebo-controlled studies in patients with primary or secondary bacterial skin infections, including impetigo, topical mupirocin ointment (in a polyethylene glycol [PEG] vehicle) resulted in a bacteriologic cure in 80-94% and clinical cure or improvement in 71-100% of patients; the PEG vehicle alone (which also has some antibacterial activity at high concentrations) resulted in a bacteriologic cure in 33-62% and clinical cure or improvement in 35-85% of patients. In one study in adult and pediatric patients with impetigo randomized to receive topical mupirocin 2% ointment for dermatologic use or topical vehicle placebo 3 times daily for 8-12 days, the bacteriologic cure rate and clinical efficacy rate in evaluable patients were 94 and 71%, respectively, in those treated with mupirocin compared with 62 and 35%, respectively, in those treated with the vehicle placebo. In evaluable pediatric patients 2 months to 15 years of age in this study, the clinical efficacy rate was 78% in those who received mupirocin ointment and 36% in those who received vehicle placebo.

In a randomized study in adult and pediatric patients with impetigo who were treated with topical mupirocin 2% ointment for dermatologic use 3 times daily for 7 days, the clinical efficacy rate (1 week after treatment) in evaluable patients was 95% in those who received mupirocin ointment formulated in a PEG vehicle (Bactroban) and 94% in those who received mupirocin ointment formulated in a vehicle without PEG (Centany); the pathogen eradication rate was the same (98%) in both groups. The clinical efficacy rate in evaluable pediatric patients 2 months to 15 years of age in this study was 95% in those who received Bactroban and 93% in those who received Centany.

The comparative efficacy of topical mupirocin and oral anti-infectives in the treatment of superficial skin infections has been evaluated. Although most studies were not blinded and some were poorly controlled in terms of the severity of infection, topical mupirocin appears to be at least as effective as oral erythromycin, cloxacillin (not commercially available in the US), dicloxacillin, or cephalexin in the treatment of impetigo and other superficial skin infections. In one unblinded study in adult and pediatric patients with impetigo randomized to receive topical mupirocin 2% ointment for dermatologic use (in a PEG vehicle) 3 times daily or oral erythromycin (30-40 mg/kg daily) for 8 days, the bacterial eradication rate was 100% in both groups and the clinical efficacy rate (1 week after treatment) was 93% in those treated with topical mupirocin compared with 78.5% in those treated with oral erythromycin. In several studies in patients with both primary and secondary superficial skin infections, topical mupirocin resulted in a bacteriologic cure in 91-100% of patients and clinical cure or improvement in 94-100% of patients, and oral erythromycin or cloxacillin resulted in bacteriologic cure in 50-91% of patients and clinical cure or improvement in 73-100% of patients. In 2 randomized, double-blind, multicenter clinical studies in adults and children with secondarily infected traumatic skin lesions, including lacerations, sutured wounds, and abrasions, topical mupirocin cream (applied 3 times daily for 10 days) or oral cephalexin (250 mg administered 4 times daily for 10 days) produced clinical efficacy rates of about 96 or 93-97%, respectively; the bacterial cure rate was 100% in both groups.

There is some evidence that topical mupirocin and topical fusidic acid (not commercially available in the US) are equally effective for the treatment of impetigo and may be more effective than other topical anti-infectives that have been used for the treatment of impetigo and other superficial skin infections (e.g., bacitracin, gentamicin, neomycin, chlortetracycline [not commercially available in the US], fixed-combination preparation containing bacitracin, neomycin, and polymyxin B sulfate).

Nasal Carriage of Staphylococcus aureus

Mupirocin calcium is used intranasally to temporarily eliminate nasal carriage of methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA). The drug also has been used intranasally to temporarily eliminate nasal carriage of methicillin-susceptible S. aureus.

Mupirocin calcium ointment for intranasal use (Bactroban Nasal) is labeled by the US Food and Drug Administration (FDA) for elimination of nasal carriage of MRSA in adult patients and health-care 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 caused by this pathogen. The manufacturer states that data are insufficient to date to establish whether the intranasal ointment is safe and effective when used as part of an intervention program to prevent autoinfection of high-risk patients from their own nasal colonization with S. aureus and that data are insufficient to date to recommend use of the ointment for general prophylaxis of any infection in any patient population.

Because nasal carriage of S. aureus is considered a risk factor for subsequent staphylococcal infections, intranasal mupirocin has been used to eliminate nasal carriage of S. aureus in carriers at high-risk of staphylococcal infections (e.g., surgical patients, cancer patients, hemodialysis patients) in an attempt to decrease the incidence of infections in these patients. It has been suggested that data are insufficient to support routine use of topical and/or systemic anti-infectives for eradication of MRSA colonization. However, some experts suggest that eradication of nasal carriage of S. aureus may be a reasonable strategy in certain patients with multiple documented recurrences of MRSA infection. In addition, there is some evidence from controlled studies in high-risk patients that use of intranasal mupirocin in S. aureus carriers can reduce the overall S. aureus infection rate in such individuals. Therefore, some experts suggest that intranasal mupirocin may be considered for hospitalized surgical, dialysis, and nonsurgical patients at risk of infection if they are known nasal carriers of S. aureus.

Permanent eradication of nasal carriage of S. aureus following topical or systemic anti-infective therapy is unlikely; recolonization generally occurs in 30-100% of patients regardless of the anti-infective agent used. Studies using intranasal mupirocin indicate that nasal carriage of S. aureus usually is eliminated within the first 1-4 days of therapy, but recolonization usually occurs 2-17 days or up to several weeks or months later until the drug is discontinued.

Dosage and Administration

Administration

Topical Administration

Mupirocin is administered topically to the skin as an ointment for dermatologic use containing 2% mupirocin in a water-miscible vehicle containing polyethylene glycol (PEG) (Bactroban, various generic preparations) or as an ointment for dermatologic use containing 2% mupirocin in a vehicle without PEG (Centany).

Mupirocin calcium is applied topically to the skin as a cream for dermatologic use containing 2% mupirocin in an oil and water-based vehicle (Bactroban).

Mupirocin ointment or cream for dermatologic use should not be applied to eyes or mucous membranes and should not be administered intranasally.

Treated areas of skin may be covered with a sterile gauze dressing if desired.

Intranasal Administration

Mupirocin calcium is applied intranasally as an ointment specifically formulated for intranasal administration (Bactroban Nasal). This intranasal formulation contains 2% mupirocin in a soft ointment vehicle of paraffin and a mixture of glycerin esters (Softisan 649).

Mupirocin ointment for intranasal use should not be applied to eyes.

Mupirocin ointment for intranasal use is administered by placing one-half (approximately 0.25 g) of the ointment contained in the single-dose tube into each nostril. The ointment should then be distributed evenly throughout the nares by pressing together and releasing the sides of the nose repetitively for approximately 1 minute. The single-use tube should be discarded after application and should not be reused.

Mupirocin intranasal ointment should not be applied concurrently with other intranasal preparations.

Although commercially available mupirocin ointment for dermatologic use has been used intranasally, the manufacturers and some clinicians state that the commercially available ointments for dermatologic use (formulated with or without PEG) should not be used intranasally. Intranasal use of ointments formulated in a PEG vehicle may irritate mucous membranes.(See Intranasal Administration under Cautions: Adverse Effects.)

Dosage

Skin Infections

Impetigo

For the topical treatment of impetigo caused by Staphylococcus aureus or Streptococcus pyogenes in adults and children 2 months of age or older, a small amount of mupirocin 2% ointment for dermatologic use should be applied to the affected area 3 times daily.

The usual duration of treatment is about 7 days (5-10 days). If a clinical response is not evident within 3-5 days, the clinician should be contacted and the infection reevaluated.

Secondary Skin Infections

For the treatment of secondarily infected traumatic skin lesions (e.g., lacerations, sutured wounds, abrasions) in adults and children 3 months of age or older, a small amount of mupirocin 2% cream for dermatologic use should be applied to the affected area 3 times daily for 10 days.

If a clinical response is not evident within 3-5 days, the clinician should be contacted and the infection reevaluated.

Nasal Carriage of Staphylococcus aureus

When mupirocin 2% ointment for intranasal use is used to eliminate nasal carriage of Staphylococcus aureus in adults and children 12 years of age or older, one-half (approximately 0.25 g) of the ointment contained in the single-dose tube should be applied into each nostril twice daily (morning and evening) for 5 days.(See Intranasal Administration under Dosage and Administration: Administration.)

The manufacturer states that safety and efficacy of more than 5 days of treatment with the intranasal ointment have not been established.

Cautions

Adverse Effects

Topical Administration

Mupirocin generally is well tolerated when applied topically to skin. Most adverse effects of topical mupirocin ointment for dermatologic use or mupirocin calcium cream for dermatologic use are mild, transient, local reactions that require discontinuance of the drug in less than 1% of patients.

Following topical application of mupirocin ointment or cream for dermatologic use, burning, stinging, pain, pruritus, and rash have occurred in less than 1-4% of patients. In addition, erythema, dry skin, tenderness, cellulitis, pain or bleeding secondary to eczema, secondary wound infection, urticaria, swelling, increased exudate, contact dermatitis, furunculosis, and exfoliative dermatitis have occurred in less than 1% of patients.

Mupirocin appears to have minimal potential for inducing allergic contact sensitization following topical application. In addition, the drug only has weak ultraviolet light-absorbing properties and is unlikely to cause phototoxicity or photoallergic dermatitis. Controlled studies in healthy individuals have not revealed evidence of local irritation, contact sensitization, phototoxicity, or photoallergic dermatitis following topical application of mupirocin to intact or irritated skin (with or without an occlusive dressing). However, although a causal relationship to the drug has not been definitely established, contact dermatitis or dermatitis has been reported in some patients receiving topical mupirocin.

Systemic reactions have been reported rarely following topical application of mupirocin or mupirocin calcium to skin. Nausea has been reported in up to 4.9% and headache has been reported in up to 4% of patients. Other systemic effects reported in less than 1% of patients receiving topical mupirocin include dizziness, abdominal pain, and ulcerative stomatitis.

Some preparations of mupirocin ointment for dermatologic use contain the drug in a polyethylene glycol (PEG) vehicle (Bactroban, various generic preparations). It has been suggested that some of the adverse local effects reported with topical mupirocin ointment may be related to the PEG vehicle rather than the drug itself since controlled studies indicate the incidence of some of these adverse effects is similar when the PEG vehicle is used topically alone. In addition to its potential to cause local effects, PEG can be absorbed percutaneously into systemic circulation following topical application to open wounds or damaged skin and then is excreted by the kidneys. Prolonged or repeated application of a PEG-containing ointment to large areas of damaged skin (e.g., burns) may result in systemic absorption of potentially toxic amounts of PEG. Rarely, renal failure and death have been associated with topical application of PEG-containing ointments in burn patients and in animal burn models. Clinicians should consider that clinically important amounts of PEG could be absorbed if a preparation containing PEG is used in patients with extensive open wounds or burns and that toxicity is possible. The manufacturers state that mupirocin ointment for dermatologic use formulated in a PEG vehicle should not be used in conditions where absorption of large quantities of PEG is possible, especially if there is evidence that the patient has moderate or severe renal impairment.

Studies using a porcine wound model indicate that topical mupirocin does not adversely affect the rate of superficial wound healing or epidermal migration. In vitro studies indicate that, at concentrations up to 100 mcg/mL, mupirocin does not appear to adversely affect the growth and proliferative lifespan of human fibroblasts in healing wounds; however, growth of these cells is inhibited at mupirocin concentrations of 700 mcg/mL or greater.

Intranasal Administration

Following intranasal administration of commercially available mupirocin calcium ointment for intranasal use (mupirocin calcium in a soft ointment base formulated with paraffin and a mixture of glycerin esters [Softisan 649]), the most frequently reported adverse effects are headache (9%), rhinitis (6%), respiratory disorders (including upper respiratory tract congestion) (5%), pharyngitis (4%), taste perversion (3%), and cough (2%). Local effects, including burning/stinging and pruritus, also have been reported in 1-2% of patients. Other systemic effects reported in less than 1% of patients receiving this intranasal preparation include blepharitis, diarrhea, dry mouth, ear pain, epistaxis, nausea, and rash.

Prior to the availability of mupirocin calcium for intranasal use, mupirocin ointment for dermatologic use in a PEG vehicle was sometimes used intranasally. Intranasal application of the ointment for dermatologic use has caused irritation of the nasal mucosa and has caused local stinging, soreness, drying, and pruritus. These local effects may have been caused by the PEG vehicle. The manufacturers and some clinicians state that mupirocin ointment for dermatologic use (formulated with or without PEG) should not be used intranasally.

Precautions and Contraindications

Mupirocin is contraindicated in patients with a history of hypersensitivity to the drug or any ingredient in the formulation.

As with other anti-infectives, prolonged use of mupirocin may result in overgrowth of nonsusceptible organisms, including fungi.

The manufacturers state that preparations of mupirocin ointment for dermatologic use formulated in a PEG vehicle should not be used in conditions where absorption of large quantities of PEG is possible, especially if there is evidence that the patient has moderate or severe renal impairment.

Commercially available mupirocin ointment for dermatologic use and mupirocin calcium cream for dermatologic use are intended for topical application to the skin only and should not be applied to eyes or mucous membranes (including intranasal mucous membranes). Patients should be cautioned that these preparations should be used as directed by their clinician and are for external use only.

Mupirocin calcium ointment for intranasal use (Bactroban Nasal) is intended only for topical intranasal application to mucous membranes of the nose and should not be applied to eyes. When this ointment was applied to the eye under testing conditions, severe symptoms such as burning and tearing occurred; symptoms resolved within days to weeks after the drug was discontinued.

If manifestations suggesting sensitivity or severe local or chemical irritation (e.g., irritation, severe pruritus, rash) occur during mupirocin therapy, the drug should be discontinued and appropriate alternative anti-infective therapy substituted.

Patients receiving topical mupirocin therapy should be advised to contact their clinician if any sign of a local adverse reaction occurs or if improvement is not evident within 3-5 days of therapy. Patients also should be instructed to discontinue mupirocin therapy and contact a clinician if they develop irritation, severe itching, or rash.

Pediatric Precautions

The safety and efficacy of mupirocin ointment for dermatologic use have not been established in children younger than 2 months of age. Use of the topical ointment in children 2 months to 16 years of age is supported by evidence from adequate and well-controlled studies in adults and children with impetigo.

The safety and efficacy of mupirocin calcium cream for dermatologic use have not been established in children younger than 3 months of age. Use of the topical cream in children 3 months to 16 years of age is supported by evidence from adequate and well-controlled studies in adults and also from a study in a limited number of children.

The safety and efficacy of mupirocin calcium ointment for intranasal use have not been established in children younger than 12 years of age.

Geriatric Precautions

In 2 well-controlled studies that included geriatric patients older than 65 years of age, there were no overall differences in efficacy and safety in this age group compared with younger adults.

Mutagenicity and Carcinogenicity

Mupirocin was not mutagenic in various in vitro and in vivo tests, including rat primary hepatocyte unscheduled DNA synthesis test, sediment analysis for DNA strand breaks, Ames test, Escherichia coli mutation assay, human lymphocyte metaphase test, mouse lymphoma assay, and mouse bone marrow micronuclei assay.

The carcinogenic potential of mupirocin has not been evaluated to date in long-term animal studies.

Pregnancy, Fertility, and Lactation

Pregnancy

Reproduction studies in rats and rabbits using subcutaneous mupirocin in dosages up to 22-78 and 43-154 times the usual topical human dosage, respectively, have not revealed evidence of harm to the fetus. There are no adequate and controlled studies to date using topical mupirocin in pregnant women, and the drug should be used during pregnancy only when clearly needed.

Fertility

Reproduction studies in rats using subcutaneous mupirocin in dosages up to 14-49 times the usual topical human dosage have not revealed evidence of impaired fertility.

Lactation

It is not known whether mupirocin is distributed into milk. The manufacturers state that, since many drugs are distributed into milk, mupirocin ointment for dermatologic use, mupirocin calcium cream for dermatologic use, and mupirocin calcium ointment for intranasal use should be used with caution in nursing women. However, it is unlikely that clinically important concentrations would be achieved in breast milk following topical application of usual dosages to the skin.

Drug Interactions

Chloramphenicol

Although the clinical importance has not been determined to date, in vitro studies using Escherichia coli indicate that chloramphenicol interferes with the antibacterial action of mupirocin on RNA synthesis.

Intranasal Preparations

Concurrent use of mupirocin calcium ointment for intranasal use and other intranasal preparations has not been studied to date. Pending further accumulation of data, the manufacturer states that the intranasal mupirocin ointment should not be used concurrently with any other intranasal preparations.

Topical Preparations

Information is not available regarding concurrent application to skin of mupirocin ointment for dermatologic use or mupirocin calcium cream for dermatologic use and other topical preparations.

Pharmacokinetics

Absorption

Mupirocin does not appear to be appreciably absorbed systemically following topical application to intact skin.

In one study in healthy adults, less than 0.3% of a topical dose of radiolabeled mupirocin was absorbed through intact skin after 24 hours under an occlusive dressing; the drug was not detected in urine or feces collected for 5 days after the dose. In this study, 2-4% of the radioactivity was present in the stratum corneum 24 hours after application and remained detectable there for at least 72 hours after application. Application of the drug to traumatized or diseased skin may result in penetration into deeper epidermal skin layers and possibly systemic circulation, but studies are needed to confirm this.

Following topical application of mupirocin 2% ointment in a vehicle without PEG (Centany) to an area 400 cm on the back of healthy volunteers once daily for 7 days, some systemic absorption of the drug occurred since 0.2-3% of the administered dose was excreted in urine as monic acid (a metabolite of mupirocin) over 24 hours following the last dose.

Following topical application of mupirocin calcium cream for dermatologic use (2% mupirocin) to various skin lesions (exceeding 10 cm in length or 100 cm in total area) 3 times daily for 5 days in adults 29-60 years of age and children 3-12 years of age, monic acid was detected in urine. In this study, percutaneous absorption was reported more frequently in children (90%) than in adults (44%); however, the manufacturer states that the degree of percutaneous absorption appears to be minimal in both groups.

Following intranasal administration of mupirocin calcium ointment for intranasal use (2% mupirocin) 3 times daily for 3 days in adults, there was no evidence of systemic absorption of the drug. Because urinary concentrations of mupirocin and serum and urinary concentrations of monic acid were below the limits of detection, it was suggested that a mean of 3.3% (range 1.2-5.1%) of a dose of mupirocin ointment for intranasal use could be absorbed systemically from the nasal mucosa of adults. The pharmacokinetics of intranasal mupirocin have not been adequately characterized in neonates or children younger than 12 years of age. However, there is some evidence that significant systemic absorption can occur if mupirocin calcium ointment for intranasal use is administered intranasally in neonates and premature infants.

Following IV infusion over 25 minutes of a single 31.3-, 61.2-, 125-, or 252-mg dose of mupirocin as the sodium salt in healthy adults, peak serum concentrations of mupirocin at the end of the infusion averaged 1.9, 1.9, 7.1, or 14.1 mcg/mL, respectively; serum concentrations of the drug declined rapidly and were undetectable within 3 hours. The pharmacokinetics of mupirocin have not been studied in patients with renal impairment.

Distribution

Mupirocin is highly bound to serum proteins (95-97% or more) in vitro.

It is not known whether mupirocin crosses the placenta in humans, but the drug crosses the placenta in rats and rabbits following IV administration.

Elimination

Following IV or oral administration, mupirocin is rapidly metabolized. Mupirocin sodium administered IV is almost completely metabolized, presumably in the liver, by conversion to monic acid. Monic acid is formed by de-esterification of the drug at the ester linkage between the ring structure and side chain; the metabolite is microbiologically inactive and rapidly eliminated in urine. Following IV administration of a single 125- or 252-mg IV dose of mupirocin as the sodium salt in healthy adults, approximately 0.5 or 5% of the dose, respectively, is excreted in urine as unchanged mupirocin and 72 or 56%, respectively, is excreted as monic acid within 12 hours.

There is some evidence that enzymes present within skin can partially inactivate mupirocin by metabolizing the drug to monic acid. In an in vitro study using a homogenate of human skin, approximately 3% of a dose of mupirocin was metabolized to monic acid over 48 hours, although similar in vitro studies using a homogenate of rat or rabbit skin indicate that up to 27% of a dose of the drug may be inactivated over 48 hours. It is doubtful whether this inactivation could occur to an appreciable extent following topical application to intact skin, and the drug appears to be active for at least 24 hours when applied topically to such skin. Any mupirocin that is absorbed systemically following topical application presumably is inactivated by conversion to monic acid and rapidly eliminated in urine. Mupirocin does not appear to be inactivated by nonspecific esterases present in blood.

Serum concentrations of mupirocin decline in a biphasic manner following IV administration. Following IV administration in healthy adults, the elimination half-life of mupirocin is 17-40 minutes and that of monic acid is 30-80 minutes.

Following topical application of mupirocin calcium cream (2% mupirocin) to various skin lesions (exceeding 10 cm in length or 100 cm in total area) in adults 29-60 years of age and children 3-12 years of age, urinary concentrations of the drug ranged from undetectable to 10.03 mcg/mL in adults and undetectable to 1.3 mcg/mL in children.

Following intranasal administration of mupirocin calcium ointment for intranasal use (3 times daily for 3 days), mupirocin and monic acid were undetectable in urine.