Class: Antibacterials
ATC Class: D06AX09
VA Class: DE101
Chemical Name: [2S - [2α(E),3β,4β,5α[2R*,3R*,(1R*,2R*)]] - 9 - [3 - Methyl - 1 - oxo - 4 - [tetrahydro - 3,4 - dihydroxy - 5 - [3 - (2 - hydroxy - 1 - methylpropyl)oxiranyl]methyl - 2H - pyran - 2 - yl] - 2 - butenyl]oxy] - nonanoic acid
Molecular Formula: C52H86CaO18•2H2O
CAS Number: 12650-69-0
Brands: Bactroban, Bactroban Nasal, Centany
Introduction
Antibacterial; pseudomonic acid antibiotic produced by Pseudomonas fluorescens.1 2 3 4 5 6 8 12 15 16 17 22 23 30 31 74 78 91 92 93 94 95
Uses for Mupirocin
Skin Infections
Topical treatment of impetigo caused by Staphylococcus aureus and Streptococcus pyogenes (group A β-hemolytic streptococci).1 3 11 16 18 20 28 30 40 41 42 43 44 45 46 47 48 49 50 56 73 79 80 83 84 91 92 93 94 95 A drug of choice, especially when limited numbers of lesions are present.79 80 84 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.79 84
Topical treatment of secondarily infected traumatic skin lesions (e.g., lacerations, sutured wounds, abrasions) that are ≤10 cm in length or ≤100 cm2 in total area and caused by susceptible S. aureus and S. pyogenes.75 78
Has been used for topical treatment of other primary or secondary superficial skin infections, including ecthyma†,2 30 48 54 69 eczema†,2 3 11 14 16 20 25 28 36 38 39 40 43 44 47 54 56 69 76 folliculitis†,2 3 11 18 20 28 30 46 47 56 69 furunculosis†,2 28 30 44 54 56 69 atopic dermatitis†,37 69 72 epidermolysis bullosa†,29 35 39 56 and minor wounds†,3 16 20 38 39 46 54 56 burns†,16 39 40 56 and ulcers†16 20 35 38 39 44 46 47 56 69 caused by susceptible bacteria.
May be preferred over systemic anti-infective therapy for treatment of impetigo and other superficial skin infections caused by susceptible bacteria since it may be as effective as and is associated with fewer adverse effects than systemic therapy.3 40 41 43 45 64 70 75 84 However, systemic anti-infectives generally are necessary for the treatment of serious or extensive 84 skin infections.3 64 70 79
Nasal Carriage of Staphylococcus aureus
Temporary elimination of nasal carriage of methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA).2 3 4 16 32 33 34 52 55 61 62 63 74 81 82 85 86 88 Also has been used intranasally to temporarily eliminate nasal carriage of methicillin-susceptible S. aureus†.2 3 4 16 32 34 81 85 86 88
Mupirocin ointment for intranasal use (Bactroban Nasal) is labeled by the 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.74
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 intranasal ointment for general prophylaxis of any infection in any patient population.74
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 subsequent staphylococcal infections in these patients†.81 85 86 87 89 90 Data are insufficient to support routine use of topical and/or systemic anti-infectives for eradication of MRSA colonization.82 85 86 87 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 infection85 and 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.81 89
Permanent eradication of nasal carriage of S, aureus following topical or systemic anti-infective therapy is unlikely;3 16 33 62 63 recolonization generally occurs in 30–100% of patients regardless of the anti-infective agent used.3 32 33 74
Mupirocin Dosage and Administration
Administration
Topical Administration
Apply topically to the skin as 2% ointment for dermatologic use in a water-miscible vehicle containing polyethylene glycol (PEG) (Bactroban, various generic preparations),1 92 93 94 95 2% ointment for dermatologic use in a vehicle without PEG (Centany),91 96 or 2% cream for dermatologic use in an oil and water-based vehicle (Bactroban).1 78
Do not apply ointment or cream for dermatologic use to eyes or mucous membranes; do not administer these preparations intranasally.1 78 91 92 93 94 95
Treated areas of skin may be covered with sterile gauze dressing if desired.1 78 91 92 93 94 95
Intranasal Administration
Apply intranasally as 2% ointment for intranasal use.74
The commercially available intranasal ointment is intended for topical intranasal application to nasal mucous membranes only; do not apply to eyes.74
Administer mupirocin ointment for intranasal use by placing one-half (approximately 0.25 g) of the ointment contained in the single-dose tube into each nostril.74 Distribute the ointment evenly throughout the nares by pressing together and releasing the sides of the nose repetitively for approximately 1 minute.74 Discard the single-use tube after application; do not reuse.74
Do not apply concurrently with other intranasal preparations.74 (See Intranasal Preparations under Interactions.)
Although mupirocin ointment for dermatologic use has been used intranasally†,3 33 52 85 the manufacturers and some clinicians state that the ointment for dermatologic use (formulated with or without PEG) should not be used intranasally.1 3 16 18 51 52 66 70 91 92 93 94 95 Intranasal use of ointments formulated in a PEG vehicle may irritate mucous membranes.1 3 16 18 51 52 66 70 92 93 94 95 (See Precautions Related to Polyethylene Glycol Vehicle under Cautions.)
Dosage
Available as mupirocin1 91 92 93 94 95 and mupirocin calcium74 78 ; dosage expressed in terms of mupirocin.1 74 78 91 92 93 94 95
Pediatric Patients
Skin Infections
Impetigo
Topical
2% ointment for dermatologic use in children 2 months to 16 years of age: Apply small amount to affected area 3 times daily.1 91 92 93 94 95
Usual duration of treatment is about 7 days (5–10 days).40 41 43 47 48 79 80 83 If clinical response not evident within 3–5 days, clinician should be contacted and the infection reevaluated.1 91 92 93 94 95
Secondary Skin Infections (Lacerations, Sutured Wounds, Abrasions)
Topical
2% cream for dermatologic use in children 3 months to 16 years of age: Apply small amount to affected area 3 times daily for 10 days.78
If clinical response not evident within 3–5 days, clinician should be contacted and the infection reevaluated.78
Nasal Carriage of Staphylococcus aureus
Intranasal
2% ointment for intranasal use in children ≥12 years of age: Apply one-half (approximately 0.25 g) of the intranasal ointment from a single-use tube into each nostril twice daily (morning and evening) for 5 days.74
Manufacturer states safety and efficacy of >5 days of treatment with the intranasal ointment not established.74
Adults
Skin Infections
Impetigo
Topical
2% ointment for dermatologic use: Apply small amount to affected area 3 times daily.1 91 92 93 94 95
Usual duration of treatment is about 7 days (5–10 days).40 41 43 47 48 79 80 83 If clinical response not evident within 3–5 days, clinician should be contacted and the infection reevaluated.1 91 92 93 94 95
Secondary Skin Infections (Lacerations, Sutured Wounds, Abrasions)
Topical
2% cream for dermatologic use: Apply small amount to affected area 3 times daily for 10 days.78
If clinical response not evident within 3–5 days, clinician should be contacted and the infection reevaluated.78
Nasal Carriage of Staphylococcus aureus
Intranasal
2% ointment for intranasal use: Apply one-half (approximately 0.25 g) of the intranasal ointment from a single-use tube into each nostril twice daily (morning and evening) for 5 days.74
Manufacturer states safety and efficacy of >5 days of treatment with the intranasal ointment not established.74
Prescribing Limits
Pediatric Patients
Skin Infections
Secondary Skin Infections (Lacerations, Sutured Wounds, Abrasions)
Topical
2% cream for dermatologic use: Maximum treatment area 10 cm in length or 100 cm2 in total area.78
Adults
Skin Infections
Secondary Skin Infections (Lacerations, Sutured Wounds, Abrasions)
Topical
2% cream for dermatologic use: Maximum treatment area 10 cm in length or 100 cm2 in total area.78
Cautions for Mupirocin
Contraindications
Warnings/Precautions
Warnings
Administration Precautions
Mupirocin ointment for dermatologic use and mupirocin cream for dermatologic use are for external use only.1 78 91 92 93 94 95 Use only for topical application to skin;1 78 91 92 93 94 95 do not use on mucous membranes (including intranasal mucous membranes).1 78 91 92 93 94 95
Mupirocin ointment for dermatologic use, mupirocin cream for dermatologic use, and mupirocin ointment for intranasal use should not be applied to eyes.1 74 78 91 92 93 94 95
When mupirocin ointment for intranasal use was applied to the eye under testing condition, severe symptoms such as burning and tearing occurred; symptoms resolved within days to weeks after the drug was discontinued.74
Sensitivity Reactions
Minimal potential for inducing allergic contact sensitization following topical application.7 9 56 57 Unlikely to cause phototoxicity or photoallergic dermatitis.2 3 4 5 9 16
Although causal relationship not established,26 43 45 46 78 contact dermatitis reported in some patients receiving topical mupirocin.1 26 43 45 46 78 91 92 93 94 95
If manifestations suggesting sensitivity or severe local or chemical irritation occur (e.g., irritation, severe pruritus, rash), discontinue mupirocin and substitute an appropriate alternative anti-infective.1 74 78 91 92 93 94 95
General Precautions
Superinfection
Prolonged use may result in overgrowth of nonsusceptible organisms, including fungi.1 74 78 91 92 93 94 95
Precautions Related to Polyethylene Glycol (PEG) Vehicle
Some preparations of mupirocin ointment for dermatologic use contain mupirocin in a PEG vehicle (Bactroban, various generic preparations).1 92 93 94 95
Some adverse local effects reported with topical mupirocin may be related to the PEG vehicle rather than the drug itself.3 4 26 39 43 45 46
Prolonged or repeated application of a PEG-containing ointment to large areas of damaged skin (e.g., burns) may result in systemic absorption1 66 67 68 71 92 93 94 95 of potentially toxic amounts of PEG.66 67 68 71 Rarely, renal failure and death have been associated with topical application of PEG-containing ointments in burn patients and in animal burn models.66 67 68 71
The manufacturers state that preparations of mupirocin ointment for dermatologic use containing the drug in a PEG vehicle should not be used in conditions where absorption of large quantities of PEG is possible, especially if there is evidence the patient has moderate or severe renal impairment.1 92 93 94 95
Although mupirocin ointment for dermatologic use has been used intranasally†,3 16 18 51 52 the manufacturers and some clinicians state that the ointment for dermatologic use (with or without a PEG) should not be used intranasally.1 3 16 18 51 52 66 70 92 93 94 95
Specific Populations
Pregnancy
Category B.1 74 78 91 92 93 94 95
Lactation
Not known whether mupirocin is distributed into milk,1 74 78 91 92 93 94 95 but clinically important concentrations are unlikely in breast milk following topical application of usual dosages to the skin.70 Use with caution.1 74 78 91 92 93 94 95
Pediatric Use
Safety and efficacy of mupirocin ointment for dermatologic use not established in children <2 months of age.1 91 92 93 94 95
Safety and efficacy of mupirocin cream for dermatologic use not established in children <3 months of age.78
Safety and efficacy of mupirocin ointment for intranasal use not established in children <12 years of age.74
Geriatric Use
When mupirocin cream for dermatologic use was used in geriatric patients >65 years of age, no overall differences in efficacy and safety relative to younger adults.78
Renal Impairment
Use preparations of mupirocin ointment for dermatologic use formulated in a PEG vehicle with caution in patients with moderate or severe renal impairment.1 92 93 94 95 (See Precautions Related to Polyethylene Glycol Vehicle under Cautions.)
Common Adverse Effects
Topical administration to skin: Local effects (burning,1 3 7 20 30 35 36 39 46 54 56 78 92 93 94 95 stinging,1 3 4 35 36 52 92 93 94 95 pain,1 3 4 7 52 56 92 93 94 95 pruritus,1 3 4 7 20 36 39 41 52 54 56 78 91 92 93 94 95 rash),1 3 4 20 57 78 92 93 94 95 nausea,1 38 56 78 92 93 94 95 headache.78
Intranasal administration: Headache,74 rhinitis,74 respiratory disorder (including upper respiratory tract congestion),74 pharyngitis,74 taste perversion,74 cough,74 local effects (burning/stinging, pruritus).74
Interactions for Mupirocin
Specific Drugs
Drug
|
Interaction
|
Comments
|
|---|
Chloramphenicol
|
Potential interference with antibacterial action of mupirocin3 19 23
|
Clinical importance unknown3 19 23
|
Intranasal preparations
|
Mupirocin ointment for intranasal use: Concurrent use with other intranasal preparations not studied to date74
|
Mupirocin ointment for intranasal use: Pending further accumulation of data, do not use concurrently with any other intranasal preparation74
|
Topical preparations
|
Mupirocin cream or ointment for dermatologic use: Information not available regarding concurrent application to skin with other topical preparations1 78 91 92 93 94 95
|
|
Mupirocin Pharmacokinetics
Absorption
Bioavailability
Not appreciably absorbed following topical application to intact skin.3 7 56 78 Application to traumatized or diseased skin may result in penetration into deeper epidermal skin layers and possible systemic circulation.3 7
In a study in healthy adults, <0.3% of a topical dose of radiolabeled mupirocin was absorbed through intact skin after 24 hours under an occlusive dressing; no drug detected in urine or feces collected for 5 days after the dose.3 7 56 In this study, 2–4% of the radioactivity was present in the stratum corneum 24 hours after application7 and remained detectable there for ≥72 hours after application.7
Following topical application of mupirocin 2% ointment in a vehicle without PEG (Centany) to an area 400 cm2 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.91
Following topical application of mupirocin calcium cream for dermatologic use (2% mupirocin) to various skin lesions (>10 cm in length or 100 cm2 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.78 Percutaneous absorption occurred more frequently in children than in adults,78 but appears to be minimal in both groups.78
No evidence of systemic absorption following repeated intranasal application of mupirocin ointment for intranasal use in adults.74 Pharmacokinetics of intranasal mupirocin not adequately characterized in neonates or children <12 years of age,74 but systemic absorption reported following intranasal administration of this ointment in neonates and premature infants.74
Distribution
Extent
Following topical application to the skin, may remain detectable in stratum corneum for at least 72 hours.1 7 92 93 94 95
Crosses the placenta in rats and rabbits following IV administration; not known whether crosses the placenta in humans.2
Not known whether mupirocin distributes into milk.1 74 78 91 92 93 94 95
Plasma Protein Binding
≥95–97%.1 3 12 74 91 92 93 94 95
Elimination
Metabolism
Rapidly metabolized following IV or oral administration.1 74 92 93 94 95 Studies using IV mupirocin sodium indicate the drug is almost completely metabolized, presumably in the liver, by conversion to the inactive metabolite, monic acid.2 3 7 78
Any mupirocin that is absorbed systemically following topical application presumably is inactivated by conversion to monic acid and rapidly eliminated in urine.2 7 56 78
Elimination Route
Mupirocin is excreted in urine mostly as monic acid.1 2 7 56 78 78 92 93 94 95
Half-life
Following IV administration in healthy adults, the elimination half-life of mupirocin is 17–40 minutes1 3 7 56 74 92 93 94 95 and that of monic acid is 30–80 minutes.1 7 56 74 92 93 94 95
Stability
Storage
Topical
Cream for Dermatologic Use
≤25°C; do not freeze.78
Ointment for Dermatologic Use
20–25°C.1 91 92 93 94 95
Intranasal
Ointment for Intranasal Use
20–25°C (may be exposed to 15–30°C).74 Do not refrigerate.74
Actions and SpectrumActions
Structurally unrelated to other currently available anti-infectives.2 5 6 8 15 17 31 40
Usually bactericidal at concentrations attained following topical application to skin of ointment or cream for dermatologic use or following intranasal application of ointment for intranasal use.1 3 4 5 8 15 23 74 78 91 92 93 94 95
Inhibits protein synthesis in susceptible bacteria by reversibly binding to bacterial isoleucine-tRNA ligase (isoleucyl-tRNA synthetase),1 2 4 5 6 11 17 19 21 23 24 74 78 91 92 93 94 95 preventing the formation of isoleucyl-tRNA from isoleucine and tRNA.2 5 16
Spectrum of activity includes some gram-positive aerobic bacteria and gram-negative aerobic bacteria; most active against gram-positives.1 2 3 8 11 12 15 56 78 91 92 93 94 95 Inactive against anaerobic bacteria,2 3 4 8 12 Chlamydia,2 4 8 12 and fungi.2 3 4 8 12
Gram-positive aerobes: Active against Staphylococci aureus1 2 3 8 11 12 15 56 78 91 92 93 94 95 (including some methicillin-resistant strains)1 3 4 33 34 52 55 62 78 92 93 94 95 and S. pyogenes (group A β-hemolytic streptococci).1 2 3 4 8 12 13 56 91 92 93 94 Active against S. aureus resistant to some other anti-infectives, including penicillins, aminoglycosides, erythromycin, chloramphenicol, and tetracycline.2 3 4 12
Strains of S. aureus naturally resistant to mupirocin reported rarely; mupirocin-resistant S. aureus have emerged during mupirocin therapy.1 3 12 17 33 58 59 63 74 78 91 92 93 94 Resistance also reported in coagulase-negative staphylococci.1 11
