MUPIROCIN (Generic for CENTANY)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Topical Administration
Cream/Ointment/Lotion Formulations
-Apply to affected area. Treated area may be covered with sterile gauze dressing if desired.
-Avoid contact with the eyes and mucosal surfaces.
-Topical cream and ointment products are not FDA-approved for nasal use.



Other Administration Route(s)
Nasal Administration
-Apply ointment inside the nose.
-After application, close the nostrils by pressing together and releasing the sides of the nose repetitively for approximately 1 minute. This will spread the ointment throughout the nares.
-Avoid contact with the eyes.
-Do not apply concurrently with any other intranasal product.

Adverse effects are uncommon and generally mild during therapy with mupirocin. Rash was reported in at least 1% of patients during topical use and was reported in less than 1% of patients during nasal use. Other adverse reactions to topical use include skin irritation (tenderness, burning, stinging, or pain) (up to 3.6%), cellulitis (less than 1%), dermatitis (less than 1%), contact dermatitis (less than 1%), increased exudate (less than 1%), erythema (less than 1%), xerosis (less than 1%), and pruritus (up to 2.4%). Rarely, bleeding secondary to eczema, pain secondary to eczema, and hives occurred. Systemic allergic reactions, including anaphylaxis/anaphylactoid reactions, urticaria, and angioedema, have also been reported with mupirocin formulations. If sensitization or severe local irritation occurs; discontinue usage. Some reactions can be attributed to the polyethylene glycol (PEG) vehicle used in the topical preparation. Systemic absorption of PEG can cause renal failure, which is potentially fatal. Renal failure has not been reported with commercially available mupirocin. The use of mupirocin over large areas of abraded skin, such as extensive burns, is not recommended.

The intranasal use of mupirocin calcium has produced the following adverse events in at least 1% of patients: rhinitis (6%), respiratory disorder, including upper respiratory tract congestion (5%), pharyngitis (4%), dysgeusia (3%), nasal irritation such as burning or stinging (2%), and cough (2%). Other adverse reactions noted in less than 1% of patients were: blepharitis, diarrhea, xerostomia, otalgia, and epistaxis. Headache (1.7% to 9%) and nausea (up to 4.9%) have been reported with topical and intranasal use. Dizziness, abdominal pain, and ulcerative stomatitis have been reported in less than 1% of patients with topical use.

Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with mupirocin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Secondary wound infection has also been reported with mupirocin use.

Avoid use of mupirocin topical ointment on burns (especially extensive burns), open wounds, or other damaged skin. Damaged epithelial surfaces allow absorption of polyethylene glycol, the vehicle for the topical ointment. Increased absorption of polyethylene glycol should be avoided, especially if there is evidence of moderate to severe renal impairment.

Mupirocin is not for ophthalmic administration. Avoid ocular exposure as ocular contact produces severe burning and tearing.

Prolonged use of mupirocin is not recommended because of possible overgrowth of resistant or non-susceptible organisms. This overgrowth may result in a superinfection, such as fungal infection.

Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including mupirocin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

Description: Mupirocin is an antibiotic that is structurally unrelated to other topical or systemic antibiotics. Because of its' unique mechanism, it has little, if any, potential for cross-resistance. Mupirocin is available as a topical ointment, topical cream, and intranasal ointment. The topical ointment is approved for impetigo caused by Staphylococcus aureus and Streptococcus pyogenes in patients >= 2 months of age. The cream is approved for secondarily infected traumatic skin lesions in patients 3 months of age and older. The intranasal ointment is used to reduce the risk of infection during institutional outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) by eradicating nasal MRSA colonization. The intranasal ointment is approved for use in pediatric patients >= 12 years of age; however, the drug has been used off-label in infants.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Staphylococcus aureus (MRSA), Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Streptococcus pyogenes (group A beta-hemolytic streptococci)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

For the treatment of impetigo and other skin and skin structure infections due to susceptible strains of S. aureus or S. pyogenes:
-for the treatment of impetigo:
Topical dosage (ointment):
Infants, Children, and Adolescents 2 months to 17 years: Apply a thin layer to the affected area(s) 3 times daily for 1 to 2 weeks. The area may be covered with a sterile gauze dressing. If a response is not evident within 3 to 5 days, the infection should be reevaluated.
-for the treatment of secondarily infected traumatic skin lesions (up to 10 cm in length or 100 cm2 in area):
Topical dosage (cream):
Infants, Children, and Adolescents 3 months to 17 years: Apply a thin layer to the affected area(s) 3 times per day for 10 days. If a response is not evident within 3 to 5 days, the infection should be reevaluated.

For the treatment of mild methicillin-resistant Staphylococcus aureus (MRSA)-associated infectious neonatal pustulosis*:
Topical dosage (ointment):
Neonates and Infants younger than 3 months: Apply a small amount to the affected area(s) 3 times daily. Clinical practice guidelines support the use of mupirocin for mild cases with localized disease.

For the treatment of infected eczema* due to susceptible strains of Staphylococcus sp. or Streptococcus sp.:
Topical dosage (ointment):
Infants, Children, and Adolescents: Apply a small amount to the affected area(s) 2 to 3 times daily for 1 to 2 weeks. Topical mupirocin ointment has similar or superior efficacy when compared with systemic antibiotics (i.e., erythromycin, ampicillin, flucloxacillin) for secondary skin infections, including infected eczema.

For the treatment of folliculitis* due to susceptible strains of Staphylococcus sp. or Streptococcus sp.:
Topical dosage (ointment):
Children and Adolescents: Apply a small amount to the affected area(s) 3 times daily for 5 to 14 days. Topical mupirocin ointment has similar or superior efficacy when compared with systemic antibiotics (i.e., ampicillin, cloxacillin, erythromycin) for primary skin infections, including folliculitis.

For methicillin-resistant S. aureus decolonization using methicillin-resistant S. aureus nasal carriage eradication to reduce the risk of infection among high-risk persons:
-for methicillin-resistant S. aureus decolonization using methicillin-resistant S. aureus nasal carriage eradication to reduce the risk of infection among high-risk inpatients, including during institutional outbreaks:
Intranasal dosage:
Neonates*: Apply a small amount in each nostril twice daily for 5 days. Consider using in combination with daily chlorhexidine baths.
Infants* and Children 1 to 11 years*: Apply a small amount (500 mg) in each nostril twice daily for 5 days. Consider using in combination with daily chlorhexidine baths.
Children and Adolescents 12 to 17 years: Apply a small amount (500 mg) in each nostril twice daily for 5 days. Consider using in combination with daily chlorhexidine baths.
-for preoperative methicillin-resistant S. aureus decolonization using methicillin-resistant S. aureus nasal carriage eradication to prevent postoperative infections*:
Intranasal dosage:
Infants, Children, and Adolescents: Apply a small amount (500 mg) in each nostril twice daily for up to 5 days pre-operatively. Consider using in combination with chlorhexidine baths.
-for postdischarge methicillin-resistant S. aureus decolonization using methicillin-resistant S. aureus nasal carriage eradication to reduce postdischarge infections and readmission*:
Intranasal dosage:
Infants, Children, and Adolescents: Apply a small amount (500 mg) in each nostril twice daily for 5 days twice monthly for 6 months. Use in combination with chlorhexidine baths and mouthwash.

Maximum Dosage Limits:
-Neonates
Safety and efficacy not established; however, topical ointment has been used off-label.
-Infants
< 2 months: Safety and efficacy not established; however, topical and intranasal ointment have been used off-label.
2 months: Maximum dosage information is not available for topical ointment.Safety and efficacy not established for topical cream or intranasal ointment; however, intranasal ointment has been used off label.
>= 3 months: Maximum dosage information is not available for topical ointment or cream. Safety and efficacy not established for intranasal ointment; however, intranasal ointment has been used off-label.
-Children
< 12 years: Maximum dosage information is not available for topical ointment or cream. Safety and efficacy not established for intranasal ointment; however, intranasal ointment has been used off-label.
12 years: Intranasal, 5 days of twice daily therapy; Topical, maximum dosage information is not available.
-Adolescents
Intranasal, 5 days of twice daily therapy; Topical, maximum dosage information is not available.

Patients with Hepatic Impairment Dosing
No dosage adjustment needed.

Patients with Renal Impairment Dosing
No dosage adjustment needed.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Mupirocin is bacteriostatic at low concentrations and bactericidal at high concentrations. Bacterial protein and RNA synthesis are inhibited when mupirocin reversibly binds to bacterial isoleucyl-transfer RNA (tRNA) synthetase. This enzyme normally promotes the conversion of isoleucine and tRNA to isoleucyl-tRNA. The epoxide side chain of mupirocin is similar to isoleucine and competes with it for binding sites on the synthetase enzyme. The cellular concentration of isoleucyl-tRNA becomes depleted, subsequently inhibiting bacterial protein and RNA synthesis. Unlike many other antibiotics, mupirocin has little effect on bacterial DNA synthesis and cell wall peptidoglycan formation.

Pharmacokinetics: Mupirocin is administered topically to the skin or the nares. Once in systemic circulation, it is rapidly metabolized to inactive monic acid and is excreted via the kidneys. The elimination half-life is 20-40 minutes for mupirocin and 30-80 minutes for monic acid.


-Route-Specific Pharmacokinetics
Topical Route
Percutaneous absorption through intact skin is minimal in both pediatric and adult patients. Following topical administration, > 97% of the drug is bound to protein. Polyethylene glycol (PEG), the vehicle used for the ointment, can be absorbed from open or damaged skin and may cause renal failure.

Other Route(s)
Intranasal Route
In adults, systemic absorption of intranasally applied mupirocin ointment is minimal. One study suggested 3.3% (range: 1.2-5.1%) of an applied dose may be absorbed from the nasal mucosa of adults. Pharmacokinetic studies have not been conducted in pediatric patients < 12 years of age.


-Special Populations
Pediatrics
Neonates
Although not approved for use in this population, the manufacturer references data suggesting significant systemic absorption following administration of the intranasal ointment to neonates and premature infants.

Children
One pharmacokinetic study found percutaneous absorption of mupirocin topical cream occurred more frequently in pediatric patients (90% of patients) than in adults (44% of patients). In this study, the cream was applied multiple times per day to various skin lesions on 10 pediatric patients (ages 3-12 years) and 16 adults. Systemic absorption was determined via urinary detection of the inactive metabolite, monic acid. Although the percentage of pediatric patients with monic acid in the urine was higher than in adults, the observed urinary concentration was comparable (0.07-1.3 mcg/ml vs 0.08-10.03 mcg/ml, respectively).