MUPIROCIN- mupirocin_ointment

Mupirocin is an RNA synthetase inhibitor antibacterial [see Microbiology (12. 4) Absorption Application of 14 The effect of the concurrent application of mupirocin ointment with other topical products has not been studied [see Dosage and Administration (2) Elimination 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: Excretion: Mupirocin is an RNA synthetase inhibitor antibacterial 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 administration. Mupirocin is highly protein bound (greater than 97%) and the effect of wound secretions on the minimum inhibitory concentrations (MICs) of mupirocin has not been determined. 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 Cross Resistance Due to its mode of action, mupirocin does not demonstrate cross resistance with other classes of antimicrobial agents. Antimicrobial Activity Mupirocin has been shown to be active against susceptible isolates of S. pyogenes in vitro [see Indications and Usage (1) in vitro Staphylococcus epidermidis Susceptibility Test Methods High-level mupirocin resistance (>=512 mcg/mL) may be determined using standard disk diffusion or broth microdilution tests. aureus 3,4,5.

Mupirocin Ointment USP, 2% is indicated for the topical treatment of impetigo due to susceptible isolates of Staphylococcus aureus (S. aureus) Streptococcus pyogenes (S. pyogenes) Mupirocin ointment is an RNA synthetase inhibitor antibacterial indicated for the topical treatment of impetigo due to susceptible isolates of Staphylococcus aureus Streptococcus pyogenes 1.

[see Warnings and Precautions (5. 6) [see Clinical Pharmacology (12. 3) 2 2 2 2.

The following adverse reactions are discussed in more detail in other sections of the labeling: [see Warnings and Precautions (5. 1) [see Warnings and Precautions (5. 2) [see Warnings and Precautions (5. 3) Clostridium difficile [see Warnings and Precautions (5. 4) 6. 1 To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U. , at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www. gov/medwatch. 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. The following local adverse reactions were reported by at least 1% of subjects in connection with the use of mupirocin ointment in clinical trials: burning, stinging, or pain in 1. 5% of subjects; itching in 1% of subjects. Rash, nausea, erythema, dry skin, tenderness, swelling, contact dermatitis, and increased exudate were reported in less than 1% of subjects. In addition to adverse reactions reported from clinical trials, the following reactions have been identified during postmarketing use of mupirocin 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 mupirocin ointment. Immune System Disorders Systemic allergic reactions, including anaphylaxis, urticaria, angioedema, and generalized rash [see Warnings and Precautions (5.

Mupirocin ointment is contraindicated in patients with known hypersensitivity to mupirocin or any of the excipients of mupirocin ointment.

Risk Summary There are insufficient human data to establish whether there is a drug-associated risk with mupirocin ointment in pregnant women. Systemic absorption of mupirocin through intact human skin is minimal following topical administration of mupirocin ointment [see Clinical Pharmacology (12. 3) The estimated background risk of major birth defects and miscarriages for the indicated population is unknown. The estimated background risk in the U. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data: Developmental toxicity studies have been performed with mupirocin administered subcutaneously to rats and rabbits at doses up to 160 mg per kg per day during organogenesis. This dose is 22 and 43 times, respectively, the human topical dose (approximately 60 mg mupirocin per day) based on calculations of dose divided by the entire body surface area. Maternal toxicity was observed (body weight loss/decreased body weight gain and reduced feeding) in both species with no evidence of developmental toxicity in rats. In rabbits, excessive maternal toxicity at the high dose precluded the evaluation of fetal outcomes. There was no developmental toxicity in rabbits at 40 mg per kg per day, 11 times the human topical dose based on calculations of dose divided by the entire body surface area. Mupirocin administered subcutaneously to rats in a pre- and postnatal development study (dosed during late gestation through lactation) was associated with reduced offspring viability in the early postnatal period at a dose of 106. 7 mg per kg, in the presence of injection site irritation and/or subcutaneous hemorrhaging. This dose is 14 times the human topical dose based on calculations of dose divided by the entire body surface area. The no-observed adverse effect level in this study was 44. 2 mg per kg per day, which is 6 times the human topical dose. Risk Summary It is not known whether mupirocin is present in human milk, has effects on the breastfed child, or has effects on milk production. However, breastfeeding is not expected to result in exposure of the child to the drug due to the minimal systemic absorption of mupirocin in humans following topical administration of mupirocin ointment [see Clinical Pharmacology (12. 3) Clinical Considerations To minimize oral exposure of the drug to children, a breast and/or nipple being treated with mupirocin ointment should be thoroughly washed prior to breastfeeding. The safety and effectiveness of mupirocin ointment have been established in the age range of 2 months to 16 years. Use of mupirocin ointment in these age-groups is supported by evidence from adequate and well-controlled trials of mupirocin ointment in impetigo in pediatric subjects studied as a part of the pivotal clinical trials in adults [see Clinical Studies (14).

NONCLINICAL TOXICOLOGY
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 in vivo Salmonella Escherichia coli In a fertility/reproductive performance study (with dosing through lactation), mupirocin administered subcutaneously to male and female rats at doses up to 100 mg per kg per day which is 14 times the human topical dose (approximately 60 mg mupirocin per day) based on calculations of dose divided by the entire body surface area, did not result in impaired fertility or impaired reproductive performance attributable to mupirocin.
CLINICAL STUDIES
The efficacy of topical mupirocin ointment in impetigo was tested in 2 trials. In the first, subjects with impetigo were randomized to receive either mupirocin ointment or vehicle placebo 3 times daily for 8 to 12 days. Clinical efficacy rates at end of therapy in the evaluable populations (adults and pediatric subjects included) were 71% for mupirocin ointment (n = 49) and 35% for vehicle placebo (n = 51). Pathogen eradication rates in the evaluable populations were 94% for mupirocin ointment and 62% for vehicle placebo. In the second trial, subjects with impetigo were randomized to receive either mupirocin ointment 3 times daily or 30 mg per kg to 40 mg per kg oral erythromycin ethylsuccinate per day (this was an unblinded trial) for 8 days. There was a follow-up visit 1 week after treatment ended. Clinical efficacy rates at the follow-up visit in the evaluable populations (adults and pediatric subjects included) were 93% for mupirocin ointment (n = 29) and 78. 5% for erythromycin (n = 28). Pathogen eradication rates in the evaluable populations were 100% for both test groups. Pediatrics There were 91 pediatric subjects aged 2 months to 15 years in the first trial described above. Clinical efficacy rates at end of therapy in the evaluable populations were 78% for mupirocin ointment (n = 42) and 36% for vehicle placebo (n = 49). In the second trial described above, all subjects were pediatric except 2 adults in the group receiving mupirocin ointment. The age range of the pediatric subjects was 7 months to 13 years. The clinical efficacy rate for mupirocin ointment (n = 27) was 96%, and for erythromycin it was unchanged (78.
REFERENCES
1. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-sixth Informational Supplement. 2. Clinical Infectious Diseases. 3. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard en dash Tenth Edition. 4. Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard en dash Twelfth Edition. 5. Antimicrob Agents Chemother.

Major Pharmaceuticals

MUPIROCIN- mupirocin_ointment Product manual source documgent