ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice.The most frequently reported ocular adverse events were conjunctivitis, decreased visual acuity, dry eye, keratitis, ocular discomfort, ocular hyperemia, ocular pain, ocular pruritus, subconjunctival hemorrhage, and tearing. These events occurred in approximately 1-6% of patients.Nonocular adverse events reported at rate of 1-4% were fever, increased cough, infection, otitis media, pharyngitis, rash, and rhinitis.. The most frequently reported ocular adverse events were conjunctivitis, decreased visual acuity, dry eye, keratitis, ocular discomfort, ocular hyperemia, ocular pain, ocular pruritus, subconjunctival hemorrhage, and tearing. These events occurred in approximately 1-6% of patients. (6) To report SUSPECTED ADVERSE REACTIONS, contact Alcon Laboratories, Inc. at 1-800-757-9195 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Long-term studies in animals to determine the carcinogenic potential of moxifloxacin have not been performed. However, in an accelerated study with initiators and promoters, moxifloxacin was not carcinogenic in rats following up to 38 weeks of oral dosing at 500 mg/kg/day (approximately 21,700 times the highest recommended total daily human ophthalmic dose for 50 kg person, on mg/kg basis).Moxifloxacin was not mutagenic in four bacterial strains used in the Ames Salmonella reversion assay. As with other quinolones, the positive response observed with moxifloxacin in strain TA 102 using the same assay may be due to the inhibition of DNA gyrase. Moxifloxacin was not mutagenic in the CHO/HGPRT mammalian cell gene mutation assay. An equivocal result was obtained in the same assay when v79 cells were used. Moxifloxacin was clastogenic in the v79 chromosome aberration assay, but it did not induce unscheduled DNA synthesis in cultured rat hepatocytes. There was no evidence of genotoxicity in vivo in micronucleus test or dominant lethal test in mice.Moxifloxacin had no effect on fertility in male and female rats at oral doses as high as 500 mg/kg/day, approximately 21,700 times the highest recommended total daily human ophthalmic dose. At 500 mg/kg orally there were slight effects on sperm morphology (head-tail separation) in male rats and on the estrous cycle in female rats.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Moxifloxacin is member of the fluoroquinolone class of anti-infective drugs (See 12.4 Microbiology).. 12.3 Pharmacokinetics. Plasma concentrations of moxifloxacin were measured in healthy adult male and female subjects who received bilateral topical ocular doses of VIGAMOX(R) solution times day. The mean steady-state Cmax (2.7 ng/mL) and estimated daily exposure AUC (45 ngohr/mL) values were 1,600 and 1,000 times lower than the mean Cmax and AUC reported after therapeutic 400 mg doses of moxifloxacin. The plasma half-life of moxifloxacin was estimated to be 13 hours.. 12.4 Microbiology. The antibacterial action of moxifloxacin results from inhibition of the topoisomerase II (DNA gyrase) and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play key role in the partitioning of the chromosomal DNA during bacterial cell division.The mechanism of action for quinolones, including moxifloxacin, is different from that of macrolides, aminoglycosides, or tetracyclines. Therefore, moxifloxacin may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to moxifloxacin. There is no cross-resistance between moxifloxacin and the aforementioned classes of antibiotics. Cross resistance has been observed between systemic moxifloxacin and some other quinolones.In vitro resistance to moxifloxacin develops via multiple-step mutations. Resistance to moxifloxacin occurs in vitro at general frequency of between 1.8 10-9 to 1 10-11 for Gram-positive bacteria.Moxifloxacin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:Aerobic Gram-positive microorganisms: Corynebacterium speciesMicrococcus luteus Staphylococcus aureus Staphylococcus epidermidis Staphylococcus haemolyticus Staphylococcus hominis Staphylococcus warneri Streptococcus pneumoniae Streptococcus viridans groupAerobic Gram-negative microorganisms: Acinetobacter lwoffii Haemophilus influenzae Haemophilus parainfluenzaeOther microorganisms: Chlamydia trachomatisEfficacy for this organism was studied in fewer than 10 infections.The following in vitro data are also available, but their clinical significance in ophthalmic infections is unknown. The safety and effectiveness of VIGAMOX(R) solution in treating ophthalmological infections due to these microorganisms have not been established in adequate and well-controlled trials.The following organisms are considered susceptible when evaluated using systemic breakpoints. However, correlation between the in vitro systemic breakpoint and ophthalmological efficacy has not been established. The list of organisms is provided as guidance only in assessing the potential treatment of conjunctival infections. Moxifloxacin exhibits in vitro minimal inhibitory concentrations (MICs) of ug/ml or less (systemic susceptible breakpoint) against most (>= 90%) strains of the following ocular pathogens.Aerobic Gram-positive microorganisms: Listeria monocytogenes Staphylococcus saprophyticus Streptococcus agalactiae Streptococcus mitis Streptococcus pyogenes Streptococcus Group C, and FAerobic Gram-negative microorganisms: Acinetobacter baumannii Acinetobacter calcoaceticus Citrobacter freundii Citrobacter koseri Enterobacter aerogenes Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Moraxella catarrhalis Morganella morganii Neisseria gonorrhoeae Proteus mirabilis Proteus vulgaris Pseudomonas stutzeriAnaerobic microorganisms: Clostridium perfringens Fusobacterium speciesPrevotella speciesPropionibacterium acnesOther microorganisms: Chlamydia pneumoniae Legionella pneumophila Mycobacterium avium Mycobacterium marinum Mycoplasma pneumoniae.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. In two randomized, double-masked, multicenter, controlled clinical trials in which patients were dosed times day for days, VIGAMOX(R) solution produced clinical cures on day 5-6 in 66% to 69% of patients treated for bacterial conjunctivitis. Microbiological success rates for the eradication of baseline pathogens ranged from 84% to 94%. Please note that microbiologic eradication does not always correlate with clinical outcome in anti-infective trials.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. VIGAMOX(R) solution is contraindicated in patients with history of hypersensitivity to moxifloxacin, to other quinolones, or to any of the components in this medication.. VIGAMOX(R) solution is contraindicated in patients with history of hypersensitivity to moxifloxacin, to other quinolones, or to any of the components in this medication. (4).

DESCRIPTION SECTION.

11 DESCRIPTION. VIGAMOX(R) (moxifloxacin hydrochloride ophthalmic solution) 0.5% is sterile solution for topical ophthalmic use. Moxifloxacin hydrochloride is an 8-methoxy fluoroquinolone anti-infective, with diazabicyclononyl ring at the C7 position.Chemical Name:1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolol[3,4-b]pyridin-6-yl]-4-oxo-3-quinoline carboxylic acid, monohydrochloride. Moxifloxacin hydrochloride is slightly yellow to yellow crystalline powder. Each mL of VIGAMOX(R) solution contains 5.45 mg moxifloxacin hydrochloride, equivalent to mg moxifloxacin base.Contains: Active: Moxifloxacin 0.5% (5 mg/mL); Inactives: Boric acid, sodium chloride, and purified water. May also contain hydrochloric acid/sodium hydroxide to adjust pH to approximately 6.8.VIGAMOX(R) solution is an isotonic solution with an osmolality of approximately 290 mOsm/kg.. chemical.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Instill one drop in the affected eye times day for days.. Instill one drop in the affected eye times day for days. (2).

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. mL bottle filled with mL sterile ophthalmic solution of moxifloxacin hydrochloride, 0.5% as base.. mL bottle filled with mL sterile ophthalmic solution of moxifloxacin hydrochloride, 0.5% as base. (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. Drug-drug interaction studies have not been conducted with VIGAMOX(R) solution. In vitro studies indicate that moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2, indicating that moxifloxacin is unlikely to alter the pharmacokinetics of drugs metabolized by these cytochrome P450 isozymes.

GERIATRIC USE SECTION.

8.5 Geriatric Use. No overall differences in safety and effectiveness have been observed between elderly and younger patients.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. VIGAMOX(R) solution is supplied as sterile ophthalmic solution in Alcons DROP-TAINER(R) dispensing system consisting of natural low density polyethylene bottle and dispensing plug and tan polypropylene closure. Tamper evidence is provided with shrink band around the closure and neck area of the package.3 mL in 4 mL bottle NDC 54868-4798-0 Storage: Store at 2C- 25C (36F 77F).

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. VIGAMOX(R) solution is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms:Corynebacterium speciesMicrococcus luteus Staphylococcus aureus Staphylococcus epidermidis Staphylococcus haemolyticus Staphylococcus hominis Staphylococcus warneri Streptococcus pneumoniae Streptococcus viridans groupAcinetobacter lwoffii Haemophilus influenzae Haemophilus parainfluenzae Chlamydia trachomatisEfficacy for this organism was studied in fewer than 10 infections.. VIGAMOX(R) solution is topical fluoroquinolone anti-infective indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms:Corynebacterium species, Micrococcus luteus, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus warneri, Streptococcus pneumoniae, Streptococcus viridans group, Acinetobacter lwoffii, Haemophilus influenzae, Haemophilus parainfluenzae, Chlamydia trachomatisEfficacy for this organism was studied in fewer than 10 infections. (1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Patients should be advised not to touch the dropper tip to any surface to avoid contaminating the contents.Patients should be advised not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis.Systemically administered quinolones including moxifloxacin have been associated with hypersensitivity reactions, even following single dose. Patients should be told to discontinue use immediately and contact their physician at the first sign of rash or allergic reaction.Rx OnlyLicensed to Alcon by Bayer Pharma AG.U.S. PAT. NO. 5,607,942; 6,716,830; 7,671,070(C) 2003-2011 NovartisManufactured byAlcon Laboratories, Inc.Fort Worth, TX 76134 USA 9007343-1011 Additional barcode label applied by:Physicians Total Care, Inc.Tulsa, Oklahoma 74146.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Moxifloxacin is member of the fluoroquinolone class of anti-infective drugs (See 12.4 Microbiology).

MICROBIOLOGY SECTION.

12.4 Microbiology. The antibacterial action of moxifloxacin results from inhibition of the topoisomerase II (DNA gyrase) and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play key role in the partitioning of the chromosomal DNA during bacterial cell division.The mechanism of action for quinolones, including moxifloxacin, is different from that of macrolides, aminoglycosides, or tetracyclines. Therefore, moxifloxacin may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to moxifloxacin. There is no cross-resistance between moxifloxacin and the aforementioned classes of antibiotics. Cross resistance has been observed between systemic moxifloxacin and some other quinolones.In vitro resistance to moxifloxacin develops via multiple-step mutations. Resistance to moxifloxacin occurs in vitro at general frequency of between 1.8 10-9 to 1 10-11 for Gram-positive bacteria.Moxifloxacin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:Aerobic Gram-positive microorganisms: Corynebacterium speciesMicrococcus luteus Staphylococcus aureus Staphylococcus epidermidis Staphylococcus haemolyticus Staphylococcus hominis Staphylococcus warneri Streptococcus pneumoniae Streptococcus viridans groupAerobic Gram-negative microorganisms: Acinetobacter lwoffii Haemophilus influenzae Haemophilus parainfluenzaeOther microorganisms: Chlamydia trachomatisEfficacy for this organism was studied in fewer than 10 infections.The following in vitro data are also available, but their clinical significance in ophthalmic infections is unknown. The safety and effectiveness of VIGAMOX(R) solution in treating ophthalmological infections due to these microorganisms have not been established in adequate and well-controlled trials.The following organisms are considered susceptible when evaluated using systemic breakpoints. However, correlation between the in vitro systemic breakpoint and ophthalmological efficacy has not been established. The list of organisms is provided as guidance only in assessing the potential treatment of conjunctival infections. Moxifloxacin exhibits in vitro minimal inhibitory concentrations (MICs) of ug/ml or less (systemic susceptible breakpoint) against most (>= 90%) strains of the following ocular pathogens.Aerobic Gram-positive microorganisms: Listeria monocytogenes Staphylococcus saprophyticus Streptococcus agalactiae Streptococcus mitis Streptococcus pyogenes Streptococcus Group C, and FAerobic Gram-negative microorganisms: Acinetobacter baumannii Acinetobacter calcoaceticus Citrobacter freundii Citrobacter koseri Enterobacter aerogenes Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Moraxella catarrhalis Morganella morganii Neisseria gonorrhoeae Proteus mirabilis Proteus vulgaris Pseudomonas stutzeriAnaerobic microorganisms: Clostridium perfringens Fusobacterium speciesPrevotella speciesPropionibacterium acnesOther microorganisms: Chlamydia pneumoniae Legionella pneumophila Mycobacterium avium Mycobacterium marinum Mycoplasma pneumoniae.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Long-term studies in animals to determine the carcinogenic potential of moxifloxacin have not been performed. However, in an accelerated study with initiators and promoters, moxifloxacin was not carcinogenic in rats following up to 38 weeks of oral dosing at 500 mg/kg/day (approximately 21,700 times the highest recommended total daily human ophthalmic dose for 50 kg person, on mg/kg basis).Moxifloxacin was not mutagenic in four bacterial strains used in the Ames Salmonella reversion assay. As with other quinolones, the positive response observed with moxifloxacin in strain TA 102 using the same assay may be due to the inhibition of DNA gyrase. Moxifloxacin was not mutagenic in the CHO/HGPRT mammalian cell gene mutation assay. An equivocal result was obtained in the same assay when v79 cells were used. Moxifloxacin was clastogenic in the v79 chromosome aberration assay, but it did not induce unscheduled DNA synthesis in cultured rat hepatocytes. There was no evidence of genotoxicity in vivo in micronucleus test or dominant lethal test in mice.Moxifloxacin had no effect on fertility in male and female rats at oral doses as high as 500 mg/kg/day, approximately 21,700 times the highest recommended total daily human ophthalmic dose. At 500 mg/kg orally there were slight effects on sperm morphology (head-tail separation) in male rats and on the estrous cycle in female rats.

NURSING MOTHERS SECTION.

8.3 Nursing Mothers. Moxifloxacin has not been measured in human milk, although it can be presumed to be excreted in human milk. Caution should be exercised when VIGAMOX(R) solution is administered to nursing mother.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL. NDC 54868-4798-0STERILEVIGAMOX(R) (moxifloxacin hydrochlorideophthalmic solution)0.5% as base3 mL image of package label.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. The safety and effectiveness of VIGAMOX(R) solution in infants below year of age have not been established.There is no evidence that the ophthalmic administration of VIGAMOX(R) solution has any effect on weight bearing joints, even though oral administration of some quinolones has been shown to cause arthropathy in immature animals.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. Plasma concentrations of moxifloxacin were measured in healthy adult male and female subjects who received bilateral topical ocular doses of VIGAMOX(R) solution times day. The mean steady-state Cmax (2.7 ng/mL) and estimated daily exposure AUC (45 ngohr/mL) values were 1,600 and 1,000 times lower than the mean Cmax and AUC reported after therapeutic 400 mg doses of moxifloxacin. The plasma half-life of moxifloxacin was estimated to be 13 hours.

PREGNANCY SECTION.

8.1 Pregnancy. Pregnancy Category C.Teratogenic Effects: Moxifloxacin was not teratogenic when administered to pregnant rats during organogenesis at oral doses as high as 500 mg/kg/day (approximately 21,700 times the highest recommended total daily human ophthalmic dose); however, decreased fetal body weights and slightly delayed fetal skeletal development were observed. There was no evidence of teratogenicity when pregnant Cynomolgus monkeys were given oral doses as high as 100 mg/kg/day (approximately 4,300 times the highest recommended total daily human ophthalmic dose). An increased incidence of smaller fetuses was observed at 100 mg/kg/day.Since there are no adequate and well-controlled studies in pregnant women, VIGAMOX(R) solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

SPL UNCLASSIFIED SECTION.

5.1 Topical Ophthalmic Use Only. NOT FOR INJECTION. VIGAMOX(R) solution is for topical ophthalmic use only and should not be injected subconjunctivally or introduced directly into the anterior chamber of the eye.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Pregnancy Category C.Teratogenic Effects: Moxifloxacin was not teratogenic when administered to pregnant rats during organogenesis at oral doses as high as 500 mg/kg/day (approximately 21,700 times the highest recommended total daily human ophthalmic dose); however, decreased fetal body weights and slightly delayed fetal skeletal development were observed. There was no evidence of teratogenicity when pregnant Cynomolgus monkeys were given oral doses as high as 100 mg/kg/day (approximately 4,300 times the highest recommended total daily human ophthalmic dose). An increased incidence of smaller fetuses was observed at 100 mg/kg/day.Since there are no adequate and well-controlled studies in pregnant women, VIGAMOX(R) solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.. 8.3 Nursing Mothers. Moxifloxacin has not been measured in human milk, although it can be presumed to be excreted in human milk. Caution should be exercised when VIGAMOX(R) solution is administered to nursing mother.. 8.4 Pediatric Use. The safety and effectiveness of VIGAMOX(R) solution in infants below year of age have not been established.There is no evidence that the ophthalmic administration of VIGAMOX(R) solution has any effect on weight bearing joints, even though oral administration of some quinolones has been shown to cause arthropathy in immature animals.. 8.5 Geriatric Use. No overall differences in safety and effectiveness have been observed between elderly and younger patients.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Topical ophthalmic use only. (5.1)Hypersensitivity and anaphylaxis have been reported with systemic use of moxifloxacin. (5.2)Prolonged use may result in overgrowth of non-susceptible organisms, including fungi. (5.3)Patients should not wear contact lenses if they have signs or symptoms of bacterial conjunctivitis. (5.4). Topical ophthalmic use only. (5.1). Hypersensitivity and anaphylaxis have been reported with systemic use of moxifloxacin. (5.2). Prolonged use may result in overgrowth of non-susceptible organisms, including fungi. (5.3). Patients should not wear contact lenses if they have signs or symptoms of bacterial conjunctivitis. (5.4). 5.1 Topical Ophthalmic Use Only. NOT FOR INJECTION. VIGAMOX(R) solution is for topical ophthalmic use only and should not be injected subconjunctivally or introduced directly into the anterior chamber of the eye.. 5.2 Hypersensitivity Reaction. In patients receiving systemically administered quinolones, including moxifloxacin, serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported, some following the first dose. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching. If an allergic reaction to moxifloxacin occurs, discontinue use of the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management should be administered as clinically indicated.. 5.3 Growth of Resistant Organisms with Prolonged Use. As with other anti-infectives, prolonged use may result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, discontinue use and institute alternative therapy. Whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such as slit-lamp biomicroscopy, and, where appropriate, fluorescein staining.. 5.4 Avoidance of Contact Lens Wear. Patients should be advised not to wear contact lenses if they have signs or symptoms of bacterial conjunctivitis.