HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information
`
`needed to use VIGAMOX® solution safely and
`effectively. See full prescribing information for
`VIGAMOX®.
`VIGAMOX® (moxifloxacin ophthalmic solution)
`0.5%
`Sterile topical ophthalmic solution
`Initial U.S. Approval: 1999
`
`-----------------INDICATIONS AND USAGE-------------­
`VIGAMOX® solution is a 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 trachomatis
`
`*Efficacy for this organism was studied in fewer than 10
`infections. (1)
`
`-----------DOSAGE FORMS AND STRENGTHS-------­
`4 mL bottle filled with 3 mL sterile ophthalmic solution
`of moxifloxacin 0.5%. (3)
`
`-------------------CONTRAINDICATIONS----------------­
`VIGAMOX® solution is contraindicated in patients with a
`history of hypersensitivity to moxifloxacin, to other
`quinolones, or to any of the components in this medication.
`(4)
`--------------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)
`
`-------------------ADVERSE REACTIONS------------------­
`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)
`
`-----------DOSAGE AND ADMINISTRATION----------­
`Instill one drop in the affected eye 3 times a day for
`7 days. (2)
`
`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.
`
`See 17 for PATIENT COUNSELING INFORMATION.
`Revised: XX/2016
`
`FULL PRESCRIBING INFORMATION:
`CONTENTS*
`
`INDICATIONS AND USAGE
`1
`2 DOSAGE AND ADMINISTRATION
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS
`5 WARNINGS AND PRECAUTIONS
`5.1
`Topical Ophthalmic Use Only
`5.2
`Hypersensitivity Reactions
`
`5.3
`Growth of Resistant Organisms with
`Prolonged Use
`5.4
`Avoidance of Contact Lens Wear
`6 ADVERSE REACTIONS
`7 DRUG INTERACTIONS
`8 USE IN SPECIFIC POPULATIONS
`8.1
`Pregnancy
`8.3
`Nursing Mothers
`8.4
`Pediatric Use
`8.5
`Geriatric Use
`
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.3
`Pharmacokinetics
`12.4 Microbiology
`13 NONCLINICAL TOXICOLOGY
`13.1
`Carcinogenesis, Mutagenesis, Impairment of
`Fertility
`14 CLINICAL STUDIES
`16 HOW SUPPLIED/STORAGE AND HANDLING
`17 PATIENT COUNSELING INFORMATION
`
`*Sections or subsections omitted from the full prescribing
`information are not listed..
`
`Reference ID: 4068949
`
`

`

`FULL PRESCRIBING INFORMATION
`1
`INDICATIONS AND USAGE
`
`VIGAMOX® solution is 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 influenza
`Haemophilus parainfluenzae*
`Chlamydia trachomatis
`
`*Efficacy for this organism was studied in fewer than 10 infections.
`
`DOSAGE AND ADMINISTRATION
`2
`Instill one drop in the affected eye 3 times a day for 7 days.
`
`DOSAGE FORMS AND STRENGTHS
`3
`4 mL bottle filled with 3 mL sterile ophthalmic solution of moxifloxacin 0.5%.
`
`CONTRAINDICATIONS
`4
`VIGAMOX® solution is contraindicated in patients with a history of hypersensitivity to moxifloxacin, to other
`quinolones, or to any of the components in this medication.
`
`WARNINGS AND PRECAUTIONS
`5
`Topical Ophthalmic Use Only
`5.1
`NOT FOR INJECTION. VIGAMOX® solution is for topical ophthalmic use only and should not be injected
`subconjunctivally or introduced directly into the anterior chamber of the eye.
`
`Hypersensitivity Reactions
`5.2
`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.
`
`Avoidance of Contact Lens Wear
`5.4
`Patients should be advised not to wear contact lenses if they have signs or symptoms of bacterial conjunctivitis.
`
`Reference ID: 4068949
`
`

`

`
`6
`ADVERSE REACTIONS
`Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical
`trials of a 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 a rate of 1-4% were fever, increased cough, infection, otitis media, pharyngitis,
`rash, and rhinitis.
`
`DRUG INTERACTIONS
`7
`Drug-drug interaction studies have not been conducted with VIGAMOX® 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.
`
`USE IN SPECIFIC POPULATIONS
`8
`Pregnancy
`8.1
`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® solution should be used
`during pregnancy only if the potential benefit justifies the potential risk to the fetus.
`
`Nursing Mothers
`8.3
`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® solution is administered to a nursing mother.
`
`
`8.4
`Pediatric Use
`The safety and effectiveness of VIGAMOX® (moxifloxacin ophthalmic solution) 0.5% have been established in all
`ages. Use of VIGAMOX® is supported by evidence from adequate and well controlled studies of VIGAMOX® in
`adults, children, and neonates [see Clinical Studies (14)].
`
`There is no evidence that the ophthalmic administration of VIGAMOX® solution has any effect on weight bearing
`joints, even though oral administration of some quinolones has been shown to cause arthropathy in immature
`animals.
`
`Geriatric Use
`8.5
`No overall differences in safety and effectiveness have been observed between elderly and younger patients.
`
`DESCRIPTION
`11
`VIGAMOX® (moxifloxacin ophthalmic solution) 0.5% is a sterile solution for topical ophthalmic use.
`
`Moxifloxacin hydrochloride is an 8-methoxy fluoroquinolone anti-infective, with a diazabicyclononyl ring at the C7
`position.
`
`Reference ID: 4068949
`
`

`

`Mol Wt 437.9
`C21H24FN3O4•HCl
`
`Chemical Name: 1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolol[3,4b]pyridin­
`
`6-yl]-4-oxo-3-quinolinecarboxylic acid, monohydrochloride. Moxifloxacin hydrochloride is a slightly yellow to
`yellow crystalline powder. Each mL of VIGAMOX® solution contains 5.45 mg moxifloxacin hydrochloride,
`equivalent to 5 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® solution is an isotonic solution with an osmolality of approximately 290 mOsm/kg.
`
`CLINICAL PHARMACOLOGY
`12
`12.1 Mechanism of Action
`Moxifloxacin is a member of the fluoroquinolone class of anti-infective drugs [see Microbiology (12.4)].
`
`Pharmacokinetics
`12.3
`Plasma concentrations of moxifloxacin were measured in healthy adult male and female subjects who received
`bilateral topical ocular doses of VIGAMOX® solution 3 times a day. The mean steady-state Cmax (2.7 ng/mL) and
`estimated daily exposure AUC (45 ng●hr/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 a 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 a general frequency of between 1.8 x 10-9 to < 1 x 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 species*
`Micrococcus luteus*
`Staphylococcus aureus
`Staphylococcus epidermidis
`
`Reference ID: 4068949
`
`

`

`Staphylococcus haemolyticus
`Staphylococcus hominis
`Staphylococcus warneri*
`Streptococcus pneumoniae
`Streptococcus viridans group
`
`Aerobic Gram-negative microorganisms:
`Acinetobacter lwoffii*
`Haemophilus influenza
`Haemophilus parainfluenzae*
`
`Other microorganisms:
`Chlamydia trachomatis
`
`*Efficacy 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® 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, a
`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 2 μg/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, G and F
`
`Aerobic 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 stutzeri
`
`Anaerobic microorganisms:
`Clostridium perfringens
`Fusobacterium species
`Prevotella species
`Propionibacterium acnes
`
`Reference ID: 4068949
`
`

`

`Other microorganisms:
`Chlamydia pneumoniae
`Legionella pneumophila
`Mycobacterium avium
`Mycobacterium marinum
`Mycoplasma pneumoniae
`
`NONCLINICAL TOXICOLOGY
`13
`Carcinogenesis, Mutagenesis, Impairment of Fertility
`13.1
`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 a 50 kg person, on a 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 a micronucleus test or a 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 STUDIES
`14
`In two randomized, double-masked, multicenter, controlled clinical trials in which patients were dosed 3 times a day
`for 4 days, VIGAMOX® 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%.
`
`
`In a randomized, double-masked, multicenter, parallel-group clinical trial of pediatric patients with bacterial
`
`conjunctivitis between birth and 31 days of age, patients were dosed with VIGAMOX® or another anti-infective
`agent. Clinical outcomes for the trial demonstrated a clinical cure rate of 80% at Day 9 and a microbiological
`eradication success rate of 92% at Day 9.
`
`
`Please note that microbiologic eradication does not always correlate with clinical outcome in anti-infective trials.
`
`HOW SUPPLIED/STORAGE AND HANDLING
`16
`VIGAMOX® solution is supplied as a sterile ophthalmic solution in Alcon’s DROP-TAINER® dispensing system
`consisting of a natural low density polyethylene bottle and dispensing plug and tan polypropylene closure. Tamper
`evidence is provided with a shrink band around the closure and neck area of the package.
`
`3 mL in a 4 mL bottle - NDC 0065-4013-03
`
`
`
`Storage: Store at 2˚C- 25˚C (36˚F - 77˚F).
`
`PATIENT COUNSELING INFORMATION
`17
`Risk of Contamination: Advise patients not to touch the dropper tip to any surface to avoid contaminating the
`contents.
`
`Concomitant Use of Contact Lenses: Advise patients not to wear contact lenses if they have signs and symptoms of
`bacterial conjunctivitis.
`
`Reference ID: 4068949
`
`

`

` Potential for Hypersensitivity Reactions: Systemically administered quinolones including moxifloxacin have been
`
`associated with hypersensitivity reactions, even following a single dose. Instruct patients to discontinue use
`immediately and contact their physician at the first sign of a rash or allergic reaction. [see Warnings and Precautions
`
`
`(5.2)].
`
`Distributed by Alcon Laboratories, Inc. Fort Worth, TX 76134 USA
`
`Licensed to Alcon by Bayer Pharma AG.
`
`© 2003-2011, 2016 Novartis
`
` XXXXXXX-MMYY
`
`Reference ID: 4068949
`
`