DOSAGE FORMS & STRENGTHS SECTION.
3 DOSAGE FORMS AND STRENGTHS 4 mL bottle filled with 3 mL of sterile ophthalmic solution of moxifloxacin 0.5%. 4 mL bottle filled with 3 mL sterile ophthalmic solution of moxifloxacin 0.5%. (3)
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) 5.1 Topical Ophthalmic Use Only NOT FOR INJECTION. MOXEZA 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 Reactions 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.
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. 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 25,000 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.
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.
PRINCIPAL DISPLAY PANEL Alcon NDC 0065-0006-03STERILE Moxeza (moxifloxacin ophthalmic solution) 0.5% Alcon3 mL Rx Only
USE IN SPECIFIC POPULATIONS SECTION.
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C. Moxifloxacin was not teratogenic when administered to pregnant rats during organogenesis at oral doses as high as 500 mg/kg/day (approximately 25,000 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 5,000 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, MOXEZA 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 MOXEZA solution is administered to a nursing mother. 8.4 Pediatric Use The safety and effectiveness of MOXEZA solution in infants below 4 months of age have not been established. There is no evidence that the ophthalmic administration of moxifloxacin 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.
INFORMATION FOR PATIENTS SECTION.
17 PATIENT COUNSELING INFORMATION 17.1 Avoid Contamination of the Product Advise patients not to touch the dropper tip to any surface to avoid contaminating the contents. 17.2 Avoid Contact Lens Wear Advise patients not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis. 17.3 Hypersensitivity Reactions Systemically administered quinolones, including moxifloxacin, have been associated with hypersensitivity reactions, even following a single dose. Patients should be told to discontinue use immediately and contact their physician at the first sign of a rash or allergic reaction. Licensed to Alcon by Bayer Pharma AG. 2010, 2012, 2016 Novartis *AVELOX is a registered trademark of Bayer AG. Alcon a Novartis company Distributed by: ALCON LABORATORIES, INC. 6201 South Freeway Fort Worth, Texas 76134 USA firstname.lastname@example.org T2017-23 February 2017
ADVERSE REACTIONS SECTION.
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 data described below reflect exposure to MOXEZA solution in 1263 patients, between 4months and 92 years of age, with signs and symptoms of bacterial conjunctivitis. The most frequently reported adverse reactions were eye irritation, pyrexia and conjunctivitis, reported in 1-2% of patients. The most common adverse reactions reported in 1-2% of patients were eye irritation, pyrexia, and conjunctivitis. (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 .
CLINICAL STUDIES SECTION.
14 CLINICAL STUDIES In one randomized, double-masked, multicenter, vehicle-controlled clinical trial in which patients with bacterial conjunctivitis were dosed with MOXEZA solution 2 times a day, MOXEZA was superior to its vehicle for both clinical and microbiological outcomes. Clinical cure achieved on Day 4 was 63% (265/424) in MOXEZA solution treated patients, versus 51% (214/423) in vehicle treated patients. Microbiologic success (eradication of baseline pathogens) was achieved on Day 4 in 75% (316/424) of MOXEZA solution treated patients versus 56% (237/423) of vehicle treated patients. Microbiologic eradication does not always correlate with clinical outcome in anti-infective trials.
INDICATIONS & USAGE SECTION.
1 INDICATIONS AND USAGE MOXEZA solution is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms: Aerococcus viridans* Corynebacterium macginleyi* Enterococcus faecalis* Micrococcus luteus* Staphylococcus arlettae* Staphylococcus aureus Staphylococcus capitis Staphylococcus epidermidis Staphylococcus haemolyticus Staphylococcus hominis Staphylococcus saprophyticus* Staphylococcus warneri* Streptococcus mitis* Streptococcus pneumoniae Streptococcus parasanguinis* Escherichia coli* Haemophilus influenza Klebsiella pneumoniae* Propionibacterium acnes Chlamydia trachomatis* *Efficacy for this organism was studied in fewer than 10 infections. MOXEZA solution is a topical fluoroquinolone anti-infective indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms: Aerococcus viridans*, Corynebacterium macginleyi*, Enterococcus faecalis*, Micrococcus luteus*, Staphylococcus arlettae*, Staphylococcus aureus, Staphylococcus capitis, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus*, Staphylococcus warneri*, Streptococcus mitis*, Streptococcus pneumoniae, Streptococcus parasanguinis*, Escherichia coli*, Haemophilus influenzae, Klebsiella pneumoniae*, Propionibacterium acnes, Chlamydia trachomatis* *Efficacy for this organism was studied in fewer than 10 infections. (1)
DOSAGE & ADMINISTRATION SECTION.
2 DOSAGE AND ADMINISTRATION Instill 1 drop in the affected eye(s) 2 times daily for 7 days. Instill 1 drop in the affected eye(s) 2 times daily for 7 days. (2)
HOW SUPPLIED SECTION.
16 HOW SUPPLIED/STORAGE AND HANDLING MOXEZA solution is supplied as a sterile ophthalmic solution in the Alcon 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 0065-0006-03 Storage: Store at 2C - 25C (36F - 77F).
11 DESCRIPTION MOXEZA 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. C21H24FN3O4HClMol Wt 437.9 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-quinolinecarboxylic acid, monohydrochloride. Each mL of MOXEZA solution contains 5.45mg moxifloxacin hydrochloride, equivalent to 5mg moxifloxacin base. Inactives: Sodium chloride, xanthan gum, boric acid, sorbitol, tyloxapol, purified water, and hydrochloric acid and/or sodium hydroxide to adjust pH. MOXEZA is a greenish-yellow, isotonic solution with an osmolality of 300-370 mOsm/kg and a pH of approximately 7.4. Moxifloxacin hydrochloride is a slightly yellow to yellow crystalline powder.
CLINICAL PHARMACOLOGY SECTION.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Moxifloxacin is a member of the fluoroquinolone class of anti-infective drugs [see Clinical Pharmacology (12.4)]. 12.3 Pharmacokinetics Moxifloxacin steady-state plasma pharmacokinetics were evaluated in healthy adult male and female subjects who were administered multiple, bilateral, topical ocular doses of MOXEZA solution two times daily for four days with a final dose on day 5. The average steady-state AUC0-12 was 8.17 5.31 ng*h/mL. Moxifloxacin Cmax following twice-daily bilateral ophthalmic administration of moxifloxacin0.5% for 5 days is approximately 0.02% of that achieved with the oral formulation of moxifloxacin hydrochloride (Cmax following oral dosing of 400 mg AVELOX*, 4.5 0.5 mcg/mL). 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 < 1x10-11 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: Aerococcus viridans* Corynebacterium macginleyi* Enterococcus faecalis* Micrococcus luteus* Staphylococcus arlettae* Staphylococcus aureus Staphylococcus capitis Staphylococcus epidermidis Staphylococcus haemolyticus Staphylococcus hominis Staphylococcus saprophyticus* Staphylococcus warneri* Streptococcus mitis* Streptococcus pneumoniae Streptococcus parasanguinis* Escherichia coli* Haemophilus influenza Klebsiella pneumoniae* Propionibacterium acnes Chlamydia trachomatis* *Efficacy for this organism was studied in fewer than 10 infections. The following in vitro data are available, but their clinical significance in ophthalmic infections is unknown. The safety and effectiveness of MOXEZA solution in treating ophthalmic infections due to these organisms have not been established in adequate and well-controlled trials. Moxifloxacin has been shown to be active in vitro against most strains of the microorganisms listed below. These organisms are considered susceptible when evaluated using systemic breakpoints; however, a correlation between the in vitro systemic breakpoint and ophthalmologic 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 mcg/mL or less (systemic susceptible breakpoint) against most ( 90%) strains of the following ocular pathogens. Aerobic Gram-positive microorganisms: Staphylococcus caprae Staphylococcus cohnii Staphylococcus lugdunensis Staphylococcus pasteuri Streptococcus agalactiae Streptococcus milleri group Streptococcus oralis Streptococcus pyogenes Streptococcus salivarius Streptococcussanguis Aerobic Gram-negative microorganisms: Acinetobacter baumannii Acinetobacter calcoaceticus Acinetobacter junii Enterobacter aerogenes Enterobacter cloacae Haemophilus parainfluenzae Klebsiella oxytoca Moraxella catarrhalis Moraxella osloensis Morganella morganii Neisseria gonorrhoeae Neisseria meningitides Pantoea agglomerans Proteus vulgaris Pseudomonas stutzeri Serratia liquefaciens Serratia marcescens Stenotrophomonas maltophilia Anaerobic microorganisms: Clostridium perfringens Peptostreptococcus anaerobius Peptostreptococcus magnus Peptostreptococcus micros Peptostreptococcus prevotii Other microorganisms: Mycobacterium tuberculosis Mycobacterium avium Mycobacterium kansasii Mycobacterium marinum
4 CONTRAINDICATIONS None. None. (4)