MOXIFLOXACIN

1 INDICATIONS AND USAGE Moxifloxacin ophthalmic solution, 0.5% 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 ) Moxifloxacin ophthalmic solution, 0.5% 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.

2 DOSAGE AND ADMINISTRATION Instill one drop in the affected eye 3 times a day for 7 days. Moxifloxacin ophthalmic solution is for topical ophthalmic use. Instill one drop in the affected eye 3 times a day for 7 days. ( 2 )

3 DOSAGE FORMS AND STRENGTHS 5 mL bottle filled with 3 mL sterile ophthalmic solution of moxifloxacin 0.5%. 5 mL bottle filled with 3 mL sterile ophthalmic solution of moxifloxacin 0.5%. ( 3 )

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

6 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% to 6% of patients. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.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 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% to 6% of patients. Nonocular adverse events reported at a rate of 1% to 4% were fever, increased cough, infection, otitis media, pharyngitis, rash, and rhinitis.

7. Drug Interactions Drug-drug interaction studies have not been conducted with moxifloxacin ophthalmic 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.

8. Use in Specific Populations 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies with moxifloxacin ophthalmic solution in pregnant women to inform any drug-associated risks. Oral administration of moxifloxacin to pregnant rats and monkeys and intravenously to pregnant rabbits during the period of organogenesis did not produce adverse maternal or fetal effects at clinically relevant doses. Oral administration of moxifloxacin to pregnant rats during late gestation through lactation did not produce adverse maternal, fetal or neonatal effects at clinically relevant doses (see Data). Data Animal Data Embryo-fetal studies were conducted in pregnant rats administered with 20, 100, or 500 mg/kg/day moxifloxacin by oral gavage on Gestation Days 6 to 1 7, to target the period of organogenesis. Decreased fetal body weight and delayed skeletal development were observed at 500 mg/kg/day [277 times the human area under the curve (AUC) at the recommended human ophthalmic dose]. The No-Observed-Adverse-Effect-Level (NOAEL) for developmental toxicity was 100 mg/kg/day (30 times the human AUC at the recommended human ophthalmic dose). Embryo-fetal studies were conducted in pregnant rabbits administered with 2, 6.5, or 20 mg/kg/day moxifloxacin by intravenous administration on Gestation Days 6 to 20, to target the period of organogenesis. Abortions, increased incidence of fetal malformations, delayed fetal skeletal ossification, and reduced placental and fetal body weights were observed at 20 mg/kg/day (1086 times the human AUC at the recommended human ophthalmic dose), a dose that produced maternal body weight loss and death. The NOAEL for developmental toxicity was 6.5 mg/kg/day (246 times the human AUC at the recommended human ophthalmic dose). Pregnant cynomolgus monkeys were administered moxifloxacin at doses of 10, 30, or 100 mg/kg/day by intragastric intubation between Gestation Days 20 and 50, targeting the period of organogenesis. At the maternal toxic doses of 2: 30 mg/kg/day, increased abortion, vomiting, and diarrhea were observed. Smaller fetuses/reduced fetal body weights were observed at 100 mg/kg/day (2864 times the human AUC at the recommended human ophthalmic dose). The NOAEL for fetal toxicity was 10 mg/kg/day (174 times the human AUC at the recommended human ophthalmic dose). In a pre- and postnatal study, rats were administered moxifloxacin by oral gavage at doses of 20, 100, and 500 mg/kg/day from Gestation Day 6 until the end of lactation. Maternal death occurred during gestation at 500 mg/kg/day. Slight increases in the duration of pregnancy, reduced pup birth weight, and decreased prenatal and neonatal survival were observed at 500 mg/kg/day (estimated 277 times the human AUC at the recommended human ophthalmic dose). The NOAEL for pre- and postnatal development was 100 mg/kg/day (estimated 30 times the human AUC at the recommended human ophthalmic dose). 8.2 Lactation Risk Summary There is no data regarding the presence of moxifloxacin ophthalmic solution in human milk, the effects on the breastfed infants, or the effects on milk production/excretion to inform risk of moxifloxacin ophthalmic solution to an infant during lactation. A study in lactating rats has shown transfer of moxifloxacin into milk following oral administration. Systemic levels of moxifloxacin following topical ocular administration are low [see Clinical Pharmacology (12.3)], and it is not known whether measurable levels of moxifloxacin would be present in maternal milk following topical ocular administration. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for moxifloxacin ophthalmic solution and any potential adverse effects on the breastfed child from moxifloxacin ophthalmic solution. 8.4 Pediatric Use The safety and effectiveness of moxifloxacin ophthalmic solution 0.5% have been established in all ages. Use of moxifloxacin ophthalmic solution is supported …

12.1 Mechanism of Action Moxifloxacin is a member of the fluoroquinolone class of anti-infective drugs [ see Microbiology ( 12.4 ) ].

11 DESCRIPTION Moxifloxacin ophthalmic solution USP, 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. The chemical name for moxifloxacin hydrochloride is 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. The molecular formula for moxifloxacin hydrochloride is C 21 H 24 FN 3 O 4 •HCl and its molecular weight is 437.9 g/mol. The chemical structure is presented below: Molecular Structure Moxifloxacin hydrochloride USP is a slightly yellow to yellow crystalline powder. Each mL of moxifloxacin ophthalmic solution USP contains 5.45 mg moxifloxacin hydrochloride USP equivalent to 5 mg moxifloxacin base. Moxifloxacin ophthalmic solution contains: Active: Moxifloxacin 0.5% (5 mg/mL); Inactives: Boric acid, sodium chloride and water for injection. May also contain hydrochloric acid and/or sodium hydroxide to adjust pH to approximately 6.8. Moxifloxacin ophthalmic solution USP, 0.5% is a yellow colored transparent isotonic solution with an osmolality of approximately 290 mOsm/kg.

Moxifloxacin Ophthalmic Solution, USP 0.5% is supplied as a sterile ophthalmic solution in a 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. NDC 17478-519-19 3 mL in 5 mL bottle Storage: Store at 2° to 25°C (36° to 77°F).