lwoffii*, haemophilus influenzae, haemophilus parainfluenzae*, chlamydia trachomatis *efficacy for this organism was studied in fewer than 10 infections. ( 1 )

reactions may require immediate emergency treatment. oxygen and airway management should be administered as clinically indicated. 5.2 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. 5.3 avoidance of contact lens wear patients should be advised not to wear contact lenses if they have signs or symptoms of bacterial conjunctivitis.

s. ( 6 ) to report suspected adverse reactions, contact akorn operating company llc at 1-800-932-5676 or fda at 1-800-fda-1088 or www.fda.gov/medwatch .

se]. 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 (1,086 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 ≥30 mg/kg/day, increased abortion, vomiting, and diarrhea were observed. smaller fetuses/reduced fetal body weights were observed at 100 mg/kg/day (2,864 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 have been established in all ages. use of moxifloxacin ophthalmic solution is supported by evidence from adequate and well controlled studies of moxifloxacin ophthalmic solution in adults, children, and neonates [see clinical studies ( 14 )] . there is no evidence that the ophthalmic administration of moxifloxacin ophthalmic 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.

ffect-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 (1,086 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 ≥30 mg/kg/day, increased abortion, vomiting, and diarrhea were observed. smaller fetuses/reduced fetal body weights were observed at 100 mg/kg/day (2,864 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).

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 less than 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 indication and usage section: aerobic gram-positive microorganisms corynebacterium species* micrococcus luteus* staphylococcus aureus staphylococcus epidermidis staphylococcus haemolyticus staphylococcus hominis staphylococcus warneri* streptococcus pneumoniae streptococcus viridans group aerobic gram-negative microorganisms acinetobacter lwoffii* haemophilus influenzae 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 moxifloxacin ophthalmic 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 mcg/ml or less (systemic susceptible breakpoint) against most (greater than or equal to 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 other microorganisms chlamydia pneumoniae legionella pneumophila mycobacterium avium mycobacterium marinum mycoplasma pneumoniae

id 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. impairment of fertility moxifloxacin had no effect on fertility in male and female rats at oral doses as high as 500 mg/kg/day, approximately 3,224 times the highest recommended total daily human ophthalmic dose, based on body surface area. at 500 mg/kg/day orally there were slight effects on sperm morphology (head-tail separation) in male rats and on the estrous cycle in female rats.

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. impairment of fertility moxifloxacin had no effect on fertility in male and female rats at oral doses as high as 500 mg/kg/day, approximately 3,224 times the highest recommended total daily human ophthalmic dose, based on body surface area. at 500 mg/kg/day orally there were slight effects on sperm morphology (head-tail separation) in male rats and on the estrous cycle in female rats.