rococcus 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.

mmatory reactions, such as fibrin, cell or flare and corneal edema, but other events, such as hypopyon, keratic precipitates or vitreous opacities may also occur. 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.

e). the no-observed-adverse-effect-level (noael) for developmental toxicity was 100 mg/kg/day (152 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 (5569 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 (1261 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 (14688 times the human auc at the recommended human ophthalmic dose). the noael for fetal toxicity was 10 mg/kg/day (894 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 1420 times the human auc at the recommended human ophthalmic dose). the noael for pre- and postnatal development was 100 mg/kg/day (estimated 152 times the human auc at the recommended human ophthalmic dose). 8.2 lactation risk summary there are 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 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.

fect-level (noael) for developmental toxicity was 100 mg/kg/day (152 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 (5569 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 (1261 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 (14688 times the human auc at the recommended human ophthalmic dose). the noael for fetal toxicity was 10 mg/kg/day (894 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 1420 times the human auc at the recommended human ophthalmic dose). the noael for pre- and postnatal development was 100 mg/kg/day (estimated 152 times the human auc at the recommended human ophthalmic dose).

on, 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 moxifloxacin ophthalmic 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 streptococcus sanguis 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

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 4741 times the highest recommended daily human ophthalmic dose. 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.