Vigamox Mechanism of Action

Pharmacology: Pharmacokinetics/Pharmacodynamics: Following topical ocular administration of VIGAMOX Solution, moxifloxacin was absorbed into the systemic circulation. Plasma concentrations of moxifloxacin were measured in 21 male and female subjects who received bilateral topical ocular doses of VIGAMOX Solution 3 times a day for 4 days. The mean steady-state Cmax and AUC were 2.7 ng/mL and 41.9 ng·hr/mL, respectively. These exposure values are approximately 1,600 and 1,200 times lower than the mean Cmax and AUC reported after well-tolerated therapeutic 400 mg oral doses of moxifloxacin. The plasma half-life of moxifloxacin was estimated to be 13 hours.
Clinical Studies: VIGAMOX Solution has been studied in patients from newborns to adults, including geriatric patients.
In three randomized, double masked, multicenter, controlled clinical trials in which patients were dosed 3 times a day for 4 days, VIGAMOX Solution produced clinical cures in 80% to 94% of patients treated for bacterial conjunctivitis. Microbiological success rates for the eradication of the baseline pathogens ranged from 85% to 97%.
In one of these trials in pediatric patients from birth to one month of age, VIGAMOX Solution produced clinical cure in 80% of patients with bacterial conjunctivitis. The microbiological success rate for the eradication of the baseline pathogens was 92%.
In a randomized, double-masked, multicenter, controlled clinical trial in which patients were dosed 2 times a day for 3 days, VIGAMOX* Solution produced clinical cure in 74% of patients treated for bacterial conjunctivitis. Microbiological success rate for the eradication of the baseline pathogens was 81%.
Special Populations: The pharmacokinetic parameters of oral moxifloxacin are not significantly altered by mild, moderate or severe renal impairment. No dosage adjustment of VIGAMOX Solution is necessary in patients with renal impairment.
Pharmacokinetic parameters of oral moxifloxacin were not significantly altered in patients with mild to moderate hepatic insufficiency (Child Pugh Classes A and B). Studies were not performed in patients with severe hepatic impairment (Child Pugh Class C). Because of the low systemic exposure by the topical route of administration, no dosage adjustment of VIGAMOX Solution is needed in patients with hepatic impairment.
Microbiology: Moxifloxacin has in vitro activity against a wide range of Gram-positive and Gram-negative microorganisms. Moxifloxacin inhibits the topoisomerase II (DNA gyrase) and topoisomerase IV required for bacterial DNA replication, transcription, repair, and recombination. The C8-methoxy moiety of moxifloxacin also lessens the selection of resistant mutants of Gram-positive bacteria compared to the C8-H moiety found in older fluoroquinolones. Moxifloxacin's bulky C-7 substituent group interferes with the quinolone efflux pump mechanism of bacteria. Moxifloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.
Fluoroquinolones, including moxifloxacin, differ in chemical structure and mode of action from β-lactam antibiotics, macrolides and aminoglycosides, and therefore may be active against bacteria resistant to β-lactam antibiotics, macrolides and aminoglycosides. Therefore, organisms resistant to these drugs may be susceptible to moxifloxacin. In vitro resistance to moxifloxacin develops slowly via multiple-step mutations and occurs at a general frequency between 10-9 to 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/USES: Gram-positive bacteria: Corynebacterium species, Microbacterium species, Micrococcus luteus [including erythromycin, gentamicin, tetracycline, and/or trimethoprim resistant strains], Staphylococcus aureus [including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline and/or trimethoprim resistant strains], Staphylococcus epidermidis [including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline and/or trimethoprim resistant strains], Staphylococcus haemolyticus [including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline and/or trimethoprim resistant strains], Staphylococcus hominis [including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline and/or trimethoprim resistant strains], Staphylococcus warneri [including erythromycin resistant strains], Streptococcus mitis [including penicillin, erythromycin, tetracycline and/or trimethoprim resistant strains], Streptococcus pneumoniae [including penicillin, erythromycin, gentamicin, tetracycline and/or trimethoprim resistant strains], Streptococcus viridans [including penicillin, erythromycin, tetracycline and/or trimethoprim resistant strains].
Gram-negative bacteria: Acinetobacter species, Haemophilus "alconae" [including ampicillin resistant strains], Haemophilus influenzae [including ampicillin resistant strains], Klebsiella pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa.
Other microorganisms: Chlamydia trachomatis.
Moxifloxacin has been shown to be active in vitro against most strains of the following organisms; however, the clinical significance of these data is unknown. (See Table 1.)

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