Moxeza - Scientific Information
|Condition:||Conjunctivitis, Bacterial, Conjunctivitis, Eye Infection, Bacterial (Conjunctivitis, Bacterial)|
|Form:||Liquid solution, Eye drops (ophthalmic)|
|Ingredients:||Moxifloxacin hydrochloride, Sodium chloride, Xanthan gum, Boric acid, Sorbitol, Tyloxapol, Purified water, and Hydrochloric acid and/or Sodium hydroxide.|
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.
C21H24FN3O4•HCl Mol 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 5.45 mg moxifloxacin hydrochloride, equivalent to 5 mg 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.
Mechanism of Action
Moxifloxacin is a member of the fluoroquinolone class of anti-infective drugs [see Clinical Pharmacology].
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 moxifloxacin AF 0.5% 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).
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 < 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 Indications and Usage section:
*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:
Streptococcus milleri group
Aerobic Gram-negative microorganisms:
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.
In one randomized, double-masked, multicenter, vehicle-controlled clinical trial in which patients with bacterial conjunctivitis were dosed with Moxezasolution 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.