Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Novartis Ireland Limited, Vista Building, Elm Park, Merrion Road, Ballsbridge, Dublin 4, Ireland.
Pharmacotherapeutic group: Ophthalmologicals; anti-infectives, other anti-infectives
ATC code: S01AE07
Moxifloxacin, a fourth-generation fluoroquinolone, inhibits the DNA gyrase and topoisomerase IV required for bacterial DNA replication, repair, and recombination.
Resistance to fluoroquinolones, including moxifloxacin generally occurs by chromosomal mutations in genes encoding DNA gyrase and topoisomerase IV. In Gram-negative bacteria, moxifloxacin resistance can be due to mutations in mar (multiple antibiotic resistance) and the qnr (quinolone resistance) gene systems. Resistance is also associated with expression of bacteria efflux proteins and inactivating enzymes. Cross-resistance with beta-lactams, macrolides and aminoglycosides is not expected due to differences in mode of action.
There are no pharmacological data correlated with clinical outcome for moxifloxacin administered as a topical agent. As a result, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) suggests the following epidemiological cut-off values (ECOFF mg/l) derived from MIC distribution curves to indicate susceptibility to topical moxifloxacin:
| Corynebacterium | ND |
| Staphylococcus aureus | 0.25 mg/l |
| Staphylococcus, coag-neg. | 0.25 mg/l |
| Streptococcus pneumoniae | 0.5 mg/l |
| Streptococcus pyogenes | 0.5 mg/l |
| Streptococcus, viridans group | 0.5 mg/l |
| Enterobacter spp. | 0.25 mg/l |
| Haemophilus influenzae | 0.125 mg/l |
| Klebsiella spp. | 0.25 mg/l |
| Moraxella catarrhalis | 0.25 mg/l |
| Morganella morganii | 0.25 mg/l |
| Neisseria gonorrhoeae | 0.032 mg/l |
| Pseudomonas aeruginosa | 4 mg/l |
| Serratia marcescens | 1 mg/l |
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of moxifloxacin in at least some types of infections is questionable.
Aerobic Gram-positive micro-organisms:
Corynebacterium species including
Corynebacterium diphtheriae
Staphylococcus aureus (methicillin susceptible)
Streptococcus pneumoniae
Streptococcus pyogenes
Streptococcus viridans Group
Aerobic Gram-negative micro-organisms:
Enterobacter cloacae
Haemophilus influenzae
Klebsiella oxytoca
Moraxella catarrhalis
Serratia marcescens
Anaerobic micro-organisms:
Proprionibacterium acnes
Other micro-organisms:
Chlamydia trachomatis
Aerobic Gram-positive micro-organisms:
Staphylococcus aureus (methicillin resistant)
Staphylococcus, coagulase-negative species (methicillin resistant)
Aerobic Gram-negative micro-organisms:
Neisseria gonorrhoeae
Other micro-organisms:
None
Aerobic Gram-negative micro-organisms:
Pseudomonas aeruginosa
Other micro-organisms:
None
Following topical ocular administration of MOXIVIG, 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 the medicinal product 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 therapeutic 400 mg oral doses of moxifloxacin. The plasma half-life of moxifloxacin was estimated to be 13 hours.
Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human exposure following administration to the eye indicating little relevance to clinical use.
As with other quinolones, moxifloxacin was also genotoxic in vitro in bacteria and mammalian cells. As these effects can be traced to the interaction with bacterial gyrase and in considerably higher concentrations to the interaction with topoisomerase II in mammalian cells, a threshold level for genotoxicity can be assumed. In in vivo tests, no evidence of genotoxicity was found, despite high doses of moxifloxacin. The therapeutic doses for human use therefore provide adequate safety margin. No indication of a carcinogenic effect was observed in an initiation promotion model in rats.
Unlike other quinolones, moxifloxacin showed no phototoxic or photogenotoxic properties in extensive in vitro and in vivo studies.
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