4.9 Overdose
No specific countermeasures after accidental overdose are recommended. In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. Concomitant administration of charcoal with a dose of 400 mg oral or intravenous moxifloxacin will reduce systemic availability of the drug by more than 80% or 20% respectively. The use of charcoal early during absorption may be useful to prevent excessive increase in the systemic exposure to moxifloxacin in cases of oral overdose.

5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Quinolone antibacterials, fluoroquinolones, ATC code: J01MA14

Mode of action

Moxifloxacin inhibits bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) that are required for bacterial DNA replication, transcription and repair.

PK/PD

Fluoroquinolones exhibit a concentration dependent killing of bacteria. Pharmacodynamic studies of fluoroquinolones in animal infection models and in human trials indicate that the primary determinant of efficacy is the AUC24/MIC ratio.

Mechanism of resistance

Resistance to fluoroquinolones can arise through mutations in DNA gyrase and topoisomerase IV. Other mechanisms may include over-expression of efflux pumps, impermeability, and protein-mediated protection of DNA gyrase. Cross resistance should be expected between moxifloxacin and other fluoroquinolones.

The activity of moxifloxacin is not affected by mechanisms of resistance that are specific to antibacterial agents of other classes.

Breakpoints

EUCAST clinical MIC and disk diffusion breakpoints for moxifloxacin (01.01.2011):

Organism
 Susceptible
 Resistant
 
Staphylococcus spp.
 ≤ 0.5 mg/l

≥ 24 mm
 > 1 mg/l

< 21 mm
 
S. pneumoniae
 ≤ 0.5 mg/l

≥ 22 mm
 > 0.5 mg/l

< 22 mm
 
Streptococcus Groups A, B, C, G
 ≤ 0.5 mg/l

≥ 18 mm
 > 1 mg/l

< 15 mm
 
H. influenzae
 ≤ 0.5 mg/l

≥ 25 mm
 ≤ 0.5 mg/l

≥ 25 mm
 
M. catarrhalis
 ≤ 0.5 mg/l

≥ 23 mm
 > 0.5 mg/l

< 23 mm
 
Enterobacteriaceae
 ≤ 0.5 mg/l

≥ 20 mm
 > 1 mg/l

< 17 mm
 
Non-species related breakpoints*
 ≤ 0.5 mg/l
 > 1 mg/l
 
* Non-species related breakpoints have been determined mainly on the basis of pharmacokinetic/pharmacodynamic data and are independent of MIC distributions of specific species. They are for use only for species that have not been given a species-specific breakpoint and are not for use with species where interpretative criteria remain to be determined.
 
Microbiological Susceptibility

The preva lence of acquired resistance may vary geographically and with time for selected species and local information of resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought where the local preva lence of resistance is such that utility of the agent in at least some types of infections is que