indication

For treatment of adults with mild to moderate infections caused by susceptible strains of Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis.

pharmacology

Grepafloxacin has in vitro activity against a wide range of gram-positive and gram-negative aerobic microorganisms, as well as some atypical microorganisms.

mechanism of action

Grepafloxacin exerts its antibacterial activity by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV, essential enzymes for duplication, transcription, and repair of bacterial DNA.

toxicity

Withdrawn from the US market in 1999 due to associations with QTc prolongation and adverse cardiovascular events.

biotransformation

Primarily hepatic via CYP1A2 and CYP3A4. The major metabolite is a glucuronide conjugate; minor metabolites include sulfate conjugates and oxidative metabolites. The oxidative metabolites are formed mainly by the cytochrome P450 enzyme CYP1A2, while the cytochrome P450 enzyme CYP3A4 plays a minor role. The nonconjugated metabolites have little antimicrobial activity compared with the parent drug, and the conjugated metabolites have no antimicrobial activity

absorption

Rapidly and extensively absorbed following oral administration. The absolute bioavailability is approximately 70%.

half life

15 ± 3 hours

drug interactions

Aluminium: Formation of non-absorbable complexes

Aminophylline: Grepafloxacin may increase the effect of aminophylline.

Amiodarone: Increased risk of cardiotoxicity and arrhythmias

Amitriptyline: Increased risk of cardiotoxicity and arrhythmias

Amoxapine: Increased risk of cardiotoxicity and arrhythmias

Astemizole: Increased risk of cardiotoxicity and arrhythmias

Bepridil: Increased risk of cardiotoxicity and arrhythmias

Bretylium: Increased risk of cardiotoxicity and arrhythmias

Caffeine: Grepafloxacin may increase the effect and toxicity of caffeine.

Calcium: Calcium may decrease the absorption of grepafloxacin. Doses should be spaced apart by at least 2 hours.

Chlorpromazine: Increased risk of cardiotoxicity and arrhythmias

Clomipramine: Increased risk of cardiotoxicity and arrhythmias

Desipramine: Increased risk of cardiotoxicity and arrhythmias

Dihydroquinidine barbiturate: Increased risk of cardiotoxicity and arrhythmias

Disopyramide: Increased risk of cardiotoxicity and arrhythmias

Doxepin: Increased risk of cardiotoxicity and arrhythmias

Dyphylline: Grepafloxacin may increase the effect of dyphylline.

Erythromycin: Increased risk of cardiotoxicity and arrhythmias

Fluphenazine: Increased risk of cardiotoxicity and arrhythmias

Imipramine: Increased risk of cardiotoxicity and arrhythmias

Iron: Formation of non-absorbable complexes

Iron Dextran: Formation of non-absorbable complexes

Josamycin: Increased risk of cardiotoxicity and arrhythmias

Magnesium: Magnesium may decrease the absorption of grepafloxacin. Doses should be spaced apart by at least 2 hours.

Magnesium oxide: Formation of non-absorbable complexes

Mesoridazine: Increased risk of cardiotoxicity and arrhythmias

Methotrimeprazine: Increased risk of cardiotoxicity and arrhythmias

Nortriptyline: Increased risk of cardiotoxicity and arrhythmias

Oxtriphylline: Grepafloxacin may increase the effect of oxtriphylline.

Perphenazine: Increased risk of cardiotoxicity and arrhythmias

Prochlorperazine: Increased risk of cardiotoxicity and arrhythmias

Promazine: Increased risk of cardiotoxicity and arrhythmias

Promethazine: Increased risk of cardiotoxicity and arrhythmias

Propiomazine: Increased risk of cardiotoxicity and arrhythmias

Protriptyline: Increased risk of cardiotoxicity and arrhythmias

Quinidine: Increased risk of cardiotoxicity and arrhythmias

Quinidine barbiturate: Increased risk of cardiotoxicity and arrhythmias

Quinupristin: This combination presents an increased risk of toxicity

Sotalol: Increased risk of cardiotoxicity and arrhythmias

Sucralfate: Formation of non-absorbable complexes

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Theophylline: Grepafloxacin may increase the effect of theophylline.

Thiethylperazine: Increased risk of cardiotoxicity and arrhythmias

Thioridazine: Increased risk of cardiotoxicity and arrhythmias

Trifluoperazine: Increased risk of cardiotoxicity and arrhythmias

Triflupromazine: Increased risk of cardiotoxicity and arrhythmias

Trimipramine: Increased risk of cardiotoxicity and arrhythmias

Zinc: Formation of non-absorbable complexes