indication

For the treatment of adults with the following infections caused by susceptible strains microorganisms: community-acquired pneumonia (caused by Chlamydia pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, or Streptococcus pneumoniae) and acute bacterial exacerbations of chronic bronchitis (caused by Chlamydia pneumoniae, Enterobacter cloacae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Staphylococcus aureus, or Streptococcus pneumoniae).

pharmacology

Sparfloxacin is a synthetic fluoroquinolone broad-spectrum antimicrobial agent in the same class as ofloxacin and norfloxacin. Sparfloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. Sparfloxacin exerts its antibacterial activity by inhibiting DNA gyrase, a bacterial topoisomerase. DNA gyrase is an essential enzyme which controls DNA topology and assists in DNA replication, repair, deactivation, and transcription. Quinolones differ in chemical structure and mode of action from (beta)-lactam antibiotics. Quinolones may, therefore, be active against bacteria resistant to (beta)-lactam antibiotics. Although cross-resistance has been observed between sparfloxacin and other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to sparfloxacin. In vitro tests show that the combination of sparfloxacin and rifampin is antagonistic against Staphylococcus aureus.

mechanism of action

The bactericidal action of sparfloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.

toxicity

Single doses of sparfloxacin were relatively non-toxic via the oral route of administration in mice, rats, and dogs. No deaths occurred within a 14-day post-treatment observation period at the highest oral doses tested, up to 5000 mg/kg in either rodent species, or up to 600 mg/kg in the dog. Clinical signs observed included inactivity in mice and dogs, diarrhea in both rodent species, and vomiting, salivation, and tremors in dogs.

biotransformation

Hepatic. Metabolized primarily by phase II glucuronidation to form a glucuronide conjugate. Metabolism does not utilize or interfere with the cytochrome P450 enzyme system.

absorption

Well absorbed following oral administration with an absolute oral bioavailability of 92%. Unaffected by administration with milk or food, however concurrent administration of antacids containing magnesium hydroxide and aluminum hydroxide reduces the oral bioavailability of sparfloxacin by as much as 50%.

half life

Mean terminal elimination half-life of 20 hours (range 16-30 hours). Prolonged in patients with renal impairment (creatinine clearance <50 mL/min).

drug interactions

Amiodarone: Increased risk of cardiotoxicity and arrhythmias

Amitriptyline: Increased risk of cardiotoxicity and arrhythmias

Amoxapine: Increased risk of cardiotoxicity and arrhythmias

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Astemizole: Increased risk of cardiotoxicity and arrhythmias

Bepridil: Increased risk of cardiotoxicity and arrhythmias

Calcium Acetate: Calcium salts such as calcium acetate may decrease the absorption of quinolone antibiotics such as sparfloxacin. Of concern only with oral administration of both agents. Interactions can be minimized by administering oral quinolone at least 2 hours before, or 6 hours after, the dose of an oral calcium supplement. Monitor for decreased therapeutic effects of oral quinolones if administered with oral calcium supplements.

Chlorpromazine: Increased risk of cardiotoxicity and arrhythmias

Clomipramine: Increased risk of cardiotoxicity and arrhythmias

Desipramine: Increased risk of cardiotoxicity and arrhythmias

Disopyramide: Increased risk of cardiotoxicity and arrhythmias

Doxepin: Increased risk of cardiotoxicity and arrhythmias

Erythromycin: Increased risk of cardiotoxicity and arrhythmias

Fluphenazine: Increased risk of cardiotoxicity and arrhythmias

Imipramine: Increased risk of cardiotoxicity and arrhythmias

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Mesoridazine: Increased risk of cardiotoxicity and arrhythmias

Methotrimeprazine: Increased risk of cardiotoxicity and arrhythmias

Nortriptyline: Increased risk of cardiotoxicity and arrhythmias

Perphenazine: Increased risk of cardiotoxicity and arrhythmias

Prochlorperazine: Increased risk of cardiotoxicity and arrhythmias

Promethazine: Increased risk of cardiotoxicity and arrhythmias

Quinidine: Increased risk of cardiotoxicity and arrhythmias

Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Thioridazine: Increased risk of cardiotoxicity and arrhythmias

Thiothixene: May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.

Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.

Trifluoperazine: Increased risk of cardiotoxicity and arrhythmias

Trimipramine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Voriconazole: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Zuclopenthixol: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).