indication

For treatment of infections caused by susceptible strains of the designated microorganisms in uncomplicated urethral gonorrhea in males and endocervical and rectal gonorrhea in females caused by Neisseria gonorrhoeae as well as non gonoccocal urethritis and cervicitis due to Chlamydia trachomatis.

pharmacology

Trovafloxacin is a broad spectrum antibiotic that inhibits DNA supercoiling in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. It is not used widely due to the risk of hepatotoxicity. It tends to have better gram-positive bacterial coverage and less gram-negative coverage than the previous fluoroquinolones. Mechanism of action of fluoroquinolones including trovafloxacin is different from that of penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines. Therefore fluoroquinolones may be active against pathogens that are resistant to these antibiotics. There is no cross-resistance between trovafloxacin and the mentioned classes of antibiotics. The overall results obtained from in vitro synergy studies, testing combinations of trovafloxacin with beta-lactams and aminoglycosides, indicate that synergy is strain specific and not commonly encountered. This agrees with results obtained previously with other fluoroquinolones. Resistance to trovafloxacin in vitro develops slowly via multiple-step mutation in a manner similar to other fluoroquinolones. Resistance to trovafloxacin in vitro occurs at a general frequency of between 1x10^-7 to 10^-10. Although cross-resistance has been observed between trovafloxacin and some other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to trovafloxacin.

mechanism of action

Trovafloxacin is a fluoronaphthyridone related to the fluoroquinolones with in vitro activity against a wide range of gram-negative and gram-positive aerobic and anaerobic microorganisms. The bactericidal action of trovafloxacin results from inhibition of 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.

toxicity

Symptoms of overdose include convulsions, decreased activity, diarrhea, sleepiness, tremors, and/or vomiting.

biotransformation

Metabolism Trovafloxacin is metabolized by conjugation (the role of cytochrome P450 oxidative metabolism of trovafloxacin is minimal). The major metabolites include the ester glucuronide, which appears in the urine (13% of the administered dose); and the N -acetyl metabolite, which appears in the feces and serum (9% and 2.5% of the administered dose, respectively). Other minor metabolites include diacid, hydroxycarboxylic acid, and sulfamate, which have been identified in both the feces and the urine in small amounts (< 4% of the administered dose).

absorption

Well-absorbed from the gastrointestinal tract after oral administration and does not depend on concomitant food intake. The absolute bioavailability is approximately 88%.

half life

Following oral administration, half-life ranged from 9.1 hours to 12.2 hours over the dosage range of 100 to 200 mg tablets. Following intravenous infusion, half-life ranged from 9.4 to 12.7 hours over a dosage range of 100 to 300 mg.

route of elimination

Approximately 50% of an oral dose is excreted unchanged (43% in the feces and 6% in the urine).

drug interactions

Aluminium: Aluminum may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the aluminum containing agent to minimize the interaction.

Calcium: Formation of non-absorbable complexes

Calcium Acetate: Calcium may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the calcium containining agent to minimize the interaction.

Calcium Chloride: Calcium may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the calcium containing agent to minimize the interaction.

Calcium Gluceptate: Calcium may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the calcium containing agent to minimize the interaction.

Didanosine: Didanosine may decrease the absorption of orally administered Trovafloxacin. The Didanosine formulation contains magnesium and aluminum ions that intefere with Trovafloxacin absorption. Administer Trovafloxacin 2 hours before or 6 hours after the Didanosine dose to minimize the interaction. This interaction is not observed with enteric coated Didanosine.

Iron: Iron may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the iron containing agent to minimize the interaction.

Iron Dextran: Formation of non-absorbable complexes

Magnesium: Formation of non-absorbable complexes

Magnesium oxide: Magnesium may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the magnesium containing agent to minimize the interaction.

Magnesium Sulfate: Magnesium may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the magnesium containing agent to minimize the interaction.

Morphine: Morphine may reduce serum levels of Trovafloxacin decreasing the efficacy of the antibiotic. IV doses of morphine should be administered at least 2 hours after a dose of Trovafloxacin given in a fasting state or 4 hours after if given in a fed state.

Quinapril: Quinapril may decrease the absorption of orally administered Trovafloxacin. The Quinapril formulation contains magnesium ions that may intefere with Trovafloxacin absorption. Administer Trovafloxacin 2 hours before or 6 hours after the Quinapril dose to minimize the interaction.

Sevelamer: Sevelamer may decrease the absorption of orally administered Trovafloxacin. The Sevelamer formulation contains iron that may intefere with Trovafloxacin absorption. Administer Trovafloxacin 2 hours before or 6 hours after the Sevelamer dose to minimize the interaction.

Sucralfate: Sucralfate may decrease the absorption of orally administered Trovafloxacin. The Sucralfate formulation contains aluminum ions that may intefere with Trovafloxacin absorption. Administer Trovafloxacin 2 hours before or 6 hours after the Sucralfate dose to minimize the interaction.

Zinc: Zinc may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the zinc containing agent to minimize the interaction.