Trovafloxacin

Pronunciation

(TROE va floks a sin)

U.S. Brand Names

Trovan® [DSC]

Synonyms

Alatrofloxacin Mesylate; CP-99,219-27

Generic Available

Use

Should be used only in life- or limb-threatening infections

Treatment of nosocomial pneumonia, community-acquired pneumonia, complicated intra-abdominal infections, gynecologic/pelvic infections, complicated skin and skin structure infections

Pregnancy Risk Factor

Pregnancy Implications

Reports of arthropathy (observed in immature animals and reported rarely in humans) have limited the use of fluoroquinolones in pregnancy. Skeletal variations and fetotoxicity were reported with trovafloxacin in animal studies. Based on limited data, quinolones are not expected to be a major human teratogen. Although quinolone antibiotics should not be used as first-line agents during pregnancy, when considering treatment for life-threatening infection and/or prolonged duration of therapy, the potential risk to the fetus must be balanced against the severity of the potential illness.

Lactation

Enters breast milk/not recommended

Contraindications

History of hypersensitivity to trovafloxacin, alatrofloxacin, quinolone antimicrobial agents, or any component of the formulation

Warnings/Precautions

For use only in serious life- or limb-threatening infections. Initiation of therapy must occur in an inpatient healthcare facility. May alter GI flora resulting in pseudomembranous colitis due to Clostridium difficile ; use with caution in patients with seizure disorders or severe cerebral atherosclerosis; photosensitivity; CNS stimulation may occur which may lead to tremor, restlessness, confusion, hallucinations, paranoia, depression, nightmares, insomnia, or lightheadedness. Hepatic reactions have resulted in death. Risk of hepatotoxicity is increased if therapy exceeds 14 days. Tendon inflammation and/or rupture have been reported with other quinolone antibiotics. Risk may be increased with concurrent corticosteroids, particularly in the elderly. Discontinue at first sign of tendon inflammation or pain.

Severe hypersensitivity reactions, including anaphylaxis, have occurred with quinolone therapy. If an allergic reaction occurs (itching, urticaria, dyspnea, facial edema, loss of consciousness, tingling, cardiovascular collapse), discontinue drug immediately. Prolonged use may result in superinfection; pseudomembranous colitis may occur and should be considered in all patients who present with diarrhea. Quinolones may exacerbate myasthenia gravis, use with caution (rare, potentially life-threatening weakness of respiratory muscles may occur).

Adverse Reactions

Note: Fatalities have occurred in patients developing hepatic necrosis.

1% to 10% (range reported in clinical trials):

Central nervous system: Dizziness (2% to 11%), lightheadedness (<1% to 4%), headache (1% to 5%)

Dermatologic: Rash (<1% to 2%), pruritus (<1% to 2%)

Gastrointestinal: Nausea (4% to 8%), abdominal pain (<1% to 1%), vomiting, diarrhea

Genitourinary: Vaginitis (<1% to 1%)

Hepatic: Increased LFTs

Local: Injection site reaction, pain, or inflammation

<1%: Phototoxicity, convulsions, dyskinesia, pseudomembranous colitis, allergic/anaphylactoid reaction, tendonitis, bronchospasm, interstitial nephritis, anaphylaxis, hepatic necrosis, pancreatitis, Stevens-Johnson syndrome; quinolones have been associated with tendon rupture

Overdosage/Toxicology

Empty the stomach by vomiting or gastric lavage. Observe carefully and give symptomatic and supportive treatment; maintain adequate hydration.

Drug Interactions

Corticosteroids: Concurrent use may increase the risk of tendon rupture, particularly in elderly patients (overall incidence rare).

Glyburide: Quinolones may increase the effect of glyburide; monitor.

Metal cations (aluminum, calcium, iron, magnesium, and zinc) bind quinolones in the gastrointestinal tract and inhibit absorption. Concurrent administration of most antacids, oral electrolyte supplements, quinapril, sucralfate, and some didanosine formulations (chewable/buffered tablets and pediatric powder for oral suspension) should be avoided. Trovafloxacin should be administered 2 hours before or 2 hours after these agents.

Probenecid: May decrease renal secretion of trovafloxacin.

Warfarin: The hypoprothrombinemic effect of warfarin may be enhanced by some quinolone antibiotics; monitor INR.

Ethanol/Nutrition/Herb Interactions

Food: Dairy products such as milk or yogurt may reduce absorption of oral trovafloxacin; avoid concurrent use. Enteral feedings may also limit absorption.

Herb/Nutraceutical: Avoid dong quai, St John's wort (may also cause photosensitization).

Stability

Store undiluted vials of solution at 15°C to 30°C (50°F to 86°F). Diluted solutions are stable for up to 7 days when refrigerated and up to 3 days at room temperature. Trovan® I.V. should not be diluted with 0.9% sodium chloride injection, USP (normal saline), alone or in combination with other diluents. A precipitate may form under these conditions. In addition, Trovan® I.V. should not be diluted with lactated Ringer's, USP.

Dilute to a concentration of 0.5-2 mg/mL in dextrose 5% in water, 0.45% sodium chloride, dextrose 5% in water and 0.45% sodium chloride, dextrose 5% in water and 0.2% sodium chloride, or lactated Ringer's in dextrose 5% in water.

Compatibility

Alatrofloxacin: Stable in D5W, D5LR, D5¹ /4NS, D5¹ /2NS, ¹ /2NS; incompatible with NS, LR

Y-site administration: Compatible: Amikacin, cyclosporine, dopamine, droperidol, fentanyl, gentamicin, ketorolac, lorazepam, LR, midazolam, nitroglycerin, ondansetron, potassium chloride, sodium bicarbonate, ¹ /2NS, tobramycin, vancomycin. Incompatible: Aztreonam, ceftazidime, ceftriaxone, dobutamine, famotidine, furosemide, heparin, insulin (regular), magnesium sulfate, morphine, piperacillin/tazobactam, ticarcillin/clavulanate

Mechanism of Action

Inhibits DNA-gyrase in susceptible organisms; inhibits relaxation of supercoiled DNA and promotes breakage of double-stranded DNA

Pharmacodynamics/Kinetics

Distribution: Concentration in most tissues greater than plasma or serum

Protein binding: 76%

Metabolism: Hepatic conjugation; glucuronidation 13%, acetylation 9%

Bioavailability: 88%

Half-life elimination: 9-12 hours

Time to peak, serum: Oral: Within 2 hours

Excretion: Feces (43% as unchanged drug); urine (6% as unchanged drug)

Dosage

Adults:

Nosocomial pneumonia: I.V.: 300 mg single dose followed by 200 mg/day orally for a total duration of 10-14 days

Community-acquired pneumonia: Oral, I.V.: 200 mg/day for 7-14 days

Complicated intra-abdominal infections, including postsurgical infections/gynecologic and pelvic infections: I.V.: 300 mg as a single dose followed by 200 mg/day orally for a total duration of 7-14 days

Skin and skin structure infections, complicated, including diabetic foot infections: Oral, I.V.: 200 mg/day for 10-14 days

Dosage adjustment in renal impairment: No adjustment is necessary

Dosage adjustment for hemodialysis: None required; trovafloxacin not sufficiently removed by hemodialysis

Dosage adjustment in hepatic impairment:

Mild to moderate cirrhosis:

Initial dose for normal hepatic function: 300 mg I.V.; 200 mg I.V. or oral; 100 mg oral

Reduced dose: 200 mg I.V.; 100 mg I.V. or oral; 100 mg oral

Severe cirrhosis: No data available

Administration

Oral: Administer without regard to meals.

I.V.: Not for I.M. or SubQ; administer IVPB over 60 minutes

Monitoring Parameters

Periodic assessment of liver function tests should be considered

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take exactly as directed: at least 2 hours before or 2 hours after antacids or other drug products containing calcium, iron, or zinc. Take entire prescription even if feeling better. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. May cause dizziness, lightheadedness, or confusion (use caution when driving or engaging in tasks that require alertness until response to drug is known); nausea or vomiting (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); or photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). If inflammation or tendon pain occurs, discontinue use immediately and report to prescriber. If signs of allergic reaction (eg, itching urticaria, respiratory difficulty, facial edema or difficulty swallowing, loss of consciousness, tingling, chest pain, palpitations) occurs, discontinue use immediately and report to prescriber. Report CNS disturbances (eg, hallucinations, gait disturbances); palpitations or chest pain; persistent diarrhea or constipation; signs of infection (eg, sore throat, chills, unusual fever, burning, itching on urination, vaginal discharge, white plaques in mouth); easy bruising or bleeding; respiratory difficulty; or worsening of condition. Report immediately any pain, inflammation, or rupture of tendon. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Do not breast-feed.

Anesthesia and Critical Care Concerns/Other Considerations

Trovafloxacin should only be used in severe life or limb threatening infections. If treatment is >14 days, monitor LFTs. In vitro trovafloxacin was more active than sparfloxacin, ofloxacin, ciprofloxacin, ceftriaxone, erythromycin, and vancomycin against S. pneumoniae . It was also more active against penicillin-resistant strains than ceftriaxone, erythromycin, or vancomycin. It has good activity against resistant organisms, and penetration of the cerebral spinal fluid giving potential in the treatment of central nervous system infections.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause dizziness; quinolones reported to cause restlessness, hallucinations, euphoria, depression, panic, and paranoia

Mental Health: Effects on Psychiatric Treatment

None reported

Dosage Forms

Injection, solution, as mesylate [alatrofloxacin]: 5 mg/mL (40 mL, 60 mL)

Tablet, as mesylate [trovafloxacin]: 100 mg, 200 mg

References

Cutler NR, Vincent J, Jhee SS, et al, "Penetration of Trovafloxacin Into Cerebrospinal Fluid in Humans Following Intravenous Infusion of Alatrofloxacin," Antimicrob Agents Chemother , 1997, 41(6):1298-300.

Dalvie DK, Khosla N, and Vincent J, "Excretion and Metabolism of Trovafloxacin in Humans," Drug Metab Dispos , 1997, 25(4):423-7.

Ernst ME, Ernst EJ, and Klepser ME, "Levofloxacin and Trovafloxacin: The Next Generation of Fluoroquinolones?" Am J Health Syst Pharm , 1997, 54(22):2569-84.

Garey KW and Amsden GW, "Trovafloxacin: An Overview," Pharmacotherapy , 1999, 19(1):21-34.

Haria M and Lamb HA, "Trovafloxacin," Drugs , 1997, 54(3):435-45.

Hecht DW and Osmolski JR, "Comparison of Activities of Trovafloxacin (CP-99,219) and Five Other Agents Against 585 Anaerobes With Use of Three Media," Clin Infect Dis , 1996, 23(Suppl 1):44-50.

Hoogkamp-Korstanje JA, " In vitro Activities of Ciprofloxacin, Levofloxacin, Lomefloxacin, Ofloxacin, Pefloxacin, Sparfloxacin, and Trovafloxacin Against Gram-Positive and Gram-Negative Pathogens From Respiratory Tract Infections," J Antimicrob Chemother , 1997, 40(3):427-31.

Teng R, Dogolo LC, Willavize SA, et al, "Oral Bioavailability of Trovafloxacin With and Without Food in Healthy Volunteers," J Antimicrob Chemother , 1997, 39(Suppl B):87-92.

Thompson KS, Chartrand SA, Sanders CC, et al, "Trovafloxacin, a New Fluoroquinolone With Potent Activity Against Streptococcus pneumoniae ," Antimicrob Agents Chemother , 1997, 41(2):478-80.

"Trovafloxacin," Med Lett Drugs Ther , 1998, 40(1022):30-1.

Vincent J, Venitz J, Teng R, et al, "Pharmacokinetics and Safety of Trovafloxacin in Healthy Male Volunteers Following Administration of Single Intravenous Doses of the Prodrug, Alatrofloxacin," J Antimicrob Chemother , 1997, 39(Suppl B):75-80.

International Brand Names

Trovan® (MX, PL)

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