No

Antibiotic, Quinolone

Acute maxillary sinusitis due to S. pneumoniae, H. influenzae, or M. catarrhalis; uncomplicated urinary tract infection due to E. coli, K. pneumoniae, or S. saprophyticus; also for acute bacterial exacerbation of chronic bronchitis and community-acquired pneumonia due to S. aureus, S. pneumoniae (including penicillin-resistant strains), H. influenzae, H. parainfluenzae, or M. catarrhalis, C. pneumoniae, L. pneumophila, or M. pneumoniae; may be used for uncomplicated skin and skin structure infection (due to S. aureus or S. pyogenes) and complicated urinary tract infection due to gram-negative Enterobacter sp, including acute pyelonephritis (caused by E. coli)

C

Clinical effects on the fetus: Avoid use in pregnant women unless the benefit justifies the potential risk to the fetus

Breast-feeding/lactation: Quinolones are known to distribute well into breast milk; consequently, use during lactation should be avoided, if possible

Hypersensitivity to levofloxacin, any component, or other quinolones; pregnancy, lactation

Not recommended in children <18 years of age; other quinolones have caused transient arthropathy in children; CNS stimulation may occur (tremor, restlessness, confusion, and very rarely hallucinations or seizures); use with caution in patients with known or suspected CNS disorders or renal dysfunction; prolonged use may result in superinfection; if an allergic reaction (itching, urticaria, dyspnea, pharyngeal or facial edema, loss of consciousness, tingling, cardiovascular collapse) occurs, discontinue the drug immediately; use caution to avoid possible photosensitivity reactions during and for several days following fluoroquinolone therapy; pseudomembranous colitis may occur and should be considered in patients who present with diarrhea

1% to 10%:

Central nervous system: Dizziness, headache, insomnia

Gastrointestinal: Nausea, vomiting, diarrhea, constipation

Neuromuscular & skeletal: Tremor, arthralgia

<1% (Limited to important or life-threatening symptoms): Cardiac failure, hypertension, bradycardia, tachycardia, seizures, elevated transaminases, pseudomembraneous colitis, leukorrhea, granulocytopenia, leukopenia, leukocytosis, thrombocytopenia, jaundice, acute renal failure, arrhythmia (torsade de pointes)

Symptoms of overdose include acute renal failure, seizures

Treatment should include GI decontamination and supportive care; not removed by peritoneal or hemodialysis

CYP1A2 enzyme inhibitor (minor) CYP1A2 enzyme inhibitor (minor)

Antineoplastic agents may decrease the absorption of quinolones.

Cimetidine, and other H₂ antagonists may inhibit renal elimination of quinolones.

Foscarnet has been associated with an increased risk of seizures with some quinolones.

Loop diuretics: Serum levels of some quinolones are increased by loop diuretic administration. May diminish renal excretion.

NSAIDs: The CNS stimulating effect of some quinolones may be enhanced, resulting in neuroexcitation and/or seizures.

Probenecid: Blocks renal secretion of quinolones, increasing concentrations.

Warfarin: The hypoprothrombinemic effect of warfarin is enhanced by some quinolone antibiotics. Levofloxacin does not alter warfarin kinetics, but may alter the gastrointestinal flora. Monitor INR closely during therapy.

Stable for 72 hours when diluted to 5 mg/mL in a compatible I.V. fluid and stored at room temperature; stable for 14 days when stored under refrigeration; stable for 6 months when frozen, do not refreeze; do not thaw in microwave or by bath immersion; incompatible with mannitol and sodium bicarbonate

As the S (-) enantiomer of the fluoroquinolone, ofloxacin, levofloxacin, inhibits DNA-gyrase in susceptible organisms thereby inhibits relaxation of supercoiled DNA and promotes breakage of DNA strands. DNA gyrase (topoisomerase II), is an essential bacterial enzyme that maintains the superhelical structure of DNA and is required for DNA replication and transcription, DNA repair, recombination, and transposition.

Absorption: Well absorbed

Distribution: V_d: 1.25 L/kg; CSF concentrations ~15% of serum levels; high concentrations are achieved in prostate and gynecological tissues, sinus, breast milk, and saliva

Protein binding: 50%

Metabolism: Hepatic, minimal

Half-life: 6 hours

Bioavailability: 100%

Time to peak serum concentration: 1 hour

Elimination: Most excreted unchanged in urine

Adults: Oral, I.V. (infuse I.V. solution over 60 minutes):

Community acquired pneumonia: 500 mg every 24 hours for 7-14 days

Acute maxillary sinusitis: 500 mg every 24 hours for 10-14 days

Uncomplicated skin infections: 500 mg every 24 hours for 7-10 days

Uncomplicated urinary tract infections: 250 mg once daily for 3 days

Complicated urinary tract infections include acute pyelonephritis: 250 mg every 24 hours for 10 days

Dosing adjustment in renal impairment:

Cl_cr 20-49 mL/minute: Administer 250 mg every 24 hours (initial: 500 mg)

Cl_cr 10-19 mL/minute: Administer 250 mg every 48 hours (initial: 500 mg for most infections; 250 mg for renal infections)

Hemodialysis/CAPD: 250 mg every 48 hours (initial: 500 mg)

Evaluation of organ system functions (renal, hepatic, ophthalmologic, and hematopoietic) is recommended periodically during therapy; the possibility of crystalluria should be assessed; WBC and signs of infection

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

May cause leukopenia; use caution with clozapine and carbamazepine; inhibits CYP1A2 isoenzyme; caution with clozapine and other psychotropics; monitor for adverse effects

No information available to require special precautions

No effects or complications reported

Oral: Take per recommended schedule, preferably on an empty stomach (1 hour before or 2 hours after meals). Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). Take complete prescription; do not skip doses. Do not take with antacids; separate by 2 hours. You may experience dizziness, lightheadedness, or confusion; use caution when driving or engaging in tasks that require alertness until response to drug is known. Small frequent meals and frequent mouth care may reduce nausea or vomiting. You may experience photosensitivity; use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight. Report palpitations or chest pain, persistent diarrhea, GI disturbances or abdominal pain, muscle tremor or pain, yellowing of eyes or skin, easy bruising or bleeding, unusual fatigue, fever, chills, signs of infection, or worsening of condition. Report immediately any rash; itching; unusual CNS changes; pain, inflammation, or rupture of tendon; or any facial swelling. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to get pregnant. Do not breast-feed.

Infuse I.V. solutions over 60 minutes

Infusion, in D₅W: 5 mg/mL (50 mL, 100 mL)

Injection: 25 mg/mL (20 mL)

Tablet: 250 mg, 500 mg

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.

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.

Martin SJ, Meyer JM, Chuck SK, et al, "Levofloxacin and Sparfloxacin: New Quinolone Antibiotics," Ann Pharmacother, 1998, 32(3):320-36.

North DS, Fish DN, and Redington JJ, "Levofloxacin, A Second-Generation Fluoroquinolone," Pharmacotherapy, 1998, 18(5):915-35.

Pfaller MA and Jones RN, "Comparative Antistreptococcal Activity of Two Newer Fluoroquinolones, Levofloxacin and Sparfloxacin," Diagn Microbiol Infect Dis, 1997, 29(3):199-201.

"Sparfloxacin and Levofloxacin," Med Lett Drugs Ther, 1997, 39(999):41-3.