Levofloxacin

Pronunciation

(lee voe FLOKS a sin)

U.S. Brand Names

Iquix®; Levaquin®; Quixin™

Generic Available

Canadian Brand Names

Levaquin®

Use

Systemic: Treatment of mild, moderate, or severe infections caused by susceptible organisms. Includes the treatment of community-acquired pneumonia, including multidrug resistant strains of S. pneumoniae (MDRSP); nosocomial pneumonia; chronic bronchitis (acute bacterial exacerbation); acute maxillary sinusitis; urinary tract infection (uncomplicated or complicated), including acute pyelonephritis caused by E. coli ; prostatitis (chronic bacterial); skin or skin structure infections (uncomplicated or complicated); prevention of inhalational anthrax (postexposure)

Ophthalmic: Treatment of bacterial conjunctivitis caused by susceptible organisms (Quixin™ 0.5% ophthalmic solution); treatment of corneal ulcer caused by susceptible organisms (Iquix® 1.5% ophthalmic solution)

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. Teratogenic effects were not observed with levofloxacin in animal studies; however, decreased body weight and increased fetal mortality were reported. 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

Excretion in breast milk unknown/not recommended

Contraindications

Hypersensitivity to levofloxacin, any component of the formulation, or other quinolones

Warnings/Precautions

Systemic: Not recommended in children <18 years of age; 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; use caution to avoid possible photosensitivity reactions during and for several days following fluoroquinolone therapy

Rare cases of torsade de pointes have been reported in patients receiving levofloxacin. Risk may be minimized by avoiding use in patients with known prolongation of QT interval, bradycardia, hypokalemia, hypomagnesemia, cardiomyopathy, or in those receiving concurrent therapy with Class Ia or Class III antiarrhythmics.

Severe hypersensitivity reactions, including anaphylaxis, have occurred with quinolone therapy. If an allergic reaction occurs (itching, urticaria, dyspnea or 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. Tendon inflammation and/or rupture has been reported; risk may be increased with concurrent corticosteroids, particularly in the elderly. Discontinue at first sign of tendon inflammation or pain. Peripheral neuropathies have been linked to levofloxacin use; discontinue if numbness, tingling, or weakness develops. Quinolones may exacerbate myasthenia gravis; use with caution (rare, potentially life-threatening weakness of respiratory muscles may occur).

Ophthalmic solution: For topical use only. Do not inject subconjunctivally or introduce into anterior chamber of the eye. Contact lenses should not be worn during treatment for bacterial conjunctivitis. Safety and efficacy in children <1 year of age (Quixin™) or <6 years of age (Iquix®) have not been established. Note: Indications for ophthalmic solutions are product concentration-specific and should not be used interchangeably.

Adverse Reactions

1% to 10%:

Central nervous system: Dizziness, fever, headache, insomnia

Gastrointestinal: Abdominal pain, constipation, diarrhea, dyspepsia, nausea, vomiting

Ocular (with ophthalmic solution use): Decreased vision (transient), foreign body sensation, transient ocular burning, ocular pain or discomfort, photophobia

Respiratory: Dyspnea, pharyngitis

<1% (Limited to important or life-threatening):

Systemic: Acute renal failure; allergic reaction (including pneumonitis rash, pneumonitis, and anaphylaxis); agranulocytosis, anaphylactoid reaction, arrhythmia (including ventricular tachycardia and torsade de pointes), arthralgia, bradycardia, cardiac failure, dysphonia, eosinophilia, erythema multiforme, granulocytopenia, hemolytic anemia, hepatic failure, hypertension, INR/prothrombin time increased, intracranial hypertension, involuntary muscle contractions, jaundice, leukocytosis, leukopenia, leukorrhea, peripheral neuropathy, photosensitivity (<0.1%), pseudomembraneous colitis, pulmonary embolism, QTc prolongation, rhabdomyolysis, seizure, Stevens-Johnson syndrome, tachycardia, taste perversion, tendon rupture, transaminases increased, thrombocytopenia, tremor

Ophthalmic solution: Allergic reaction, lid edema, ocular dryness, ocular itching

Postmarketing and/or case reports: Systemic: EEG abnormalities, encephalopathy

Overdosage/Toxicology

Symptoms of overdose include acute renal failure, seizures

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

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. Levofloxacin should be administered 2 hours before or 2 hours after these agents.

Probenecid: May decrease renal secretion of levofloxacin.

QTc-prolonging agents: Effects may be additive with levofloxacin. Avoid concurrent use with Class Ia and Class III antiarrhythmics, erythromycin, cisapride, antipsychotics, and cyclic antidepressants.

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

Stability

Solution for injection:

Vial: Store at room temperature; protect from light. When diluted to 5 mg/mL in a compatible I.V. fluid, solution is stable for 72 hours when stored at room temperature; stable for 14 days when stored under refrigeration. When frozen, stable for 6 months; do not refreeze. Do not thaw in microwave or by bath immersion.

Premixed: Store at 25°C (77°F); protect from freezing and light.

Tablet, oral solution: Store at 25°C (77°F); excursions permitted to 15°C to 25°C (59°F to 77°F).

Ophthalmic solution: Store at 15°C to 25°C (59°F to 77°F).

Compatibility

Stable in D5LR, D5NS, D5W, NS; incompatible with mannitol 20%, sodium bicarbonate 5%

Y-site administration: Compatible: Amikacin, aminophylline, ampicillin, caffeine citrate, cefotaxime, cimetidine, clindamycin, dexamethasone sodium phosphate, dobutamine, dopamine, epinephrine, fentanyl, gentamicin, isoproterenol, lidocaine, linezolid, lorazepam, metoclopramide, morphine, oxacillin, pancuronium, penicillin G sodium, phenobarbital, phenylephrine, sodium bicarbonate, vancomycin. Incompatible: Acyclovir, alprostadil, furosemide, heparin, indomethacin, nitroglycerin, sodium nitroprusside. Variable (consult detailed reference): Insulin (regular)

Mechanism of Action

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.

Pharmacodynamics/Kinetics

Absorption: Rapid and complete

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

Protein binding: 50%

Metabolism: Minimally hepatic

Bioavailability: 99%

Half-life elimination: 6-8 hours

Time to peak, serum: 1-2 hours

Excretion: Primarily urine (as unchanged drug)

Dosage

Oral, I.V.: Adults:

Note: Sequential therapy (intravenous to oral) may be instituted based on prescriber's discretion.

Chronic bronchitis (acute bacterial exacerbation): 500 mg every 24 hours for at least 7 days

Inhalational anthrax: 500 mg every 24 hours for 60 days, beginning as soon as possible after exposure

Maxillary sinusitis (acute): 500 mg every 24 hours for 10-14 days

Pneumonia:

Community-acquired: 500 mg every 24 hours for 7-14 days or 750 mg every 24 hours for 5 days (efficacy of 5-day regimen for MDRSP not established)

Nosocomial: 750 mg every 24 hours for 7-14 days

Prostatitis (chronic bacterial): 500 mg every 24 hours for 28 days

Skin infections:

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

Complicated: 750 mg every 24 hours for 7-14 days

Urinary tract infections:

Uncomplicated: 250 mg once daily for 3 days

Complicated, including acute pyelonephritis: 250 mg every 24 hours for 10 days

Ophthalmic:

Conjunctivitis (0.5% ophthalmic solution): Children 1 year and Adults:

Treatment day 1 and day 2: Instill 1-2 drops into affected eye(s) every 2 hours while awake, up to 8 times/day

Treatment day 3 through day 7: Instill 1-2 drops into affected eye(s) every 4 hours while awake, up to 4 times/day

Corneal ulceration (1.5% ophthalmic solution): Children 6 years and Adults:

Treatment day 1 through day 3: Instill 1-2 drops into affected eye(s) every 30 minutes to 2 hours while awake and ~4-6 hours after retiring.

Treatment day 4 to treatment completion: Instill 1-2 drops into affected eye(s) every 1-4 hours while awake.

Dosing adjustment in renal impairment: Administer first dose as indicated in patients with normal renal function, then adjust dose as follows:

Chronic bronchitis, acute maxillary sinusitis, uncomplicated skin infection, community-acquired pneumonia, chronic bacterial prostatitis, or inhalational anthrax:

Clcr 20-49 mL/minute: 250 mg every 24 hours

Clcr 10-19 mL/minute: 250 mg every 48 hours

Hemodialysis/CAPD: 250 mg every 48 hours

Uncomplicated UTI: No dosage adjustment required

Complicated UTI, acute pyelonephritis: Clcr 10-19 mL/minute: 250 mg every 48 hours

Complicated skin infection, community-acquired pneumonia, or nosocomial pneumonia:

Clcr 20-49 mL/minute: Administer 750 mg every 48 hours

Clcr 10-19 mL/minute: Administer 500 mg every 48 hours

Hemodialysis/CAPD: 250 mg every 48 hours

Administration

Oral: Tablets may be administered without regard to meals. Oral solution should be administered 1 hour before or 2 hours after meals.

I.V.: Infuse 250-500 mg I.V. solution over 60 minutes; infuse 750 mg I.V. solution over 90 minutes. Too rapid of infusion can lead to hypotension. Avoid administration through an intravenous line with a solution containing multivalent cations (eg, magnesium, calcium).

Monitoring Parameters

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

Dietary Considerations

Tablets may be taken without regard to meals. Oral solution should be administered on an empty stomach (1 hour before or 2 hours after a meal).

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. If administered by infusion; report immediately any chest or back pain, tightness in chest, difficulty swallowing, swelling of face or mouth, or redness, swelling or pain at infusion site. Oral: 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 advised by prescriber to restrict fluid intake. Ophthalmic: Use as directed. You may experience 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 signs of inflammation or tendon pain occur, discontinue use immediately and report to prescriber. If allergic reaction occurs (itching, urticaria, respiratory difficulty, facial edema, difficulty swallowing, loss of consciousness, tingling, chest pain, palpitations), discontinue use immediately and report to prescriber. Report persistent diarrhea or constipation; signs of infection (unusual fever or chills); vaginal itching or foul-smelling vaginal discharge; or easy bruising or bleeding. Pregnancy/breast-feeding precautions: Breast-feeding is not recommended.

Ophthalmic: Wash hands before instilling solution. Sit or lie down to instill. Open eye, look at ceiling, and instill prescribed amount of solution. Close eye and roll eye in all directions, and apply gentle pressure to inner corner of eye. Do not let tip of applicator touch eye; do not contaminate tip of applicator (may cause eye infection, eye damage, or vision loss). Temporary stinging or blurred vision may occur. Report persistent pain, burning, vision changes, swelling, itching, or worsening of condition. Discontinue medication and contact prescriber immediately if you develop a rash or allergic reaction. Do not wear contact lenses.

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

Mental Health: Effects on Psychiatric Treatment

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

Dosage Forms

Infusion [premixed in D5W] (Levaquin®): 250 mg (50 mL); 500 mg (100 mL); 750 mg (150 mL)

Injection, solution [preservative free] (Levaquin®): 25 mg/mL (20 mL, 30 mL)

Solution, ophthalmic:

Iquix®: 1.5% (5 mL)

Quixin™: 0.5% (5 mL) [contains benzalkonium chloride]

Solution, oral (Levaquin®): 25 mg/mL (480 mL) [contains benzyl alcohol]

Tablet (Levaquin®): 250 mg, 500 mg, 750 mg

Levaquin® Leva-Pak: 750 mg (5s)

References

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.

International Brand Names

Cravit® (ID, JP, SG, TH, TR); Cravit Ophthalmic® (TH); Cravit Ophth Soln® (SG); Cravox® (ID); Elequine® (CR, DO, GT, HN, MX, PA, SV); Floxlevo® (AR); Levaquin® (AR, BR, CA, CO); Levofloxacin® (BR); Levoxacin® [inj.] (IT); Levoxacin® (IT); Levoxetina® (SV); Mosardal® (ID); Nislev® (ID); Oftaquix® (DE, DK, FI, SE); Prixar® (IT); Reskuin® (ID); Tavanic® (AR, AT, BE, BR, CH, CL, CO, CR, CZ, DE, DO, EC, ES, FI, FR, GB, GT, HN, HR, HU, IE, IL, IN, IT, MX, NL, PA, PL, PT, SE, SI, SV, TR, ZA)

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