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Levofloxacin

Pronunciation

Class: Quinolones
VA Class: AM900
Chemical Name: (S)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid hydrate (2:1)
Molecular Formula: C18H20FN3O4•½H2O
CAS Number: 138199-71-0
Brands: Levaquin

Warning(s)

    Serious Adverse Effects
  • Fluoroquinolones, including levofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that have occurred together.1 Discontinue immediately and avoid use of fluoroquinolones, including levofloxacin, in patients who have experienced any of these serious adverse reactions.1 (See Warnings under Cautions.)

  • Fluoroquinolones, including levofloxacin, may exacerbate muscle weakness in patients with myasthenia gravis.1 Avoid in patients with known history of myasthenia gravis.1

  • Because of risk of serious adverse reactions, use levofloxacin for treatment of acute bacterial sinusitis, acute bacterial exacerbations of chronic bronchitis, or uncomplicated urinary tract infections (UTIs) only when no other treatment options available.1

Introduction

Antibacterial; fluoroquinolone; the levorotatory isomer of ofloxacin.1 4 5 12

Uses for Levofloxacin

Respiratory Tract Infections

Treatment of acute bacterial sinusitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.1 18 90

Treatment of acute bacterial exacerbations of chronic bronchitis caused by susceptible Staphylococcus aureus, S. pneumoniae, H. influenzae, H. parainfluenzae, or M. catarrhalis.1 19 20

Use for treatment of acute bacterial sinusitis or acute bacterial exacerbations of chronic bronchitis only when no other treatment options available.1 140 145 Because systemic fluoroquinolones, including levofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient (see Cautions)1 140 145 and because acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis may be self-limiting in some patients,1 risks of serious adverse reactions outweigh benefits of fluoroquinolones for patients with these infections.140 145

Treatment of community-acquired pneumonia (CAP) caused by susceptible S. aureus, S. pneumoniae (including multidrug-resistant S. pneumoniae [MDRSP]), H. influenzae, H. parainfluenzae, Klebsiella pneumoniae, Legionella pneumoniae, M. catarrhalis, Chlamydophila pneumoniae (formerly Chlamydia pneumoniae), or Mycoplasma pneumoniae.1 21 31 95

Treatment of nosocomial pneumonia caused by susceptible S. aureus (oxacillin-susceptible [methicillin-susceptible] strains only), S. pneumoniae, H. influenzae, Escherichia coli, K. pneumoniae, Pseudomonas aeruginosa, or Serratia marcescens.1 Adjunctive therapy should be used as clinically indicated.1 If Ps. aeruginosa are known or suspected to be involved in the infection, concomitant use of an antipseudomonal β-lactam is recommended.1

Consult current IDSA clinical practice guidelines available at for additional information on management of respiratory tract infections.31 51

Skin and Skin Structure Infections

Treatment of mild to moderate uncomplicated skin and skin structure infections (including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections) caused by susceptible S. aureus or S. pyogenes (group A β-hemolytic streptococci.1 27

Treatment of complicated skin and skin structure infections caused by susceptible S. aureus (oxacillin-susceptible [methicillin-susceptible] strains only), Enterococcus faecalis, S. pyogenes, or Proteus mirabilis.1

For initial empiric treatment of mild to moderate community-acquired, extrabiliary, complicated intra-abdominal infections in adults (e.g., perforated or abscessed appendicitis), IDSA recommends either monotherapy with cefoxitin, ertapenem, moxifloxacin, tigecycline, or the fixed combination of ticarcillin and clavulanic acid, or a combination regimen that includes either a cephalosporin (cefazolin, ceftriaxone, cefotaxime, cefuroxime) or fluoroquinolone (ciprofloxacin, levofloxacin) in conjunction with metronidazole.39

Consult current IDSA clinical practice guidelines available at for additional information on management of skin and skin structure infections.26 43

Urinary Tract Infections (UTIs) and Prostatitis

Treatment of mild to moderate uncomplicated UTIs caused by susceptible E. coli, K. pneumoniae, or S. saprophyticus.1 Generally considered alternative for treatment of uncomplicated UTIs.143

Use for treatment of uncomplicated UTIs only when no other treatment options available.1 140 145 Because systemic fluoroquinolones, including levofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient(see Cautions)1 140 145 and because uncomplicated UTIs may be self-limiting in some patients,1 risks of serious adverse reactions outweigh benefits of fluoroquinolones for patients with uncomplicated UTIs.140 145

Treatment of mild to moderate complicated UTIs caused by susceptible E. faecalis, Enterobacter cloacae, E. coli, K. pneumoniae, P. mirabilis, or P. aeruginosa.1

Treatment of acute pyelonephritis caused by susceptible E. coli, including cases with concurrent bacteremia.1

Treatment of chronic prostatitis caused by susceptible E. coli, E. faecalis, or S. epidermidis.1

Endocarditis

Alternative for treatment of endocarditis (native or prosthetic valve or other prosthetic material) caused by fastidious gram-negative bacilli known as the HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens, Kingella).127 AHA and IDSA recommend ceftriaxone (or other third or fourth generation cephalosporin),127 but state that a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) may be considered in patients who cannot tolerate cephalosporins.127 Consultation with an infectious disease specialist recommended.127

GI Infections

Alternative for treatment of Salmonella gastroenteritis (with or without bacteremia) in HIV-infected adults.440 CDC, NIH, and IDSA recommend ciprofloxacin as drug of choice;440 other fluoroquinolones (levofloxacin, moxifloxacin) also may be effective.440 Depending on in vitro susceptibility, other alternatives are co-trimoxazole and third generation cephalosporins (ceftriaxone, cefotaxime).440 Role of long-term anti-infective treatment (secondary prophylaxis) in HIV-infected individuals with recurrent bacteremia not well established;440 weigh benefits of such prophylaxis against risks of long-term anti-infective therapy.440

Treatment of Shigella infections when anti-infectives indicated.440 477 Anti-infectives generally indicated in addition to fluid and electrolyte replacement for treatment of patients with severe shigellosis, dysentery, or underlying immunosuppression.292 440 Empiric treatment regimen can be used initially, but in vitro susceptibility testing indicated since resistance is common.292 A fluoroquinolone (preferably ciprofloxacin or, alternatively, levofloxacin or moxifloxacin) generally recommended, but consider that fluoroquinolone-resistant Shigella reported in the US.440 Depending on in vitro susceptibility, alternatives include co-trimoxazole or azithromycin (not recommended in those with bacteremia);440 ceftriaxone or azithromycin has been recommended when susceptibility of the isolate is unknown or ampicillin- or co-trimoxazole-resistant strains are involved.292 477

Treatment of travelers’ diarrhea.305 525 677 679 If caused by bacteria, may be self-limited and resolve within 3–7 days without anti-infective treatment;305 525 if diarrhea is moderate or severe, associated with fever or bloody stools, persisting for >3 days, or extremely disruptive to travel plans, short-term (1–3 days) anti-infective treatment usually recommended.305 525 Fluoroquinolones (ciprofloxacin, levofloxacin) usually drugs of choice when anti-infective treatment, including self-treatment, indicated.305 525 677 679 Azithromycin is a treatment alternative if fluoroquinolones should not be used (e.g., children, pregnant women) and a drug of choice for travelers in areas with a high prevalence of fluoroquinolone-resistant Campylobacter (e.g., South and Southeast Asia) or when there is no response after 48 hours of fluoroquinolone treatment.305 525 Rifaximin is an alternative for treatment of travelers’ diarrhea caused by enterotoxigenic E. coli.305 525

Prevention of travelers’ diarrhea in individuals traveling for relatively short periods to areas where enterotoxigenic E. coli and other causative bacterial pathogens (e.g., Shigella) are known to be susceptible to the drug.525 677 679 CDC and most experts do not recommend routine anti-infective prophylaxis in individuals traveling to areas of risk.440 525 Consider prophylaxis only in certain travelers, including short-term travelers who are high-risk individuals (e.g., HIV-infected or other immunocompromised individuals, travelers with poorly controlled diabetes mellitus or chronic renal failure) and those taking critical trips during which even a short episode of diarrhea could adversely affect the purpose of the trip.305 525 The principal preventive measures for travelers are prudent dietary practices.525 If anti-infective prophylaxis used, a fluoroquinolone (ciprofloxacin, levofloxacin) has been recommended for nonpregnant adults,305 440 525 but consider the increasing incidence of fluoroquinolone resistance in pathogens that cause travelers’ diarrhea (e.g., Campylobacter, Shigella).305 525 Weigh use of anti-infective prophylaxis against use of prompt, early self-treatment with anti-infectives, a strategy that can limit duration of illness to 6–24 hours in most cases.525

Anthrax

Inhalational anthrax (postexposure) to reduce incidence or progression of disease following suspected or confirmed exposure to aerosolized Bacillus anthracis spores.1 CDC, US Public Health Service Advisory Committee on Immunization Practices (ACIP), US Working Group on Civilian Biodefense, and US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommend oral ciprofloxacin and oral doxycycline as initial drugs of choice for prophylaxis following such exposures, including exposures that occur in the context of biologic warfare or bioterrorism.663 668 683 686 Some of these experts state that levofloxacin or other oral fluoroquinolones (moxifloxacin, ofloxacin) are alternatives for postexposure prophylaxis when ciprofloxacin or doxycycline cannot be used.663 668

Alternative for treatment of inhalational anthrax when a parenteral regimen not available (e.g., supply or logistic problems because large numbers of individuals require treatment in a mass-casualty setting).668 683 A multiple-drug parenteral regimen (ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective) preferred for initial treatment of inhalational anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.668 683 686

Chlamydial Infections

Alternative for treatment of urogenital infections caused by Chlamydia trachomatis.344 CDC recommends azithromycin or doxycycline;344 alternatives are erythromycin, levofloxacin, or ofloxacin.344

Gonorrhea and Associated Infections

Was used in the past for treatment of uncomplicated gonorrhea caused by susceptible Neisseria gonorrhoeae.114

Because quinolone-resistant N. gonorrhoeae (QRNG) widely disseminated worldwide, including in the US344 857 (see Resistance in Neisseria gonorrhoeae under Cautions), CDC states fluoroquinolones no longer recommended for treatment of gonorrhea and should not be used routinely for any associated infections that may involve N. gonorrhoeae (e.g., pelvic inflammatory disease [PID], epididymitis).344

Alternative for treatment of PID.344 (See Pelvic Inflammatory Disease under Uses.)

Alternative for treatment of acute epididymitis.344 CDC recommends a single IM dose of ceftriaxone in conjunction with oral doxycycline for acute epididymitis most likely caused by sexually transmitted chlamydia and gonorrhea or a single IM dose of ceftriaxone in conjunction with oral levofloxacin or ofloxacin for treatment of acute epididymitis most likely caused by sexually transmitted chlamydia and gonorrhea and enteric bacteria (e.g., in men who practice insertive anal sex).344 Levofloxacin or ofloxacin can be used alone if acute epididymitis most likely caused by enteric bacteria (e.g., in men who have undergone prostate biopsy, vasectomy, or other urinary tract instrumentation procedure) and gonorrhea ruled out (e.g., by gram, methylene blue, or gentian violet stain).344

Meningitis and CNS Infections

Suggested as a possible alternative for use in conjunction with other anti-infectives for the treatment of meningitis caused by susceptible bacteria.64 65 Safety and efficacy not established;63 only very limited clinical experience.683

Tuberculosis

Alternative (second-line) agent for use in multiple-drug regimens for treatment of active tuberculosis caused by Mycobacterium tuberculosis.218 231 276 440

Although potential role of fluoroquinolones and optimal length of therapy not fully defined, ATS, CDC, IDSA, and others state that use of fluoroquinolones as alternative (second-line) agents can be considered for treatment of active tuberculosis in patients intolerant to certain first-line agents and in those with relapse, treatment failure, or M. tuberculosis resistant to certain first-line agents.218 231 276 440 If a fluoroquinolone used in multiple-drug regimens for treatment of active tuberculosis, ATS, CDC, IDSA, and others recommend levofloxacin or moxifloxacin.218 231 276 440

Consider that fluoroquinolone-resistant M. tuberculosis reported and there are increasing reports of extensively drug-resistant tuberculosis (XDR tuberculosis).70 71 72 74 75 XDR tuberculosis is caused by M. tuberculosis resistant to rifampin and isoniazid (multiple-drug resistant strains) that also are resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial (capreomycin, kanamycin, amikacin).71 72

Consult most recent ATS, CDC, and IDSA recommendations for treatment of tuberculosis for more specific information.218 440

Other Mycobacterial Infections

Has been used in multiple-drug regimens for treatment of disseminated infections caused by M. avium complex (MAC).440

ATS and IDSA state that role of fluoroquinolones in treatment of MAC infections not established.671 If a fluoroquinolone is included in multiple-drug treatment regimen (e.g., for macrolide-resistant MAC infections), moxifloxacin or levofloxacin may be preferred,440 671 although many strains are resistant in vitro.671

Consult most recent ATS, CDC, and IDSA recommendations for treatment of other mycobacterial infections for more specific information.440 671

Nongonococcal Urethritis

Alternative for treatment of nongonococcal urethritis (NGU).344 CDC recommends azithromycin or doxycycline;344 alternatives are erythromycin, levofloxacin, or ofloxacin.344

Pelvic Inflammatory Disease

Alternative for treatment of acute PID.344 Do not use in any infections that may involve N. gonorrhoeae.114 116 344 (See Resistance in Neisseria gonorrhoeae under Cautions.)

When combined IM and oral regimen used for treatment of mild to moderately severe acute PID, CDC recommends a single IM dose of ceftriaxone, cefoxitin (with oral probenecid), or cefotaxime given in conjunction with oral doxycycline (with or without oral metronidazole).344 If a parenteral cephalosporin not feasible (e.g., because of cephalosporin allergy), CDC states regimen of oral levofloxacin, ofloxacin, or moxifloxacin given in conjunction with oral metronidazole can be considered if community prevalence and individual risk of gonorrhea is low and diagnostic testing for gonorrhea performed.344 If QRNG are identified or if in vitro susceptibility cannot be determined (e.g., only nucleic acid amplification test [NAAT] for gonorrhea available), consultation with infectious disease specialist recommended.344

Plague

Treatment of plague, including pneumonic and septicemic plague, caused by Yersinia pestis.1 683 688 Streptomycin (or gentamicin) historically has been considered regimen of choice for treatment of plague;292 538 683 688 alternatives are doxycycline (or tetracycline), chloramphenicol (a drug of choice for plague meningitis), fluoroquinolones (ciprofloxacin [a drug of choice for plague meningitis], levofloxacin, moxifloxacin), or co-trimoxazole (may be less effective than other alternatives).292 538 683 688 Regimens recommended for treatment of naturally occurring or endemic bubonic, septicemic, or pneumonic plague also recommended for plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism.683 688

Postexposure prophylaxis following high-risk exposure to Y. pestis (e.g., household, hospital, or other close contact with an individual who has pneumonic plague; laboratory exposure to viable Y. pestis; confirmed exposure in the context of biologic warfare or bioterrorism).1 683 688 Drugs of choice for such prophylaxis are doxycycline (or tetracycline) or a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin); co-trimoxazole and chloramphenicol are alternatives.683 688

Levofloxacin Dosage and Administration

Administration

Administer orally or by slow IV infusion.1 2 Do not give IM, sub-Q, intrathecally, or intraperitoneally.1 2

IV route indicated in patients who do not tolerate or are unable to take the drug orally and in other patients when the IV route offers a clinical advantage.1 2 If IV route used initially, switch to oral route when clinically indicated.1

Patients receiving oral or IV levofloxacin should be well hydrated and instructed to drink fluids liberally to prevent highly concentrated urine and formation of crystals in urine.1 2

Oral Administration

Administer tablets without regard to meals.1 3 5 Administer oral solution 1 hour before or 2 hours after meals.1 (See Pharmacokinetics.)

Administer orally at least 2 hours before or 2 hours after antacids containing magnesium or aluminum, metal cations (e.g., iron), sucralfate, multivitamins or dietary supplements containing iron or zinc, or buffered didanosine (pediatric oral solution admixed with antacid).1 5 (See Interactions.)

IV Infusion

Premixed injection for IV infusion containing 5 mg/mL in 5% dextrose (single-use flexible container): Use without further dilution.1

Concentrate for injection containing 25 mg/mL (single-use vials): Must be diluted prior to IV infusion.2

Do not admix with other drugs or infuse simultaneously through same tubing with other drugs.1 2 Do not infuse through same tubing with any solution containing multivalent cations (e.g., magnesium).1 2 If same administration set is used for sequential infusion of several different drugs, flush tubing before and after administration using an IV solution compatible with levofloxacin and the other drug(s).1 2

Premixed injection for IV infusion and concentrate for injection for IV infusion contain no preservatives;1 2 discard any unused portions.1 2

For solution and drug compatibility information, see Compatibility under Stability.

Dilution

Concentrate for injection containing 25 mg/mL (single-use vials): Dilute with a compatible IV solution prior to IV infusion to provide a solution containing 5 mg/mL.2 6

Rate of Administration

Administer doses of 250 or 500 mg by IV infusion over 60 minutes;1 2 administer doses of 750 mg by IV infusion over 90 minutes.1 2

Rapid IV infusion or injection is associated with hypotension and must be avoided.1 2

Dosage

Dosage of oral and IV levofloxacin is identical.1

Dosage adjustments not needed when switching from IV to oral administration.1

Pediatric Patients

Anthrax
Postexposure Prophylaxis Following Inhalational Exposure
Oral or IV

Children ≥6 months of age weighing <50 kg: 8 mg/kg (up to 250 mg) every 12 hours for 60 days.1

Children ≥6 months of age weighing >50 kg: 500 mg once daily for 60 days.1

Initiate prophylaxis as soon as possible following suspected or confirmed exposure to aerosolized B. anthracis.1 663 668 683

Optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores unclear.663 683 767 CDC, ACIP, US Working Group on Civilian Biodefense, and USAMRIID recommend that anti-infective postexposure prophylaxis in unvaccinated individuals be continued for ≥60 days following a confirmed exposure.663 668 682 683

If used in conjunction with anthrax vaccine, ACIP and USAMRIID recommend continuing anti-infective prophylaxis until 14 days after the third vaccine dose (even if this results in >60 days of anti-infective prophylaxis).663 683

Because safety of levofloxacin given for >14 days in children and adolescents not studied, manufacturer states use for prolonged periods only when potential benefits outweigh risks.1 (See Pediatric Use under Cautions.)

Plague
Treatment or Prophylaxis of Plague
Oral or IV

Children ≥6 months of age weighing <50 kg: 8 mg/kg (up to 250 mg) every 12 hours for 10–14 days.1

Children ≥6 months of age weighing >50 kg: 500 mg once daily for 10–14 days.1 Higher dosage (i.e., 750 mg once daily) may be used if clinically indicated.1

Initiate as soon as possible after suspected or known exposure to Y. pestis.1

Adults

Respiratory Tract Infections
Acute Bacterial Sinusitis
Oral or IV

500 mg once every 24 hours for 10–14 days.1 (See Respiratory Tract Infections under Uses.)

Alternatively, 750 mg once every 24 hours for 5 days.1

Acute Bacterial Exacerbations of Chronic Bronchitis
Oral or IV

500 mg once every 24 hours for 7 days.1 (See Respiratory Tract Infections under Uses.)

Community-acquired Pneumonia (CAP)
Oral or IV

500 mg once every 24 hours for 7–14 days.1

Alternatively, 750 mg once every 24 hours for 5 days (except MDRSP).1

If used for empiric treatment of CAP or treatment of CAP caused by Ps. aeruginosa, IDSA and ATS recommend 750 mg once daily.31

IDSA and ATS state that CAP should be treated for a minimum of 5 days and patients should be afebrile for 48–72 hours before discontinuing anti-infective therapy.31

Nosocomial Pneumonia
Oral or IV

750 mg once every 24 hours for 7–14 days.1

Skin and Skin Structure Infections
Uncomplicated Infections
Oral or IV

500 mg once every 24 hours for 7–10 days.1

Complicated Infections
Oral or IV

750 mg once every 24 hours for 7–14 days.1

Urinary Tract Infections (UTIs) and Prostatitis
Uncomplicated UTIs
Oral or IV

250 mg once every 24 hours for 3 days.1 (See Urinary Tract Infections [UTIs] and Prostatitis under Uses.)

Complicated UTIs
Oral or IV

250 mg once every 24 hours for 10 days.1

Alternatively, 750 mg once every 24 hours for 5 days can be used for treatment of complicated UTIs caused by E. coli, K. pneumoniae, or P. mirabilis.1

Acute Pyelonephritis
Oral or IV

250 mg once every 24 hours for 10 days.1

Alternatively, 750 mg once every 24 hours for 5 days can be used for treatment of acute pyelonephritis caused by E. coli, including cases with concurrent bacteremia.1

Chronic Prostatitis
Oral or IV

500 mg once every 24 hours for 28 days.1

GI Infections
Salmonella Gastroenteritis
Oral or IV

HIV-infected: 750 mg once daily.440

Recommended duration is 7–14 days if CD4+ T-cells ≥200 cells/mm3 (≥14 days if bacteremic or infection is complicated) or 2–6 weeks if CD4+ T-cells <200 cells/mm3.440

Role of long-term treatment (secondary prophylaxis) in those with recurrent bacteremia not well established;440 weigh benefits against risks of long-term anti-infective exposure.440 Consider secondary prophylaxis in those with CD4+ T-cells <200 cells/mm3 and severe diarrhea.440

Shigella Infections
Oral or IV

HIV-infected: 750 mg once daily.440

Recommended duration of treatment is 7–10 days for gastroenteritis or ≥14 days for bacteremic infections.440 Up to 6 weeks may be required for recurrent infections, especially if CD4+ T-cells <200 cells/mm3.440

Treatment of Travelers’ Diarrhea
Oral

500 mg once daily for 1–3 days.305 679

Prevention of Travelers’ Diarrhea
Oral

500 mg once daily.305 677

Anti-infective prophylaxis generally discouraged (see GI Infections under Uses);305 525 677 if such prophylaxis used, give during period of risk (not exceeding 2–3 weeks) beginning day of travel and continuing for 1 or 2 days after leaving area of risk.305

Anthrax
Postexposure Prophylaxis of Anthrax
Oral or IV

500 mg once daily.1 668 682

Initiate prophylaxis as soon as possible following suspected or confirmed exposure to aerosolized B. anthracis.1 663 668 683

Optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores unclear.663 683 767 Because of the possible persistence of spores in lung tissue following an aerosol exposure, CDC, ACIP, US Working Group on Civilian Biodefense, and USAMRIID recommend that anti-infective postexposure prophylaxis in unvaccinated individuals be continued for ≥60 days following a confirmed exposure (including in laboratory workers with confirmed exposures to B. anthracis cultures).599 663 668 682 683

If used in conjunction with anthrax vaccine, ACIP and USAMRIID recommend continuing anti-infective prophylaxis until 14 days after the third vaccine dose (even if this results in >60 days of anti-infective prophylaxis).663 683

Fully or partially vaccinated laboratory workers or other individuals working in occupations that result in repeated exposure to aerosolized B. anthracis spores: ACIP recommends anti-infective prophylaxis for ≥30 days in conjunction with any remaining indicated vaccine doses if there is any type of disruption of personal protective equipment.663

Unvaccinated workers following an occupational exposure to B. anthracis spores: ACIP recommends anti-infective prophylaxis for 60 days in conjunction with postexposure vaccination;663 continue anti-infective prophylaxis until 14 days after third vaccine dose (even if this results in >60 days of anti-infective prophylaxis).663

Because safety of levofloxacin given for >28 days in adults not studied, manufacturer states use for prolonged periods only when potential benefits outweigh risks.1

Treatment of Inhalational Anthrax
Oral or IV

500 mg once daily668 for ≥60 days.668 683 686

Initial parenteral regimen preferred;668 683 686 use oral regimen after clinical improvement occurs or when a parenteral regimen not available (e.g., mass casualty setting).668 683 686 Continue for total duration of ≥60 days if inhalational anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.668 683 686

Because safety of levofloxacin given for >28 days in adults not studied, manufacturer states use for prolonged periods only when potential benefits outweigh risks.1

Chlamydial Infections
Urogenital Infections
Oral

500 mg once daily for 7 days recommended by CDC for infections caused by C. trachomatis.344

Gonorrhea and Associated Infections
Epididymitis
Oral

500 mg once daily for 10 days recommended by CDC.344

Use only when epididymitis most likely caused by sexually transmitted enteric bacteria (e.g., E. coli) and N. gonorrhoeae ruled out.344 (See Gonorrhea and Associated Infections under Uses.)

Mycobacterial Infections
Active Tuberculosis
Oral or IV

0.5–1 g once daily.218 Must be used in conjunction with other antituberculosis agents.218

ATS, CDC, and IDSA state data insufficient to date to support intermittent levofloxacin regimens for treatment of tuberculosis.218

Disseminated MAC Infections
Oral

HIV-infected: 500 mg once daily.440

Nongonococcal Urethritis
Oral

500 mg once daily for 7 days recommended by CDC.344

Pelvic Inflammatory Disease
Oral

500 mg once daily for 14 days given in conjunction with oral metronidazole (500 mg twice daily for 14 days).344

Use only when cephalosporins not feasible, community prevalence and individual risk of gonorrhea low, and in vitro susceptibility confirmed.344 (See Pelvic Inflammatory Disease under Uses.)

IV

500 mg once daily;344 used with or without IV metronidazole (500 mg every 8 hours).344

Use only when cephalosporins not feasible, community prevalence and individual risk of gonorrhea are low, and in vitro susceptibility confirmed.344 (See Pelvic Inflammatory Disease under Uses.)

Plague
Treatment or Prophylaxis of Plague
Oral or IV

500 mg once daily for 10–14 days.1 Higher dosage (i.e., 750 mg once daily) may be used if clinically indicated.1

Initiate as soon as possible after suspected or known exposure to Y. pestis.1

Special Populations

Hepatic Impairment

Dosage adjustments not required.1

Renal Impairment

Although dosage adjustments not needed when 250-mg doses used for treatment of uncomplicated UTIs in adults with renal impairment, dosage adjustments are required for other indications in adults with Clcr <50 mL/minute.1 (See Table 1.)

Dosage recommendations not provided by manufacturer for pediatric patients with renal impairment.1

Table 1. Dosage for Adults with Renal Impairment1

Usual Daily Dosage for Normal Renal Function (Clcr ≥ 50 mL/min)

Clcr (mL/min)

Dosage for Renal Impairment

250 mg

20–49

Dosage adjustment not required

250 mg

10–19

Uncomplicated UTIs: Dosage adjustment not required. Other infections: 250 mg every 48 hours

250 mg

Hemodialysis or CAPD patients

Information not available

500 mg

20–49

Initial 500-mg dose, then 250 mg once every 24 hours

500 mg

10–19

Initial 500-mg dose, then 250 mg once every 48 hours

500 mg

Hemodialysis or CAPD patients

Initial 500-mg dose, then 250 mg once every 48 hours; supplemental doses not required after dialysis

750 mg

20–49

750 mg every 48 hours

750 mg

10–19

Initial 750-mg dose, then 500 mg once every 48 hours

750 mg

Hemodialysis or CAPD patients

Initial 750-mg dose, then 500 mg once every 48 hours; supplemental doses not required after dialysis

Geriatric Patients

No dosage adjustments except those related to renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Cautions for Levofloxacin

Contraindications

  • Known hypersensitivity to levofloxacin or other quinolones.1

Warnings/Precautions

Warnings

Disabling and Potentially Irreversible Serious Adverse Reactions

Systemic fluoroquinolones, including levofloxacin, associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient.1 140 145 May occur within hours to weeks after a systemic fluoroquinolone is initiated;1 have occurred in all age groups and in patients without preexisting risk factors for such adverse reactions.1

Immediately discontinue levofloxacin at first signs or symptoms of any serious adverse reactions.1 140 145

Avoid systemic fluoroquinolones, including levofloxacin, in patients who have experienced any of the serious adverse reactions associated with fluoroquinolones.1 140 145

Tendinitis and Tendon Rupture

Systemic fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups.1 128 129

Risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in older adults (usually those >60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.1 128 129 (See Geriatric Use under Cautions.)

Other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis.1 Tendinitis and tendon rupture have been reported in patients receiving fluoroquinolones who did not have any risk factors for such adverse reactions.1

Fluoroquinolone-associated tendinitis and tendon rupture most frequently involve the Achilles tendon;1 also reported in rotator cuff (shoulder), hand, biceps, thumb, and other tendon sites.1

Tendinitis and tendon rupture can occur within hours or days after levofloxacin is initiated or as long as several months after completion of therapy and can occur bilaterally.1

Immediately discontinue levofloxacin if pain, swelling, inflammation, or rupture of a tendon occurs.1 128 129 (See Advice to Patients.)

Avoid systemic fluoroquinolones, including levofloxacin, in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture.1

Peripheral Neuropathy

Systemic fluoroquinolones, including levofloxacin, are associated with an increased risk of peripheral neuropathy.1

Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness reported with systemic fluoroquinolones, including levofloxacin.1 130 Symptoms may occur soon after initiation of the drug and, in some patients, may be irreversible.1 130

Immediately discontinue levofloxacin if symptoms of peripheral neuropathy (e.g., pain, burning, tingling, numbness, and/or weakness) occur or if there are other alterations in sensations (e.g., light touch, pain, temperature, position sense, vibratory sensation).1 130 (See Advice to Patients.)

Avoid systemic fluoroquinolones, including levofloxacin, in patients who have experienced peripheral neuropathy.1

CNS Effects

Systemic fluoroquinolones, including levofloxacin, are associated with an increased risk of CNS effects.1

Convulsions, increased intracranial pressure (including pseudotumor cerebri), and toxic psychosis reported with fluoroquinolones, including levofloxacin.1 Fluoroquinolones may also cause CNS stimulation, which may lead to tremors, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, nightmares, insomnia, and, rarely, suicidal thoughts or acts.1 These CNS effects may occur after first dose.1

If CNS effects occur, immediately discontinue levofloxacin and institute appropriate measures.1 (See Advice to Patients.)

Use with caution in patients with known or suspected CNS disorders that predispose to seizures or lower the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or with other risk factors that predispose to seizures or lower the seizure threshold (e.g., certain drugs, renal impairment).1

Avoid systemic fluoroquinolones, including levofloxacin, in patients who have experienced CNS effects associated with fluoroquinolones.1

Exacerbation of Myasthenia Gravis

Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in myasthenia gravis patients;1 death or need for ventilatory support reported.1

Avoid use in patients with known history of myasthenia gravis.1 (See Advice to Patients.)

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions reported in patients receiving fluoroquinolones, including levofloxacin.1 These reactions often occur with first dose.1

Some hypersensitivity reactions have been accompanied by cardiovascular collapse, hypotension or shock, seizures, loss of consciousness, tingling, angioedema (e.g., edema or swelling of the tongue, larynx, throat, or face), airway obstruction (e.g., bronchospasm, shortness of breath, acute respiratory distress), dyspnea, urticaria, pruritus, and other severe skin reactions.1

Other serious and sometimes fatal adverse reactions reported with fluoroquinolones, including levofloxacin, that may or may not be related to hypersensitivity reactions include one or more of the following: fever, rash or other severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome); vasculitis, arthralgia, myalgia, serum sickness; allergic pneumonitis; interstitial nephritis, acute renal insufficiency or failure; hepatitis, jaundice, acute hepatic necrosis or failure; anemia (including hemolytic and aplastic), thrombocytopenia (including thrombotic thrombocytopenic purpura), leukopenia, agranulocytosis, pancytopenia, and/or other hematologic effects.1

Immediately discontinue levofloxacin at first appearance of rash, jaundice, or any other sign of hypersensitivity.1 Institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).1

Photosensitivity Reactions

Moderate to severe photosensitivity/phototoxicity reactions reported with fluoroquinolones, including levofloxacin1

Phototoxicity may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) on areas exposed to sun or artificial ultraviolet (UV) light (usually the face, neck, extensor surfaces of forearms, dorsa of hands).1

Avoid unnecessary or excessive exposure to sunlight or artificial UV light (tanning beds, UVA/UVB treatment) while receiving levofloxacin.1 If patient needs to be outdoors, they should wear loose-fitting clothing that protects skin from sun exposure and use other sun protection measures (sunscreen).1

Discontinue levofloxacin if photosensitivity or phototoxicity (sunburn-like reaction, skin eruption) occurs.1

Other Warnings/Precautions

Hepatotoxicity

Severe hepatotoxicity, including acute hepatitis, has occurred in patients receiving levofloxacin and sometimes resulted in death.1 Most cases occurred within 6–14 days of initiation of levofloxacin therapy and were not associated with hypersensitivity reactions.1 The majority of fatalities were in geriatric patients ≥65 years of age.1 (See Geriatric Use under Cautions.)

Immediately discontinue levofloxacin in any patient who develops symptoms of hepatitis (e.g., loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of the skin or eyes, light colored bowel movements, or dark colored urine).1

Prolongation of QT Interval

Prolonged QT interval leading to ventricular arrhythmias, including torsades de pointes, reported with some fluoroquinolones, including levofloxacin.1 37

Avoid use in patients with a history of prolonged QT interval or uncorrected electrolyte disorders (e.g., hypokalemia).1 Also avoid use in those receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.1

Risk of prolonged QT interval may be increased in geriatric patients.1 (See Geriatric Use under Cautions.)

Musculoskeletal Effects

Increased incidence of musculoskeletal disorders (arthralgia, arthritis, tendinopathy, gait abnormality) reported in pediatric patients receiving levofloxacin.1 Use in pediatric patients only for inhalational anthrax (postexposure) or treatment or prophylaxis of plague and only in those 6 months of age or older.1 (See Pediatric Use under Cautions.)

Fluoroquinolones, including levofloxacin, cause arthropathy and osteochondrosis in immature animals of various species.1 118 119 120 121 122 125 126 Persistent lesions in cartilage reported in levofloxacin studies in immature dogs.1

Hypoglycemia or Hyperglycemia

Hypoglycemia or hyperglycemia reported with fluoroquinolones, including levofloxacin.1 82 Blood glucose disturbances usually have occurred in patients with diabetes receiving insulin or oral hypoglycemic agents.1 82

Carefully monitor blood glucose concentrations in diabetic patients.1 82 Discontinue levofloxacin and immediately initiate appropriate therapy if hypoglycemic reaction occurs.1

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.1 Institute appropriate therapy if superinfection occurs.1

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.1 96 98 99 C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including levofloxacin, and may range in severity from mild diarrhea to fatal colitis.1 96 98 99 102 106 107 C. difficile produces toxins A and B which contribute to development of CDAD;1 96 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.1

Outbreaks of severe CDAD caused by fluoroquinolone-resistant C. difficile have been reported with increasing frequency over the last several years.101 102 103 104 106

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.1 96 98 99 Obtain careful medical history since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.1 96 98 99

If CDAD is suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible.1 96 98 99 Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), appropriate anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.1 96 98 99

Selection and Use of Anti-infectives

Use for treatment of acute bacterial sinusitis, acute bacterial exacerbations of chronic bronchitis, or uncomplicated UTIs only when no other treatment options available.1 140 145 Because levofloxacin, like other systemic fluoroquinolones, has been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient, risks of serious adverse reactions outweigh benefits for patients with these infections.140 145

To reduce development of drug-resistant bacteria and maintain effectiveness of levofloxacin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1

Resistance in Neisseria gonorrhoeae

N. gonorrhoeae with decreased susceptibility to fluoroquinolones (quinolone-resistant N. gonorrhoeae; QRNG) has been reported with increasing frequency over the past several years.53 109 114 132 344 857

US data indicate that QRNG has continued to increase among men who have sex with men and among heterosexual males and is now present in all regions of the country.114 857

CDC states that fluoroquinolones, including levofloxacin, no longer recommended for treatment of gonorrhea and should not be used routinely for any associated infections that may involve N. gonorrhoeae (e.g., PID, epididymitis).114 116 344

Specific Populations

Pregnancy

Category C.1

Use during pregnancy only if potential benefits justify potential risks to fetus.1

No adequate and well-controlled studies in pregnant women;1 animal studies (rats and rabbits) did not reveal evidence of fetal harm.1

Lactation

Distributed into milk following oral or IV administration.80

Discontinue nursing or the drug.1

Pediatric Use

May be used for inhalational anthrax (postexposure) or for treatment or prophylaxis of plague in adolescents and children ≥6 months of age.1 Safety and efficacy not established for any other indication in this age group.1

Safety and efficacy not established for any indication in infants <6 months of age.1

Increased incidence of musculoskeletal disorders reported in pediatric patients receiving levofloxacin.1 Causes arthropathy and osteochondrosis in juvenile animals.1 (See Musculoskeletal Effects under Cautions.)

AAP states use of systemic fluoroquinolones may be justified in children <18 years of age in special circumstances when there are no safe and effective alternatives and after careful assessment of the risks and benefits for the individual patient.110 292

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1

Risk of severe tendon disorders, including tendon rupture, is increased in older adults (usually those >60 years of age).1 128 129 This risk is further increased in those receiving concomitant corticosteroids.1 128 129 (See Tendinitis and Tendon Rupture under Cautions.) Use caution in geriatric adults, especially those receiving concomitant corticosteroids.1

Serious and sometimes fatal hepatotoxicity reported with levofloxacin;1 majority of fatalities have occurred in geriatric patients ≥65 years of age.1 (See Hepatotoxicity under Cautions.)

Risk of prolonged QT interval leading to ventricular arrhythmias may be increased in geriatric patients, especially those receiving concurrent therapy with other drugs that can prolong QT interval (e.g., class IA or III antiarrhythmic agents) or with risk factors for torsades de pointes (e.g., known QT prolongation, uncorrected hypokalemia).1 (See Prolongation of QT Interval under Cautions.)

Consider age-related decreases in renal function when selecting dosage.1 (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Pharmacokinetics not studied in patients with hepatic impairment, but pharmacokinetic alterations unlikely.1

Renal Impairment

Substantially decreased clearance and increased half-life.1 Use with caution and adjust dosage.1 (See Renal Impairment under Dosage and Administration.)

Perform appropriate renal function tests prior to and during therapy.1

Common Adverse Effects

GI effects (nausea, diarrhea, constipation), headache, insomnia, dizziness.1

Interactions for Levofloxacin

Not metabolized by and does not inhibit CYP isoenzymes.1 Pharmacokinetic interactions with drugs metabolized by CYP isoenzymes unlikely.1

Drugs That Prolong QT Interval

Potential pharmacologic interaction (additive effect on QT interval prolongation).1 Avoid use in patients receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.1 (See Prolongation of QT Interval under Cautions.)

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Antacids (aluminum- or magnesium-containing)

Decreased absorption of oral levofloxacin1 5 7

Administer oral levofloxacin at least 2 hours before or 2 hours after such antacids1

Antiarrhythmic agents

Potential additive effects on QT interval prolongation1

Procainamide: Increased half-life and decreased clearance of procainamide84

Avoid levofloxacin in patients receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents1

Anticoagulants, oral (warfarin)

Enhanced warfarin effects and clinical bleeding1

Monitor PT, INR, or other suitable coagulation tests and monitor for bleeding1

Antidiabetic agents (e.g., insulin, glyburide)

Alterations in blood glucose (hyperglycemia and hypoglycemia) reported1

Closely monitor blood glucose;1 if hypoglycemic reaction occurs, immediately discontinue levofloxacin and initiate appropriate therapy1

Cimetidine

Slightly increased levofloxacin AUC and half-life1

Not considered clinically important;1 levofloxacin dosage adjustments not warranted1

Corticosteroids

Increased risk of tendinitis or tendon rupture, especially in patients >60 years of age1

Use concomitantly with caution1

Cyclosporine or tacrolimus

Possible increased AUC of cyclosporine or tacrolimus92

Manufacturer of levofloxacin states dosage adjustments not needed for either drug when levofloxacin used with cyclosporine;1 some clinicians suggest monitoring plasma concentrations of cyclosporine or tacrolimus92

Didanosine

Possible decreased absorption of oral levofloxacin1

Administer oral levofloxacin at least 2 hours before or 2 hours after buffered didanosine (pediatric oral solution admixed with antacid)1

Digoxin

No evidence of clinically important effect on pharmacokinetics of digoxin or levofloxacin1 83

Dosage adjustments not needed for either drug1

Iron preparations

Decreased absorption of oral levofloxacin1

Administer oral levofloxacin at least 2 hours before or after ferrous sulfate and dietary supplements containing iron1

Multivitamins and mineral supplements

Decreased absorption of oral levofloxacin1 94

Administer oral levofloxacin at least 2 hours before or 2 hours after supplements containing zinc, calcium, magnesium, or iron1 94

NSAIAs

Possible increased risk of CNS stimulation, seizures;1 91 animal studies suggest risk may be less than that associated with some other fluoroquinolones91

Probenecid

Slightly increased levofloxacin AUC and half-life1

Not considered clinically important;1 levofloxacin dosage adjustments not required1

Psychotherapeutic agents

Fluoxetine or imipramine: Potential additive effect on QT interval prolongation85

Tests for opiates

Possibility of false-positive results for opiates in patients receiving some quinolones, including levofloxacin, when commercially available urine screening immunoassay kits are used1

Positive opiate urine screening test results may need to be confirmed using more specific methods1

Sucralfate

Decreased absorption of oral levofloxacin1

Administer oral levofloxacin at least 2 hours before or 2 hours after sucralfate1 86

Theophylline

No evidence of clinically important pharmacokinetic interaction with levofloxacin;1 increased theophylline concentrations and increased risk of theophylline-related adverse effects reported with some other quinolones1

Closely monitor theophylline concentrations and make appropriate dosage adjustments;1 consider that adverse theophylline effects (e.g., seizures) may occur with or without elevated theophylline concentrations1

Levofloxacin Pharmacokinetics

Absorption

Bioavailability

Approximately 99%.1

Rapidly absorbed from GI tract.1 Peak plasma concentrations usually attained 1–2 hours after an oral dose;1 steady-state plasma concentrations attained within 48 hours with once-daily regimens.1

Tablets and oral solution are bioequivalent.1

Plasma concentrations and AUC after oral administration are similar to those after IV administration.1

Food

Tablets: Food slightly prolongs time to peak plasma concentration and slightly decreases peak concentrations (approximately 14%);1 86 not considered clinically important.1

Oral solution: Food slightly prolongs time to peak plasma concentration and decreases peak concentrations by approximately 25%.1

Distribution

Extent

Widely distributed into body tissues and fluids, including skin, blister fluid, and lungs.1

Distributed into CSF.5 64 65 Following IV administration of 400 or 500 mg twice daily, CSF concentrations have been reported to be up to 47% of concurrent plasma concentrations.64 65

Distributed into milk following oral or IV administration.80

Plasma Protein Binding

24–38% bound to serum proteins, principally albumin.1

Elimination

Metabolism

Undergoes limited metabolism to inactive metabolites.1 Not metabolized by CYP isoenzymes.1

Elimination Route

Eliminated principally as unchanged drug in urine by glomerular filtration and active tubular secretion.1 Approximately 87% of an oral dose eliminated in urine and <4% eliminated in feces.1

Half-life

Terminal elimination half-life approximately 6–8 hours after oral or IV administration.1

Special Populations

Increased clearance and decreased plasma levofloxacin concentrations in pediatric patients ≥6 months of age relative to those in adults.1

Pharmacokinetics in geriatric individuals with normal renal function similar to that in younger adults.1

Pharmacokinetics not studied in patients with hepatic impairment, but pharmacokinetic alterations unlikely.1

Decreased clearance and prolonged half-life in patients with impaired renal function.1 Half-life may be 27 hours in those with Clcr 20–49 mL/minute and 35 hours in those with Clcr <20 mL/minute.1

Stability

Storage

Oral

Solution

25°C (may be exposed to 15–30°C).1

Tablets

15–30°C in well-closed containers.1

Parenteral

For Injection, for IV Infusion

15–30°C; protect from light.2 After dilution to a concentration of 5 mg/mL with compatible IV solution, stable for up to 72 hours at ≤25°C or up to 14 days at 5°C.2

Diluted solutions containing 5 mg/mL may be frozen in glass or plastic IV containers for ≤6 months at -20°C;2 after thawing at room temperature or in a refrigerator, do not refreeze.2

Contains no preservatives; discard any unused portions.2

Injection, for IV Infusion

≤25°C (may be exposed to ≤40°C); do not freeze.1 Protect from light and excessive heat.1

Contains no preservatives;1 discard any unused portions.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility2 HID

Compatible

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% in sodium chloride 0.9%

Dextrose 5% in water

Plasma-Lyte 56 and dextrose 5%

Sodium chloride 0.9%

Sodium lactate 1/6 M

Variable

Mannitol 20%

Sodium bicarbonate 5%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Linezolid

Incompatible

Micafungin sodium

Y-Site CompatibilityHID

Compatible

Amikacin sulfate

Aminophylline

Ampicillin sodium

Anidulafungin

Bivalirudin

Caffeine citrate

Caspofungin acetate

Cefotaxime sodium

Ceftaroline fosamil

Clindamycin phosphate

Daptomycin

Dexamethasone sodium phosphate

Dexmedetomidine HCl

Dobutamine HCl

Dopamine HCl

Doripenem

Epinephrine HCl

Fenoldopam mesylate

Fentanyl citrate

Gentamicin sulfate

Hetastarch in lactated electrolyte injection

Hydromorphone HCL

Isoproterenol HCl

Lidocaine HCl

Linezolid

Lorazepam

Magnesium sulfate

Metoclopramide HCl

Morphine sulfate

Oxacillin sodium

Pancuronium bromide

Penicillin G sodium

Phenobarbital sodium

Phenylephrine HCl

Posaconazole

Potassium chloride

Sodium bicarbonate

Vancomycin HCl

Incompatible

Acyclovir sodium

Alprostadil

Azithromycin

Furosemide

Heparin sodium

Indomethacin sodium trihydrate

Nitroglycerin

Sodium nitroprusside

Telavancin HCl

Variable

Insulin, regular

Actions and Spectrum

  • Usually bactericidal.1

  • Like other fluoroquinolones, levofloxacin inhibits bacterial DNA gyrase and topoisomerase IV.1 4 39

  • Spectrum of activity includes gram-positive aerobic bacteria, some gram-negative aerobic bacteria, some anaerobic bacteria, and some other organisms (e.g., Chlamydia, Mycoplasma, Mycobacterium).1 3 13 14 15 16 17 40 41 42

  • More active in vitro against gram-positive bacteria, (including S. pneumoniae) and anaerobes than some other fluoroquinolones (e.g., ciprofloxacin, ofloxacin),3 13 14 15 16 17 but less active in vitro than ciprofloxacin against Pseudomonas aeruginosa.3 14 17

  • Gram-positive aerobes: Active in vitro and in clinical infections against S. aureus (oxacillin-susceptible [methicillin-susceptible] strains only), S. epidermidis (oxacillin-susceptible strains only), S. saprophyticus, S. pneumoniae (including penicillin-resistant strains), S. pyogenes (group A β-hemolytic streptococci, GAS), and Enterococcus faecalis (many strains only moderately susceptible).1 3 Also active in vitro against S. haemolyticus, S. agalactiae (group B streptococci, GBS), groups C, G, and F streptococci, S. milleri, and viridans streptococci.1 3 Active against Bacillus anthracis in vitro and in a primate infection model.1 93

  • Gram-negative aerobes: Active in vitro and in clinical infections against H. influenzae, H. parainfluenzae,1 K. pneumoniae, M. catarrhalis, E. cloacae, E. coli, P. mirabilis, S. marcescens, Ps. aeruginosa (some may develop resistance during therapy), and Legionella pneumophila.1 3 Also active in vitro against Acinetobacter, Bordetella pertussis, Citrobacter, E. aerogenes, E. sakazakii, K. oxytoca, Morganella morganii, Pantoea agglomerans, P. vulgaris, Providencia, and Ps. fluorescens.1 Active against Y. pestis in vitro and in a primate infection model.1

  • Anaerobes and other organisms: Active in vitro and in clinical infections against C. pneumoniae 1 and M. pneumoniae.1 3 Also active in vitro against Clostridium perfringens,1 3 Mycobacterium tuberculosis,40 41 111 and M. fortuitum.42

  • N. gonorrhoeae with decreased susceptibility to levofloxacin and other fluoroquinolones (quinolone-resistant N. gonorrhoeae; QRNG) are widely disseminated worldwide, including in the US.53 109 114 132 344

  • Some cross-resistance occurs between levofloxacin and other fluoroquinolones.1

Advice to Patients

  • Advise patients to read manufacturer’s patient information (medication guide) prior to initiating levofloxacin therapy and each time prescription refilled.1

  • Advise patients that antibacterials (including levofloxacin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1

  • Importance of completing full course of therapy, even if feeling better after a few days.1

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with levofloxacin or other antibacterials in the future.1

  • Advise patients that the oral solution should be taken 1 hour before or 2 hours after meals;1 tablets may be taken without regard to meals1

  • Levofloxacin should be taken at the same time each day and with liberal amounts of fluids to prevent highly concentrated urine and formation of crystals in urine.1

  • Importance of taking levofloxacin at least 2 hours before or 2 hours after aluminum- or magnesium-containing antacids, metal cations (e.g., iron), sucralfate, multivitamins containing iron or zinc, or buffered didanosine (pediatric oral solution prepared as an admixture with antacid).1

  • Inform patients that systemic fluoroquinolones, including levofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that may occur together in same patient.1 140 145 Advise patients to immediately discontinue levofloxacin and contact a clinician if they experience any signs or symptoms of serious adverse effects (e.g., unusual joint or tendon pain, muscle weakness, a “pins and needles” tingling or pricking sensation, numbness of the arms or legs, confusion, hallucinations) while taking the drug.1 140 145 Advise patients to talk with a clinician if they have any questions or concerns.1 140 145

  • Inform patients that systemic fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups and this risk is increased in adults >60 years of age, individuals receiving corticosteroids, and kidney, heart, or lung transplant recipients.1 Symptoms may be irreversible.1 Importance of resting and refraining from exercise at the first sign of tendinitis or tendon rupture (e.g., pain, swelling, or inflammation of a tendon or weakness or inability to use a joint) and importance of immediately discontinuing the drug and contacting a clinician.1 (See Tendinitis and Tendon Rupture under Cautions.)

  • Inform patients that peripheral neuropathies have been reported with systemic fluoroquinolones, including levofloxacin, and that symptoms may occur soon after initiation of the drug and may be irreversible.1 Importance of immediately discontinuing levofloxacin and contacting a clinician if symptoms of peripheral neuropathy (e.g., pain, burning, tingling, numbness, and/or weakness) occur.1

  • Inform patients that systemic fluoroquinolones, including levofloxacin, have been associated with CNS effects (e.g., convulsions, dizziness, lightheadedness, increased intracranial pressure).1 Importance of informing clinician of any history of convulsions before initiating therapy with the drug.1 Importance of contacting a clinician if persistent headache with or without blurred vision occurs.1

  • Advise patients that levofloxacin may cause dizziness and lightheadedness;1 caution patients not to engage in activities requiring mental alertness and motor coordination (e.g., driving a vehicle, operating machinery) until effects of the drug on the individual are known.1

  • Advise patients that systemic fluoroquinolones, including levofloxacin, may worsen myasthenia gravis symptoms;1 importance of informing clinician of any history of myasthenia gravis.1 Importance of immediately contacting a clinician if any symptoms of muscle weakness, including respiratory difficulties, occur.1

  • Inform patients that levofloxacin may be associated with hypersensitivity reactions (including anaphylactic reactions), even after first dose.1 Importance of immediately discontinuing levofloxacin and contacting a clinician at first sign of rash or any symptom of hypersensitivity (e.g., hives, other skin reaction, rapid heartbeat, difficulty swallowing or breathing, throat tightness, hoarseness, swelling of lips, tongue, or face).1

  • Inform patients that photosensitivity/phototoxicity reactions reported following exposure to sun or UV light in patients receiving fluoroquinolones.1 Importance of avoiding or minimizing exposure to sunlight or artificial UV light (e.g., tanning beds, UVA/UVB treatment) and using protective measures (e.g., wearing loose-fitting clothes, sunscreen) if outdoors during levofloxacin therapy.1 Importance of discontinuing levofloxacin and contacting a clinician if a sunburn-like reaction or skin eruption occurs.1

  • Inform patients that severe hepatotoxicity (including acute hepatitis and fatal events) reported in patients receiving levofloxacin.1 Importance of immediately discontinuing levofloxacin and informing a clinician if any signs or symptoms of liver injury (e.g., loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of the skin and eyes, light colored bowel movements, dark colored urine) occur.1

  • Importance of informing clinician of personal or family history of QT interval prolongation or proarrhythmic conditions (e.g., recent hypokalemia, bradycardia, recent myocardial ischemia) and of concurrent therapy with any drugs that may affect QT interval (e.g., class IA [quinidine, procainamide] or class III [e.g., amiodarone, sotalol] antiarrhythmic agents).1 Importance of contacting a clinician if symptoms of prolonged QT interval (e.g., prolonged heart palpitations, loss of consciousness) occur.1

  • Advise patients with diabetes mellitus receiving insulin or oral antidiabetic agents that fluoroquinolones, including levofloxacin, may cause hypoglycemic reactions.1 Importance of discontinuing levofloxacin and contacting a clinician if a hypoglycemic reaction occurs.1

  • Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.1 Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.1

  • If considering levofloxacin for a pediatric patient (see Pediatric Use under Cautions), importance of parent informing clinician if the child has a history of joint-related problems.1 Importance of parent contacting a clinician if the child develops any joint-related problems during or following levofloxacin therapy.1

  • Advise patients receiving levofloxacin for inhalational anthrax (postexposure) or for treatment or prophylaxis of plague that human efficacy studies have not been performed for ethical and feasibility reasons; use in these conditions based on animal efficacy studies.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., drugs that may affect QT interval, antidiabetic agents, warfarin), as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

levoFLOXacin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

125 mg/5 mL*

Levaquin

Janssen

levoFLOXacin Solution

Tablets, film-coated

250 mg (of anhydrous levofloxacin)*

Levaquin

Janssen

levoFLOXacin Tablets

500 mg (of anhydrous levofloxacin)*

Levaquin

Janssen

levoFLOXacin Tablets

750 mg (of anhydrous levofloxacin)*

Levaquin

Janssen

levoFLOXacin Tablets

Parenteral

For injection, concentrate, for IV infusion

equivalent to levofloxacin 25 mg/mL (500 mg)*

levoFLOXacin Concentrate, for IV Infusion

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

levoFLOXacin in Dextrose

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion

equivalent to levofloxacin 5 mg/mL (250, 500, or 750 mg) in 5% Dextrose*

Levaquin in Dextrose Injection Premix (in flexible containers)

Janssen

levoFLOXacin in Dextrose Injection

AHFS DI Essentials. © Copyright 2017, Selected Revisions September 30, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Janssen Pharmaceuticals Inc. Levaquin (levofloxacin) tablets, film coated for oral use, solution for oral use, and solution in 5% dextrose for IV use prescribing information. Titusville, NJ; 2016 Jul.

2. Claris Lifesciences Inc. Levofloxacin injection, solution. North Brunswick, NJ; 2014 Sept.

3. Davis R, Bryson HM. Levofloxacin: a review of its antibacterial activity, pharmacokinetics and therapeutic efficacy. Drugs. 1994; 47:677-700. [PubMed 7516863]

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