Levofloxacin

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

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  Fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups.^{1 128 129} This risk is further 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 Tendinopathy and Tendon Rupture under Cautions.)

  
  

REMS:

FDA approved a REMS for levofloxacin to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of levofloxacin and consists of the following: medication guide. See the FDA REMS page () or the ASHP REMS Resource Center ().

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 exacerbations of chronic bronchitis caused by susceptible Staphylococcus aureus, S. pneumoniae, H. influenzae, H. parainfluenzae, or M. catarrhalis.^{1 19 20}

Treatment of community-acquired pneumonia (CAP) caused by susceptible S. aureus, S. pneumoniae (including penicillin-resistant strains with penicillin MICs ≥2 mcg/mL), H. influenzae, H. parainfluenzae, Klebsiella pneumoniae, Legionella pneumoniae, M. catarrhalis, Chlamydophila pneumoniae (formerly Chlamydia pneumoniae), or Mycoplasma pneumoniae.^{1 21 31 95}

Select regimen for empiric treatment of CAP based on most likely pathogens and local susceptibility patterns; after pathogen is identified, modify to provide more specific therapy (pathogen-directed therapy).³¹ Do not use a fluoroquinolone alone for empiric treatment of CAP in patients requiring treatment in an intensive care unit (ICU).³¹

For empiric outpatient treatment of CAP in previously healthy adults without risk factors for drug-resistant S. pneumoniae (DRSP), IDSA and ATS recommend monotherapy with a macrolide (azithromycin, clarithromycin, erythromycin) or, alternatively, doxycycline.³¹ If risk factors for DRSP are present (e.g., chronic heart, lung, liver, or renal disease, diabetes mellitus, alcoholism, malignancy, asplenia, immunosuppression, history of anti-infective treatment during previous 3 months), IDSA and ATS recommend empiric outpatient treatment with a fluoroquinolone with enhanced activity against S. pneumoniae (gemifloxacin, levofloxacin, moxifloxacin) or, alternatively, a combination regimen that includes a β-lactam effective against S. pneumoniae (high-dose amoxicillin or fixed combination of amoxicillin and clavulanic acid or, alternatively, ceftriaxone, cefpodoxime, or cefuroxime) given in conjunction with a macrolide or doxycycline.³¹

For empiric inpatient treatment of CAP in non-ICU patients, IDSA and ATS recommend adults receive monotherapy with a fluoroquinolone with enhanced activity against S. pneumoniae (gemifloxacin, levofloxacin, moxifloxacin) or, alternatively, a regimen that includes a β-lactam (usually cefotaxime, ceftriaxone, or ampicillin) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline.³¹ For empiric inpatient treatment of CAP in ICU patients when Pseudomonas and oxacillin-resistant (methicillin-resistant) Staphylococcus aureus are not suspected, IDSA and ATS recommend a combination regimen that includes a β-lactam (cefotaxime, ceftriaxone, fixed combination of ampicillin and sulbactam) given in conjunction with either azithromycin or a fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin).³¹

For empiric treatment of CAP in adults with risk factors for Ps. aeruginosa, IDSA and ATS recommend a combination regimen that includes an antipneumococcal, antipseudomonal β-lactam (cefepime, imipenem, meropenem, fixed combination of piperacillin and tazobactam) and ciprofloxacin or levofloxacin; one of these β-lactams, an aminoglycoside, and azithromycin; or one of these β-lactams, an aminoglycoside, and an antipneumococcal fluoroquinolone.³¹ If Ps. aeruginosa has been identified by appropriate microbiologic testing, these experts recommend treatment with a combination regimen that includes an antipseudomonal β-lactam (cefepime, ceftazidime, aztreonam, imipenem, meropenem, piperacillin, ticarcillin) and ciprofloxacin, levofloxacin, or an aminoglycoside or, alternatively, a combination regimen that includes an aminoglycoside and ciprofloxacin or levofloxacin.³¹

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

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 26}

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

Urinary Tract Infections (UTIs) and Prostatitis

Treatment of mild to moderate uncomplicated UTIs caused by susceptible E. coli, K. pneumoniae, or S. saprophyticus.¹

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

Anthrax

Postexposure prophylaxis to prevent development of inhalational anthrax following suspected or confirmed exposure to aerosolized Bacillus anthracis spores.¹ Approval for this indication based on a surrogate end point derived from a primate model of inhalational anthrax that predicts clinical benefit based on plasma levofloxacin concentrations achievable in humans with recommended oral or IV dosages.^{1 93} CDC and others recommend ciprofloxacin or doxycycline as initial drug of choice for such prophylaxis.^{33 47} Other fluoroquinolones (e.g., gatifloxacin, levofloxacin, moxifloxacin, ofloxacin) considered alternatives to ciprofloxacin when needed.³³

Alternative for treatment of inhalational anthrax† when a parenteral regimen is not available (e.g., supply or logistic problems because large numbers of individuals require treatment in a mass-casualty setting).^{33 47} A multiple-drug parenteral regimen (ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective) is 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.^{33 35 47}

Chlamydial Infections

Alternative for treatment of urogenital infections caused by C. trachomatis†, including presumptive treatment of chlamydial infections in patients with gonorrhea.¹¹ CDC and others recommend azithromycin or doxycycline as drugs of choice; erythromycin, ofloxacin, or levofloxacin are alternatives.^{11 52}

Endocarditis

Alternative for treatment of native or prosthetic valve endocarditis† caused by fastidious gram-negative bacilli known as the HACEK group (Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Haemophilus aphrophilus, H. influenzae, H. parainfluenzae, H. paraphrophilus, Kingella denitrificans, K. kingae).⁵⁵ AHA and IDSA recommend ceftriaxone or ampicillin-sulbactam as drugs of choice,⁵⁵ but a fluoroquinolone (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin) may be considered when β-lactam anti-infectives cannot be used.⁵⁵ Consultation with an infectious disease specialist is recommended.⁵⁵

Gonorrhea and Associated Infections

Has been used for treatment of uncomplicated urethral, endocervical, or rectal gonorrhea† caused by susceptible Neisseria gonorrhoeae.¹¹

Has been used for treatment of disseminated gonococcal infections† caused by susceptible N. gonorrhoeae.¹¹

Treatment of epididymitis† most likely caused by sexually transmitted enteric bacteria (e.g., E. coli) or when culture or nucleic acid amplification tests are negative for N. gonorrhoeae.^{11 52 115}

Although fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin) were previously considered drugs of choice for treatment of uncomplicated gonorrhea,^{11 114} CDC currently states that fluoroquinolones should not be used for treatment of gonorrhea or any associated infections involving N. gonorrhoeae (e.g., pelvic inflammatory disease [PID], epididymitis).^{52 114 115 116}

Quinolone-resistant N. gonorrhoeae (QRNG) has been reported with increasing frequency worldwide and is widespread in the US.^{11 52 53 109 110 114 115 116} (See Resistance in Neisseria gonorrhoeae under Cautions.)

For treatment of uncomplicated cervical, urethral, or rectal gonorrhea, CDC and others recommend IM ceftriaxone or oral cefixime; IM ceftriaxone is drug of choice for pharyngeal infections.^{11 52 114 115}

For initial treatment of disseminated gonococcal infections, CDC recommends IM or IV ceftriaxone as drug of choice and IV cefotaxime, IV ceftizoxime (no longer commercially available in the US), or IM spectinomycin (not currently commercially available in the US) as alternatives.^{11 115} Initial parenteral regimen should be continued for 24–48 hours after improvement begins; therapy can be switched to oral cefixime or oral cefpodoxime and continued to complete ≥1 week of treatment.^{11 115} CDC states that fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) may be an alternative treatment option for disseminated infections only if in vitro susceptibility can be documented by culture.¹¹⁵

For empiric treatment of epididymitis, especially when gonococcal or chlamydial infection is likely (e.g., in those <35 years of age), CDC recommends an initial regimen of IM ceftriaxone and oral doxycycline.^{11 115} Levofloxacin or ofloxacin should be used only if epididymitis is not caused by gonorrhea (i.e., results of culture or nucleic acid amplification testing are negative for N. gonorrhoeae) or is most likely caused by sexually transmitted enteric bacteria.^{11 52 115}

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.⁴⁷

Mycobacterial Infections

Alternative for use in multiple-drug regimens for treatment of active tuberculosis†.⁴⁰

CDC, ATS, and IDSA state that use of fluoroquinolones can be considered in patients with relapse, treatment failure, or Mycobacterium tuberculosis resistant to isoniazid and/or rifampin or when first-line drugs cannot be tolerated.⁴⁰ There have been recent reports of extensively drug-resistant tuberculosis (XDR tuberculosis).^{71 72} 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}

Although there is clinical experience with several fluoroquinolones in the treatment of tuberculosis (e.g., ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin),^{40 73 76 77 78 79} levofloxacin and moxifloxacin are the fluoroquinolones recommended by CDC, ATS, and IDSA and levofloxacin may be preferred on the basis of cumulative experience.⁴⁰

The most recent CDC, ATS, and IDSA recommendations for treatment of tuberculosis should be consulted for more specific information.⁴⁰

Nongonococcal Urethritis

Alternative for treatment of nongonococcal urethritis† (NGU).¹¹ CDC recommends azithromycin or doxycycline as drugs of choice;¹¹ erythromycin, ofloxacin, and levofloxacin are alternatives.¹¹

Pelvic Inflammatory Disease

Treatment of acute pelvic inflammatory disease† (PID).^{11 52 115} Do not use if QRNG may be involved or if in vitro susceptibility cannot be tested.^{11 52 115} (See Resistance in Neisseria gonorrhoeae under Cautions.)

When a parenteral regimen is indicated for PID, CDC recommends a regimen of IV cefoxitin and IV or oral doxycycline or IV clindamycin and IV or IM gentamicin or, alternatively, IV ampicillin-sulbactam and IV or oral doxycycline.^{11 115}

When an oral regimen is indicated for PID, CDC recommends a regimen that consists of a single dose of ceftriaxone, cefoxitin (with oral probenecid), or cefotaxime given with oral doxycycline (with or without oral metronidazole).^{11 115} If a parenteral cephalosporin is not feasible, a regimen of oral levofloxacin or oral ofloxacin given with or without oral metronidazole may be considered only if the community prevalence and individual risk of gonorrhea is low.¹¹⁵

Prior to use of a fluoroquinolone for treatment of PID, tests for gonorrhea must be performed.¹¹⁵ If the nucleic acid amplification test is positive for N. gonorrhoeae, a parenteral cephalosporin is recommended.¹¹⁵ If the culture for gonorrhea is positive, treatment should be based on results of in vitro susceptibility testing.¹¹⁵ If the isolate is QRNG or in vitro susceptibility cannot be assessed, a parenteral cephalosporin is recommended.¹¹⁵

Although levofloxacin may be effective used alone against susceptible organisms, metronidazole usually is included in the PID regimen to provide coverage against anaerobes.¹¹

Plague

Alternative for treatment of plague† caused by Yersinia pestis, including naturally occurring plague and plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism.^{47 48} Regimen of choice is streptomycin (or gentamicin) with or without doxycycline;^{8 30 47 48} alternatives are doxycycline, chloramphenicol (drug of choice for plague meningitis), fluoroquinolones (e.g., ciprofloxacin, levofloxacin), or co-trimoxazole (may be less effective than other alternatives).^{8 30 47 48}

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).^{47 48} Drugs of choice for such prophylaxis are doxycycline (or tetracycline) or a fluoroquinolone (e.g., ciprofloxacin, levofloxacin, ofloxacin); co-trimoxazole and chloramphenicol are alternatives.^{47 48}

Travelers’ Diarrhea

Treatment of travelers’ diarrhea†^{2 27 28 29 130} caused by susceptible bacteria (e.g., enterotoxigenic E. coli, Shigella, Salmonella, Campylobacter, Vibrio parahaemolyticus).^{27 28 29} Generally self-limited and may resolve within 3–4 days without anti-infective treatment;^{8 27 29 108} if diarrhea is moderate or severe, persists for >3 days, or is associated with fever or bloody stools, short-term (1–3 days) anti-infective treatment may be indicated.^{8 27 29 108 130} Fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin, ofloxacin) usually drugs of choice when anti-infective treatment, including self-treatment, is indicated.^{2 27 28 29 108 130} Azithromycin is an alternative for those who should not receive fluoroquinolones (e.g., children, pregnant women) and may be a drug of choice for travelers in areas with a high prevalence of fluoroquinolone-resistant Campylobacter (e.g., Thailand, India) or those who have not responded after 48 hours of fluoroquinolone treatment.^{8 27 29 130} Rifaximin is another alternative for treatment of travelers’ diarrhea caused by noninvasive E. coli.^{27 29 130}

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.^{2 28 29} CDC and others do not recommend anti-infective prophylaxis in most individuals traveling to areas of risk;^{8 27 29 108 130} the principal preventive measures are prudent dietary practices.^{29 108 130} If anti-infective prophylaxis is used (e.g., in immunocompromised individuals such as those with HIV infection), a fluoroquinolone (ciprofloxacin, levofloxacin, ofloxacin, norfloxacin) is recommended for nonpregnant adults,^{27 29 130} although the increasing incidence of quinolone resistance in pathogens that cause travelers’ diarrhea (e.g., Campylobacter) should be considered.^{27 29}

Levofloxacin Dosage and Administration

Administration

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

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

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

Oral Administration

Manufacturer states tablets may be given without regard to meals.^{1 3 5} Administer oral solution 1 hour before or 2 hours after meals.¹ (See Pharmacokinetics.)

IV Infusion

Concentrate for injection (single-use vials containing 25 mg/mL) must be diluted prior to IV infusion.¹

Premixed injection for IV infusion in 5% dextrose (containing 5 mg/mL) may be used without further dilution.¹

Concentrate for injection and premixed injection for IV infusion contain no preservatives; discard any unused portions.¹

Additives or other drugs should not be infused simultaneously through the same IV line.¹

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

Dilution

Dilute concentrate for injection (single-use vials containing 25 mg/mL) with a compatible IV solution prior to IV infusion to provide a solution containing 5 mg/mL.^{1 6}

Rate of Administration

Administer by IV infusion over ≥60–90 minutes depending on dosage.¹ Because of the risk of hypotension, avoid rapid IV injection or infusion.¹

Administer 250- or 500-mg doses by IV infusion over 60 minutes and 750-mg doses over 90 minutes.¹

Dosage

Dosage of oral and IV levofloxacin is identical.¹ No dosage adjustment needed when switching from IV to oral administration, or vice versa.¹

Pediatric Patients

Anthrax

Postexposure Prophylaxis Following Inhalational Exposure

Oral or IV

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

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

Initiate as soon as possible following suspected or confirmed exposure to aerosolized B. anthracis.¹ Switch from IV or oral therapy may be instituted at discretion of clinician.¹

Safety of levofloxacin given for >14 days in children younger than 18 years of age has not been evaluated.¹ Manufacturer states prolonged therapy should be used only when potential benefits outweigh risks.¹ (See Pediatric Use under Cautions.)

Adults

Respiratory Tract Infections

Acute Bacterial Sinusitis

Oral or IV

500 mg once every 24 hours for 10–14 days.¹

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

Acute Exacerbations of Chronic Bronchitis

Oral or IV

500 mg once every 24 hours for 7 days.¹

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 can be used for treatment of CAP caused by S. pneumoniae (penicillin-susceptible strains), H. influenzae, H. parainfluenzae, C. pneumoniae, or M. pneumoniae.¹

When 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

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

Anthrax

Postexposure Prophylaxis Following Inhalational Exposure

Oral or IV

500 mg once daily.^{1 33 34} Initiate as soon as possible following suspected or confirmed exposure to aerosolized B. anthracis.¹

Optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores is unclear,^{47 56} but prolonged postexposure prophylaxis usually required.^{33 47} A duration of 60 days may be adequate for a low-dose exposure, but a duration >4 months may be necessary to reduce the risk following a high-dose exposure.⁵⁶ CDC, US Working Group on Civilian Biodefense, and US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommend that 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).^{33 34 47 59} The US Public Health Service Advisory Committee on Immunization Practices (ACIP) and USAMRIID recommend that individuals who are partially or fully vaccinated against anthrax receive postexposure prophylaxis for ≥30 days;^{47 60} if given in conjunction with anthrax vaccine, continue prophylaxis for at least 7–14 days after the third vaccine dose.^{47 60}

Safety of levofloxacin given for >28 days has not been evaluated.¹ Manufacturer states prolonged therapy should be used only when potential benefits outweigh risks.¹

Treatment of Inhalational Anthrax†

Oral or IV

500 mg once daily³³ for ≥60 days.^{33 35 47}

Initial parenteral regimen preferred; use oral regimen for initial treatment only when a parenteral regimen is not available (e.g., supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting).^{33 35} 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.^{33 35 47}

Chlamydial Infections†

Urogenital Infections†

Oral

500 mg once daily for 7 days recommended by CDC and others.^{11 52}

Gonorrhea and Associated Infections†

Uncomplicated Urethral, Endocervical, or Rectal Gonorrhea†

Oral

250 mg as a single dose has been used for infections caused by susceptible Neisseria gonorrhoeae.¹¹

Because of increased prevalence of quinolone-resistant N. gonorrhoeae (QRNG), CDC no longer recommends fluoroquinolones for treatment of gonorrhea or any associated infections involving N. gonorrhoeae (e.g., PID, epididymitis).^{52 114 115 116} (See Gonorrhea and Associated Infections under Uses.)

Unless the presence of coexisting chlamydial infection has been excluded by appropriate testing, patients being treated for gonorrhea should also receive an anti-infective regimen effective for presumptive treatment of chlamydia (e.g., a single dose of oral azithromycin or a 7-day regimen of oral doxycycline).¹¹

Disseminated Gonococcal Infections†

IV, then Oral

250 mg IV once daily has been used for initial treatment.¹¹ IV regimen is continued for 24–48 hours after improvement begins, then switched to 500 mg orally once daily to complete ≥1 week of treatment.¹¹

Because of increased prevalence of QRNG, CDC no longer recommends fluoroquinolones for treatment of gonorrhea or any associated infections involving N. gonorrhoeae (e.g., PID, epididymitis).^{114 115 116} Use as an alternative treatment option for disseminated infections only if in vitro susceptibility can be documented by culture.¹¹⁵ (See Gonorrhea and Associated Infections under Uses.)

Unless the presence of coexisting chlamydial infection has been excluded by appropriate testing, patients being treated for gonorrhea should also receive an anti-infective regimen effective for presumptive treatment of chlamydia (e.g., a single dose of oral azithromycin or a 7-day regimen of oral doxycycline).¹¹

Epididymitis†

Oral

500 mg once daily for 10 days recommended by CDC and others.^{11 52 115}

Should be used only when epididymitis† most likely caused by sexually transmitted enteric bacteria (e.g., Escherichia coli) or when culture or nucleic acid amplification tests are negative for N. gonorrhoeae.^{11 115}

Mycobacterial Infections†

Active Tuberculosis†

Oral or IV

0.5–1 g once daily.⁴⁰ Must be used in conjunction with other antituberculosis agents.⁴⁰

Multiple-drug regimen usually given for 12–18 months when rifampin-resistant M. tuberculosis are involved; for 18–24 months when isoniazid- and rifampin-resistant strains are involved; or for 24 months when the strain is resistant to isoniazid, rifampin, ethambutol, and/or pyrazinamide.⁴⁰

Nongonococcal Urethritis†

Oral

500 mg once daily for 7 days recommended by CDC.¹¹

Pelvic Inflammatory Disease†

Oral

500 mg once daily given for 14 days; used with or without oral metronidazole (500 mg twice daily for 14 days).^{11 52 115}

Should be used for treatment of PID only when cephalosporins are not feasible, community prevalence and individual risk of gonorrhea is low, and in vitro susceptibility has been confirmed.¹¹⁵ (See Pelvic Inflammatory Disease under Uses.)

IV

500 mg once daily; used with or without IV metronidazole (500 mg every 8 hours).^{11 52}

Should be used for treatment of PID only when cephalosporins are not feasible, community prevalence and individual risk of gonorrhea is low, and in vitro susceptibility has been confirmed.¹¹⁵ (See Pelvic Inflammatory Disease under Uses.)

Travelers’ Diarrhea†

Treatment of Travelers’ Diarrhea†

Oral

500 mg once daily for 1–3 days.^{2 27 29 130}

Prevention of Travelers’ Diarrhea†

Oral

500 mg once daily during the period of risk.^{27 28 130}

Although anti-infective prophylaxis generally is discouraged,^{27 28 29 130} some clinicians state that it can be given during the period of risk (for ≤3 weeks) beginning the day of travel and continuing for 1 or 2 days after leaving the area of risk.^{28 130}

Special Populations

Hepatic Impairment

Dosage adjustments not required.¹

Renal Impairment

Dosage adjustments required in adults with Cl_cr <50 mL/minute.¹ (See Table 1.)No dosage recommendations provided by manufacturer for pediatric patients with renal impairment.¹

Table 1. Dosage for Adults with Renal Impairment1

Usual Dosage (Clcr ≥ 50 mL/min)	Clcr (mL/min)	Dosage for Renal Impairment
250 mg	20–49	Dosage adjustment not required
250 mg	Hemodialysis or CAPD Patients	Information not available
250 mg	10–19	Uncomplicated UTIs: Dosage adjustment not required Other infections: 250 mg every 48 hours
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	Initial 750-mg dose, then 750 mg once 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

Tendinopathy and Tendon Rupture

Fluoroquinolones, including levofloxacin, are associated with increased risk of tendinitis and tendon rupture in all age groups.^{1 128 129} This risk is further 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 risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis.^{1 128 129} Tendinitis and tendon rupture have been reported in patients receiving fluoroquinolones who did not have any of these risk factors.¹

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

Tendon rupture can occur during or following fluoroquinolone therapy and has been reported up to several months after completion of therapy.¹

Discontinue if pain, swelling, inflammation, or rupture of a tendon occurs.^{1 128 129} Advise patients to rest and refrain from exercise and contact a clinician at the first sign of tendinitis or tendon rupture (e.g., pain, swelling, or inflammation of a tendon; weakness or inability to use a joint).^{1 128 129} (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 may 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), urticaria, pruritus, and other severe skin reactions.¹

In addition, other possible severe and potentially fatal reactions (may be hypersensitivity reactions or of unknown etiology) have been reported most frequently after multiple doses.¹ These include 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

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

Relative potential of the various fluoroquinolones to cause photosensitivity/phototoxicity unclear.¹³¹ Factors that contribute to susceptibility to this adverse effect during fluoroquinolone therapy include patient's skin pigmentation, frequency and duration of exposure to sun and UV light, use of protective clothing and sunscreen, concomitant use of other drugs, and dosage and duration of fluoroquinolone therapy.¹³¹

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 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 fatal cases of hepatotoxicity were in geriatric patients ≥65 years of age.¹ (See Geriatric Use under Cautions.)

Levofloxacin should be discontinued in any patient who experiences 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

CNS Effects

Seizures and toxic psychoses reported with fluoroquinolones, including levofloxacin.¹ Increased intracranial pressure and CNS stimulation, which may lead to tremor, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia,