Generic Name: 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

Introduction

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

Uses for Levaquin

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

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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}

Levaquin 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 Levaquin

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, depression, nightmares, insomnia, and, rarely, suicidal thoughts or acts, also reported.¹ These may occur following first dose.¹

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

If CNS effects occur, discontinue levofloxacin and institute appropriate measures.¹

Peripheral Neuropathy

Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness reported with fluoroquinolones, including levofloxacin.¹

To prevent development of an irreversible condition, discontinue levofloxacin if symptoms of neuropathy (e.g., pain, burning, tingling, numbness, and/or weakness) or other alterations of sensation (e.g., light touch, pain, temperature, position sense, vibratory sensation) occur.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 97 98 99 100} C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including levofloxacin, and may range in severity from mild diarrhea to fatal colitis.^{1 96 97 98 99 100 102 106 107} 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} 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

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.^{1 96 97 98 99 100} Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.^{1 96 97 98 99 100}

If CDAD is suspected or confirmed, discontinuance of levofloxacin may be needed.^{1 96 97 98 99 100} Some mild cases may respond to discontinuance alone.^{1 96 97 98 99 100} Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, appropriate anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.^{1 96 97 98 99 100}

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 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 may be increased in geriatric patients.¹ (See Geriatric Use under Cautions.)

Musculoskeletal Effects

Increased incidence of musculoskeletal disorders (arthralgia, arthritis, tendonopathy, gait abnormality) reported in pediatric patients receiving levofloxacin.¹ Use in pediatric patients only for prevention of inhalational anthrax (postexposure) 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 Relevance of these adverse effects in immature animals to use in humans unknown.^{1 117 123 124 125} Safety and efficacy not established in children and adolescents <18 years of age for any indication other than prophylaxis of inhalational anthrax (postexposure) (see Pediatric Use under Cautions) and safety and efficacy not established in pregnant or lactating women (see Pregnancy and see Lactation under Cautions).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

Selection and Use of Anti-infectives

When prescribing a fluoroquinolone, consider potential benefits and risks for the individual patient.^{128 129} Most patients tolerate the drugs, but serious adverse reactions (e.g., CNS effects, QT prolongation, C. difficile-associated diarrhea and colitis, damage to liver, kidneys, or bone marrow, alterations in glucose homeostatis) may occur rarely.^{128 129}

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.^{11 52 53 109 110 114}

Recent 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

CDC states that fluoroquinolones should not be used to treat proven or suspected gonorrhea,^{114 115 116} including infections acquired within the US or acquired while traveling abroad.¹¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Distributed into milk following oral or IV administration;⁸⁰ discontinue nursing or the drug.¹

Pediatric Use

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

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

AAP states use of fluoroquinolones may be justified in children <18 years of age in special circumstances after careful assessment of the risks and benefits for the individual patient and after these benefits and risks have been explained to the parents or caregivers.⁸

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 Tendinopathy and Tendon Rupture under Cautions.) Use caution in geriatric adults, especially those receiving concomitant corticosteroids.¹

Risk of fatal hepatotoxicity may be increased in geriatric patients.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

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 Levaquin

Does not inhibit and is not metabolized by 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 levofloxacin1 5 7	Administer levofloxacin at least 2 hours before or after such antacids1
Antiarrhythmic agents	Potential additive effects on QT interval prolongation1 Procainamide: Increased half-life and decreased clearance of procainamide84	Avoid levofloxacin in those receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents1
Anticoagulants, oral (warfarin)	Possible enhanced warfarin effects1	Monitor PT, INR, or other suitable coagulation tests and monitor for bleeding1
Antidiabetic agents (e.g., insulin, glyburide)	Hyperglycemia and hypoglycemia reported1	Closely monitor blood glucose; discontinue levofloxacin if a hypoglycemic reaction occurs1
Cimetidine	Slightly increased levofloxacin concentrations1	Not considered clinically important; dosage adjustments not required1
Corticosteroids	Increased risk of tendinitis or tendon rupture, especially in patients >60 years of age1 128 129
Cyclosporine or tacrolimus	Increased AUC of cyclosporine or tacrolimus92	Manufacturer of levofloxacin states dosage adjustments not required;1 some clinicians suggest monitoring plasma concentrations of the immunosuppressive agent92
Didanosine	Possible decreased absorption of oral levofloxacin1	Administer levofloxacin at least 2 hours before or after buffered didanosine (pediatric oral solution admixed with antacid)1
Digoxin	No evidence of clinically important effect on pharmacokinetics of digoxin or levofloxacin1 83
Iron preparations	Decreased absorption of levofloxacin1	Administer levofloxacin at least 2 hours before or after ferrous sulfate and dietary supplements containing iron1
Multivitamins and mineral supplements	Decreased absorption of levofloxacin1 94	Administer levofloxacin at least 2 hours before or 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	Increased levofloxacin concentrations1	Not considered clinically important; 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 levofloxacin1	Administer levofloxacin at least 2 hours before or after sucralfate1 86
Theophylline	No evidence of pharmacokinetic interaction;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; consider that adverse theophylline effects (e.g., seizures) may occur with or without elevated theophylline concentrations1

Levaquin Pharmacokinetics

Absorption

Bioavailability

Approximately 99%.^{1 51}

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 51}

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 Cl_cr 20–49 mL/minute and 35 hours in those with Cl_cr <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.¹ After dilution to a concentration of 5 mg/mL with compatible IV solution, store for up to 72 hours at ≤25°C or up to 14 days at 5°C.¹

Diluted solutions containing 5 mg/mL may be frozen in glass or plastic IV containers for ≤6 months at -20°C; after thawing at room temperature or in a refrigerator, do not refreeze.¹

Contains no preservatives; discard any unused portions.¹

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; discard any unused portions.¹

Compatibility

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

Parenteral

Solution Compatibility^{1 49}

Compatible
Dextrose 5% in Ringer’s injection, lactated
Dextrose 5% in sodium chloride 0.9%
Dextrose 5% in sodium chloride 0.45% with potassium chloride 0.15%
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 Compatibility49

Compatible
Linezolid

Y-Site Compatibility49

Compatible
Amikacin sulfate
Aminophylline
Ampicillin sodium
Bivalirudin
Caffeine citrate
Cefotaxime sodium
Cimetidine HCl
Clindamycin phosphate
Daptomycin
Dexamethasone sodium phosphate
Dexmedetomidine HCl
Dobutamine HCl
Dopamine HCl
Epinephrine HCl
Fenoldopam mesylate
Fentanyl citrate
Gentamicin sulfate
Hetastarch in lactated electrolyte injection (Hextend)
Isoproterenol HCl
Lidocaine HCl
Linezolid
Lorazepam
Metoclopramide HCl
Morphine sulfate
Oxacillin sodium
Pancuronium bromide
Penicillin G sodium
Phenobarbital sodium
Phenylephrine HCl
Sodium bicarbonate
Vancomycin HCl
Incompatible
Acyclovir sodium
Alprostadil
Azithromycin
Drotrecogin alfa (activated)
Furosemide
Heparin sodium
Indomethacin sodium trihydrate
Lansoprazole
Nitroglycerin
Propofol
Sodium nitroprusside
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 41 42 43}

• More active in vitro against gram-positive bacteria, (including S. pneumoniae) and anaerobes than some other fluoroquinolones (e.g., ciprofloxacin, norfloxacin, 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), and Enterococcus faecalis (many strains only moderately susceptible).^{1 3} Also active in vitro against S. haemolyticus, S. agalactiae (group B streptococci), 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

• 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,^{41 43 111} and M. fortuitum.⁴²

• Strains of N. gonorrhoeae with decreased susceptibility to levofloxacin and other fluoroquinolones (quinolone-resistant N. gonorrhoeae; QRNG) reported with increasing frequency.^{11 52 53 109 110 114}

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

Advice to Patients

• 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 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 formation of highly concentrated urine.¹

• Importance of taking levofloxacin at least 2 hours before or after multivitamins containing iron or zinc; aluminum- or magnesium-containing antacids; or didanosine chewable/dispersible buffered tablets, buffered powder for oral solution, or pediatric powder for oral solution prepared as an admixture with antacid.¹

• Increased risk of tendinitis and tendon rupture in all age groups and further increased risk in adults >60 years of age, individuals receiving corticosteroids, and kidney, heart, or lung transplant recipients.^{1 128 129} 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, weakness or inability to use a joint), discontinuing the drug, and contacting a clinician regarding changing to an anti-infective that is not a fluoroquinolone.^{1 128 129} (See Tendinopathy and Tendon Rupture under Cautions.)

• Potential for levofloxacin to cause dizziness and lightheadedness; need for caution when operating machinery or driving a motor vehicle until effects of drug on individual are known.¹

• May be associated with hypersensitivity reactions (including anaphylactic reactions), even following the first dose.¹ Importance of immediately discontinuing levofloxacin and informing clinician at the 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

• Risk of photosensitivity/phototoxicity reactions following exposure to sun or UV light while 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 Discontinue levofloxacin and inform a clinician if a sunburn-like reaction or skin eruption occurs.¹

• Importance of discontinuing levofloxacin and consulting clinician if symptoms of peripheral neuropathy (e.g., pain, burning, tingling, numbness, weakness) develop.¹

• Importance of informing clinician if pediatric patient has a history of joint-related problems before taking levofloxacin.¹

• Advise patients that seizures have been reported and importance of informing clinician about any history of seizures before taking levofloxacin.¹

• Advise diabetic patients that hypoglycemic reactions have been reported and to discontinue levofloxacin and contact 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

• Importance of discontinuing levofloxacin and consulting clinician if symptoms of hepatotoxicity (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, dark colored urine) develop.¹

• Advise patient that levofloxacin may prolong QT interval and should be avoided in those receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.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).¹

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, especially drugs that may affect QT interval (e.g., cisapride, erythromycin, antipsychotic agents, tricyclic antidepressants).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.

Levofloxacin

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Solution	125 mg/5mL	Levaquin	Ortho-McNeil
	Tablets, film-coated	250 mg (of anhydrous levofloxacin)	Levaquin	Ortho-McNeil
		500 mg (of anhydrous levofloxacin)	Levaquin	Ortho-McNeil
		750 mg (of anhydrous levofloxacin)	Levaquin	Ortho-McNeil
Parenteral	For injection, concentrate, for IV infusion	equivalent to levofloxacin 25 mg/mL (500 or 750 mg)	Levaquin	Ortho-McNeil

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)	Ortho-McNeil

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Levaquin 250MG Tablets (JANSSEN): 10/$168.00 or 30/$484.97

Levaquin 500MG Tablets (JANSSEN): 10/$185.98 or 30/$532.99

Levaquin 750MG Tablets (MCNEIL): 30/$779.99 or 90/$2,229.80

Levofloxacin 250MG Tablets (LUPIN PHARMACEUTICALS): 50/$30.99 or 150/$80.97

Levofloxacin 500MG Tablets (LUPIN PHARMACEUTICALS): 50/$35.99 or 150/$95.97

Levofloxacin 750MG Tablets (LUPIN PHARMACEUTICALS): 20/$25.99 or 60/$69.97