Video: Latest Treatment for Hep C.

Levaquin

Pronunciation

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

Warning(s)

  • Systemic 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.)

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

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 multidrug-resistant S. pneumoniae [MDRSP]), H. influenzae, H. parainfluenzae, Klebsiella pneumoniae, Legionella pneumoniae, M. catarrhalis, Chlamydophila pneumoniae (formerly Chlamydia pneumoniae), or Mycoplasma pneumoniae.1 21 31 95

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

Slideshow: The Shocking Truth About Antibiotic Resistance

Urinary Tract Infections (UTIs) and Prostatitis

Treatment of mild to moderate uncomplicated UTIs caused by susceptible E. coli, K. pneumoniae, or S. saprophyticus.1 Generally considered alternative for treatment of uncomplicated UTIs (e.g., acute cystitis) and used in these infections only when other urinary anti-infectives likely to be ineffective or cannot be used.143

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

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

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

Endocarditis

Alternative for treatment of 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

GI Infections

Alternative for treatment of >Salmonella gastroenteritis (with or without bacteremia) in HIV-infected adults.412 CDC, NIH, and IDSA recommend ciprofloxacin as drug of choice; other fluoroquinolones (levofloxacin, moxifloxacin) also may be effective.412 Depending on in vitro susceptibility, other alternatives are co-trimoxazole and third generation cephalosporins (ceftriaxone, cefotaxime).412 Role of long-term anti-infective treatment (secondary prophylaxis) in HIV-infected individuals with recurrent bacteremia not well established; weigh benefits of such prophylaxis against risks of long-term anti-infective therapy.412

Treatment of shigellosis caused by susceptible Shigella when anti-infectives indicated.412 477 Anti-infectives generally indicated in addition to fluid and electrolyte replacement for treatment of patients with severe shigellosis, dysentery, or underlying immunosuppression.292 412 Empiric treatment regimen can be used initially, but in vitro susceptibility testing indicated since resistance is common.292 Fluoroquinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin) are drugs of choice when susceptibility of the isolate is unknown or ampicillin- or co-trimoxazole-resistant strains are involved.292 412 477

Treatment of travelers’ diarrhea2 28 305 525 caused by susceptible bacteria (e.g., enterotoxigenic E. coli, Shigella, Salmonella, Campylobacter, Vibrio parahaemolyticus).28 305 525 If caused by bacteria, may be self-limited and resolve within 3–5 days without anti-infective treatment;305 525 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.305 525 Fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin, ofloxacin) usually drugs of choice when anti-infective treatment, including self-treatment, is indicated.2 28 305 525 Azithromycin is an alternative if fluoroquinolones should not be used (e.g., children, pregnant women) and a drug of choice for travelers in areas with a high prevalence of fluoroquinolone-resistant Campylobacter (e.g., South and Southeast Asia) or when there is no response after 48 hours of fluoroquinolone treatment.305 525 Rifaximin is another alternative for treatment of travelers’ diarrhea caused by noninvasive E. coli.305 525

Prevention of travelers’ diarrhea in individuals traveling for relatively short periods to areas where enterotoxigenic E. coli and other causative bacterial pathogens (e.g., Shigella) are known to be susceptible to the drug.2 28 525 CDC and others do not recommend anti-infective prophylaxis in most individuals traveling to areas of risk;305 412 525 the principal preventive measures are prudent dietary practices.525 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;305 412 525 azithromycin and rifaximin are alternatives.305 Weigh use of anti-infective prophylaxis against use of prompt, early self-treatment with anti-infectives, a strategy that can limit duration of illness to 6–24 hours in most cases.525

Anthrax

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.319 CDC and others recommend azithromycin or doxycycline as drugs of choice; erythromycin,319 328 ofloxacin,319 or levofloxacin are alternatives.319 328

Gonorrhea and Associated Infections

Has been used for treatment of uncomplicated urethral, endocervical, or rectal gonorrhea caused by susceptible Neisseria gonorrhoeae.114

Treatment of acute epididymitis.319 328 CDC recommends an initial regimen of IM ceftriaxone and oral doxycycline in all patients;319 additional therapy includes ofloxacin or levofloxacin, but fluoroquinolones should be used alone only when epididymitis is most likely caused by sexually transmitted enteric bacteria (e.g., E. coli) or nucleic acid amplification test (NAAT) is negative for N. gonorrhoeae.319 328

Because quinolone-resistant N. gonorrhoeae (QRNG) is widely disseminated worldwide, including in the US319 328 (see Resistance in Neisseria gonorrhoeae under Cautions), CDC and others no longer recommend levofloxacin for treatment of gonorrhea or any associated infections that may involve N. gonorrhoeae (e.g., pelvic inflammatory disease [PID], epididymitis).319 328

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 caused by Mycobacterium tuberculosis.40 412

Has been used in multiple-drug regimens for treatment of disseminated infections caused by M. avium complex (MAC).412

CDC, ATS, and IDSA state that use of fluoroquinolones can be considered in patients with relapse, treatment failure, or M. 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

ATS and IDSA state that role of fluoroquinolones in treatment of MAC infections not established.671 If a fluoroquinolone is included in treatment regimen (e.g., for macrolide-resistant MAC infections), moxifloxacin or levofloxacin may be preferred,412 671 although many strains are resistant in vitro.671

Consult most recent CDC, ATS, and IDSA recommendations for treatment of tuberculosis and other mycobacterial infections for more specific information.40 412 671

Nongonococcal Urethritis

Alternative for treatment of nongonococcal urethritis (NGU).319 CDC recommends azithromycin or doxycycline as drugs of choice;319 erythromycin, ofloxacin, and levofloxacin are alternatives.319

Pelvic Inflammatory Disease

Has been used as alternative for treatment of acute PID.319 328 Do not use in any infections that may involve N. gonorrhoeae.114 116 319 328 (See Resistance in Neisseria gonorrhoeae under Cautions.)

When an oral regimen used for treatment of mild to moderately severe acute PID, CDC recommends a single IM dose of ceftriaxone, cefoxitin (with oral probenecid), or cefotaxime given in conjunction with oral doxycycline (with or without oral metronidazole).319 Although fluoroquinolones no longer recommended for PID, 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.319

Plague

Treatment of plague, including pneumonic and septicemic plague, caused by Yersinia pestis.1 47 48 Considered alternative for treatment of plague, 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;30 47 48 292 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).30 47 48 292

Postexposure prophylaxis of plague.1 47 48 Used 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

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 weighing <50 kg: 8 mg/kg (up to 250 mg) every 12 hours for 60 days.1

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

Initiate 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.)

Plague
Treatment or Prophylaxis of Plague
Oral or IV

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

Children weighing >50 kg: 500 mg once daily for 10–14 days.1

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

Adults

Respiratory Tract Infections
Acute Bacterial Sinusitis
Oral or IV

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

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 (except MDRSP).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

GI Infections
Salmonella Gastroenteritis
Oral

HIV-infected: 750 mg once daily.412

Recommended duration is 7–14 days if CD4+ T-cells ≥200 cells/mm3 (≥14 days if bacteremic or infection is complicated) or 2–6 weeks if CD4+ T-cells <200 cells/mm3.412

Role of long-term treatment (secondary prophylaxis) in those with recurrent bacteremia not well established; weigh benefits against risks of long-term anti-infective exposure.412 Consider secondary prophylaxis in those with CD4+ T-cells <200 cells/mm3 and severe diarrhea.412

IV

HIV-infected: 750 mg once daily.412

Shigella Infections
Oral

HIV-infected: 750 mg once daily.412

Recommended duration of treatment is 7–10 days for gastroenteritis or ≥14 days for bacteremic infections.412 Up to 6 weeks may be required for recurrent infections, especially if CD4+ T-cells <200 cells/mm3.412

IV

HIV infected: 750 mg once daily.412

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.319 328

Gonorrhea and Associated Infections
Uncomplicated Urethral, Endocervical, or Rectal Gonorrhea
Oral

Not recommended by CDC or others for treatment of gonorrhea or any associated infections that may involve N. gonorrhoeae (e.g., PID, epididymitis).319 328 (See Gonorrhea and Associated Infections under Uses.)

Epididymitis
Oral

500 mg once daily for 10 days recommended by CDC and others.319 328

Use only when epididymitis most likely caused by sexually transmitted enteric bacteria (e.g., E. coli) or NAAT negative for N. gonorrhoeae.319 328

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

Disseminated MAC Infections
Oral

HIV-infected: 500 mg once daily.412

Nongonococcal Urethritis
Oral

500 mg once daily for 7 days recommended by CDC.319

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).319

Use only when cephalosporins not feasible, community prevalence and individual risk of gonorrhea are low, and in vitro susceptibility confirmed.319 (See Pelvic Inflammatory Disease under Uses.)

IV

500 mg once daily; used with or without IV metronidazole (500 mg every 8 hours).319

Use only when cephalosporins not feasible, community prevalence and individual risk of gonorrhea are low, and in vitro susceptibility confirmed.319 (See Pelvic Inflammatory Disease under Uses.)

Plague
Treatment or Prophylaxis of Plague
Oral or IV

500 mg once daily for 10–14 days.1

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

Travelers’ Diarrhea
Treatment of Travelers’ Diarrhea
Oral

500 mg once daily for 1–3 days.2 305

Prevention of Travelers’ Diarrhea
Oral

500 mg once daily during the period of risk.28 305

Although anti-infective prophylaxis generally is discouraged,28 305 525 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.305

Special Populations

Hepatic Impairment

Dosage adjustments not required.1

Renal Impairment

Dosage adjustments required in adults with Clcr <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 Daily Dosage for Normal Renal Function (Clcr ≥ 50 mL/min)

Clcr (mL/min)

Dosage for Renal Impairment

250 mg

20–49

Dosage adjustment not required

250 mg

10–19

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

250 mg

Hemodialysis or CAPD patients

Information not available

500 mg

20–49

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

500 mg

10–19

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

500 mg

Hemodialysis or CAPD patients

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

750 mg

20–49

750 mg every 48 hours

750 mg

10–19

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

750 mg

Hemodialysis or CAPD patients

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

Geriatric Patients

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

Cautions for Levaquin

Contraindications

  • Known hypersensitivity to levofloxacin or other quinolones.1

Warnings/Precautions

Warnings

Tendinopathy and Tendon Rupture

Systemic 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.)

Myasthenia Gravis Patients

May exacerbate muscle weakness in myasthenia gravis patients;1 need for ventilatory support and death reported.1

Avoid use in patients with known history of myasthenia gravis.1

Sensitivity Reactions

Hypersensitivity Reactions

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

Some hypersensitivity reactions have been accompanied by cardiovascular collapse, hypotension or shock, seizures, loss of consciousness, tingling, angioedema (e.g., edema or swelling of the tongue, larynx, throat, or face), airway obstruction (e.g., bronchospasm, shortness of breath, acute respiratory distress), 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 (including pseudotumor cerebri) 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 Symptoms may occur soon after initiation of the drug and may be irreversible.1

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

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

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

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

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

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

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

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, tendinopathy, 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 homeostasis) 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.53 109 114 132 319 328

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 and others state that fluoroquinolones, including levofloxacin, should not be used to treat gonorrhea or any associated infections that may involve N. gonorrhoeae (e.g., PID, epididymitis).114 116 319 328

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) or for treatment or prophylaxis of plague in adolescents and children ≥6 months of age.1 Safety and efficacy not established for any other indication in this age group.1

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

Increased incidence of musculoskeletal disorders reported in pediatric patients receiving levofloxacin.1 Causes arthropathy 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 and/or caregivers.110 292

Geriatric Use

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

Risk of severe tendon disorders, including tendon rupture, is increased in older adults (usually those >60 years of age).1 128 129 This risk is further increased in those receiving concomitant corticosteroids.1 128 129 (See 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 oral levofloxacin1 5 7

Administer oral 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)

Enhanced warfarin effects and clinical bleeding1

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

Possible increased AUC of cyclosporine or tacrolimus92

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

Didanosine

Possible decreased absorption of oral levofloxacin1

Administer oral levofloxacin at least 2 hours before or 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 oral levofloxacin1

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

Multivitamins and mineral supplements

Decreased absorption of oral levofloxacin1 94

Administer oral levofloxacin at least 2 hours before or 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 oral levofloxacin1

Administer oral 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 Clcr 20–49 mL/minute and 35 hours in those with Clcr <20 mL/minute.1

Stability

Storage

Oral

Solution

25°C (may be exposed to 15–30°C).1

Tablets

15–30°C in well-closed containers.1

Parenteral

For Injection, for IV Infusion

15–30°C; protect from light.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 Compatibility1 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

  • N. gonorrhoeae with decreased susceptibility to levofloxacin and other fluoroquinolones (quinolone-resistant N. gonorrhoeae; QRNG) are widely disseminated worldwide, including in the US.53 109 114 132 319 328

  • 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.)

  • Advise patients that levofloxacin may worsen myasthenia gravis symptoms; importance of immediately contacting clinician if any worsening muscle weakness or breathing problems occur.1

  • 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

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

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

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, 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.

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

Levofloxacin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

125 mg/5 mL*

Levaquin

Janssen

Levofloxacin Solution

Tablets, film-coated

250 mg (of anhydrous levofloxacin)*

Levaquin

Janssen

Levofloxacin Tablets

500 mg (of anhydrous levofloxacin)*

Levaquin

Janssen

Levofloxacin Tablets

750 mg (of anhydrous levofloxacin)*

Levaquin

Janssen

Levofloxacin Tablets

Parenteral

For injection, concentrate, for IV infusion

equivalent to levofloxacin 25 mg/mL (500 or 750 mg)*

Levaquin

Janssen

Levofloxacin Concentrate, for IV Infusion

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

Levofloxacin in Dextrose

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion

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

Levaquin in Dextrose Injection Premix (in flexible containers)

Janssen

Levofloxacin in Dextrose Injection

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. 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

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 18, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

1. Janssen Pharmaceuticals Inc. Levaquin (levofloxacin) tablets, oral solution, concentrate for IV use, and solution in 5% dextrose for IV use prescribing information. Titusville, NJ; 2013 Jul.

2. Adachi JA, Ostrosky-Zeichner L, DuPont HL et al. Empirical antimicrobial therapy for travelers’ diarrhea. Clin Infect Dis. 2000; 31:1079-83. [IDIS 456005] [PubMed 11049792]

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

4. Zhanel GC, Ennis K, Vercaigne L et al. A critical review of the fluoroquinolones: focus on respiratory tract infections. Drugs. 2002. 62:13-59.

5. Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet. 1997; 32:101-19. [PubMed 9068926]

6. Williams NA, Bornstein M, Johnson K. Stability of levofloxacin in intravenous solutions in polyvinyl chloride bags. Am J Health-Syst Pharm. 1996; 53:2309-13. [IDIS 373309] [PubMed 8893070]

7. Shiba K, Sakai O, Shimada J et al. Effects of antacids, ferrous sulfate, and ranitidine on absorption of DR-3355 in humans. Antimicrob Agents Chemother. 1992; 36:2270-4. [IDIS 303571] [PubMed 1444308]

9. Christ W, Lehnert T, Ulbrich B. Specific toxicologic aspects of the quinolones. Rev Infect Dis. 1988; 10(Suppl 1):S141-6. [IDIS 311600] [PubMed 3279489]

10. Reviewer’s comments (personal observations) on ciprofloxacin 8:12.18.

12. Une T, Fujimoto T, Sato K et al. In vitro activity of DR-3355, an optically active ofloxacin. Antimicrob Agents Chemother. 1988; 32:1336-40. [IDIS 248086] [PubMed 3195996]

13. Plouffe JF and the Franklin County Pneumonia Study Group. Levofloxacin in vitro activity against bacteremic isolates of Streptococcus pneumoniae. Diagn Microbiol Infect Dis. 1996; 25:43-5. [PubMed 8831044]

14. Goa KL, Bryson HM, Markham A. Sparfloxacin: a review of its antibacterial activity, pharmacokinetic properties, clinical efficacy and tolerability in lower respiratory tract infections. Drugs. 1997; 53:700-25. [PubMed 9098667]

15. Hecht DW, Wexler HM. In vitro susceptibility of anaerobes to quinolones in the United States. Clin Infect Dis. 1996; 23(Suppl 1):S2-8.

16. Eliopoulos GM. In vitro activity of fluoroquinolones against gram-positive bacteria. Drugs. 1995; 49(Suppl 2):48-57. [PubMed 8549407]

17. Hooper DC. Quinolones. In: Mandell GL, Bennett JE, Dolin R eds. Mandell, Douglas and Bennett’s principles and practice of infectious diseases. 4th ed. New York: Churchill Livingstone; 1995:366-7.

18. Adeglass J, DeAbate AC, McElvaine P et al. Comparison of the effectiveness of levofloxacin and amoxicillin-clavulanate for the treatment of acute sinusitis in adults. Otolaryngol Head Neck Surg. 1999; 120:320-7. [PubMed 10064632]

19. DeAbate CA, Russell M, McElvaine P et al. Safety and efficacy of oral levofloxacin versus cefuroxime axetil in acute bacterial exacerbation of chronic bronchitis. Respir Care. 1997; 42:206-13.

20. Habib MP, Gentry LO, Rodriguez-Gomez G et al. A multicenter, randomized study comparing the efficacy and safety of oral levofloxacin vs cefaclor in the treatment of acute bacterial exacerbations of chronic bronchitis. Proceedings of ICAAC New Orleans 1996. Abstract L002.

21. File TM Jr, Segreti J, Dunbar L et al. A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin vs ceftriaxone and/or cefuroxime axetil in the treatment of adults with community-acquired pneumonia. Antimicrob Agents Chemother. 1997; 41:1965-72. [IDIS 393395] [PubMed 9303395]

22. Anon. Consensus statement: therapeutic recommendations for community-acquired pneumonia and acute exacerbations of chronic bronchitis. Hosp Med. 1997; 33(Suppl):26-7.

23. Nicodemo AC, Robledo JA, Jasovich A et al. A multicenter, double-blind, randomized study comparing the efficacy and safety of oral levofloxacin versus ciprofloxacin in the treatment of uncomplicated skin and skin structure infections. Int J Clin Pract. 1998; 52:69-74. [PubMed 9624783]

24. Richard GA, Klimberg IN, Fowler CL et al. Levofloxacin versus ciprofloxacin versus lomefloxacin in acute pyelonephritis. Urology. 1998; 52:51-5. [PubMed 9671870]

25. Richard GA, Childs S, Fowler C et al. A comparison of levofloxacin (LVFX) and ciprofloxacin (cipro) for the treatment of complicated urinary tract infections (cUTI). Clin Infect Dis. 1996; 23:914.

26. Nichols R, Smith J, Gentry LO et al. Multicenter, open-label, active-controlled, randomized comparison of levofloxacin (LVFX) QD vs. ciprofloxacin (CIP) BID in 469 adults with mild-to-moderate skin and skin structure infections. Clin Infect Dis. 1996; 23:913.

28. Caeiro JP, Dupont HL. Management of travelers’ diarrhoea. Drugs. 1998; 56:73-81. [PubMed 9664200]

30. Anon. Choice of antibacterial drugs. Med Lett Treat Guid. 2007; 5:33-50.

31. Mandell LA, Wunderink RG, Anzueto A et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007; 44 Suppl 2:S27-72. [PubMed 17278083]

32. Heffelfinger JD, Dowell SF, Jorgensen JH et al. Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the drug-resistance streptococcus pneumoniae therapeutic working group. Arch Intern Med. 2000; 160:1399-1408. [IDIS 448719] [PubMed 10826451]

33. Inglesby TV, O’Toole T, Henderson DA et al for the Working Group on Civilian Biodefense. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA. 2002; 287:2236-52. [IDIS 480001] [PubMed 11980524]

34. Centers for Disease Control and Prevention. Update: investigation of anthrax associated with intentional exposure and interim public health guidelines, October 2001. MMWR Morb Mortal Wkly Rep. 2001; 50:889-93. [IDIS 471389] [PubMed 11686472]

35. Centers for Disease Control and Prevention. Update: investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. MMWR Morb Mortal Wkly Rep. 2001; 50:909-19. [IDIS 471910] [PubMed 11699843]

36. Jernigan JA, Stephens DS, Ashford DA et al. Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States. Emerg Infect Dis. 2001; 7:933-44. [PubMed 11747719]

37. Morganroth J, DiMarco JP, Anzueto A et al. A randomized trial comparing the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with community-acquired pneumonia. Chest. 2005; 128:3398-406. [PubMed 16304291]

38. Bishai W. Current issues on resistance, treatment guidelines, and the appropriate use of fluoroquinolones for respiratory tract infections. Clin Ther. 2002; 24:838-50. [IDIS 483635] [PubMed 12117077]

39. Bearden DT, Danziger LH. Mechanism of action of and resistance to quinolones. Pharmacotherapy. 2001; 21:224S-32S. [IDIS 472236] [PubMed 11642689]

40. Centers for Disease Control and Prevention. Treatment of tuberculosis, American Thoracic Society, CDC, and Infectious Diseases Society of America. MMWR Recomm Rep. 2003; 52(RR-11):1-88.

41. Alvirez-Freites EJ, Carter JL, Cynamon MH. In vitro and in vivo activities of gatifloxacin against Mycobacterium tuberculosis. 2002; 46:1022-5.

42. Yang SC, Hsueh PR, Lai HC et al. High prevalence of antimicrobial resistance in rapidly growing mycobacteria in Taiwan. Antimicrob Agents Chemother. 2003; 47:1958-62. [PubMed 12760874]

43. Tomioka H, Sato K, Akaki T et al. Comparative in vitro antimicrobial activities of the newly synthesized quinolone HSR-903, sitafloxacin (DU-6859s), gatifloxacin (AM-1155), and levofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex. Antimicrob Agents Chemother. 1999; 43:3001-4. [PubMed 10582897]

44. Zhanel GG, Palatnick L, Nichol KA et al. Antimicrobial resistance in respiratory tract Streptococcus pneumoniae isolates: results of the Canadian respiratory organism susceptibility study, 1997 to 2002. Antimicrob Agents Chemother. 2003; 47:1867-74. [PubMed 12760860]

45. Kays MB, Smith DW, Wack ME et al. Levofloxacin treatment failure in a patient with fluoroquinolone-resistant Streptococcus pneumoniae pneumonia. Pharmacotherapy. 2002; 22:395-9. [IDIS 478076] [PubMed 11898897]

46. Graham DR, Talan DA, Nichols RL et al. Once-daily, high-dose levofloxacin versus ticarcillin-clavulanate alone or followed by amoxicillin-clavulanate for complicated skin and skin-structure infections: a randomized, open-label trial. Clin Infect Dis. 2002; 35:381-9. [IDIS 485421] [PubMed 12145720]

47. US Army Medical Research Institute of Infectious Disease. USAMRIID’s medical management of biologic casualties handbook. 5th ed. USAMRIID: Fort Detrick, MD; 2004 Aug.

48. Inglesby TV, Dennis DT, Henderson DA et al for the Working Group on Civilian Biodefense. Plague as a biological weapon: medical and public health management. JAMA. 2000; 283:2281-90. [IDIS 446671] [PubMed 10807389]

49. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:997-1001.

50. Frean JA, Arntzen L, Capper T et al. In vitro activities of 14 antibiotics against 100 human isolates of Yersinia pestis from a Southern African plague focus. Antimicrob Agents Chemother. 1996; 40:2646-7. [IDIS 376128] [PubMed 8913481]

51. Norrby, SR. Levofloxacin. Expert Opin Pharmacother. 1999; 1:109-19. [PubMed 11249554]

53. Centers for Disease Control and Prevention. Increases in fluoroquinolone-resistant Neisseria gonorrhoeae among men who have sex with men—United States, 2003, and revised recommendations for gonorrhea treatment, 2004. MMWR Morb Mortal Wkly Rep. 2004; 53:3235-8.

55. Baddour LM, Wilson WR, Bayer AS et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation. 2005; 111:e394-433. [PubMed 15956145]

56. Brookmeyer R, Johnson E, Bollinger R. Modeling the optimum duration of antibiotic prophylaxis in an anthrax outbreak. Proc Natl Acad Sci. 2003; 100:10129-32. [PubMed 12890865]

57. Stevens DL, Bisno AL, Chambers HF et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis. 2005; 41;1373-406. [PubMed 16231249]

58. Graham DR, Talan DA, Nichols RL et al. Once-daily, high-dose levofloxacin versus ticarcillin-clavulanate alone or followed by amoxicillin-clavulanate for complicated skin and skin-structure infections: a randomized, open-label trial. Clin Infect Dis. 2002; 35:381-9. [IDIS 485421] [PubMed 12145720]

59. Centers for Disease Control and Prevention. Additional options for preventive treatment for persons exposed to inhalational anthrax. MMWR Morb Mortal Wkly Rep. 2001; 50:1142.

60. Centers for Disease Control and Prevention. Use of anthrax vaccine in response to terrorism: supplemental recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2002; 51:1024-6. [IDIS 489786] [PubMed 12458919]

61. American Thoracic Society and the Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005; 171:388-416. [PubMed 15699079]

62. Anon. Drugs for pneumonia. Med Lett Treat Guid. 2003; 1:83-8.

63. Tunkel AR, Hartman BJ, Kaplan SL et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004; 39:1267-84. [IDIS 537717] [PubMed 15494903]

64. Scotton PG, Pea F, Giobbia M et al. Cerebrospinal fluid penetration of levofloxacin in patients with spontaneous acute bacterial meningitis. Clin Infect Dis. 2001; 33:e109-11. [PubMed 11577376]

65. Pea F, Pavan F, Nascimben E et al. Levofloxacin disposition in cerebrospinal fluid in patients with external ventriculostomy. Antimicrob Agents Chemother. 2003; 47:3104-8. [PubMed 14506016]

66. Scotton PG, Tonon E, Giobbia M et al. Rhodococcus equi nosocomial meningitis cured by levofloxacin and shunt removal. Clin Infect Dis. 2000; 30:223-4. [PubMed 10619769]

67. Nau R, Schmidt T, Kaye K et al. Quinolone antibiotics in therapy of experimental pneumococcal meningitis in rabbits. Antimicrob Agents Chemother. 1995; 39:593-7. [PubMed 7793857]

68. Kuhn F, Cottagnoud M, Acosta F et al. Cefotaxime acts synergistically with levofloxacin in experimental meningitis due to penicillin-resistant pneumococci and prevents selection of levofloxacin-resistant mutants in vitro. Antimicrob Agents Chemother. 2003; 47:2487-91. [PubMed 12878509]

69. Cottagnoud P, Cottagnoud M, Acosta F et al. Meropenem prevents levofloxacin-induced resistance in penicillin-resistant pneumococci and acts synergistically with levofloxacin in experimental meningitis. Eur J Clin Microbiol Infect Dis. 2003; 22:656-62. [PubMed 14557920]

70. Granich RM, Oh P, Lewis B et al. Multidrug resistance among persons with tuberculosis in California, 1994-2003. JAMA. 2005; 293:2732-9. [PubMed 15941802]

71. World Health Organization. Extensively drug-resistant tuberculosis (XDR-TB): recommendations for prevention and control. Wkly Epidemiol Rec. 2006; 45:430-2.

72. Gandhi NR, Moll A, Sturm AW et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006; 368:1575-80. [PubMed 17084757]

73. Johnson JL, Hadad DJ, Boom WH et al. Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis. 2006; 10:605-12. [PubMed 16776446]

74. Aubry A, Veziris N, Cambau E et al. Novel gyrase mutations in quinolone-resistant and -hypersusceptible clinical isolates of Mycobacterium tuberculosis: functional analysis of mutant enzymes. Antimicrob Agents Chemother. 2006; 50:104-12. [PubMed 16377674]

75. Huang TS, Kunin CM, Lee SS et al. Trends in fluoroquinolone resistance of Mycobacterium tuberculosis complex in a Taiwanese medical centre: 1995-2003. J Antimicrob Chemother. 2005; 56:1058-62. [PubMed 16204341]

76. Yew WW, Chan CK, Leung CC et al. Comparative roles of levofloxacin and ofloxacin in the treatment of multidrug-resistant tuberculosis. Chest. 2003; 124:1476-81. [PubMed 14555582]

77. Marra F, Marra CA, Moadebi S et al. Levofloxacin treatment of active tuberculosis and the risk of adverse events. Chest. 2005; 128:1406-13. [PubMed 16162736]

78. Ziganshina LE, Vizel AA, Squire SB. Fluoroquinolones for treating tuberculosis. Cocrane Database Syst Rev. 2005; Jul 20:CD004795.

79. El-Sadr WM, Perlman DC, Matts JP et al. Evaluation of an intensive intermittent-induction regimen and duration of short-course treatment for human immunodeficiency virus-related pulmonary tuberculosis. Clin Infect Dis. 1998; 26:1148-58.

80. Cahill JB, Bailey EM, Chien S et al. Levofloxacin secretion in breast milk: a case report. Pharmacotherapy; 2005; 25:116-8.

81. Flatz L, Cottagnoud M, Kuhn F et al. Ceftriaxone acts synergistically with levofloxacin in experimental meningitis and reduces levofloxacin-induced resistance in penicillin-resistant pneumococci. J Antimicrob Chemother. 2004; 53:305-10. [PubMed 14729741]

82. Friedrich LV, Dougherty R. Fatal hypoglycemia associated with levofloxacin. Pharmacotherapy; 2004; 24:1807-12.

83. Chien SC, Rogge MC, Williams RR et al. Absence of a pharmacokinetic interaction between digoxin and levofloxacin. J Clin Pharm Ther. 2002; 27:7-12. [PubMed 11846857]

84. Bauer LA, Black DJ, Lill JS et al. Levofloxacin and ciprofloxacin decrease procainamide and N-acetylprocainamide renal clearances. Antimicrob Agents Chemother. 2005; 49:1649-51. [PubMed 15793163]

85. Nykamp DL, Blackmon CL, Schmidt PE et al. QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine. Ann Pharmacother. 2005; 39:543-6. [PubMed 15687478]

86. Lee LJ, Hafkin B, Lee ID et al. Effects of food and sucralfate on a single oral dose of 500 milligrams of levofloxacin in healthy subjects. Antimicrob Agents Chemother. 1997; 41:2196-200. [PubMed 9333047]

87. Amsden GW, Whitaker AM, Johnson PW. Lack of bioequivalence of levofloxacin when coadministered with a mineral-fortified breakfast of juice and cereal. J Clin Pharmacol. 2003; 43:990-5. [PubMed 12971031]

88. Wallace AW, Victory JM, Amsden GW. Lack of bioequivalence when levofloxacin and calcium-fortified orange juice are coadministered to healthy volunteers. J Clin Pharmacol. 2003; 43:539-44. [PubMed 12751275]

89. Wright DH, Pietz SL, Konstantinides FN et al. Decreased in vitro fluoroquinolone concentrations after admixture with an enteral feeding formulation. J Parenter Enteral Nutr. 2000; 24:42-8.

90. Poole M, Anon J, Paglia M et al. A trial of high-dose, short-course levofloxacin for the treatment of acute bacterial sinusitis. Otolaryngol Head Neck Surg. 2006; 134:10-7. [PubMed 16399173]

91. Hori S, Kizu J, Kawamura M. Effects of anti-inflammatory drugs on convulsant activity of quinolones: a comparative study of drug interactions between quinolones and anti-inflammatory drugs. J Infect Chemother. 2003; 9:314-20. [PubMed 14691652]

92. Federico S, Carrano R, Capone D et al. Pharmacokinetic interaction between levofloxacin and ciclosporin or tacrolimus in kidney transplant recipients: ciclosporin, tacrolimus and levofloxacin in renal transplantation. Clin Pharmacokinet. 2006; 45:169-75. [PubMed 16485913]

93. Kao LM, Bush K, Barnewall R et al. Pharmacokinetic considerations and efficacy of levofloxacin in an inhalational anthrax (postexposure) rhesus monkey model. Antimicrob Agents Chemother. 2006; 50:3535-42. [PubMed 17065619]

94. Pai MP, Allen SE, Amsden GW. Altered steady state pharmacokinetics of levofloxacin in adult cystic fibrosis patients receiving calcium carbonate. J Cyst Fibros. 2006; 5:153-7. [PubMed 16481224]

95. Anzueto A, Niederman MS, Pearle J et al. Community-acquired pneumonia recovery in the elderly (CAPRIE): efficacy and safety of moxifloxacin therapy versus that of levofloxacin therapy. Clin Infect Dis. 2006; 42:73-81. [PubMed 16323095]

96. Cohen SH, Gerding DN, Johnson S et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010; 31:431-55. [PubMed 20307191]

98. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. Am J Gastroenterol. 1997; 92:739-50. [IDIS 386628] [PubMed 9149180]

99. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease. Am J Health-Syst Pharm. 1998; 55:1407-11. [IDIS 407213] [PubMed 9659970]

101. McDonald LC, Killgore GE, Thompson A et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005; 353:2433-41. [PubMed 16322603]

102. Loo VG, Poirier L, Miller MA et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005; 353:2442-9. [PubMed 16322602]

103. McDonald LC, Owings M, Jernigan DB. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerg Infect Dis. 2006; 12:409-15. [PubMed 16704777]

104. Bartlett JG, Peri TM. The new Clostridium difficile–what does it mean? N Engl J Med. 2005; 353:2503-5.

105. Centers for Disease Control and Prevention. Severe Clostridium difficile-associated disease in populations previously at low risk–four states, 2005. MMWR Morb Mortal Wkly Rep. 2005; 54:1201-5.

106. Kazakova SV, Ware K, Baughman B et al. A hospital outbreak of diarrhea due to an emerging epidemic strains of Clostridium difficile. Arch Intern Med. 2006; 166:2518-24. [PubMed 17159019]

107. Dhalla IA, Mamdani MM, Simor AE et al. Are broad-spectrum fluoroquinolones more likely to cause Clostridium difficile-associated disease? Antimicrob Agents Chemother. 2006; 50:3216-9.

109. Knapp JS, Ohye R, Neal SW et al. Emerging in vitro resistance to quinolones in penicillinase-producing Neisseria gonorrhoeae strains in Hawaii. Antimicrob Agents Chemother. 1994; 38:2200-3. [IDIS 335752] [PubMed 7811047]

110. Bradley JS, Jackson MA, Committee on Infectious Diseases et al. The use of systemic and topical fluoroquinolones. Pediatrics. 2011; 128:e1034-45.

111. Ruiz-Serrano MJ, Alcala L, Martinez L et al. In vitro activities of six fluoroquinolones against 250 clinical isolates of Mycobacterium tuberculosis susceptible or resistant to first-line antituberculosis drugs. Antimicrob Agents Chemother. 2000; 44:2567-8.

112. Kam KM, Yip CW, Cheung TL et al. Stepwise decrease in moxifloxacin susceptibility amongst clinical isolates of multidrug-resistant Mycobacterium tuberculosis: correlation with ofloxacin susceptibility. Microb Drug Resist. 2006; 12:7-11. [PubMed 16584301]

113. Shandil RK, Jayaram R, Kaur P et al. Moxifloxacin, ofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis: evaluation of in vitro and pharmacodynamic indices that best predict in vivo efficacy. Antimicrob Agents Chemother. 2007; 51:576-82. [PubMed 17145798]

114. . Update to CDC’s sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep. 2007; 56:332-6. [PubMed 17431378]

116. Douglas JM Jr. Dear colleague letter: Fluoroquinolones are no longer recommended for the treatment of gonorrhea in the United States. Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Department of Health & Human Services; 2007 April 12.

117. Ball P. Long-term use of quinolones and their safety. Rev Infect Dis. 1989; 11(Suppl 5):S1365-9. [IDIS 307993] [PubMed 2672258]

118. Davis GJ, McKenzie ME. Toxicologic evaluation of ofloxacin. Am J Med. 1989; 87(Suppl 6C):43S-46S. [PubMed 2690619]

119. Mayer DG. Overview of toxicological studies. Drugs. 1987; 34(Suppl 1):150-3. [PubMed 3325258]

120. Kato M, Onodera T. Morphological investigation of cavity formation in articular cartilage induced by ofloxacin in rats. Fund Appl Toxicol. 1988; 11:110-9.

121. Hooper DC, Wolfson JS. Fluoroquinolone antimicrobial agents. N Engl J Med. 1991; 324:384-94. [IDIS 277079] [PubMed 1987461]

122. Paton JH, Reeves DS. Fluoroquinolone antibiotics: microbiology, pharmacokinetics and clinical uses. Drugs. 1988; 36:193-228. [IDIS 245416] [PubMed 3053126]

123. Maggiolo F, Caprioli S, Suter F. Risk/benefit analysis of quinolone use in children: the effect on diarthrodial joints. J Antimicrob Chemother. 1990; 26:469-71. [PubMed 2254219]

124. Pfister K, Mazur D, Vormann J et al. Diminished ciprofloxacin-induced chondrotoxicity by supplementation with magnesium and vitamin E in immature rats. Antimicrob Agents Chemother. 2007; 51:1022-7. [PubMed 17210779]

125. Stahlmann R. Safety profile of the quinolones. J Antimicrob Chemother. 1990; 26(Suppl D):31-44. [PubMed 2286589]

126. Christ W, Lehnert T, Ulbrich B. Specific toxicologic aspects of the quinolones. Rev Infect Dis. 1988; 10(Suppl 1):S141-6. [IDIS 311600] [PubMed 3279489]

128. Food and Drug Administration. FDA news. FDA requests boxed warnings on fluoroquinolone antimicrobial drugs. 2008 Jul 8. From FDA website.

129. Food and Drug Administration. Information for healthcare professionals: Fluoroquinolone antimicrobial drugs. 2008 Jul 8. From FDA website.

131. Schering-Plough. Avelox (moxifloxacin hydrochloride) tablets and Avelox I.V. (moxifloxacin hydrochloride in sodium chloride injection) prescribing information. Kenilworth, NJ; 2008 Oct.

132. Knapp JS, Washington JA, Doyle LJ et al. Persistence of Neisseria gonorrhoeae strains with decreased susceptibility to ciprofloxacin and ofloxacin in Cleveland, Ohio, from 1992 through 1993. Antimicrob Agents Chemother. 1994; 38:2194-6. [IDIS 335751] [PubMed 7811045]

143. Gupta K, Hooton TM, Naber KG et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011; 52:e103-20. [PubMed 21292654]

292. American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.

305. . Advice for travelers. Treat Guidel Med Lett. 2012; 10:45-56. [PubMed 22777212]

319. Workowski KA, Berman S, Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010; 59(RR-12):1-110.

328. . Drugs for sexually transmitted infections. Treat Guidel Med Lett. 2010; 8:53-60; quiz 1p following 60. [PubMed 20585282]

412. Panel on Opportunistic Infections in HIV-infected Adults and Adolescents. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America (May 7, 2013). Updates may be available at HHS AIDS Information (AIDSinfo) website.

477. Guerrant RL, Gilder TV, Steiner TS et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis. 2001; 32:331-50. [IDIS 466024] [PubMed 11170940]

525. Centers for Disease Control and Prevention. CDC health information for international travel, 2014. Atlanta, GA: US Department of Health and Human Services. Updates may be available at CDC website.

671. Griffith DE, Aksamit T, Brown-Elliott BA et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007; 175:367-416. [PubMed 17277290]

681. Centers for Disease Control and Prevention. Diagnosis and management of foodborne illnesses: a primer for physicians. MMWR Recomm Rep. 2001; 50(RR-2):1-69.

Hide
(web4)