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Medication News & Update

AMDA dosing of LEVAQUIN (levofloxacin)  for pneumonia missed something important!

  The American Medical Director Association recently published in a newsletter

dosing guidelines for treatment of pneumonia. While these guidelines are in line with the recommendations from Centers For Disease Control they made no mention of adjustment considerations for dosing in patients with renal impairment. The majority of elderly nursing home patients average range of renal function falls within a range of 30-45ml/min indicating moderate to sever renal impairment. The manufacturer recommendations and clinical literature indicate reduction of dosage by 50% for such patients. This is certainly an important consideration which should have been addressed by an organization whose patient population is mostly comprised of individuals falling into such a category with respect to renal function. The quinolones are very efficacious antibiotics but are not without risk to this frail elderly group. This class of antibiotics poses the following risk :

Peripheral Neuropathy
Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving quinolones.
 

QUINOLONES MAY HAVE THE POTENTIAL TO PROLONG THE QTc INTERVAL OF THE ELECTROCARDIOGRAM IN SOME PATIENTS. DUE TO THE LACK OF CLINICAL EXPERIENCE, GATIFLOXACIN SHOULD BE AVOIDED IN PATIENTS WITH KNOWN PROLONGATION OF THE QTc INTERVAL, PATIENTS WITH UNCORRECTED HYPOKALEMIA, AND PATIENTS RECEIVING CLASS IA (E.G. QUINIDINE, PROCAINAMIDE) OR CLASS III (E.G. AMIODARONE, SOTALOL) ANTIARRHYTHMIC AGENTS.

Ruptures of the shoulder, hand, and Achilles tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones. Tendon rupture can occur during or after therapy with quinolones.

Quinolones may cause central nervous system (CNS) events including nervousness, agitation, insomnia, anxiety, nightmares, or paranoia.

As with other quinolones, disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic (e. g., glyburide) or with insulin. In these patients, the monitoring of blood glucose is recommended.

  Just some food for thought when prescribing your next dose of levofloxacin 500mg  daily for 5 days for pneumonia. Please consider reducing that dose to 250mg daily for 5 days.

 Levaquin information

Levofloxacin
Iquix® | Levaquin® | Quixin | Quixin™

Classification:
• Antiinfective Agents
    • Quinolones
• Ophthalmic Agents
    • Ophthalmic Antiinfectives
        • Quinolones

Description, Mechanism of Action, Pharmacokinetics

Description: Levofloxacin is a fluoroquinolone antiinfective available for oral, intravenous, or ophthalmic administration. It is the optically active L-isomer of ofloxacin. Systemic levofloxacin has a slightly longer half-life than ofloxacin and can be administered once-daily. Levofloxacin is approximately twice as potent in vitro as ofloxacin against a variety of aerobic gram-positive and gram-negative bacteria, including tubercle bacilli. Pseudomonas aeruginosa and Enterococcus faecalis are only moderately susceptible, while Serratia marcescens is resistant. Because plasma concentrations of levofloxacin are similar after intravenous or oral administration, these routes can be considered interchangeable. Unlike ciprofloxacin, levofloxacin does not interact significantly with theophylline. Levofloxacin is FDA approved for the treatment of bacterial conjunctivitis, sinusitis, chronic bronchitis, community-acquired pneumonia (including cases caused by penicillin-resistant strains of Streptococcus pneumoniae), skin and skin structure infections, complicated urinary tract infections and acute pyelonephritis. Levofloxacin tablets and injection were FDA approved for the treatment of these infections on December 20, 1996; a subsequent approval for treatment of nosocomial pneumonia was granted in November 2002. Two levofloxacin ophthalmic solutions, Quixin™ (0.5% levofloxacin) and Iquix™ (1.5% levofloxacin), are also FDA-approved. Quixin™ was approved August 22, 2000 for the treatment of bacterial conjunctivitis and Iquix™ was approved March 1, 2004 for treatment of bacterial corneal ulcers. An oral solution was approved November 2004.

Mechanism of Action: Levofloxacin inhibits bacterial topoisomerase IV and DNA gyrase, both of which are type II topoisomerases. Topoisomerases alter DNA by introducing superhelical twists into double-stranded DNA and by facilitating unwinding of DNA strands. DNA gyrase has two subunits encoded by the gyrA gene (A subunits) which cause strand breaks on a bacterial chromosome and then reseal the chromosome after supercoiling. Levofloxacin and other fluoroquinolones inhibit the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription. Although human cells do not contain DNA gyrase, they do contain a topoisomerase enzyme that functions in the same manner. This mammalian enzyme is not affected by bactericidal concentrations of quinolones.

Levofloxacin is approximately twice as potent in vitro as ofloxacin and is bactericidal against a variety of aerobic gram-positive and gram-negative bacteria; it exhibits 2-fold greater inhibitor and bactericidal activities than ofloxacin against tubercle bacilli. Fluoroquinolones, including levofloxacin, exhibit concentration-dependent killing; both the AUC/MIC and Cmax/MIC ratios have been shown to correlate with efficacy. Levofloxacin exhibits a post-antibiotic effect (PAE) against many gram-positive and gram-negative organisms. Organisms may not resume growth for about 0.5—4 hours after exposure to levofloxacin, despite undetectable drug levels.

Levofloxacin has been shown to be active in vitro and in clinical infections against Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus pyogenes, Enterobacter cloacae, Escherichia coli, Haemophilus sp., Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, and Pseudomonas aeruginosa. Although it is active against staphylococcus, development of resistance to other fluoroquinolones suggests that staphylococcus resistance may also become a problem with levofloxacin. In addition, levofloxacin is only moderately active against Enterococcus faecalis and Pseudomonas aeruginosa and is only indicated for the treatment of urinary tract infection caused by these organisms.

Pharmacokinetics: Levofloxacin can be administered orally, intravenously, or ophthalmically. Following oral administration, levofloxacin is rapidly absorbed and has an absolute bioavailability of about 99%. Food does not appear to significantly affect bioavailability. Peak plasma concentrations are achieved approximately 1—2 hours after an oral dose. Mean peak and trough plasma concentrations following multiple once-daily 500 mg doses are 5.7 mcg/ml and 0.5 mcg/ml, respectively, with oral dosing and 6.4 mcg/ml and 0.6 mcg/ml, respectively, with intravenous dosing. After intravenous dosing, women appear to have increased exposure to levofloxacin compared to men. A pharmacokinetic study in healthy men and women reported that women had a 24% greater exposure to levofloxacin and a slower clearance.[8639] After ophthalmic administration, a small amount of levofloxacin is systemically absorbed. Levofloxacin is about 24—38% bound to serum proteins, primarily albumin, and is widely distributed into body tissues; lung tissue concentrations are approximately 2—5 times higher than plasma concentrations. Levofloxacin undergoes limited metabolism and approximately 87% of a dose is excreted unchanged in urine. The only metabolites identified in humans are the desmethyl and N-oxide metabolites; these inactive metabolites account for <5% of a dose. Renal clearance of levofloxacin is greater than glomerular filtration, suggesting active tubular secretion. The mean elimination half-life of levofloxacin is 6—8 hours and is prolonged in patients with renal impairment.

Description, Mechanism of Action, Pharmacokinetics last revised 1/10/2006 1:43:00 PM

Indications

† non-FDA-approved indication

Dosage

NOTE: To reduce the development of drug-resistant bacteria and maintain the effectiveness of antibacterial drugs, this drug should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

The following organisms are generally considered susceptible to levofloxacin in vitro; however, safety and effectiveness in treating clinical infections due to these microorganisms may not be established: Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter lwoffii; Bacillus anthracis†; Bordetella pertussis; Campylobacter jejuni†; Chlamydia pneumoniae; Chlamydia trachomatis†; Citrobacter diversus; Citrobacter freundii; Clostridium perfringens; Corynebacterium jeikeium†; Enterobacter aerogenes; Enterobacter agglomerans; Enterobacter cloacae; Enterobacter sakazakii; Enterococcus faecalis (many strains are only moderately susceptible); Escherichia coli; Haemophilus influenzae (beta-lactamase negative); Haemophilus influenzae (beta-lactamase positive); Haemophilus parainfluenzae; Helicobacter pylori†; Klebsiella oxytoca; Klebsiella pneumoniae; Legionella pneumophila; Listeria monocytogenes†; Moraxella catarrhalis; Morganella morganii; Mycobacterium tuberculosis†; Mycoplasma pneumoniae; Neisseria gonorrhoeae†; Peptostreptococcus sp.†; Propionibacterium sp.†; Proteus mirabilis; Proteus vulgaris; Providencia rettgeri; Providencia stuartii; Pseudomonas aeruginosa; Pseudomonas cepacia†; Pseudomonas fluorescens; Salmonella sp.†; Serratia marcescens; Shigella sp.†; Staphylococcus aureus (MSSA); Staphylococcus epidermidis; Staphylococcus saprophyticus; Streptococcus agalactiae (group B streptococci); Streptococcus pneumoniae (including penicillin-resistant strains); Streptococcus pyogenes (group A beta-hemolytic streptococci); Vibrio parahaemolyticus†; Viridans streptococci; Yersinia enterocolitica†; Yersinia pestis†.

For the treatment of acute bacterial sinusitis due to H. influenzae, M. catarrhalis, or S. pneumoniae:
Oral dosage:
Adults: 500 mg PO every 24 hours for 10—14 days, alternatively, 750 mg PO every 24 hours for 5 days (e.g., Leva-pak®).
Intravenous dosage:
Adults: 500 mg IV administered over 60 minutes every 24 hours for 10—14 days or 750 mg IV administered over 90 minutes every 24 hours.

For the treatment of urinary tract infection (UTI):
•for the treatment of mild to moderate complicated UTI due to E. cloacae, E. faecalis, E. coli, K. pneumoniae, P. mirabilis, or P. aeruginosa:
Oral dosage:
Adults: 250 mg PO every 24 hours for 10 days.
Intravenous dosage:
Adults: 250 mg IV administered over 60 minutes every 24 hours for 10 days.
•for the treatment of uncomplicated UTI (mild to moderate acute cystitis) in women due to E. coli, K. pneumoniae, or S. saprophyticus:
Oral dosage:
Adults: 250 mg PO every 24 hours for 3 days.

For the treatment of acute pyelonephritis caused by E. coli:
Oral dosage:
Adults: 250 mg PO every 24 hours for 10 days.
Intravenous dosage:
Adults: 250 mg IV administered over 60 minutes every 24 hours for 10 days.

For the treatment of acute bacterial exacerbation of chronic bronchitis due to H. influenzae, H. parainfluenzae, M. catarrhalis, S. aureus, or S. pneumoniae:
Oral dosage:
Adults: 500 mg PO every 24 hours for 7 days.
Intravenous dosage:
Adults: 500 mg IV administered over 60 minutes every 24 hours for 7 days.

For the treatment of pneumonia:
•for the treatment of nosocomial pneumonia due to methicillin-susceptible S. aureus, P. aeruginosa, S. marcescens, E. coli, K. pneumoniae, H. influenzae, or S. pneumoniae:
Intravenous followed by oral dosage:
Adults: Initially, 750 mg IV every 24 hours. When clinically indicated, switch to 750 mg PO every 24 hours for a total of 7—15 days of therapy.
•for the treatment of community-acquired pneumonia (CAP) in adult outpatients, adult patients treated in the nursing home, or in adult inpatients in whom Pseudomonas infection is NOT an issue and are either on medical ward, in the ICU, and/or are b-lactam sensitive:
Oral or Intravenous dosage:
Adults: 750 mg PO/IV every 24 hours for 5 days (can be accomplished using Leva-Pak®). Another approved regimen is 500 mg PO/IV every 24 hours for 7—14 days.[5151][8697][8698]
•for the treatment of CAP in adult ICU patients in whom Pseudomonas infection is an issue:
Oral or Intravenous dosage:
Adults: 750 mg PO/IV every 24 hours in combination with an antipseudomonal agent plus an aminoglycoside.[8697][8698] NOTE: Use of aminoglycosides in elderly patients appear to be associated with worse outcomes.[8699]
•for the treatment of CAP in adult ICU patients with b-lactam sensitivity and in whom Pseudomonas infection is an issue:
Oral or Intravenous dosage:
Adults: 750 mg PO/IV every 24 hours in combination with aztreonam.[8697][8698]

For the treatment of uncomplicated mild to moderate skin and skin structure infections including an abscess, cellulitis, furunculosis, impetigo, pyoderma, or wound infections due to S. aureus or S. pyogenes:
Oral dosage:
Adults: 500 mg PO every 24 hours for 7—10 days.
Intravenous dosage:
Adults: 500 mg IV administered over 60 minutes every 24 hours for 7—10 days.
•for the treatment of mild, moderate, or severe complicated skin and skin structure infections due to methicillin-sensitive S. aureus, E. faecalis, S. pyogenes, or P. mirabilis:
Oral or Intravenous dosage:
Adults: 750 mg PO/IV once daily for 7—14 days.

For the treatment of infections due to Chlamydia trachomatis† or Neisseria gonorrhoeae† (gonorrhea†):
NOTE: Due to the increased prevalence of quinolone-resistant N. gonorrhoeae, the CDC recommends that fluoroquinolones should not be used for the treatment of gonorrhea that may have been acquired in Asia, the Pacific Islands (including Hawaii), California, or any area with increased quinolone-resistant N. gonorrhoeae (i.e., England or Wales). In addition, the CDC recommends that quinolones not be used as first line treatment of gonorrhea in men who have sex with men.[5257]
•for the treatment of non-gonococcal urethritis (NGU)† or cervicitis caused by Chlamydia trachomatis†:
Oral dosage:
Adults and adolescents: The CDC recommends 500 mg PO once daily for 7 days as an alternative to doxycycline or azithromycin, which are considered first-line agents.[1632]
•for the treatment of uncomplicated gonorrhea† (e.g., cervicitis†, proctitis†, or urethritis†):
Oral dosage:
Adults and adolescents: The CDC recommends 250 mg PO as a single dose in combination with a regimen effective against uncomplicated genital C. trachomatis infection (e.g., azithromycin as a single dose or doxycycline for 7 days), if chlamydial infection is not ruled out.[1632]
•for the treatment of disseminated gonococcal infection in patients allergic to beta-lactam drugs†:
Intravenous and oral dosage:
Adults and adolescents: The CDC recommends 250 mg IV every 24 hours. Parenteral levofloxacin should be continued for 24—48 hours after clinical improvement begins, at which time therapy may be switched to oral levofloxacin 500 mg PO once daily to complete a 7 day treatment course.[1632]

For the treatment of acute or chronic bacterial prostatitis or epididymitis†:
Oral dosage:
Adults: For chronic bacterial prostatitis, the approved dose is 500 mg PO once daily for 28 days. In a noncomparative study, levofloxacin 200—600 mg/day PO was administered for 3—14 days to a small number of patients with acute or chronic prostatitis or epididymitis; clinical cure rates were 100% in patients with acute prostatitis, 74% in patients with chronic prostatitis, and 88% in those with epididymitis.[1506] Levofloxacin is only available as 250 mg or 500 mg tablets in the US; potential differences in bioavailability between formulations in the US and those used in this study should be taken into account.
•for the treatment of epididymitis† most likely caused by enteric organisms, or for patients allergic to cephalosporins and/or tetracyclines:
Oral dosage:
Adults and adolescents: The CDC recommends 500 mg PO once daily for 10 days.[1632]

For the treatment of pelvic inflammatory disease (PID):
Intravenous dosage:
Adults and adolescents: The CDC recommends levofloxacin 500 mg IV once daily with or without metronidazole IV, depending on clinical presentation and local resistance patterns, as an alternative to first-line regimens. Parenteral therapy may be discontinued 24 hours after a patient improves clinically; oral therapy (see oral dosage) should be continued to complete a total treatment course of 14 days.[1632]
Oral dosage:
Adults and adolescents: 500 mg PO once daily for 14 days. The CDC recommends levofloxacin 500 mg PO once daily with or without metronidazole PO, depending on clinical presentation and local resistance patterns, for 14 days. Patients who do not respond to oral therapy within 72 hours should be switched to parenteral therapy.[1632]

For the treatment of obstetric infections† and gynecologic infections† (including intrauterine infection, cervicitis†, adnexitis, bartholinitis, Bartholin's abscess and mastitis) caused by C. trachomatis†, E. coli, Peptostreptococcus sp.†, S. aureus, Streptococcus sp.:
Oral dosage:
Adults: In a non-comparative trial of 197 women with various obstetric and gynecologic infections, levofloxacin 200—300 mg/day PO in divided doses for 3—14 days improved clinical symptoms in 93% of patients. Chlamydia trachomatis was eradicated in 93% of patients; eradication rates of >95% were observed for other commonly isolated organisms.[1507] Levofloxacin is only available as 250 mg or 500 mg tablets in the US; potential differences in bioavailability between formulations in the US and those used in this study prevent definitive dosage recommendations for this indication.

For the treatment of otitis media†, otitis externa†, tonsillitis†, pharyngitis†, or sialadenitis† due to H. influenzae, M. catarrhalis, P. aeruginosa, Staphylococcus sp., or Streptococcus sp.:
NOTE: Efficacy rates were lower in patients with Pseudomonas aeruginosa infection than in patients with infection due to other organisms.
Oral dosage:
Adults: In noncomparative studies, administration of levofloxacin 100—200 mg PO 2—3 times per day for 3—14 days resulted in clinical efficacy rates of 74—92% and bacteriologic eradication rates of 80—97%.[1508] [1509] Levofloxacin is only available as 250 mg or 500 mg tablets in the US; potential differences in bioavailability between formulations in the US and those used in this study prevent definitive dosage recommendations for this indication.

For use in combination with amoxicillin and rabeprazole for eradication of Helicobacter pylori† infection:
Oral dosage:
Adults: A prospective, open label study evaluated the effectiveness of levofloxacin-based dual (levofloxacin/rabeprazole) and triple (levofloxacin/amoxicillin/rabeprazole) therapy in eradicating H. pylori. Patients (n=160) were randomized into 4 groups (3 dual and 1 triple therapy regimen). The dual regimens consisted of levofloxacin 500 mg PO once daily with rabeprazole (20 mg PO once daily) for 5, 7, or 10 days. The triple regimen included levofloxacin 500 mg PO once daily, amoxicillin (1000 mg PO twice daily), and rabeprazole (20 mg PO once daily) for 7 days. Triple therapy resulted in a significantly higher eradication rate (> 90%) than dual therapy at any duration (<= 70%).[3937]

For the treatment of bacterial gastroenteritis† caused by Campylobacter jejuni†, Salmonella sp.†, or Shigella sp.†:
Oral dosage:
Adults: In noncomparative studies, levofloxacin 200—300 mg/day PO for 5—7 days resulted in a clinical cure rate of 97% in 114 patients with bacterial gastroenteritis and bacteriologic eradication rates of 99% for Shigella sp., and 71% for Campylobacter jejuni and Salmonella sp.[1510] Levofloxacin is only available as 250 mg or 500 mg tablets in the US; potential differences in bioavailability between formulations in the US and those used in this study prevent definitive dosage recommendations for this indication.

For the treatment of bacterial conjunctivitis caused by Acinetobacter lwoffii, Corynebacterium species, S. aureus, H. influenzae, S. epidermidis, S. marcescens, S. pneumoniae, Streptococcus (groups C/F), Streptococcus (group G), or Viridans streptococci:
Ophthalmic dosage (Quixin™):
Adults and children: On days 1 and 2, instill 1—2 drops of a 0.5% levofloxacin ophthalmic solution in affected eye(s) every 2 hours while awake up to 8 times per day. On days 3 through 7, instill 1—2 drops in affected eye(s) every 4 hours while awake up to 4 times per day.
•for the treatment of bacterial corneal ulcer due to Corynebacterium species, P. aeruginosa, S. marcescens, S. aureus, S. epidermidis, S. pneumoniae, or Viridans streptococci:
Ophthalmic dosage (Iquix®):
Adults and children: On days 1 through 3, instill 1—2 drops of a 1.5% levofloxacin ophthalmic solution in affected eye(s) every 30 minutes to 2 hours while awake and approximately 4 and 6 hours after retiring. On days 4 through treatment completion, instill 1—2 drops in affected eye(s) every 1—4 hours while awake.
•for the treatment of other ophthalmic infection† including hordeolum, chronic dacryocystitis, and meibomianitis:
Oral dosage:
Adults: In noncomparative studies of 108 patients with ophthalmic infections, levofloxacin 100 mg PO three times per day for 3—14 days resulted in clinical and bacteriologic efficacy rates of 92% and 88%, respectively.[1511] Levofloxacin is only available as 250 mg or 500 mg tablets in the US; potential differences in bioavailability between formulations in the US and those used in this study prevent definitive dosage recommendations for this indication.

For the treatment of osteitis† of the jaw, periodontitis†, or pericoronitis† caused by Streptococcus sp. and gram-positive anaerobes:
Oral dosage:
Adults: In noncomparative studies of 203 patients with odontogenic infection, levofloxacin 200—300 mg/day PO for 3—14 days resulted in clinical and bacteriologic efficacy rates of 83% and 87%, respectively.[1512] Levofloxacin is only available as 250 mg or 500 mg tablets in the US; potential differences in bioavailability between formulations in the US and those used in this study prevent definitive dosage recommendations for this indication.

For the initial treatment of anthrax† infection due to exposure to Bacillus anthracis as an alternative to ciprofloxacin:
NOTE: Recommendations for pregnant and immunosuppressed persons are the same as for non-pregnant or non-immunosuppressed persons.[3370]
•for inhalation anthrax infection in the contained casualty setting:
Intravenous dosage:
Adults: In vitro studies suggest levofloxacin 500 mg IV every 24 hours could be substituted for ciprofloxacin. Total treatment is for 60 days; switch to oral therapy as soon as possible. Postexposure vaccination might permit the duration of antibiotic therapy to be shortened to 30—45 days, with concomitant administration of the anthrax vaccine at weeks 0, 2, and 4. If antibiotic susceptibility testing allows, intravenous penicillin or, as third-line, intravenous doxycycline could be used as alternatives. The risk of serious infection following anthrax exposure supports the use of fluoroquinolones as initial therapy in pregnant women; change to alternatives when possible. Women who are breast-feeding should be treated with the same antibiotic as the infant.[3370]
•for inhalation anthrax infection in the mass casualty setting:
Oral dosage:
Adults: In vitro studies suggest levofloxacin 500 mg PO every 24 hours for a total of 60 days could be substituted for ciprofloxacin. If antibiotic susceptibility testing allows, amoxicillin or, as third-line, doxycycline could be used as alternatives. The risk of serious infection following anthrax exposure supports the use of fluoroquinolones as initial therapy in pregnant women; change to alternatives when possible. Women who are breast-feeding should be treated with the same antibiotic as the infant.[3370]
•for cutaneous anthrax infection:
Oral dosage:
Adults: In vitro studies suggest levofloxacin 500 mg PO every 12 hours for a total of 60 days could be substituted for ciprofloxacin. If antibiotic susceptibility testing allows, amoxicillin or doxycycline might be substituted for levofloxacin. The risk of serious infection following anthrax exposure supports the use of fluoroquinolones as initial therapy in pregnant women; amoxicillin should be substituted for levofloxacin when possible.[3370]

For anthrax prophylaxis† as an alternative to ciprofloxacin following exposure to Bacillus anthracis regardless of the route of exposure:
Oral dosage:
Adults: In vitro studies suggest levofloxacin 500 mg PO every 12 hours for a total of 60 days could be substituted for ciprofloxacin. The risk of serious infection following anthrax exposure supports the use of fluoroquinolones as initial therapy in pregnant women; amoxicillin should be substituted for levofloxacin if susceptibility testing allows.[3370]

For the treatment of plague† infection due to exposure to Yersinia pestis†:
•for the treatment of plague† in an individual patient or in a contained casualty setting:
NOTE: Streptomycin is the drug of choice to treat plague in most patients; gentamicin is the preferred agent in pregnant women.[3371]
Intravenous dosage:
Adults and adolescents: In vitro studies suggest that levofloxacin 500 mg IV every 12 hours for 10 days can be used. If antibiotic susceptibility testing allows, intravenous streptomycin or gentamicin, or, as third-line, intravenous doxycycline, ciprofloxacin, or chloramphenicol could be used as alternatives. The risk of serious infection following plague exposure supports the use of fluoroquinolones as initial therapy in pregnant women; change to alternatives when possible. Women who are breast-feeding should be treated with the same antibiotic as the infant.[3371]
•for the treatment of plague† in a mass casualty setting:
NOTE: Doxycycline is the treatment of choice for plague in the mass casualty setting.[3371]
Oral dosage:
Adults and adolescents: In vitro studies suggest that levofloxacin 500 mg PO every 12 hours for 10 days can be used. If antibiotic susceptibility testing allows, doxycycline, ciprofloxacin, or chloramphenicol could be used as alternatives. The risk of serious infection following plague exposure supports the use of fluoroquinolones as initial therapy in pregnant women; change to alternatives when possible. Women who are breast-feeding should be treated with the same antibiotic as the infant.[3371]

For plague prophylaxis† following exposure to Yersinia pestis†:
NOTE: Doxycycline is the treatment of choice for plague prophylaxis.
Oral dosage:
Adults and adolescents: In vitro studies suggest that levofloxacin 500 mg PO every 12 hours for 7 days can be used. If antibiotic susceptibility testing allows, doxycycline, ciprofloxacin, or chloramphenicol could be used as alternatives. The risk of serious infection following plague exposure supports the use of fluoroquinolones as initial therapy in pregnant women; change to alternatives when possible. Women who are breast-feeding should be treated with the same antibiotic as the infant.[3371]

For the treatment of severe acute respiratory syndrome (SARS)†:
NOTE: Other than supportive care, there is no established treatment for SARS. SARS is associated with a virus and the use of an antibacterial agent is based on an empiric treatment protocol.[4114]
Oral or Intravenous dosage:
Adults: 500 mg PO or IV once daily, adding ribavirin and corticosteroids on evidence of worsening disease.[4114]

Maximum Dosage Limits:
•Adults: Usually 750 mg/day PO or IV; occasionally higher dosages have been suggested.
•Elderly: Usually 750 mg/day PO or IV; occasionally higher dosages have been suggested.
•Adolescents: Maximum dosage information not available.
•Children: Safe and effective use not established for systemic dosage.

Patients with hepatic impairment:
No dosage adjustment needed.

Patients with renal impairment:
Acute bacterial exacerbation of bronchitis, community acquired pneumonia, uncomplicated skin and skin structure infections, and chronic bacterial prostatitis:
CrCl >= 50 ml/min: No dosage adjustment needed.
CrCl 20—49 ml/min: Initial dose is 500 mg PO/IV, followed by 250 mg PO/IV every 24 hours.
CrCl 10—19 ml/min: Initial dose is 500 mg PO/IV, followed by 250 mg PO/IV every 48 hours.
Community acquired pneumonia and acute bacterial sinusitis:
CrCl >= 50 ml/min: No dosage adjustment needed.
CrCl 20—49 ml/min: Initial dose is 500 or 750 mg PO/IV depending on organisms being treated. Patients receiving 500 mg PO/IV should receive subsequent doses of 250 mg PO/IV every 24 hours. Those receiving 750 mg PO/IV should receive subsequent doses of 750 mg PO every 48 hours.
CrCl 10—19 ml/min: Initial dose is 500 or 750 mg PO/IV depending on organisms being treated. Patients receiving 500 mg PO/IV should receive subsequent doses of 250 mg PO/IV every 48 hours. Those receiving 750 mg PO/IV should receive subsequent doses of 500 mg PO every 48 hours.
Complicated skin and skin structure infections and nosocomial pneumonia:
CrCl >= 50 ml/min: No dosage adjustment needed.
CrCl 20—49 ml/min: Initial dose is 750 mg PO/IV, followed by 750 mg PO/IV every 48 hours.
CrCl 10—19 ml/min: Initial dose is 750 mg PO/IV, followed by 500 mg PO/IV every 48 hours.
Complicated urinary tract infection and acute pyelonephritis:
CrCl >= 20 ml/min: No dosage adjustment needed.
CrCl 10—19 ml/min: Initial dose is 250 mg PO/IV, followed by 250 mg PO/IV every 48 hours.
Uncomplicated urinary tract infection:
No dosage adjustment required.

Intermittent hemodialysis:
The initial dose is 500 or 750 mg PO/IV depending on infection being treated. Patients receiving 500 mg PO/IV should receive subsequent doses of 250 mg PO/IV every 48 hours. Those receiving 750 mg PO/IV should receive subsequent doses of 500 mg PO every 48 hours. Levofloxacin is not significantly removed from the body during hemodialysis.

Peritoneal dialysis:
The initial dose is 500 or 750 mg PO/IV depending on infection being treated. Patients receiving 500 mg PO/IV should receive subsequent doses of 250 mg PO/IV every 48 hours. Those receiving 750 mg PO/IV should receive subsequent doses of 500 mg PO every 48 hours. Levofloxacin is not significantly removed from the body during peritoneal dialysis.

†non-FDA-approved indication

Indications...Dosage last revised 2/6/2006 3:15:00 PM

Administration Guidelines

NOTE: Levofloxacin is not recommended for use in persons under 18 years of age, or in pregnant or lactating women. Levofloxacin causes arthropathy and osteochondrosis in juvenile animals of several species.

Oral Administration
•Tablets: Levofloxacin tablets can be taken with or without food; however, they should be taken at least two hours before or two hours after any antacid, multivitamin, or other medication that contains divalent or trivalent cations.
•Oral solution: Take 1 hour before or 2 hours after eating. The oral solution should also be taken at least two hours before or two hours after any antacid, multivitamin, or other medication that contains divalent or trivalent cations.

Ophthalmic Administration
•Apply topically to the eye taking care to avoid contamination. For ophthalmic use only. Do not inject subconjunctivally or introduce directly into the anterior chamber of the eye.
•Instruct patient on proper instillation of eye solution (see Patient Information).
•Do not to touch the tip of the dropper to the eye, fingertips, or other surface.

Intravenous Administration
•Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
•500 mg/20 ml vials: To prepare a dosage of 250 mg or 500 mg, withdraw 10 ml or 20 ml, respectively, from a 20 ml vial and dilute with a compatible intravenous solution (e.g., D5W, NS) to a total volume of 100 ml. The concentration of the diluted solution should be 5 mg/ml prior to administration. Solutions contain no preservatives; any unused portions must be discarded.
•750 mg/30 ml vials: To prepare a dosage of 750 mg, withdraw 30 ml from a 30 ml vial and dilute with a compatible intravenous solution (e.g., D5W, NS) to a total volume of 100 ml. The concentration of the diluted solution should be 5 mg/ml prior to administration. Solutions contain no preservatives; any unused portions must be discarded.
•Premixed levofloxacin injection: No dilution is necessary.

Intravenous infusion:
•Infuse doses of <= 500 mg IV over 60 minutes and doses of 750 mg IV over 90 minutes. Shorter infusions or bolus injections should be avoided because of the risk of hypotension.

Administration last revised 8/8/2005 6:58:00 PM

Contraindications/Precautions

• Absolute contraindications are in italics.

This drug does not treat viral infection (e.g., common cold). Prescribing levofloxacin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Patients should be told to complete the full course of treatment, even if they feel better earlier.

The safe and effective use of levofloxacin has not been established in children and adolescents below the age of 18 years. Fluoroquinolones, including levofloxacin, cause arthropathy and osteochondrosis in juvenile animals of several species.

Levofloxacin can cause increased intracranial pressure and CNS stimulation, which may lead to convulsions or toxic psychosis (see Adverse Reactions). Thus, levofloxacin should be used with caution in patients with a known or suspected CNS disorders (e.g., seizure disorder, severe cerebrovascular disease), or in the presence of other risk factors (e.g., certain drug therapy, renal dysfunction) that may predispose to seizures or lower seizure threshold.

Levofloxacin is contraindicated in patients with known quinolone hypersensitivity. Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have occurred even after the first dose of the drug. Levofloxacin should be immediately discontinued at the first appearance of a skin rash or any other sign of hypersensitivity (see Adverse Reactions).

Treatment with an antibacterial agent, including levofloxacin, can alter the normal flora of the colon and allow overgrowth of Clostridium difficile. Pseudomembranous colitis may develop from a toxin produced by Clostridium difficile. Therefore, this diagnosis should be considered in any patient who presents with diarrhea after administration of levofloxacin.

Whenever clinical judgment dictates, patients receiving ophthalmic levofloxacin should be examined with the aid of magnification, such as slitlamp biomicroscopy, and where appropriate, fluorescein staining. Patients should be advised not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis.

Because fluoroquinolones have been associated with tendon rupture, levofloxacin should be discontinued at the first sign of tendon pain.

Levofloxacin should be used with caution in patients who have dehydration. Although levofloxacin is more soluble than other quinolones, adequate hydration should be maintained to ensure the formation of a dilute urine, thereby preventing crystalluria.

Levofloxacin is extensively eliminated by the kidneys. Administer with caution in patients with renal impairment and adjust levofloxacin dosage in patients with a creatinine clearance less than 50 ml/minute (see Dosage).

Moderate to severe phototoxicity reactions have been observed in patients exposed to direct sunlight while receiving a fluoroquinolone.[7476] Although phototoxicity has occurred only rarely during levofloxacin therapy, patients should avoid excessive sunlight (UV) exposure. Therapy should be discontinued if phototoxicity occurs.

Disturbances of blood glucose have been reported in patients with diabetes mellitus who were receiving an oral hypoglycemic agent or insulin concomitantly with levofloxacin (see Adverse Reactions); careful monitoring of blood glucose is recommended.

Levofloxacin is classified as pregnancy category C. There are no adequate and well-controlled studies in pregnant women. However, levofloxacin was associated with decreased fetal body weight and increased fetal mortality when administered to rats at dosages greatly exceeding those used in humans (based on surface area or body weight). Therefore, levofloxacin should be used during pregnancy only when the potential benefit outweighs the potential risk to the fetus.

Levofloxacin is an optical isomer of ofloxacin. There are no data on the pharmacokinetics of levofloxacin in lactating women. Based on data with ofloxacin, it can be presumed that levofloxacin is excreted in human breast milk. Fluoroquinolones have been associated with arthropathy in juvenile animals of several species. The manufacturer states that because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue levofloxacin therapy.[5151] Two other fluoroquinolones, ciprofloxacin and ofloxacin, are considered to be compatible with breast-feeding by the American Academy of Pediatrics.[4201]

Some quinolones, including levofloxacin, have been associated with QT prolongation and infrequent cases of arrhythmia. During post-marketing surveillance, rare cases of torsade de pointes have been spontaneously reported in patients receiving quinolones, including levofloxacin. Levofloxacin should be avoided in patients with known QT prolongation, patients with uncorrected hypokalemia, and patients receiving class IA or class III antiarrhythmic agents (see Drug Interactions).

No overall safety differences have been noted with the use of levofloxacin in the elderly compared to use in younger adults. The pharmacokinetics of levofloxacin did not differ significantly when creatinine clearance is considered. Since levofloxacin is known to be substantially excreted by the kidney and elderly patients may also have decreased renal function, care should be taken in dose selection. It may be useful to monitor renal function. Additionally, elderly patients may be more susceptible to drug-associated effects on the QT interval. Therefore, caution is advised when using levofloxacin with concomitant drugs that can result in prolongation of the Q T interval or in patients with risk factors for torsades de pointes.

Levofloxacin is not effective for treating syphilis. Use of high doses of antibiotics for short periods of time to treat gonorrhea may mask or delay the symptoms of incubating syphilis. Serologic test for syphilis should be done at the time of diagnosis of gonorrhea. Patients treated with levofloxacin should have a follow-up serologic test for syphilis after three months.

Contraindications last revised 10/19/2005 2:09:00 PM

Drug Interactions

Oral quinolone absorption may be reduced by concurrent medications. Quinolone antibiotics can chelate with divalent or trivalent cations.[4690] [5151] The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain aluminum salts (like aluminum hydroxide), calcium salts (including calcium carbonate), iron salts, magnesium salts, and/or zinc salts. Chelation of divalent cations with levofloxacin is less than with other fluoroquinolones; nevertheless, compounds that contain divalent or trivalent cations should be taken at least 2 hours before or 2 hours after orally administered levofloxacin.[5151] Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids (e.g., aluminum hydroxide, magnesium hydroxide, calcium carbonate or combination antacids containing aluminum, magnesium or calcium); sucralfate; magnesium citrate; magnesium salicylate; polysaccharide-iron complex; quinapril (tablets contain magnesium); and multivitamins that contain iron, calcium, manganese, or zinc.[5151] It is not yet clear if bismuth subsalicylate (Pepto-Bismol®) can interfere with fluoroquinolone bioavailability.

Because many food products contain divalent or trivalent cations, these foods may significantly decrease the absorption of levofloxacin. Clinicians should warn patients about all dairy products and other high calcium- and iron-containing foods. These foods should be taken at least 2 hours before or 2 hours after orally administered levofloxacin.[5151] Enteral feedings may also affect the serum concentrations of quinolone antimicrobials. The enteral formulation Ensure® (Ross Products Division, Abbott Laboratories, Columbus, OH) significantly decreased the serum concentrations of ciprofloxacin, levofloxacin, and ofloxacin tablets by 83%, 61%, and 46%, respectively, when they were crushed and mixed with 240 ml of Ensure®.[4116]

Some quinolones can inhibit the hepatic clearance of caffeine [4662] [4666], which is commonly found in beverages (e.g., coffee, green tea [6531], other teas, and colas), some over-the-counter medications, and dietary supplements (e.g., guarana [4679]). Some quinolone antibiotics may also inhibit the hepatic clearance of theobromine which is commonly found in teas and chocolate. Enoxacin and, to a lesser extent, ciprofloxacin, grepafloxacin, levofloxacin, and norfloxacin decrease the clearance of caffeine. The effect of ciprofloxacin is less than that of enoxacin but more significant than that of norfloxacin. Caffeine toxicity can result and can manifest as nausea/vomiting, nervousness, anxiety, tachycardia, or seizures. This interaction is dose-dependent (i.e., higher doses produce more significant inhibition). The elderly and individuals who consume large amounts of caffeine-containing beverages should receive particular attention while taking quinolone antibiotics.

Didanosine, ddI, may also decrease fluoroquinolone bioavailability due to the buffering agents in didanosine tablets and powder. Delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with quinolones.[5151] [5489]

Sevelamer could potentially interfere with the absorption of antibiotics such as the quinolones; however, no drug interaction data are available. Potential drug interactions can be minimized by administering antibiotics at least 1 hour before or 3 hours after sevelamer doses.[4827]

Concurrent use of warfarin and quinolones may result in an increased PT/INR. Patients receiving this combination should be closely monitored for adverse effects. A review of case reports submitted to the FDA show that an interaction may occur 2—16 days following the addition of quinolone therapy to a patient receiving warfarin therapy. In a study of healthy volunteers, single doses of warfarin during a multiple-dose regimen of levofloxacin did not result in changes of prothrombin times or in the concentrations of either warfarin enantiomer.[2559] The use of only a single dose of warfarin decreases the relevance of these results. There have been post-marketing reports that levofloxacin enhances the effects of warfarin. Elevations of the prothrombin time when levofloxacin and warfarin were used concurrently resulted in episodes of bleeding.[5151]

Some fluoroquinolones reduce the hepatic clearance of theophylline. In a crossover study of healthy volunteers, levofloxacin did not significantly affect the plasma concentration, AUC, or other pharmacokinetic parameters of intravenously administered theophylline. Nevertheless, because concomitant administration of other quinolones with theophylline has resulted in increased serum theophylline concentrations with a subsequent increase in risk of seizures, theophylline levels should be closely monitored when levofloxacin is coadministered.[5151]

Concomitant use of levofloxacin can result in increased serum concentrations of either cyclosporine or tacrolimus. In a clinical study involving healthy volunteers, levofloxacin did not significantly affect the pharmacokinetic disposition of cyclosporine.[5151] However, in renal transplant patients stabilized on either cyclosporine microemulsion or tacrolimus, addition of levofloxacin resulted in reduced metabolism of both cyclosporine and tacrolimus.[8776] Higher AUC values for both cyclosporine and tacrolimus were observed but increased adverse reactions and supratherapeutic serum concentrations were not noted. Serum concentrations of cyclosporine and tacrolimus should be monitored and changes made only if adverse reactions or supratherapeutic concentrations occur. In the study of healthy volunteers, cyclosporine caused a slight increase in the half-life of levofloxacin and a slight decrease in the maximum serum concentration of levofloxacin; these changes were considered to be clinically unimportant.[5151]

No significant drug interaction was detected between digoxin and levofloxacin when administered concomitantly in a clinical study involving healthy volunteers.[5151]

When probenecid or cimetidine was administered to patients receiving levofloxacin, an increase in the AUC and half-life of levofloxacin was observed. However, these changes were not substantial enough to warrant a dosage adjustment.[5151]

Hyperglycemia and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Rare cases of severe hypoglycemia have been reported with concomitant use of quinolones and glyburide. Therefore, close monitoring of blood glucose is recommended when these agents are coadministered.[5015] [5019] [5151]

The pharmacokinetic disposition of procainamide with coadministration of levofloxacin has not been studied. However, ofloxacin has been reported to reduce renal clearance of procainamide. After single doses of procainamide, peak procainamide concentrations increased from 4.8 mcg/ml before ofloxacin to 5.8 mcg/ml after ofloxacin. Renal clearance of NAPA increased slightly, but this was not statistically significant. The investigators proposed that ofloxacin impaired the active renal tubular secretion of procainamide.[5780] [5798] Because levofloxacin is the L-isomer of ofloxacin, the potential for an interaction between procainamide and levofloxacin should be considered.[5151]

Some quinolones have been associated with QT prolongation and in rare cases, torsades de pointes (TdP).[4951] [5149] [5150] Rare cases of TdP has been reported with levofloxacin.[5149] [5150] [5151] Although levofloxacin has been associated with a possible risk for TdP [4951], substantial evidence is currently lacking to establish causality.[4951] The manufacturer advises that the risk of TdP during levofloxacin therapy may be reduced by avoiding concurrent administration with class IA antiarrhythmics (disopyramide [4954], procainamide [4977], quinidine [4976]) and class III antiarrhythmics (amiodarone [4950], dofetilide [4947], ibutilide [4949], sotalol [4960]), and to avoid levofloxacin administration to patients with significant risk factors for TdP (e.g., hypokalemia, significant bradycardia, and cardiomyopathy).[5151] Examples of other general risk factors for TdP include congenital long QT syndrome, female sex, elderly patients, hypomagnesemia, and underlying cardiac disease. Other medications which may prolong the QT interval should be used cautiously with levofloxacin including: tricyclic antidepressants [4951]; certain tetracyclic antidepressants (e.g., amoxapine [5288], maprotiline [5491]); some antipsychotic medications [4951] [5381] (such as phenothiazines, haloperidol [42] [336] [5036], pimozide [5250], risperidone [5144], sertindole [5381], and ziprasidone [4959]), astemizole [140] [5130]; arsenic trioxide [4952]; bepridil [4953]; beta-agonists [4951] [5038] [5047]; cisapride [1215] [1864] [1865] [5137] [5713]; chloroquine [4951] [4955] [4956]; clozapine [5146]; cyclobenzaprine [5156] [5155]; dolasetron [5037]; droperidol [3610] [4962]; halofantrine [4968]; halothane [5188]; flecainide [331] [5016] [5484]; halogenated anesthetics [5188], levomethadyl [5079] [5081]; local anesthetics [5040] [5624] [5625]; some macrolides [4951] (e.g., clarithromycin [4964], erythromycin [327] [328] [4978], telithromycin [4880], troleandomycin [5149]); methadone [4951]; octreotide [4951]; palonosetron [5148]; pentamidine [168] [335] [5612]; probucol [5276]; propafenone [5014] [5146]; ranolazine [8747], tacrolimus [4049]; terfenadine [141] [231] [5131]; and vardenafil [4942]. This list is not inclusive of all agents that may cause QT interval prolongation.

Quinolones [7476] and retinoids [5254] may cause photosensitivity; coadminister with caution. Patients should take care and use proper techniques to limit sunlight and UV exposure. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.[7476]

The concomitant administration of quinolones, including levofloxacin, and nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk of CNS stimulation and convulsive seizures.[5151]

Doxercalciferol is converted in the liver to 1,25-dihydroxyergocalciferol, the major active metabolite, and 1-alpha, 24-dihydroxyvitamin D2, a minor metabolite. Although not specifically studied, cytochrome P450 enzyme inhibitors including quinolones may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if quinolones are coadministered with doxercalciferol.[7566] [6904]

Interactions last revised 3/2/2006 12:05:00 PM

Adverse Reactions

In clinical trials conducted in the US, the overall incidence of adverse events reported with oral levofloxacin was 6.2%. The most frequently reported adverse events were nausea/vomiting (8.7%), diarrhea (5.4%), headache (5.4%), and constipation (3.1%). Headache was also a common adverse reaction for ophthalmic levofloxacin. Other adverse events occurring in >1% of patients, regardless of relationship to oral levofloxacin therapy, were insomnia (2.9%), dizziness (2.5%), abdominal pain (2%), dyspepsia (2%), maculopapular rash (1.7%), vaginitis (1.8%), flatulence (1.6%), pruritus (1.6%), and pain (1.4%). Oral levofloxacin was discontinued in 3.7% of patients due to adverse experiences.

Convulsions and toxic psychosis have been reported in patients receiving quinolones. Quinolones may cause increased intracranial pressure and central nervous system stimulation which may lead to tremor, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, nightmares, insomnia, and rarely, seizures (<0.3%). These reactions can occur after the first dose of a fluoroquinolone; however, they are more common with elevated serum drug concentrations, especially in patients with substantial accumulation of the drug due to renal impairment. If these reactions occur in a patient receiving levofloxacin, the drug should be discontinued. As with other quinolones, levofloxacin should be used with caution in patients with a CNS disorder or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold (see Precautions).

Serious and sometimes fatal events, some due to hypersensitivity and some due to uncertain etiology, have been reported in patients receiving quinolones. Clinical manifestations may include fever, maculopapular rash or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome), allergic pneumonitis, anaphylactic shock, erythema multiforme, hemolytic anemia, or rhabdomyolysis. Many of these adverse events have been reported during the post-marketing experience with levofloxacin outside the US; however, a case of autoimmune hemolytic anemia was reported in the US following levofloxacin therapy for cellulitis.[4405] Levofloxacin should be discontinued immediately at the first appearance of a skin rash or any other sign of hypersensitivity.

Some quinolones, including levofloxacin, have been associated with QT prolongation, and torsade de pointes. During post-marketing surveillance with levofloxacin, rare cases of torsade de pointes have been reported.

Quinolones, including levofloxacin, have been associated with peripheral neuropathy. Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons have been reported. This has resulted in cases of paresthesias, hypoesthesia, dysesthesia, and weakness. Levofloxacin should be stopped if patients experience symptoms of neuropathy including pain, burning, tingling, numbness, and/or weakness, or are found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength. Cessation of therapy can prevent the development of an irreversible condition.

Treatment with an antibacterial agent, including levofloxacin, can alter the normal flora of the colon and allow overgrowth of Clostridium difficile. Pseudomembranous colitis may develop from a toxin produced by Clostridium difficile. Therefore, this diagnosis should be considered in any patient who presents with diarrhea after administration of levofloxacin.

Tendon rupture has been reported with fluoroquinolone therapy.[582] Twenty-five cases have been reported, 3 cases in the US, in patients ranging from 33 to 85 years old. Ruptures have occurred unilaterally and bilaterally, and have involved the Achilles tendon, hand tendons, or shoulder joint. Concomitant corticosteroid therapy was documented in 14 patients and may be a relevant risk factor.

Moderate to severe photosensitivity reactions have been observed in patients exposed to direct sunlight while receiving a fluoroquinolone. Although phototoxicity has occurred only rarely during levofloxacin therapy, patients should avoid excessive sunlight (UV) exposure. Levofloxacin therapy should be discontinued if photosensitivity occurs.

Disturbances of blood glucose, primarily hypoglycemia, have been reported rarely in diabetic patients receiving an oral hypoglycemic agent or insulin concomitantly with levofloxacin; careful monitoring of blood glucose is recommended. One fatality due to hypoglycemia was reported in an elderly type 2 diabetic patient who was receiving levofloxacin.[7503] Other abnormal laboratory findings reported during levofloxacin therapy included eosinophilia and leukopenia (especially decreased lymphocytes).

Rapid intravenous injection of levofloxacin may result in hypotension. Hypotension can be prevented by administering levofloxacin injection slowly over 60 minutes.

In clinical trials using multiple-dose therapy, ophthalmologic abnormalities have been reported in patients being treated with other quinolones. The relationship of the drugs to these adverse events has not been established.

Crystalluria and cylindruria have been reported with other quinolones. These adverse reactions have not yet been reported with levofloxacin therapy.

The most frequently reported (occurring in approximately 1—3% of patients) adverse reactions associated with use of ophthalmic levofloxacin was transient visual impairment/blurred vision, fever, foreign body sensation, headache, transient ocular irritation (primarily burning), ocular pain or discomfort, pharyngitis (throat irritation), and photophobia. Other reported reactions occurring in less than 1% of patients included allergic reactions, blepharedema, chemosis, corneal erosion, diplopia, floaters, hyperemia, lid erythema, ocular pruritus, and xerophthalmia.

Adverse Reactions last revised 2/10/2005 12:52:00 PM

Monitoring Parameters

Monitoring Parameters
•serum creatinine/BUN: baseline

Patient Education

Levofloxacin injection

What is levofloxacin injection?
LEVOFLOXACIN (Levaquin™) is a fluoroquinolone antibiotic. Levofloxacin kills certain bacteria or stops their growth. It is used to treat urinary tract, prostate, skin, sinus and lung infections, as well as other infections. Generic levofloxacin injections are not yet available.

What should my health care professional know before I receive levofloxacin?
They need to know if you have any of these conditions:
•dehydration
•kidney disease
•long exposure to sunlight (working outdoors)
•seizures (convulsions)
•stomach problems (especially colitis)
•stroke
•an unusual or allergic reaction to levofloxacin, fluoroquinolone antibiotics, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I use this medicine?
Levofloxacin is for slow infusion into a vein, usually over 60 minutes. It is usually given by a health care professional in a hospital or clinic. If you are told to give yourself infusions of levofloxacin, make sure you understand the procedure and follow the directions carefully. Finish the full course prescribed by your prescriber or health care professional even if you think your condition is better. Do not stop taking except on your prescriber's advice.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, use it as soon as you can. If it is almost time for your next dose, use only that dose. Do not take double or extra doses.

What drug(s) may interact with levofloxacin?
•arsenic trioxide
•astemizole
•bepridil
•caffeine
•certain heart medications for irregular rhythm (e.g., amiodarone, disopyramide, dofetilide, flecainide, ibutilide, quinidine, procainamide, sotalol)
•certain medications for depression or other mental problems (e.g., tricyclic antidepressants, amoxapine, maprotiline, phenothiazines, haloperidol, pimozide, risperidone, sertindole, and ziprasidone)
•cimetidine
•cisapride
•clarithromycin
•cyclobenzaprine
•cyclosporine
•didanosine (ddI)
•dolasetron
•doxercalciferol
•droperidol
•erythromycin
•levomethadyl
•medicines for diabetes
•NSAIDs such as Advil®, Aleve®, ibuprofen, Motrin®, naproxen
•pentamidine
•probucol
•retinoid products such as tretinoin (Retin-A®, Renova®) or isotretinoin (Accutan®)
•terfenadine
•theophylline
•troleandomycin
•warfarin

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from using levofloxacin?
Side effects that you should report to your prescriber or health care professional as soon as possible:
Rare or uncommon:
•confusion
•difficulty breathing
•irregular heartbeat, palpitations or chest pain
•joint, muscle or tendon pain
•nightmares
•changes in your thought process
•redness, blistering, peeling or loosening of the skin, including inside the mouth
•seizures
•severe or watery diarrhea
•skin rash, itching
•swelling of the face or neck
•tremor or restlessness
•vision changes
•vomiting

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•constipation or diarrhea
•difficulty sleeping
•dizziness or drowsiness
•headache
•intestinal gas or bloating
•nausea or stomach upset

What should I watch for while taking levofloxacin?
Tell your prescriber or health care professional if your symptoms do not improve in 2 to 3 days.

You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how levofloxacin affects you. To reduce the risk of dizzy or fainting spells, do not sit or stand up quickly, especially if you are an older patient.

If you are a diabetic monitor your blood glucose carefully. If you get an unusual reaction stop using levofloxacin and call your prescriber or health care professional for advice.

If you get severe or watery diarrhea, do not treat yourself. Call your prescriber or health care professional for advice.

Drink several glasses of water a day. Cut down on drinks that contain caffeine.

Keep out of the sun, or wear protective clothing outdoors and use a sunscreen. Do not use sun lamps or sun tanning beds or booths.

If you are going to have surgery, tell your prescriber or health care professional that you are using levofloxacin.

Where can I keep my medicine?
Keep out of the reach of children.

Store either at room temperature below 25 degrees C (77 degrees F), or in a refrigerator, between 2 and 8 degrees C (36 and 46 degrees F) for up to 14 days. Protect the injection solution from light or heat. Do not allow the injection solution to freeze. Follow manufacturer's advice on the storage of diluted solutions. Throw away any unused injection solution

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 08/31/2005]

Levofloxacin oral solution

What is levofloxacin oral solution?
LEVOFLOXACIN (Levaquin®) is an antibiotic. Levofloxacin kills certain bacteria or stops their growth. It is used to treat urinary tract, prostate, skin, sinus and lung infections, as well as other infections. Generic levofloxacin oral solution is not yet available.

What should my health care professional know before I take levofloxacin?
They need to know if you have any of these conditions:
•dehydration
•kidney disease
•seizures (convulsions)
•stomach problems (especially colitis)
•stroke
•an unusual or allergic reaction to levofloxacin, fluoroquinolone antibiotics, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I take this medicine?
Take levofloxacin oral solution by mouth 1 hour before, or 2 hours after eating. Do not take with magnesium/aluminum antacids, sucralfate, Videx® (didanosine) chewable/buffered tablets or pediatric powder, or with other products containing calcium, iron or zinc. Levofloxacin oral solution may be taken at least two hours before or two hours after taking these products. Use a specially marked spoon or container to measure your medicine. Ask your pharmacist if you do not have one; household spoons are not always accurate. Follow the directions on the prescription label. Take your doses at regular intervals. Do not take your medicine more often than directed. Finish the full course prescribed by your prescriber or health care professional even if you think your condition is better. Do not stop taking except on your prescriber's advice.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What drug(s) may interact with levofloxacin?
•aluminum salts
•antacids
•arsenic trioxide
•astemizole
•bepridil
•calcium salts
•caffeine
•certain heart medications for irregular rhythm (e.g., amiodarone, disopyramide, dofetilide, ibutilide, quinidine, procainamide, sotalol)
•certain medicines for depression or mental problems (e.g., amoxapine, haloperidol, maprotiline, phenothiazines, risperidone, sertindole, ziprasidone)
•cimetidine
•cisapride
•clarithromycin
•cyclobenzaprine
•cyclosporine
•dairy products
•didanosine (ddI)
•dolasetron
•doxercalciferol
•droperidol
•erythromycin
•levomethadyl
•iron (ferrous sulfate) preparations
•magnesium salicylate
•magnesium salts
•manganese
•medicines for diabetes
•multivitamins containing calcium, iron, manganese, or zinc
•NSAIDs such as Advil®, Aleve®, ibuprofen, Motrin®, naproxen
•pentamidine
•probucol
•retinoid products such as tretinoin (Retin-A®, Renova®) or isotretinoin (Accutan®)
•sevelamer
•sucralfate
•terfenadine
•theophylline
•troleandomycin
•warfarin
•zinc salts

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking levofloxacin?
Side effects that you should report to your prescriber or health care professional as soon as possible:
Rare or uncommon:
•confusion
•difficulty breathing
•irregular heartbeat, palpitations or chest pain
•joint, muscle or tendon pain
•nightmares
•changes in your thought process
•redness, blistering, peeling or loosening of the skin, including inside the mouth
•seizures
•severe or watery diarrhea
•skin rash, itching
•swelling of the face or neck
•tremor or restlessness
•vision changes
•vomiting

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•constipation or diarrhea
•difficulty sleeping
•dizziness or drowsiness
•headache
•intestinal gas or bloating
•nausea or stomach upset

What should I watch for while taking levofloxacin?
Tell your prescriber or health care professional if your symptoms do not improve in 2 to 3 days.

If you are a diabetic monitor your blood glucose carefully. If you get an unusual reaction stop taking levofloxacin and call your prescriber or health care professional for advice.

You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how levofloxacin affects you. To reduce the risk of dizzy or fainting spells, do not sit or stand up quickly, especially if you are an older patient.

Drink several glasses of water a day. Cut down on drinks that contain caffeine.

Antacids can stop levofloxacin from working. If you get an upset stomach and want to take an antacid, make sure it has been at least 2 hours since you last took levofloxacin, or at least 2 to 4 hours before your next dose.

Calcium, iron, and zinc preparations can also stop levofloxacin from working properly. Take calcium tablets, iron tablets, zinc tablets, or vitamins that contain calcium, iron, or zinc at least 2 hours before or two hours after levofloxacin.

Keep out of the sun, or wear protective clothing outdoors and use a sunscreen. Do not use sun lamps or sun tanning beds or booths.

If you notice symptoms such as pain, burning, tingling, numbness and/or weakness, stop taking levofloxacin and contact your healthcare provider immediately.

If you notice pain or swelling of a tendon or around a joint, stop taking levofloxacin. Call your healthcare provider. Rest the affected area. Do not exercise or take levofloxacin until your healthcare provider tells you to do so.

If you are going to have surgery, tell your prescriber or health care professional that you are taking levofloxacin.

Where can I keep my medicine?
Keep out of the reach of children.

Store at room temperature between 15 and 30 degrees C (59 to 86 degrees F); keep container tightly closed. Throw away any unused medicine after the expiration date.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 08/31/2005]

Levofloxacin tablets

What are levofloxacin tablets?
LEVOFLOXACIN (Levaquin™) is an antibiotic. Levofloxacin kills certain bacteria or stops their growth. It is used to treat urinary tract, prostate, skin, sinus and lung infections, as well as other infections. Generic levofloxacin tablets are not yet available.

What should my health care professional know before I take levofloxacin?
They need to know if you have any of these conditions:
•dehydration
•kidney disease
•seizures (convulsions)
•stomach problems (especially colitis)
•stroke
•an unusual or allergic reaction to levofloxacin, fluoroquinolone antibiotics, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I take this medicine?
Take levofloxacin tablets by mouth with or without food. Follow the directions on the prescription label. Swallow tablets whole with a full glass of water. Take your doses at regular intervals. Do not take your medicine more often than directed. Finish the full course prescribed by your prescriber or health care professional even if you think your condition is better. Do not stop taking except on your prescriber's advice.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What drug(s) may interact with levofloxacin?
•aluminum salts
•antacids
•arsenic trioxide
•astemizole
•bepridil
•calcium salts
•caffeine
•certain heart medications for irregular rhythm (e.g., amiodarone, disopyramide, dofetilide, ibutilide, quinidine, procainamide, sotalol)
•certain medicines for depression or mental problems (e.g., amoxapine, haloperidol, maprotiline, phenothiazines, risperidone, sertindole, ziprasidone)
•cimetidine
•cisapride
•clarithromycin
•cyclobenzaprine
•cyclosporine
•dairy products
•didanosine (ddI)
•dolasetron
•doxercalciferol
•droperidol
•erythromycin
•levomethadyl
•iron (ferrous sulfate) preparations
•magnesium salicylate
•magnesium salts
•manganese
•medicines for diabetes
•multivitamins containing calcium, iron, manganese, or zinc
•NSAIDs such as Advil®, Aleve®, ibuprofen, Motrin®, naproxen
•pentamidine
•probucol
•retinoid products such as tretinoin (Retin-A®, Renova®) or isotretinoin (Accutan®)
•sevelamer
•sucralfate
•terfenadine
•theophylline
•troleandomycin
•warfarin
•zinc salts

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking levofloxacin?
Side effects that you should report to your prescriber or health care professional as soon as possible:
Rare or uncommon:
•confusion
•difficulty breathing
•irregular heartbeat, palpitations or chest pain
•joint, muscle or tendon pain
•nightmares
•changes in your thought process
•redness, blistering, peeling or loosening of the skin, including inside the mouth
•seizures
•severe or watery diarrhea
•skin rash, itching
•swelling of the face or neck
•tremor or restlessness
•vision changes
•vomiting

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•constipation or diarrhea
•difficulty sleeping
•dizziness or drowsiness
•headache
•intestinal gas or bloating
•nausea or stomach upset

What should I watch for while taking levofloxacin?
Tell your prescriber or health care professional if your symptoms do not improve in 2 to 3 days.

If you are a diabetic monitor your blood glucose carefully. If you get an unusual reaction stop taking levofloxacin and call your prescriber or health care professional for advice.

You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how levofloxacin affects you. To reduce the risk of dizzy or fainting spells, do not sit or stand up quickly, especially if you are an older patient.

Drink several glasses of water a day. Cut down on drinks that contain caffeine.

Antacids can stop levofloxacin from working. If you get an upset stomach and want to take an antacid, make sure it has been at least 2 hours since you last took levofloxacin, or at least 2 to 4 hours before your next dose.

Calcium, iron, and zinc preparations can also stop levofloxacin from working properly. Take calcium tablets, iron tablets, zinc tablets, or vitamins that contain calcium, iron, or zinc at least 2 hours before or two hours after levofloxacin.

Keep out of the sun, or wear protective clothing outdoors and use a sunscreen. Do not use sun lamps or sun tanning beds or booths.

If you notice symptoms such as pain, burning, tingling, numbness and/or weakness, stop taking levofloxacin and contact your healthcare provider immediately.

If you notice pain or swelling of a tendon or around a joint, stop taking levofloxacin. Call your healthcare provider. Rest the affected area. Do not exercise or take levofloxacin until your healthcare provider tells you to do so.

If you are going to have surgery, tell your prescriber or health care professional that you are taking levofloxacin.

Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.

Store at room temperature between 25°and 30 degrees C (59°to 85 degrees F) and keep in a tightly closed container. Throw away any unused medicine after the expiration date.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 10/14/2004]

 
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