Indications and Usage:
To reduce the development of drug-resistant bacteria and maintain the effectiveness of levofloxacin and other antibacterial drugs, levofloxacin 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.
Levofloxacin tablets are indicated for the treatment of adults (≥ 18 years of age) with mild, moderate and severe infections caused by susceptible strains of the designated microorganisms in the conditions listed in this section.
Nosocomial Pneumonia: Levofloxacin is indicated for the treatment of nosocomial pneumonia due to methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae or Streptococcus pneumoniae. Adjunctive therapy should be used as clinically indicated. Where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an anti-pseudomonal beta-lactam is recommended.
Community-Acquired Pneumonia: Levofloxacin is indicated for the treatment of community-acquired pneumonia due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multi-drug-resistant Streptococcus pneumoniae [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila or Mycoplasma pneumoniae.
Acute Bacterial Sinusitis: Levofloxacin is indicated for the treatment of acute bacterial sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.
Acute Bacterial Exacerbation of Chronic Bronchitis: Levofloxacin is indicated for the treatment of acute bacterial exacerbation of chronic bronchitis due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae or Moraxella catarrhalis.
Complicated Skin and Skin Structure Infections: Levofloxacin is indicated for the treatment of complicated skin and skin structure infections due to methicillin-susceptible Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes or Proteus mirabilis.
Uncomplicated Skin and Skin Structure Infections: Levofloxacin is indicated for the treatment of uncomplicated skin and skin structure infections (mild to moderate), including abscesses, cellulitis, furuncles, impetigo, pyoderma and wound infections, due to methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes.
Chronic Bacterial Prostatitis: Levofloxacin is indicated for the treatment of chronic bacterial prostatitis due to Escherichia coli, Enterococcus faecalis or methicillin-susceptible Staphylococcus epidermidis.
Complicated Urinary Tract Infections: Levofloxacin is indicated for the treatment of complicated urinary tract infections due to Escherichia coli, Klebsiella pneumoniae or Proteus mirabilis.
Acute Pyelonephritis: Levofloxacin is indicated for the treatment of acute pyelonephritis caused by Escherichia coli, including cases with concurrent bacteremia.
Uncomplicated Urinary Tract Infections: Levofloxacin is indicated for the treatment of uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae or Staphylococcus saprophyticus.
Inhalational Anthrax (Post-Exposure): Levofloxacin is indicated for inhalational anthrax (post-exposure) to reduce the incidence or progression of the disease following exposure to aerosolized Bacillus anthracis. The effectiveness of levofloxacin is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit. Levofloxacin has not been tested in humans for the post-exposure prevention of inhalation anthrax. The safety of levofloxacin in adults for durations of therapy beyond 28 days or in pediatric patients for durations of therapy beyond 14 days has not been studied. Prolonged levofloxacin therapy should only be used when the benefit outweighs the risk.
Pharmacology:
Pharmacodynamics:
Levofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone antimicrobial agent. The antibacterial activity of ofloxacin resides primarily in the L-isomer. The mechanism of action of levofloxacin and other fluoroquinolones antimicrobials involves the inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination.
Pharmacokinetics:
Absorption: Levofloxacin is rapidly and essentially completely absorbed after oral administration. Peak plasma concentrations are usually attained 1 to 2 hours after oral dosing. The absolute bioavailability of levofloxacin from a approximately 99%, demonstrating complete oral absorption of levofloxacin. Oral administration of a levofloxacin with food prolongs the time to peak concentration by approximately 1 hour and decreases the peak concentration by approximately 14% following intake of the tablet. Therefore, levofloxacin tablets can be administered without regard to food.
Distribution: The mean volume of distribution of levofloxacin generally ranges from 74 to 112 L after single and multiple 500 mg doses, indicating widespread distribution into body tissues.Levofloxacin also penetrates well into lung tissues.Levofloxacin is approximately 24–38% bound to serum proteins across all species studied, as determined by the equilibrium dialysis method. Levofloxacin is mainly bound to serum albumin in humans. Levofloxacin binding to serum proteins is independent of the drug concentration.
Metabolism: Levofloxacin undergoes limited metabolism in humans and is primarily excreted as unchanged drug in the urine.Less than 5% of an administered dose was recovered in the urine as the desmethyl and N-oxide metabolites, the only metabolites identified in humans. These metabolites have little relevant pharmacological activity.
Excretion: Levofloxacin is excreted largely as unchanged drug in the urine. The mean terminal plasma elimination half-life of levofloxacin ranges from approximately 6 to 8 hours, following single or multiple doses of levofloxacin given orally.Renal clearance in excess of the glomerular filtration rate suggests that tubular secretion of levofloxacin occurs in addition to its glomerular filtration. Concomitant administration of either cimetidine or probenecid results in approximately 24% and 35% reduction in the levofloxacin renal clearance, respectively, indicating that the secretion of levofloxacin occurs in the renal proximal tubule.
Drug Interactions:
Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins
Levofloxacin Tablets: Antacids containing magnesium, aluminum as well as sucralfate, metal cations such as iron and multivitamins preparations with zinc or didanosine may substantially interfere with the gastrointestinal absorption of levofloxacin, resulting in systemic levels considerably lower than desired. These agents should be taken at least 2 hours before or 2 hours after oral levofloxacin administration.
Warfarin: There have been reports during the postmarketing experience in patients that levofloxacin enhances the effects of warfarin. Elevations of the prothrombin time in the setting of concurrent warfarin and levofloxacin use have been associated with episodes of bleeding. Prothrombin time or other suitable anticoagulation tests should be closely monitored if levofloxacin is administered concomitantly with warfarin. Patients should also be monitored for evidence of bleeding.
Antidiabetic Agents: Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with fluoroquinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are co-administered.
Non-Steroidal Anti-Inflammatory Drugs: The concomitant administration of a non-steroidal anti-inflammatory drug with a fluoroquinolone, including levofloxacin, may increase the risk of CNS stimulation and convulsive seizures.
Theophylline: Concomitant administration of other fluoroquinolones with theophylline has resulted in prolonged elimination half-life, elevated serum theophylline levels and a subsequent increase in the risk of theophylline-related adverse reactions in the patient population. Therefore, theophylline levels should be closely monitored and appropriate dosage adjustments made when levofloxacin is co-administered. Adverse reactions, including seizures, may occur with or without an elevation in serum theophylline levels.
Undesirable Effects:
Serious and Otherwise Important Adverse Reactions
The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of the labeling:
●Tendon effects
●Hypersensitivity reactions
●Other serious and sometimes fatal reactions
●Hepatotoxicity
●Central nervous system effects
●Clostridium difficile-associated diarrhea
●Peripheral neuropathy
●Prolongation of the QT Interval
●Musculoskeletal disorders in pediatric patients
●Blood glucose disturbances
●Photosensitivity/Phototoxicity
●Development of drug-resistant bacteria
Warning:
Fluoroquinolones, Including Levofloxacin, Are Associated With An Increased Risk Of Tendinitis And Tendon Rupture In All Age Groups. This Risk Is Further Increased In Older Patients Usually Over 60 Years Of Age, In Patients Taking Corticosteroid Drugs, And In Patients With Kidney, Heart Or Lung Transplants (Please Read The Warnings And Precautions Section Carefully)
Contraindication:
Levofloxacin is contraindicated in individuals with a known hypersensitivity to levofloxacin or other quinolone antibacterials.
Pregnancy
Lactation
Pediatric Use
Geriatric Use