Lexovin™

[Levofloxacin]

Active Ingredients

Levoxin 250 mg tablet: Each film coated tablet contains 256.23 mg of levofloxacin hemihydrate corresponding to 250 mg of levofloxacin.

Levoxin 500 mg tablet: Each film coated tablet contains 512.46 mg of levofloxacin hemihydrate corresponding to 500 mg of levofloxacin.

Description / Properties

Levoxin (levofloxacin tablets) are synthetic broad spectrum antibacterial agents for oral administration. Chemically, levofloxacin, a chiral fluorinated carboxyquionolone, is the pure(-)-(S)-enantiomer of the racemic drug substance ofloxacin. The chemical name is(-) -(S)-9-fluoro 2,3 dihydro-3-methyl-10-(4-methyl- 1-piper- azinyl)-7-oxo-7H-pyrido[1,2,3Źde]1,4-benzoxazine-6-carboxylic acid hemihydrate.

Pharmacology

Antibacterial Activity

Levoxin is a wide-spectrum antibacterial agent against gram-positive and gram-negative bacteria, including anaerobes. Levoxin has shown strong anti-bacterial activities against Staphylococcus spp, Streptococcus Pneumoniae, Streptococcus Pyogenes, Streptococcus hemolyticus, Enterobacter spp, Escherichia coli, klebsiella spp, Serratia spp, Enterococus spp, Proteus spp, and other glucose non-fermentive gram-negative rods, Pseudomonas aeruginosa, Haemophilus influenzae, and Neisseria gonorrhoeae. Moreover, Levoxin has shown antibacterial activity against Chlamydia trachomatis. Levoxin has had excellent protective and treatment effects in mice.

Mechanism of Action

The main mechanism of action of Levoxin is the inhibition of DNA gyrase. It is two folds stronger than that of ofloxacin. There is not much difference between the MIC and MBC. The activity of Levoxin is bactericidal. In the observation of bacterial morphology, bacteriolysis can be seen in the concentration around MIC..

Pharmacokinetics

Absorption Orally administered levofloxacin is rapidly and almost completely absorbed with peak plasma concentrations being obtained within 1 hour. The absolute bio-availability is approximately 100%. Food has little effect on the absorption of levofloxacin.

Distribution In Plasma

Approximately 30-40% of levofloxacin is bound to serum protein. 500mg once daily multiple dosing with levofloxacin showed negligible accumulation. There is modest but predictable accumulation of levofloxacin after doses of 500mg twice daily. Steady state is achieved within 3 days.

Penetration into Tissues and Body Fluids

Penetration into Bronchial mucosa, Epithelial Lining Fluid (ELF). Maximum levofloxacin concentrations in bronchial mucosa and epithelial lining fluid were 8.3 ug/ml and 10.8 ug/ml respectively. These were reached approximately one hour after administration.

Penetration into Lung Tissue

Maximum levofloxacin concentrations in lung tissues were approximately 11.3 ug/ml and were reached between 4 and 6 hours after administration.

Metabolism

Levofloxacin is metabolised to a very small extent, the metabolites being desmethyl levofloxacin and levofloxacin N-oxide. These metabolites account for <5% of the dose excreted in urine. Levofloxacin is stereochemically stable and does not undergo chiral inversion.

Elimination

Following oral administration, levofloxacin is eliminated relatively slowly from the plasma (t'/z:6-8h). Excretion is primarily by the renal route (>85% of the administered dose). There are no major differences in the pharmacokinetics of levofloxacin following intravenous and oral administration, suggesting that the oral and intravenous routes are interchangable.

Special Populations

Geriatric:

There are no significant differences in levofloxacin pharmacokinetics between young and elderly subjects when subjects' differences in creatinine clearance are taken into consideration. Following a 500 mg oral dose of levofloxacin to healthy elderly subjects (66-80 years of age), the mean terminal plasma elimination half-life of levofloxacin was about 7.6 hours, as compared to approximately 6 hours in younger adults. The difference was attributable to the variation in renal function status of the subjects and was not believed to be clinically significant. Drug absorption appears to be unaffected by age. Levofloxacin dose adjustment based on age alone is not necessary.

Pediatric:

The pharmacokinetics of levofloxacin in pediatric subjects have not been studied. Gender: There are no significant differences in levofloxacin pharmacokinetics between male and female subjects when subjects' differences in creatinine clearance are taken into consideration. Following a 500 mg oral dose of levofloxacin to healthy male subjects, the mean terminal plasma elimination half-life of levofloxacin was about 7.5 hours, as compared to approximately 6.1 hours in female subjects. This difference was attributable to the variation in renal function status of the male and female subjects and was not believed to be clinically significant. Drug absorption appears to be unaffected by the gender of the subjects. Dose adjustment based on gender alone is not necessary.

Renal insufficiency:

Clearance of levofloxacin is substantially reduced and plasma elimination half-life is substantially prolonged in patients with impaired renal function (creatinine clearance<50 mL/min), requiring dosage adjustment in such patients to avoid accumulation. Neither hemodialysis nor continuous ambulatory peritoneal dialysis (CAPD) is effective in removal of levofloxacin from the body, indicating that supplemental doses of levofloxacin are not required following hemodialysis or CAPD .

Hepatic insufficiency:

Pharmacokinetic studies in hepatically impaired patients have not been conducted. Due to the limited extent of levofloxacin metabolism, the pharmacokinetics of levofloxacin are not expected to be affected by hepatic impairment.

Indications

Levoxin 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 below: Acute maxillary sinusistis due to Strepcoccus pneumoniae, Haemophilus influenzae or Moraxella catarrhilis. Acute bacterial exacerbation of chronic bronchitis due to Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis. Community-acquired pneumonia due to Staphylococcus aureus, Streptococcus pneumoniae (including penicillin-resistant strains, MIC value for penicillin?2ug/mL). Haemophilus influenzae. Haemophilus parainfluenzae, klebsiella pneumoniae. Moraxella catarrhalis, Chlamydia pneumoniae. Legionella pneumophila or Mycoplasma pneumoniae. Complicated skin and skin structure infections due to methicillin-sensitive Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes or Proteus mirabilis. Uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellutitis, furuncles, impetigo pyoderma, wound infections, due to Staphylococcus aureus, or Streptococcus pyogenes. Complicated urinary tract infections (mild to moderate) due to Enterococcus faecalis, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa. Acute pyelonephritis (mild to moderate) caused by Escherichia coli. Uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus

Contraindication

Levofloxacin is contraindicated in persons with a history of hypersensitivity to levofloxacin, quinolone antimicrobial agents, or any other components of this product.

Drug Interactions

If you take concomitantly other drugs, ask your doctor or pharmacist, whether they are one of the here mentioned drugs. This also applies to drugs, which were not prescribed by your doctor. There are indications of a pronounced lowering of the cerebral seizure threshold when quinolones are given concurrently with other agents which lower the seizure threshold (e.g. theophylline). This applies also to the concomitant administration of quinolones and fenbufen or non-steroidal antiphlogistics (drugs for the treatment of rheumatic diseases). The effect of levofloxacin is significantly reduced when administered together with sucralfate (drug for the protection of the gastric mucous membrane). This also applies to concomitant administration of magnesium-or aluminium-containing antacids (drugs for the treatment of heartburn or gastric pain) or of iron salts (drugs for the treatment of anemia). Levoxin Tablets should be taken at least 2 hours before or after administration of these preparations. The elimination (renal clearance) of levofloxacin was slightly reduced by cimetidine and probenicid. However, these interactions are unlikely to be of clinical relevance. Levofloxacin should be given carefully when it is coadministered with drugs that affect a certain mode of elimination (tubular secretion) such as probenicid and cimetidine. This applies especially to patients with impaired renal function. The half life of cyclosporin was slightly increased when coadministered with levofloxacin.