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 fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination.

Absorption: Levofloxacin is rapidly and essentially completely absorbed after oral administration. Peak plasma concentrations are usually attained one to two hours after oral dosing. The absolute bioavailability of a 500 mg tablet and a 750 mg tablet of levofloxacin are both approximately 99%, demonstrating complete oral absorption of levofloxacin.

Distribution: The mean volume of distribution of levofloxacin generally ranges from 74 to 112 L after single and multiple 500 mg or 750 mg doses, indicating widespread distribution into body tissues.

Metabolism: Levofloxacin is stereochemically stable in plasma and urine and does not invert metabolically to its enantiomer, D-ofloxacin. Levofloxacin undergoes limited metabolism in humans and is primarily excreted as unchanged drug in the urine. Following oral administration, approximately 87% of an administered dose was recovered as unchanged drug in urine within 48 hours, whereas less than 4% of the dose was recovered in feces in 72 hours. 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 or intravenously.

Indication and Usage:
Levofloxacin is indicated in the following conditions:
• Acute bacterial sinusitis
• Acute bacterial exacerbation of chronic bronchitis
• Nosocomial pneumonia
• Community-acquired pneumonia
• Complicated skin and skin structure infections
• Uncomplicated skin and skin structure infections
• Chronic bacterial prostatitis
• Complicated urinary tract infections
• Acute pyelonephritis
• Uncomplicated urinary tract infections

Levofloxacin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as
Aerobic gram-positive microorganisms:
Enterococcus faecalis (many strains are only moderately susceptible)
Staphylococcus aureus (methicillin-susceptible strains)
Staphylococcus epidermidis (methicillin-susceptible strains)
Staphylococcus saprophyticus
Streptococcus pneumoniae (including multi-drug resistant strains [MDRSP])
Streptococcus pyogenes
MDRSP (including Multi-drug resistant Streptococcus pneumoniae)
Aerobic gram-negative microorganisms:
Enterobacter cloacae
Escherichia coli
Haemophilus influenzae
Haemophilus parainfluenzae
Klebsiella pneumoniae
Legionella pneumophila
Moraxella catarrhalis
Proteus mirabilis
Pseudomonas aeruginosa
Serratia marcescens
As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with levofloxacin.
Other microorganisms:
Chlamydia pneumoniae
Mycoplasma pneumoniae

Dosage and Administration: The usual dose of levofloxacin is 250 mg or 500 mg or 750 mg administered orally every 24 hours, as indicated by infection and described in the following dosing chart.

Note: Dosage may be adjusted according to the kind of infection and severity of the symptoms.

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

Adverse Reactions: In clinical trials, the following events, of potential medical importance, occurred at a rate of 0.1% to 0.9%, regardless of drug relationship
Body as a Whole:
General Disorders: Ascites, allergic reaction, asthenia, edema, fever, headache, hot flashes, influenza-like symptoms, leg pain, malaise, rigors, substernal chest pain, syncope, multiple organ failure, changed temperature sensation, withdrawal syndrome
Cardiovascular Disorders General: Cardiac failure, hypertension, hypertension aggravated, hypotension, postural hypotension
Central and Peripheral Nervous System Disorders: Convulsions (seizures), hyperesthesia, hyperkinesia, hypertonia, hypoesthesia, involuntary muscle contractions, migraine, paresthesia, paralysis, speech disorder, stupor, tremor, vertigo, encephalopathy, abnormal gait, leg cramps, intracranial hypertension, ataxia
Gastro-Intestinal System Disorders: Dry mouth, dysphagia, esophagitis, gastritis, gastroesophageal reflux, G.I. hemorrhage, glossitis, intestinal obstruction, pancreatitis, tongue edema, melena, stomatitis
Hearing and Vestibular Disorders: Earache, ear disorder NOS, tinnitus
Heart Rate and Rhythm Disorders: Arrhythmia, arrhythmia ventricular, atrial fibrillation, bradycardia, cardiac arrest, ventricular fibrillation, heart block, palpitation, supraventricular tachycardia, ventricular tachycardia, tachycardia
Liver and Biliary System Disorders: Abnormal hepatic function, cholecystitis, cholelithiasis, hepatic enzymes increased, hepatic failure, jaundice
Metabolic and Nutritional Disorders: Hypomagnesemia, thirst, dehydration, electrolyte abnormality, fluid overload, gout, hyperglycemia, hyperkalemia, hypernatremia, hypoglycemia, hypokalemia, hyponatremia, hypophosphatemia, nonprotein nitrogen increase, weight decrease
Musculo-Skeletal System Disorders: Arthralgia, arthritis, arthrosis, myalgia, osteomyelitis, skeletal pain, synovitis, tendonitis, tendon disorder
Myo, Endo, Pericardial and Valve Disorders: Angina pectoris, myocardial infarction Neoplasms: Carcinoma, thrombocythemia
Other Special Senses Disorders: Parosmia, taste perversion
Platelet, Bleeding and Clotting Disorders: Hematoma, epistaxis, prothrombin decreased, pulmonary embolism, purpura, thrombocytopenia
Psychiatric Disorders: Abnormal dreaming, agitation, anorexia, anxiety, confusion, depression, hallucination, impotence, nervousness, paroniria, sleep disorder, somnolence
Red Blood Cell Disorders: Anemia.
Reproductive Disorders: Dysmenorrhea, leucorrhea
Resistance Mechanism Disorders: Abscess, bacterial infection, fungal infection, herpes simplex, moniliasis, otitis media, sepsis, infection
Respiratory System Disorders: Airways obstruction, aspiration, asthma, bronchitis, bronchospasm, chronic obstructive airway disease, coughing, hemoptysis, epistaxis, hypoxia, laryngitis, pleural effusion, pleurisy, pneumonitis, pneumonia, pneumothorax, pulmonary edema, respiratory depression, respiratory disorder, respiratory insufficiency, upper respiratory tract infection
Skin and Appendages Disorders: Alopecia, bullous eruption, dry skin, eczema, genital pruritus, increased sweating, rash, skin disorder, skin exfoliation, skin ulceration, urticaria
Urinary System Disorders: Abnormal renal function, acute renal failure, hematuria, oliguria, urinary incontinence, urinary retention, urinary tract infection
Vascular (Extracardiac) Disorders: Flushing, cerebrovascular disorder, gangrene, phlebitis, purpura, thrombophlebitis (deep)
Vision Disorders: Abnormal vision, eye pain, conjunctivitis

Warning & Special precautions:
Pregnancy: Teratogenic Effects
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. Levofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers: Levofloxacin has not been measured in human milk. Because of the potential for serious adverse reactions from levofloxacin in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
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 is not expected to be affected by hepatic impairment.

Interactions: Tablets with 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 two hours before or two hours after levofloxacin administration. No significant effect of levofloxacin on the peak plasma concentrations, AUC, and other disposition parameters for Theophylline, Warfarin, Cyclosporine, Digoxin, Probenecid and Cimetidine.
Non-steroidal anti-inflammatory drugs: The concomitant administration of a non-steroidal anti-inflammatory drug with a quinolone, including levofloxacin, may increase the risk of CNS stimulation and convulsive seizures.
Antidiabetic agents: Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are co-administered.

Overdosage: In the event of an acute overdosage, the stomach should be emptied. The patient should be observed and appropriate hydration maintained. Levofloxacin is not efficiently removed by hemodialysis or peritoneal dialysis.

Storage: Store below 30ºC. Protect from light, heat and moisture.
Keep all medication out of the reach of the children.