Lefloxin

Levofloxacin.

LEFLOXIN 100 MG TABLET: Each film coated tablet contains Levofloxacin 100 mg.
LEFLOXIN 500 MG TABLET: Each film coated tablet contains Levofloxacin 500 mg.
LEFLOXIN (750 MG TABLET): Each film coated tablet contains Levofloxacin 750 mg.
LEFLOXIN IV INFUSION: Each ml contains Levofloxacin 5 mg.

Pharmacology: Pharmacodynamics: Levofloxacin is an active (-)-S form of ofloxacin belonging to fluoroquinolones group. Levofloxacin has a broad spectrum activity by inhibiting DNA gyrase (type II DNA topoisomerases) and topoisomerase IV which is an essential enzyme for the bacterial living and DNA replication. Levofloxacin is considered to be about twice as active as ofloxacin, the racemic substance.
In vitro, Levofloxacin is active against both gram-positive and gram-negative bacteria as following: Gram-positive bacteria: Enterococcus faecalis, Staphylococcus aureus, Staphylococcus saprophyticus, Streptococcus pneumoniae including multidrug-resistant strains (MDRSP), Streptococcus pyogenes.
Gram-negative bacteria: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis, Pseudomonas aeruginosa, Legionella pneumophila.
Others: Chlamydophila pneumoniae (Chlamydia pneumoniae), Mycoplasma pneumoniae, Bacillus anthracis, some strains of Mycobacterium tuberculosis, Mycobacterium fortuitum.
Pharmacokinetics: Levofloxacin is rapidly absorbed and peak plasma concentrations occur within 1 to 2 hours after oral administration. Bioavailability is approximately 99%. Levofloxacin is widely distributed into body tissues. The drug is also distributed to bronchial mucosa and lungs, but penetration into CSF is relatively poor. About 30 to 40% of Levofloxacin is bound to plasma proteins. It is excreted largely unchanged, mainly in the urine. Only small amounts are metabolized to inactive metabolites. The elimination half-life is 6 to 8 hours, however this may be prolonged in patients with renal impairment, therefore dosing interval or dosage adjustment may be required. It is not removed by hemodialysis or peritoneal dialysis.

For treatment of susceptible bacterial infectious diseases as following: 1.Community-acquired pneumonia: Caused by Staphylococcus aureus, Streptococcus pneumoniae including multidrug-resistant strains (MDRSP), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae (Chlamydia pneumoniae), Legionella pneumophila, Mycoplasma pneumoniae.
2. Nosocomial pneumonia: Caused by methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae.
In case of infected by Pseudomonas aeruginosa, combination therapy with antipseudomonal β-lactam is recommended to cover bacterial infection appropriately.
3. Skin infections, uncomplicated: e.g. abscesses, furuncles, impetigo, pyoderma, cellulitis, wound infections caused by Staphylococcus aureus, Streptococcus pyogenes.
4. Skin infections, complicated: Caused by methicillin-susceptible Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes, Proteus mirabilis.
5. Urinary tract infections (mild to moderate): Caused by Enterococcus faecalis, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus saprophyticus.
6. Pyelonephritis (mild to moderate): Caused by Escherichia coli.
7. Acute bacterial sinusitis: Caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis.
8. Acute bacterial exacerbation of chronic bronchitis: Caused by Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis.
9. Chronic bacterial prostatitis: Caused by Escherichia coli, Enterococcus faecalis or Staphylococcus epidermidis.
10. Empirical treatment for community acquired pneumonia.
11. Third-Line therapy for Helicobacter pylori infection: Levofloxacin-based Triple Therapy: Levofloxacin, in combination with other antimicrobial agent and proton pump inhibitor as triple therapy, is indicated for the treatment of patients with gastric ulcer caused by Helicobacter pylori infection and duodenal ulcer disease.

LEFLOXIN Intravenous (IV) infusion: Lefloxin IV should only be administered by intravenous infusion.
The dosage depends on the type and severity of the infection and the sensitivity of the causative pathogen.
As with antibiotic therapy in general, administration of Lefloxin IV should be continued for a minimum of 2 to 3 days after the patient has become afebrile or evidence of bacterial eradication has been obtained. (It is usually possible to switch from initial intravenous treatment to the oral route.)
Lefloxin injection should be slowly infused IV, 60 or 90 minutes every 24 hours, over a period of at least 60 minutes for the 250 mg or 500 mg dose or 90 minutes for the 750 mg dose.
The treatment doses are described in the table as follows. (See Tables 1 and 2.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

LEFLOXIN TABLET: Continuously taking the drug until finish the course or as doctor's prescription.
Adults: Administer 100 mg 2-3 times daily, and increased if necessary, 200 mg 3 times daily or as doctor's order.
For specific indications, dosage are in the table as follows. (See Tables 3 and 4.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Hepatic impairment: Adjustment of Levofloxacin dosage in patients with hepatic insufficiency is not expected to be necessary because Levofloxacin is mainly excreted by kidney.
Pediatric use: Safety of the drug have not been established for any other indication in this age group, the drug must not be used in pediatric patients.
Geriatric use: Dosage of Levofloxacin should be selected carefully because Levofloxacin is substantially eliminated by the kidneys. If geriatric patients have decreased renal function, dosage adjusted as needed based on renal function.

Overdose and treatment: In case of overdose of Levofloxacin, confusion, dizziness, impairment of consciousness and seizures may be found. The stomach should be emptied. Antacid may be used for protection of gastric mucosa. No specific antidote exists. The patient should be observed and treated by symptomatic treatment. Appropriate hydration should be maintained. Levofloxacin is not removed by hemodialysis or peritoneal dialysis.

Levofloxacin is contraindicated in the following patients: 1. Patients with a history of hypersensitivity to Levofloxacin and any other quinolones.
2. Patients with epilepsy.
3. Patients with history of tendon disorder related to fluoroquinolones administration.
4. Children or adolescents below the age of 16 years.
5. Pregnant women.
6. Breastfeeding women.

(Based on Notification of the Ministry of Public Health): 1. Do not use the drug in patients with a history of hypersensitivity to the drug or any other quinolones.
2. Pregnant women and breastfeeding women should avoid the use of this drug.
3. If the symptoms of rash, malaise, myalgia, arthralgia and tendonitis had occurred after the administration of the drug, the patient should discontinue this drug and consult the physician immediately.
4. The drug may cause hepatic and renal toxicities.
5. Do not use this drug or used with caution in patients with central nervous system (CNS) disorder that may predispose to seizure dosing dependent.
6. This drug may cause prolongation of QT interval, so this drug should be used with caution in patient who has risks of prolongation of QT interval including geriatric, cardiac disease especially arrhythmia, hypertension, and hypokalemia.
7. Avoid using this drug with other drugs that cause prolongation of QT interval including antiarrhythmic class IA (quinidine, procainamide), class III (amiodarone), cisapride, erythromycin, antipsychotics, and tricyclic antidepressants.
8. This drug may cause phototoxicity reaction including Toxic Epidermal Necrolysis, Stevens-Johnson syndrome, and Erythema Multiforme.
9. This drug should be used with caution in diabetic patient because this drug may cause dysglycemia.
10. Concomitant use of this drug and warfarin may increase the activities of warfarin.
Warning: 1. Levofloxacin is more soluble than other quinolones, adequate hydration of patients receiving Levofloxacin. Levofloxacin should be maintained to prevent the formation of highly concentrated urine.
2. Serious colitis with bloody stool, such as pseudomembranous colitis: If such symptoms as abdominal pain and frequent diarrhea are noted, treatment with Levofloxacin should be discontinued immediately and appropriate therapeutic measures taken.
3. Rhabdomyolysis characterized by myalgia, weakness, elevated CK (CPK) and increased myoglobin in plasma and urine, etc., and accompany with acute exacerbation of renal function.
4. Tendon disorder such as Achilles tendonitis or tendon rupture: If symptoms such as pain and edema in the peritendinous region are observed, treatment with Levofloxacin should be discontinued immediately and appropriate therapeutic measures taken. The risk of tendonitis and tendon rupture is increased in those over age 60, in those on concomitant corticosteroid therapy and transplant recipients.
5. Levofloxacin may inhibit the growth of Mycobacterium tuberculosis, and therefore, may give false-negative results in the bacteriological diagnosis of tuberculosis.
6. Some undesirable effects may impair the patient's ability to concentrate and react, and therefore may constitute a risk in situation where these abilities are of special importance (e.g. driving a car or operating machinery).
7. Hepatitis fulminant, hepatic function disorder or jaundice (initial syndromes: nausea, vomiting, anorexia, malaise, pruritus, etc.).
8. Pancytopenia, agranulocytosis (initial symptoms: pyrexia, pharynx pain, malaise, etc.), hemolytic anemia with hemoglobinuria or thrombocytopenia.
9. Interstitial pneumonia or eosinophilic pneumonia accompanied with pyrexia, cough, dyspnea, abnormal chest X-ray, or eosinophilia, etc.
10. Psychiatric symptoms such as confusion, delirium, depression.
11. Hypersensitivity vasculitis: If symptoms such as pyrexia, abdominal pain, arthralgia, purpura or maculopapules, and skin biopsy evidence of leukocytoclastic vasculitis are observed, treatment with Levofloxacin should be discontinued immediately and appropriate therapeutic measures taken.
12. Patients received Levofloxacin dose of 750 mg may develop some adverse reaction such as dizziness, headache, nausea or vomiting more than Levofloxacin dose of 500 mg.

Use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria. Moreover, culture and sensitivity test should be performed in order to determine the causative microorganism and to prevent further development of drug resistance.
LEFLOXIN should be administrated with caution in the following patients: Patients with impaired renal function; Patients with known or suspected CNS disorder that may predispose to seizure; Patients exposed to direct sunlight; Diabetic patients receiving concomitant treatment with an oral hypoglycemic agent or with insulin preparations; Patients with serious heart disease, e.g. arrhythmia and ischemic heart disease. QT prolonged may occur. Patients with uncorrected electrolytes imbalance (e.g. hypokalemia, hypomagnesemia) and patients receiving Class IA and III antiarrhythmic agents; Patients with myasthenia gravis, symptoms may be exacerbated.
Severe hepatotoxicity, including acute hepatitis, has occurred during taking this drug especially in geriatric patients. This drug should be discontinued in any patient who experiences loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of the eyes and skin, light colored feces or dark colored urine.
Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile and fungi. C. difficile produces toxins which contribute to development of C. difficile associated diarrhea and colitis (CDAD).
Use in the Elderly: LEFLOXIN should be administrated with caution in geriatric patients.

There are no adequate and well-controlled studies of Levofloxacin in pregnant women, then the drug is contraindicated in pregnant woman or women suspected of being pregnant.
In the absence of human data and due to the experimental risk of damage by fluoroquinolones to the weight-bearing cartilage of the growing organism and Levofloxacin can be excreted in human milk, the drug must not be used in breastfeeding women. If the drug is necessary for the breastfeeding women, patients should discontinue nursing.

Adverse effects may occur including nausea, vomiting, abdominal pain, loss of appetite, abdominal distension, colitis, bloody stool, hypoglycemia, hyperglycemia, headache, dizziness, somnolence, insomnia, numbness, tremor, restlessness, palpitation, confusion, delirium, depression, seizure, consciousness disturbed, abnormal vision, hearing loss, ageusia, anosmia, hallucination, arthralgia, myalgia, tendinopathy, tendinitis, tendon rupture (Achilles tendon rupture), weakness, exacerbation of myasthenia gravis, rhabdomyolysis, abnormal gait, rash, pruritis, urticaria, bronchospasm, dyspnea, interstitial pneumonia, eosinophilic pneumonia, angioedema, hypotension, hypersensitivity reaction, anaphylactic reaction, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN) or Lyell's Syndrome, Erythema multiforme, hypersensitivity vasculitis, increased liver enzymes (ALT, AST), increased bilirubin, increased creatinine, hepatitis, hepatitis fulminant, jaundice, acute renal failure, interstitial nephritis, hematologic effects such as eosinophilia, leukopenia, thrombocytopenia, agranulocytosis, pancytopenia, hemolytic anemia, tiredness, overgrowth of fungi, development of drug-resistant bacteria, allergic pneumonitis, fever, arrhythmia, cardiac arrest, tachycardia, Torsades de pointes, prolonged QT interval, edema, pancreatitis, edema of the face, edema of the tongue.
Others: phlebitis.

1. Concomitant use of Levofloxacin and antacid, sucralfate, metal cations medications or multivitamins which compose of magnesium, aluminium, ferrous sulfate, zinc, calcium or iron may decrease the absorption of Levofloxacin. Levofloxacin should be administered at least 2 hours before or 2 hours after such the drugs. Although, there are no data concerning an interaction of intravenous quinolones with such the drugs, quinolones should not be co-administered with any solution containing such the drugs through the same intravenous line.
2. Concomitant use of Levofloxacin and theophylline, non-steroidal anti-inflammatory agents (e.g. fenbufen) possible increased risk of CNS stimulation which leads to seizures. Concomitant use of these drugs should be avoided.
3. Concomitant use of Levofloxacin and warfarin may result in increased prothrombin time. Patients receiving the drugs concomitantly should be monitored.
4. Concomitant use of Levofloxacin and antidiabetic agents may alter blood glucose concentrations and symptomatic hyperglycemia or hypoglycemia. Careful monitoring of blood glucose concentrations is recommended.
5. Concomitant use of Levofloxacin and antidepressant agents (e.g. fluoxetine, imipramine), antiarrhythmic agents may have additive effect on QT interval prolongation. Concomitant use of these drugs should be avoided.

LEFLOXIN Intravenous (IV) infusion: Lefloxin IV infusion is ready-to-use isotonic solution that dilution is not required before IV infusion.
Levofloxacin solutions should be inspected visually for particulate matter prior to administration. The solutions should be discharged if there are cloudy or contain precipitates.
The Levofloxacin solutions must be used in 3 hours after perforation of the rubber stopper. Any unused portions of the solution should be discarded.
Levofloxacin should not be admixed with other drugs or infused simultaneously through the same tubing with other drugs. Levofloxacin should not be infused through the same tubing with any solution containing multivalent cations (e.g. magnesium). If the same administration set is used for sequential infusion of several different drugs, the tubing should be flushed before and after administration of Levofloxacin with an intravenous solution that is compatible with both Levofloxacin and other drugs.

LEFLOXIN IV INFUSION: Protect from light. Store below 30°C.
Levofloxacin is photosensitive drug. Take the vial out of package only as needed.
The maximum efficacy of the drug is assured for 3 days, if the drug is exposed to light.
Use the drug as soon as possible after perforation of the rubber stopper (within 3 hours).
LEFLOXIN TABLET: Store below 30°C.

Quinolones

J01MA12 - levofloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.

100-mg/500-mg FC tab/IV infusion: D; 750-mg FC tab: S