Levixa

Each film-coated tablet contains: Levofloxacin hemihydrate USP equivalent to Levofloxacin 500 mg.
Levofloxacin is a synthetic broad-spectrum antibacterial agent. Chemically, levofloxacin, a chiral fluorinated carboxyquinolone, is the pure(-)-(S)-enantiomer of the racemic drug substance ofloxacin. The chemical name is (-)-(S)-9fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4benzoxazine-6-carboxylic acid hemihydrate.
The empirical formula is C18H20FN3O4 1/2 H2O and the molecular weight is 370.38. Levofloxacin is a light yellowish-white to yellow-white crystal or crystalline powder.

Pharmacology: Pharmacokinetics: Absorption: Levofloxacin is rapidly and almost completely absorbed after oral administration. Peak plasma concentrations are usually attained one to two hours after oral dosing. The absolute bioavailability of levofloxacin from 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. Levofloxacin reaches its peak levels in skin tissues and in blister fluid of healthy subjects at approximately 3 hours after dosing. Levofloxacin also penetrates well into lung tissues. Lung tissue concentrations were generally 2- to 5-fold higher than plasma concentrations and ranged from approximately 2.4 to 11.3 mcg/g over a 24-hour period after a single 500 mg oral dose. Levofloxacin is mainly bound approximately 24 to 38% to serum albumin in humans.
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 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.
Microbiology: Mechanism of Action: The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase, enzymes required for DNA replication, transcription, repair and recombination.
Drug Resistance: Levofloxacin and other fluoroquinolones differ in chemical structure and mode of action from aminoglycosides, macrolides and beta-lactam antibiotics. Levofloxacin may, therefore, be active against bacteria resistant to these antimicrobials. Although cross-resistance has been observed between levofloxacin and some other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to levofloxacin.
Antimicrobial activity: Levofloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations. Levofloxacin has been shown to be active against a wide range of Gram-negative and Gram-positive microorganisms both in vitro and in clinical infections as described as follows.
Aerobic Gram-Positive Microorganisms: Enterococcus faecalis, Staphylococcus aureus (methicillin-susceptible strains), Staphylococcus epidermidis (methicillin-susceptible strains), Staphylococcus saprophyticus, Streptococcus pneumoniae (including multi-drug resistant strains), Streptococcus pyogenes.
Aerobic Gram-Negative Microorganisms: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumonia, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, Pseudomonas aeuriginosa, Serratia marcescens.
Other Microorganisms: Chlamydophila pneumonia, Mycoplasma pneumonia.

Indicated for the treatment of mild, moderate and severe infections due to levofloxacin-susceptible microorganisms: (a) acute bacterial sinusitis; (b) acute bacterial exacerbations of chronic bronchitis; (c) community acquired pneumonia; (d) complicated urinary tract infections including pyelonephritis; (e) chronic bacterial prostatitis and  (f) skin and soft tissue infections.

The usual dose of levofloxacin tablets is 250 mg, 500 mg, or 750 mg administered orally every 24 hours, as indicated by infection. It may be taken on an empty stomach or with meals. The dosage should be determined according to the sensitivity of the causative organism and the severity of the infection. For patients with normal renal function (creatinine clearance >50 mL/min), the following daily dosages are recommended: Acute bacterial exacerbations of chronic bronchitis: 500 mg for 7 days.
Nosocomial Pneumonia: 750 mg for 7-14 days.
Community-acquired Pneumonia: 500 mg for 7-14 days.
Acute Bacterial Sinusitis: 500 mg for 10-14 days.
Uncomplicated Skin and Skin Structure Infections: 500 mg for 7-10 days.
Complicated Skin and Skin Structure Infections: 750 mg for 7-14 days.
Chronic Bacterial Prostatitis: 500 mg for 28 days.
Uncomplicated Urinary Tract Infections: 500 mg 3 days.
Complicated Urinary Tract Infections: 750 mg 5 days.
Acute Pyelonephritis: 750 mg 5 days.
Administration in Renal Impairment: Levofloxacin is administered with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced. In patients with impaired renal function (creatinine clearance <50 mL/min), adjustment of the dosage regimen is necessary to avoid the accumulation of levofloxacin due to decreased clearance.

Based on animal studies, the most important adverse reactions to expect following acute overdosage of Levofloxacin are central nervous system symptoms such as confusion, dizziness, impairment of consciousness and convulsive seizures. The treatment of an overdosage is symptomatic and multivitamin preparations with zinc may interfere with the gastrointestinal absorption of levofloxacin, resulting in systemic levels considerably lower than desired. So, these agents should be taken at least two hours before or two hours after oral levofloxacin tablet.
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.
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.
Geriatric Use: There was no apparent difference in the frequency or severity of adverse reactions in elderly adults compared with younger adults. The pharmacokinetic properties of levofloxacin in elderly subjects are similar to those in younger subjects. Drug absorption appears to be unaffected by age. Dosage adjustment is necessary for elderly patients with impaired renal function.

The use of LEVOFLOXACIN is contraindicated in: Previous hypersensitivity reaction to levofloxacin, other quinolones or any other ingredient.
Epilepsy.
Patients with history of tendon disorders associated with fluoroquinolone administration.
Children or adolescents (under 18 years of age).
Pregnancy and lactation.

The safety and efficacy of levofloxacin in pediatric patients and adolescents (under the age of 18 years), pregnant women, and lactating women have not been established.
Caution should be exercised when using levofloxacin in patients: Prone to seizures, such as patients with pre-existing central nervous system lesions; Being treated with fenbufen or non-steroidal anti-inflammatory medicines, using medicines which lower the cerebral seizure threshold, such as theophylline; Driving or operating machinery, as the use of levofloxacin may alter the ability to drive or to operate machinery, Being tested for tuberculosis as levofloxacin inhibit the growth of ,Mycobacterium tuberculosis and therefore may give false-negative results in the bacteriological diagnosis of tuberculosis; Exposed to ultraviolet light such as sunlight through window glass or longer wavelength ultraviolet (UVA) from sunbeds, in order to prevent photosensitisation.

Tendinopathy and Tendon Rupture: Fluoroquinolones, including levofloxacin are associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon and rupture of the Achilles tendon may require surgical repair. Tendinitis and tendon rupture in the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendon sites have also been reported. The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is further increased in older patients usually over 60 years of age, in those taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Tendon rupture can occur during or after completion of therapy; cases occurring up to several months after completion of therapy have been reported. Levofloxacin should be discontinued if the patient experiences pain, swelling, inflammation or rupture of a tendon. Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact physician regarding changing to a non-quinolone antimicrobial drug.
Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving therapy with fluoroquinolones, including levofloxacin. These reactions often occur following the first dose. Some reactions have been accompanied by cardiovascular collapse, hypotension/shock, seizure, loss of consciousness, tingling, angioedema (including tongue, laryngeal, throat, or facial edema/swelling), airway obstruction (including bronchospasm, shortness of breath, and acute respiratory distress), dyspnea, urticaria, itching, and other serious skin reactions. Levofloxacin should be discontinued immediately at the first appearance of a skin rash or any other sign of hypersensitivity. Serious acute hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures, including oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway management, as clinically indicated.
Hepatotoxicity: Severe hepatotoxicity (including acute hepatitis and fatal events) have been reported for patients treated with levofloxacin. Severe hepatotoxicity generally occurred within 14 days of initiation of therapy and most cases occurred within 6 days. Most cases of severe hepatotoxicity were not associated with hypersensitivity. The majority of fatal hepatotoxicity reports occurred in patients 65 years of age or older and most were not associated with hypersensitivity. Treatment should be discontinued immediately if the patient develops signs and symptoms of hepatitis.
Central Nervous System Effects: Convulsions and toxic psychoses have been reported in patients receiving fluoroquinolones, including levofloxacin. Fluoroquinolones may also cause increased intracranial pressure and central nervous system stimulation which may lead to tremors, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, nightmares, insomnia, and, rarely, suicidal thoughts or acts. If these reactions occur in patients receiving levofloxacin, the drug should be discontinued and appropriate measures instituted. Levofloxacin should be used with caution in patients with a known or suspected central nervous system (CNS) disorder that may predispose them to seizures or lower the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or in the supportive. LEVOFLOXACIN is not effectively removed by hemodialysis or peritoneal dialysis.

Concurrent administration levofloxacin tablets with antacids containing magnesium or aluminum, sucralfate, metal cations such as iron, and presence of other risk factors that may predispose them to seizures or lower the seizure threshold (e.g., certain drug therapy, renal dysfunction).
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 levofloxacin. Levofloxacin should be discontinued if the patient experiences symptoms of neuropathy including, pain, burning, tingling, numbness, and/or weakness or other alterations of sensation including light touch, pain, temperature, position sense, and vibratory sensation in order to prevent the development of an irreversible condition.
Prolongation of the QT interval: Levofloxacin have been associated with prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia. Rare cases of torsades de pointes have been spontaneously reported in patients receiving levofloxacin.
Blood Glucose Disturbances: Disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported with levofloxacin, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g., glyburide) or with insulin. In these patients, careful monitoring of blood glucose is recommended.
Photosensitivity/Phototoxicity: Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, V area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of fluoroquinolones after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if photosensitivity/phototoxicity occurs.

Store at temperatures not exceeding 30°C. Protect from light.

Quinolones

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

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