For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only

Bredin (Nimodipine Tablets)

 

  Description:

Voxin (Levofloxacin Tablets) Tablets is a synthetic broad spectrum antibacterial agent available for oral administration. Chemically, Levofloxacin, a chiral fluorinated carboxyquinolone, 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-piperazinyl) -7-oxo-7=-pyrido [1,2,3-de]-1,4-benzoxazine-6-carboxylic acid hemihydrate.1
Its empirical formula is C18 H20 FN3 O4 . H2O and its molecular weight is 370.38. The molecule exists as a zwitterion at the pH conditions in the small intestine.
Voxin-250: Light pink coloured, oblong, biconvex, film coated tablets, plain on both sides.
Voxin-500: Light pink coloured, oblong, biconvex, film coated tablets, scored on one side and plain on the other.

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  Composition:

VOXIN-250
Each film coated tablet contains:
Levofloxacin Hemihydrate equivalent to
Levofloxacin ......................... 250 mg
Colours: Ferric Oxide Red, Titanium Dioxide

VOXIN-500
Each film coated tablet contains:
Levofloxacin Hemihydrate equivalent to
Levofloxacin ....................... 500 mg
Colours: Ferric Oxide Red, Titanium Dioxide

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  Clinical Pharmacology:

The mechanism of action of Levofloxacin involves inhibition of bacterial topoisomerase IV and DNA gyrase, enzymes required for DNA replication, transcription, repair and recombination. Levofloxacin has in vitro activity against the following gram-negative and gram-positive microorganisms. Levofloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.2

Aerobic gram-positive microorganisms
Enterococcus faecalis (moderately susceptible)
Staphylococcus aureus (methicillin-susceptible strains)
Staphylococcus saprophyticus
Streptococcus pneumoniae (including penicillin-resistant strains*)
Streptococcus pyogenes
Aerobic gram-negative microorganisms
Enterobacter cloacae
Escherichia coli
Haemophilus influenzae
Haemophilus parainfluenzae
Klebsiella pneumoniae
Legionella pneumophila
Moraxella catarrhalis
Proteus mirabilis
Pseudomonas aeruginosa
(some strains of Pseudomonas aeruginosa may develop resistance  rapidly during treatment with Levofloxacin.)

Other microorganisms
Chlamydia pneumoniae
Mycoplasma pneumoniae

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  Pharmacokinetics:

Levofloxacin is rapidly and essentially completely absorbed after oral administration. Peak plasma concentrations are attained 1-2 hrs after oral dosing. The absolute bioavailability of a 500 mg tablet is approximately 99%.

The mean SD peak and trough plasma concentrations attained following multiple once-daily oral dosage regimens were approximately 5.7 1.4g/mL  and approximately 0.5 g/mL after the 500 mg doses.

Oral administration of a 500-mg Levofloxacin tablet with food slightly prolongs the time to peak concentration by approximately 1 hour and slightly decreases the peak concentration by approximately 14%. Therefore, Levofloxacin tablets can be administered without regard to food. The mean Volume of distribution (Vd) of Levofloxacin generally ranges from 74 to 112 L after single and multiple 500 mg dose. Levofloxacin reaches its peak levels in skin tissues and in blister fluid of healthy subjects at approximately 3 hours after dosing.

Levofloxacin is approximately 24 to 38% bound to serum proteins. Levofloxacin is mainly bound to serum albumin in humans. The binding of Levofloxacin to serum proteins is independent of the drug concentration.

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.

Levofloxacin is excreted more or less unchanged drug in the urine. The mean terminal elimination half-life (t1/2) of Levofloxacin ranges from approximately 6 to 8 hours following single or multiple doses of Levofloxacin given orally or intravenously. The mean apparent total body clearance and renal clearance range from approx. 144-226 ml/min and 96-142ml/min.

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  Special Populations:

There are no significant differences in Levofloxacin pharmacokinetics between young and elderly subjects when the subjects' differences in creatinine clearance are taken into consideration. Levofloxacin dose adjustment based on age alone is not necessary.

The pharmacokinetics of Levofloxacin in pediatric subjects have not been studied.

There are no significant differences in Levofloxacin pharmacokinetics between male and female subjects. Dose adjustment based on gender alone is not necessary.

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. Pharmacokinetic studies in hepatically impaired patients have not been conducted.

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  Indications and Usage:

VOXIN 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.3

Acute maxillary sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.

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), 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, cellulitis, 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.

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  Containdications:

Levofloxacin is contraindicated in persons with a history of hypersensitivity to Levofloxacin and /or other quinolones.

 
  Warnings:

The safety and efficacy of Levofloxacin in pediatric patients, adolescents (under the age of 18 years), pregnant women, and nursing mother have not been established.

Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving therapy with quinolones, including Levofloxacin. Levofloxacin should be discontinued immediately at the first appearance of a skin rash or any other sign of hypersensitivity.

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  Precautions:

Levofloxacin should be administered with caution in the presence of renal insufficiency.

Moderate to severe phototoxicity reactions have been observed in patients exposed to direct sunlight while receiving drugs in this class. Excessive exposure to sunlight should be avoided.

As with other quinolones, Levofloxacin should be used with caution in any patient with a known or suspected CNS disorder that may predispose to seizures or lower the seizure threshold.

As with other quinolones, disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g., glyburide/glibenclamide) or with insulin. In these patients, careful monitoring of blood glucose is recommended.

 
  Drug Interactions:

Antacids, Sucralfate, Metal Cations, Multivitamins Concurrent administration of VOXIN tablets with antacids containing magnesium as well as sucralfate metal cations such as iron and multivitamin preparations with zinc may interfere with the gastrointestinal absorption of Levofloxacin resulting in systemic levels considerably lower than desired.

Theophylline, Warfarin, Cyclosporine, Digoxin, Probenecid and Cimetidine: No significant effect of Levofloxacin on the plasma concentrations, AUC, and other disposition parameters for theophylline was detected in a clinical study.

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.

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  Adverse Reactions:

Most frequent observed adverse reactions are:
Body as a Whole: Asthenia, edema, fever, malaise, rigors, substernal chest pain
Autonomic, Central and Peripheral Nervous System Disorders: Postural hypotension, syncope abnormal coordination, coma, convulsions (seizures), hyperkinesia, hypertonia, hypoaesthesia, involuntary muscle contractions, paresthesia, paralysis, speech disorder, stupor, tremor, vertigo
Cardiovascular Disorders: Cardiac failure, circulatory failure, hypertension, hypotension
Heart Rate and Rhythm Disorders: Arrhythmia, atrial fibrillation, bradycardia, cardiac arrest, heart block, palpitation, supraventricular tachycardia, tachycardia, ventricular fibrillation 
Respiratory System Disorders:  Asthma, coughing, dyspnea, haemoptysis, hypoxia, pleural effusion, respiratory insufficiency
Gastro-Intestinal System Disorders: Dry mouth, dysphagia, gastroenteritis, G.I. hemorrhage, pancreatitis, pseudomembranous colitis, tongue edema
Liver and Biliary System Disorders: Abnormal hepatic function, cholelithiasis, hepatic coma, jaundice
Metabolic and Nutritional Disorders: Aggravated diabetes mellitus, dehydration, hyperglycemia, hyperkalemia, hypoglycemia, hypokalemia, increased LDH, weight decrease
Musculo-Skeletal System Disorders: Arthralgia, arthritis, arthrosis, muscle weakness, myalgia, osteomyelitis, rhabdomyolysis, synovitis, tendinitis
Neoplasms: Carcinoma 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.

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  Dosage and Administration:

The usual dose of VOXIN tablets is 250 mg or 500 mg administered orally. The dosage guidelines as per the infection are given as under.

Infection Daily dose Frequency Duration

Acute Bacterial Exacerbation of Chronic Bronchitis

500 mg q24h 7 days

Community Acquired Pneumonia

500 mg q24h 7-14 days

Acute Maxillary Sinusitis

500 mg q24h 10-14 days

Uncomplicated SSSI

500 mg q24h 7-10 days

Complicated UTI

250 mg q24h 10 days

Acute pyelonephritis

250 mg q24h 10 days

Uncomplicated UTI

250 mg q24h 3 days

 

 
  Storage instructions:

Store at a temperature below 250C, protect from light and moisture.

 

  Presentation:

Blister pack of 10 X 5 tablets.

 

  References:
  1. Tubercle and Lung Disease 1995; 76: 377 - 80
  2. Drugs 1994; 47(4): 677-700
  3. Clinical Therapeutics 1998; 20 (6): 1049 - 70

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