Lemin 500mg Tablet (Levofloxacin)

Lemin 500mg Tablet (Levofloxacin)

Lemin 500mg Tablet (Levofloxacin)

LEMIN (Levofloxacin) is a synthetic broad-spectrum antibacterial agent. Chemically, levofloxacin, a chiral fluorinated carboxyquinilone, is the pure (-)-(S)-enantiomer of the racemic drug substance ofloxacin with a chemical name of (-)-(S)-9-fluoro-2, 3- dihydro-3-methyl-10- (4-methyl- piperazinyl)-7-oxo-7H-pyrido [1,2,3,-de] [1,4] benzoxazine6-carboxylic acid. The molecular formula is C18H20FN3O4 and the structural formula is:

COMPOSITION

LEMIN (Levofloxacin) is available for oral administration as:

LEMIN Tablet 250mg, Each film-coated tablet contains: 

Levofloxacin …250mg

LEMIN Tablet 500mg 

Each film-coated tablet contains:

Levofloxacin …500mg

CLINICAL PHARMACOLOGY   

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 main mechanism of action of levofloxacin involves the inhibition of bacterial topoisomerase IV and DNA gyrase (both or which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination. Levofloxacin has in vitro activity against the following gram-negative and gram-positive micro-organisms. It is often bactericidal at concentrations equal to or slightly greater than inhibitory concentration. It is generally considered to be about twice as active as its isomer, ofloxacin.

Microbiology:

Levofloxacin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections.           

Commonly susceptible species

Aerobic Gram-positive bacteria Staphylococcus aureus methicillin-susceptible, Staphylococcus saprophyticus, Streptococci group C and G, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes.

Aerobic Gram- negative bacteria

Burkholderia cepacia, Eikenella corrodens, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Pasteurella multocida, Proteus vulgaris, Providencia rettgeri.

Anaerobic bacteria: 

Peptostreptococcus

Other

Chlamydophila pneumoniae, Chlamydophila psittaci, Chlamydia trachomatis, Legionella pneumophila, Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma urealyticum.

Species for which acquired resistance may be a problem

Aerobic Gram-positive bacteria Enterococcus faecalis, Staphylococcus aureus methicillin-resistant, Coagulase negative Staphylococcus spp.

Aerobic Gram- negative bacteria

Acinetobacter baumannii, Citrobacter freundii, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Escherichia coli, Morganella morganii, Proteus mirabi lis, Providencia stuarti i, Pseudomonas aeruginosa, Serratia marcescens.

Anaerobic bacteria

Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotamic ron, Bacteroides vulgatus, Clostridium difficile.Levofloxacin has been shown to be active against Bacillus anthracis in vitro

Pharmacokinetics:        

Levofloxacin is rapidly and almost completely absorbed with absolute bioavailability of 99% following oral use with peak plasma concentrations achieved within 1-2 hours of a dose. The mean volume of distribution of Levofloxacin ranges from 74 to 112 L after single or multiple 500mg or 750mg doses indicating distribution into body tissues including the bronchial mucosa and lungs, but penetration into CSF is relatively poor. Levofloxacin is approximately 24% to 38% bound to plasma proteins. It is only metabolised to a small degree to in-active metabolites. The elimination half-life of Levofloxacin is 6 to 8 hours although this may be prolonged in patients with renal impairment. Approximately 87% of an administered dose w as recovered as unchanged drug in urine within 48 hours, whereas less than 4% of the dose w as recovered in feces in 72 hours and less than 5% of an administered dose is recovered in the urine. It is not removed by hemodialysis or peritoneal dialysis.

Special Population

Renal Insufficiency Clearance of levofloxacin is substantially reduced and plasma elimination half-life is substantially prolonged in patients with impaired renal function (creatinine clearance <50ml/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.   

Indications:     

LEMIN (Levofloxacin) is indicated for the treatment of adults (>18 years of age) with mild, moderate, and severe infections caused by susceptible strains of the designated micro-organisms in the conditions listed below:

− Acute bacterial sinusitis.

− Acute bacterial exacerbation of chronic bronchitis.

− Communit y- acquired pneumonia and nosocomial pneumonia.

− Complicated skin and skin structure infections.

− Uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections.

− Chronic bacterial prostatitis.

− Complicated urinary tract infections (mild to moderate).

− Uncomplicated urinary tract infections (mild to moderate).

− Acute pyelonephritis (mild to moderate).

− Inhalational anthrax, post-exposure.

DOSAGE AND ADMINISTRATION

LEMIN (Levofloxacin) Tablets 250mg and 500mg administered orally every 24 hours. The dosage depends on the types and severity of the infections and the sensitivity of the presumed, causative pathogen.

LEMIN (Levofloxacin) Tablets should be swallowed without crushing and with sufficient amount of liquid. LEMIN (Levofloxacin) Tablets can be administered without regard to food.

LEMIN (Levofloxacin) Tablets should be administered at least two hours before or two hours after antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or didanosine chewable/buffered tablets or the pediatric powder for oral solution. The dosage guidelines as per the infection are given as under:

Dosage in adult patients with normal renal function

(Creatinine clearance > 50mL/min)

 

INDICATIONS DAILY DOSE

(mg)

DURATION

(DAYS)

 

Acute Bacterial Sinusitis

                         

500 mf od

 

10-14

 

Acute Bacterial Exacerbation of chronic Bronchitis

 

250mg to 500mg

once daily

 

7 – 10

 

Community Acquired Pneumonia  and Nosocomial  Pneumonia

 

500mg od or bid

750mg od

 

7 – 14

 

Uncomplicated skin and skin soft tissue Infections

 

500mg od

 

7-10

 

Uncomplicated Urinary Tract Infections

 

250mg  od

 

3

 

Complicated Urinary Tract Infections

 

250mg  od

 

              750mg  od

 

10

5

 

Acute Pyelonephritis

 

250mg  od

 

750mg  od

 

10

5

 

Chronic Bacterial Prostatitis

 

500mg  od

 

28

 

Inhalational Anthrax

 (Post-Exposure)

 

500mg  od

 

 

60

 

ADVERSE REACTIONS

Levofloxacin is usually well tolerated. However, following are the adverse effects reported during its therapy.

Common: Moniliasis, insomnia, headache, dizziness, dyspnea, nausea, diarrhea, constipation, abdominal pain, vomiting, dyspepsia, rash, pruritus, vaginitis, edema and chest pain.

Less common: Genital moniliasis, anemia, thrombocytopenia, granulocytopenia, allergic reaction, hyperglycemia, hypoglycemia, hyperkalemia, anxiety, agitation, confusion, depression, hallucination, nightmare, sleep disorder, anorexia, abnormal dreaming, tremor, convulsions, paresthesia, vertigo, hypertonia, hyperkinesias, abnormal gait, sonolence, syncope, epistaxis, cardiac arrest, palpitation, ventricular tachycardia, ventricular arrhythmia, phlebitis, gastritis, stomatitis, pancreatitis, esophagitis, gastroenteritis, glossitis, pseudomembraneous/C. difficile colitis, abnormal hepatic function, increased hepatic enzymes, increased alkaline phosphatase, urticaria, arthralgia, tendonitis, myalgia, skeletal pain, abnormal renal function and acute renal failure.

CONTRAINDICATIONS

Levofloxacin is contraindicated in:

− Patients with a history of hypersensitivity to this drug and/or other quinolone antibacterial.

− Children or growing adolescents.

PRECAUTIONS

General

Although levofloxacin is more soluble than other quinolones, adequate hydration of patients receiving levofloxacin should be maintained to prevent the formation of highly concentrated urine.

Tendinitis and tendon rupture

Tendinitis may rarely occur. It most frequently involves the Achilles tendon and may lead to tendon rupture. The risk of tendinitis and tendon rupture is increased in the elderly and in patients using corticosteroids. Close monitoring of these patients is therefore necessary if they are prescribed levofloxacin. All patients should consult their physician if they experience symptoms of tendinitis.

Clostridium difficile-associated disease

Diarrhea, particularly if severe, persistent and/or bloody, during or after treatment with levofloxacin may be symptomatic of Clostridium difficile-associated disease, the most severe form of which is pseudomembranous colitis. If pseudomembranous colitis is suspected, levofloxacin must be stopped immediately and patients should be treated with supportive measures with specific therapy without delay.

Patients predisposed to seizures

Quinolones, should be used with extreme caution in patients predisposed to seizures, such as patients with pre-existing central nervous system lesions, concomitant treatment with fenbufen and similar non-steroidal anti-inflammatory drugs or with drugs which lower the cerebral seizure threshold, such as theophylline.

Patients with G-6- phosphate dehydrogenase deficiency

Patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity may be prone to hemolytic reactions when treated with quinolone antibacterial agents and so levofloxacin should be used with caution.

Hypoglycemia

As with all quinolones, hypoglycemia has been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent or with insulin. In these diabetic patients, careful monitoring of blood glucose is recommended.

Prevention of photosensitization

Although photosensitisation is very rare with levofloxacin, it is recommended that patients should not expose themselves unnecessarily to strong sunlight or to artificial UV rays (e.g. sunray lamp, solarium), in order to prevent photosensitisation.

Patients treated with Vitamin K antagonists

Due to possible increase in coagulation tests (PT/INR) and/or bleeding in patients treated with levofloxacin in combination with a vitamin K antagonist (e.g. warfarin), coagulation tests should be monitored when these drugs are given concomitantly.

Psychotic reactions

Caution is recommended if levofloxacin is to be used in psychotic patients or in patients

with history of psychiatric disease.

QT interval prolongation

Caution should be taken when using fluoroquinolones, including levofloxacin, in patients with known risk factors for prolongation of the QT interval such as, for example:

 − congenital long QT syndrome

− concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides)

− uncorrected electrolyte imbalance (e.g., hypokalemia, hypomagnesemia)

− elderly

− cardiac disease (e.g., heart failure, myocardial infarction, bradycardia)

Peripheral neuropathy

Sensory or sensorimotor peripheral neuropathy has been reported in patients receiving fluoroquinolones, including levofloxacin, which can be rapid in its onset. Levofloxacin should be discontinued if the patient experiences symptoms of neuropathy in order to prevent the development of an irreversible condition.

Renal Insufficiency

Clearance of levofloxacin is substantially reduced and plasma elimination half-life is substantially prolonged in patients with impaired renal function (creatinine clearance <50mL/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.

Geriatric Use

Caution should be used when prescribing levofloxacin to elderly patients especially those on corticosteroids. Patients should be informed of potential side effects and advised to discontinue levofloxacin and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur.

Pregnancy

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

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.

OVERDOSAGE

In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. Antacids may be used for protection of gastric mucosa. Hemodialysis, including peritoneal dialysis and CAPD, are not effective in removing levofloxacin from the body. No specific antidote exists.

STORAGE

Store at 25°C (Excursions permitted between 15°C-30°C). Protect from sunlight & moisture.

The expiration date refers to the product correctly stored at the required conditions.

PRESENTATION    

LEMIN Levofloxacin) Tablets 250mg are available in Alu-Alu pack of 10’s.

LEMIN Levofloxacin) Tablets 500mg are available in Alu-Alu pack of 10’s.