Tigeron 500/Tigeron 750

Tigeron 500/Tigeron 750

levofloxacin

Manufacturer:

Kusum Healthcare

Distributor:

Kusum Healthcare
Full Prescribing Info
Contents
Levofloxacin hemihydrate.
Description
Each film coated tablet contains: Levofloxacin hemihydrate equivalent to Levofloxacin 500/750 mg.
Excipients/Inactive Ingredients: Microcrystalline cellulose, povidone K-30, crospovidone, colloidal anhydrous silica, magnesium stearate, opadry pink 03B84681, isopropyl alcohol and purified water.
Action
Pharmacotherapeutic group: Quinolone antibacterials, fluoroquinolones. ATC Code: J01MA12.
Pharmacology: Pharmacodynamics: Levofloxacin is a synthetic antibacterial agent of the fluoroquinolone class and is the S (-) enantiomer of the racemic active substance ofloxacin.
Mechanism of action: As a fluoroquinolone antibacterial agent, levofloxacin acts on the DNA-DNA gyrase complex and topoisomerase IV.
Pharmacokinetics: Absorption: Orally administered levofloxacin is rapidly and almost completely absorbed with peak plasma concentrations being obtained within 1-2 h. The absolute bioavailability is 99-100%.
Food has little effect on the absorption of levofloxacin.
Steady state conditions are reached within 48 hours following a 500 mg once or twice daily dosage regimen.
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.
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.
Elimination: 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. The mean apparent total body clearance and renal clearance range from approximately 144 to 226 mL/min and 96 to 142 mL/min, respectively. Renal clearance in excess of the glomerular filtration rate suggests that tubular secretion of levofloxacin occurs in addition to its glomerular filtration. Concomitant administration of either cimetidine or probenecid results in approximately 24% and 35% reduction in the levofloxacin renal clearance, respectively, indicating that secretion of levofloxacin occurs in the renal proximal tubule.
Hepatic impairment: The pharmacokinetics of levocetirizine in hepatically impaired subjects have not been tested. Patients with chronic liver diseases (hepatocellular, cholestatic, and biliary cirrhosis) given 10 or 20 mg of the racemic compound cetirizine as a single dose had a 50% increase in half life along with a 40% decrease in clearance compared to healthy subjects.
Pharmacokinetic/pharmacodynamic relationship: The action on histamine-induced skin reactions is out of phase with the plasma concentrations.
Microbiology: Commonly susceptible species: Aerobic Gram-positive bacteria: Bacillus anthracis, Staphylococcus aureus methicillin-susceptible, Staphylococcus saprophyticus, Streptococci group C and G, Streptococcus agalactiae, Streptococcus pneumonia, Streptococcus pyogenes.
Aerobic Gram-negative bacteria: Eikenella corrodens, Haemophilus influenza, Haemophilus para-influenzae, Klebsiella oxytoca, Moraxella catarrhalis, Pasteurella multocida, Proteus vulgaris, Providencia rettgeri.
Anaerobic bacteria: Peptostreptococcus.
Others: Chlamydophila pneumonia, Chlamydophila psittaci, Chlamydia trachomatis, Legionella pneumophila, Mycoplasma pneumonia, 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.
# Methicillin resistant S. aureus are very likely to possess co-resistance to fluoroquinolones, including levofloxacin.
Aerobic Gram-negative bacteria: Acinetobacter baumannii, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumonia, Morganella morganii, Proteus mirabilis, Providencia stuartii, Pseudomonas aeruginosa, Serratia marcescens.
Anaerobic bacteria: Bacteroides fragilis.
Inherently Resistant Strains: Aerobic Gram-positive bacteria: Enterococcus faecium.
Indications/Uses
In adults with infections of mild or moderate severity, Tigeron tablets are indicated for the treatment of the following infections when due to levofloxacin-susceptible microorganisms: Acute bacterial sinusitis; Acute bacterial exacerbations of chronic bronchitis; Community-acquired pneumonia; Complicated urinary tract infections including pyelonephritis; Chronic bacterial prostatitis; Skin and soft tissue infections (Uncomplicated and complicated); Inhalation Anthrax.
Before prescribing Tigeron, consideration should be given to national and/or local guidance on the appropriate use of fluoroquinolones.
Dosage/Direction for Use
Recommended doses for adult patients with normal kidney function with creatinine clearance more than 50 ml/min. (See Tables 1 and 2.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Dosage for patients with liver function disorders: Dosage adjustment is not necessary because Levofloxacin is insignificantly metabolised in liver.
Mode of administration: Tigeron tablets should be swallowed without crushing and with sufficient amount of liquid. The tablets may be taken during meals or between meals. Tigeron tablets should be taken at least two hours before or after iron salts, antacids and sucralfate administration since reduction of absorption can occur.
Overdosage
Symptoms: The most important signs to be expected following acute overdosage of Tigeron tablets are central nervous system symptoms such as confusion, dizziness, impairment of consciousness, and convulsive seizures, increases in QT interval as well as gastro-intestinal reactions such as nausea and mucosal erosions.
Treatment: In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. Ant-acids may be used for protection of gastric mucosa. Hemodialysis, including peritoneal dialysis and CAPD, are not effective in removing levofloxacin from the body.
Contraindications
Tigeron tablets must not be used: In patients hypersensitive to levofloxacin or other quinolones or any of the excipients; In patients with epilepsy; In patients with history of tendon disorders related to fluoroquinolone administration; In children or growing adolescents; During pregnancy; In breast-feeding women.
Warnings
Serious adverse reactions including tendinitis, tendon rupture, peripheral neuropathy, seizures and exacerbation of myasthenia gravis.
Fluoroquinolones, including Levofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together (see PRECAUTIONS), including: Tendinitis and tendon rupture (see PRECAUTIONS).
Peripheral neuropathy (see PRECAUTIONS); Patients predisposed to seizures (see PRECAUTIONS); Discontinue TIGERON immediately and avoid the use of fluoroquinolones, including TIGERON, in patients who experience any of these serious adverse reactions (see PRECAUTIONS).
Fluoroquinolones, including TIGERON, may exacerbate muscle weakness in patients with myasthenia gravis. Avoid TIGERON in patients with a known history of myasthenia gravis (see PRECAUTIONS).
Because fluoroquinolones, including TIGERON, have been associated with serious adverse reactions (see PRECAUTIONS), reserve TIGERON for use in patients who have no alternative treatment options for the following indications: Uncomplicated urinary tract infection (see INDICATIONS); Acute bacterial exacerbation of chronic bronchitis (see INDICATIONS); Acute bacterial sinusitis (see INDICATIONS).
Special Precautions
Methicillin resistant S. aureus are very likely to possess co-resistance to fluoroquinolones, including levofloxacin. Therefore levofloxacin is not recommended for the treatment of known or suspected MRSA infections unless laboratory results have confirmed susceptibility of the organism to levofloxacin (and commonly recommended antibacterial agents for the treatment of MRSA infections are considered inappropriate).
Levofloxacin may be used in the treatment of Acute Bacterial Sinusitis and Acute Exacerbation of Chronic Bronchitis when these infections have been adequately diagnosed.
Resistance to fluoroquinolones of E. coli - the most common pathogen involved in urinary tract infections - varies across the European Union. Prescribers are advised to take into account the local prevalence of resistance in E. coli to fluoroquinolones.
Inhalation Anthrax: Use in human is based on in vitro Bacillus anthracis susceptibility data and on animal experimental data together with limited human data. Treating physicians should refer to national and/or international consensus documents regarding the treatment of anthrax.
Tendinitis and tendon rupture: Tendinitis may rarely occur. It most frequently involves the Achilles tendon and may lead to tendon rupture. Tendinitis and tendon rupture, sometimes bilateral, may occur within 48 hours of starting treatment with levofloxacin and have been reported up to several months after discontinuation of treatment. The risk of tendinitis and tendon rupture is increased in patients aged over 60 years, in patients receiving daily doses of 1000 mg and in patients using corticosteroids. The daily dose should be adjusted in elderly patients based on creatinine clearance. 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. If tendinitis is suspected, treatment with levofloxacin must be halted immediately, and appropriate treatment (e.g. immobilisation) must be initiated for the affected tendon.
Clostridium difficile-associated disease: Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment with levofloxacin (including several weeks after treatment), may be symptomatic of Clostridium difficile associated disease (CDAD). CDAD may range in severity from mild to life threatening, the most severe form of which is pseudomembranous colitis. It is therefore important to consider this diagnosis in patients who develop serious diarrhoea during or after treatment with levofloxacin. If CDAD is suspected or confirmed, levofloxacin should be stopped immediately and appropriate treatment initiated without delay. Antiperistaltic medicinal products are contraindicated in this clinical situation.
Patients predisposed to seizures: Quinolones may lower the seizure threshold and may trigger seizures. Levofloxacin is contraindicated in patients with a history of epilepsy and, as with other quinolones, should be used with extreme caution in patients predisposed to seizures or concomitant treatment with active substances that lower the cerebral seizure threshold, such as theophylline. In case of convulsive seizures, treatment with levofloxacin should be discontinued.
Patients with G-6-phosphate dehydrogenase deficiency: Patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity may be prone to haemolytic reactions when treated with quinolone antibacterial agents. Therefore, if levofloxacin has to be used in these patients, potential occurrence of haemolysis should be monitored.
Patients with renal impairment: Since levofloxacin is excreted mainly by the kidneys, the dose of Tigeron should be adjusted in patients with renal impairment.
Hypersensitivity reactions: Levofloxacin can cause serious, potentially fatal hypersensitivity reactions (e.g. angioedema up to anaphylactic shock), occasionally following the initial dose. Patients should discontinue treatment immediately and contact their physician or an emergency physician, who will initiate appropriate emergency measures.
Severe bullous reactions: Cases of severe bullous skin reactions such as Stevens Johnson syndrome or toxic epidermal necrolysis have been reported with levofloxacin. Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.
Dysglycaemia: As with all quinolones, disturbances in blood glucose, including both hypoglycaemia and hyperglycaemia have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycaemic agent (e.g., glibenclamide) or with insulin. Cases of hypoglycaemic coma have been reported. In diabetic patients, careful monitoring of blood glucose is recommended.
Prevention of photosensitisation: Photosensitisation has been reported 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), during treatment and for 48 hours following treatment discontinuation 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: Psychotic reactions have been reported in patients receiving quinolones, including levofloxacin. In very rare cases these have progressed to suicidal thoughts and self-endangering behavior sometimes after only a single dose of levofloxacin. In the event that the patient develops these reactions, levofloxacin should be discontinued and appropriate measures instituted. 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, antipsychotics). Uncorrected electrolyte imbalance (e.g. hypokalemia, hypomagnesemia) cardiac disease (e.g. heart failure, myocardial infarction, bradycardia) Elderly patients and women may be more sensitive to QTc prolonging medications. Therefore, caution should be taken when using fluoroquinolones, including levofloxacin, in these populations.
Peripheral neuropathy: Peripheral sensory neuropathy and peripheral sensory motor neuropathy have 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.
Hepatobiliary disorders: Cases of hepatic necrosis up to fatal hepatic failure have been reported with levofloxacin, primarily in patients with severe underlying diseases, e.g. sepsis. Patients should be advised to stop treatment and contact their doctor if signs and symptoms of hepatic disease develop such as anorexia, jaundice, dark urine, pruritus or tender abdomen.
Exacerbation of myasthenia gravis: Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. Post marketing serious adverse reactions, including deaths and the requirement for respiratory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Levofloxacin is not recommended in patients with a known history of myasthenia gravis.
Vision disorders: If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately.
Superinfection: The use of levofloxacin, especially if prolonged, may result in overgrowth of non-susceptible organisms. If superinfection occurs during therapy, appropriate measures should be taken.
Interference with laboratory tests: In patients treated with levofloxacin, determination of opiates in urine may give false positive results. It may be necessary to confirm positive opiate screens by more specific method. Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and, therefore, may give false negative results in the bacteriological diagnosis of tuberculosis.
Effects on Ability to Drive and Use Machines: Some undesirable effects (e.g. dizziness/vertigo, drowsiness, visual disturbances) may impair the patient's ability to concentrate and react, and therefore may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery).
Use In Pregnancy & Lactation
Pregnancy: There are limited amount of data from the use of levofloxacin in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. However in the absence of human data and due to that experimental data suggest a risk of damage by fluoroquinolones to the weight bearing cartilage of the growing organism, levofloxacin must not be used in pregnant women.
Lactation: Tigeron tablet is contraindicated in breastfeeding women. There is insufficient information on the excretion of levofloxacin in human milk; however, other fluoroquinolones are excreted in breast milk. In the absence of human data and due to that experimental data suggest a risk of damage by fluoroquinolones to the weight bearing cartilage of the growing organism, levofloxacin must not be used in breastfeeding women.
Fertility: Levofloxacin caused no impairment of fertility or reproductive performance in rats.
Adverse Reactions
The adverse reactions are described according to the MedDRA system organ class as follows.
Frequencies are defined using the following convention: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Infections and infestations: Uncommon: Fungal infection including Candida infection, pathogen resistance.
Blood and lymphatic system disorders: Uncommon: Leukopenia, eosinophilia.
Rare: Thrombocytopenia, neutropenia.
Not known: Pancytopenia, agranulocytosis, haemolytic anaemia.
Immune system disorders: Rare: Angioedema, hypersensitivity.
Not known: Anaphylactic shocka, anaphylactoid shocka.
Metabolism and nutrition disorders: Uncommon: Anorexia.
Rare: Hypoglycaemia particularly in diabetic patients.
Not known: Hyperglycaemia, hypoglycaemic coma.
Psychiatric disorders: Common: Insomnia.
Uncommon: Anxiety, confusional state, nervousness.
Rare: Psychotic reactions (with e.g. hallucination, paranoia), depression, agitation, abnormal dreams, nightmares.
Not known: Psychotic disorders with self-endangering behaviour including suicidal ideation or suicide attempt.
Nervous system disorders: Common: Headache, dizziness.
Uncommon: Somnolence, tremor, dysgeusia.
Rare: Convulsion, paraesthesia.
Not known: Peripheral sensory neuropathy, peripheral sensory motor neuropathy, parosmia including anosmia, dyskinesia, extrapyramidal disorder, ageusia, syncope, benign intracranial hypertension.
Eye disorders: Rare: Visual disturbances such as blurred vision.
Not known: Transient vision loss.
Ear and labyrinth disorders: Uncommon: Vertigo.
Rare: Tinnitus.
Not known: Hearing loss, hearing impaired.
Cardiac disorders: Rare: Tachycardia, palpitation.
Not known: Ventricular tachycardia which may result in cardiac arrest, ventricular arrhythmia, and torsade de pointes (reported predominantly in patients with risk factors of QT prolongation), electrocardiogram QT prolonged.
Vascular disorders: Rare: Hypotension.
Respiratory, thoracic and mediastinal disorders: Uncommon: Dyspnoea.
Not known: Bronchospasm, pneumonitis allergic.
Gastrointestinal disorders: Common: Diarrhoea, vomiting, nausea.
Uncommon: Abdominal pain, dyspepsia, flatulence, constipation.
Not known: Diarrhoea - haemorrhagic which in very rare cases may be indicative of enterocolitis, including pseudomembranous colitis, pancreatitis.
Hepatobiliary disorders: Common: Hepatic enzyme increased (ALT/AST, alkaline phosphatase, GGT).
Uncommon: Blood bilirubin increased.
Not known: Jaundice and severe liver injury, including cases with fatal acute liver failure, primarily in patients with severe underlying diseases, hepatitis.
Skin and subcutaneous tissue disordersb: Uncommon: Rash, pruritus, urticaria, hyperhidrosis.
Not known: Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, photosensitivity reaction, leukocytoclastic vasculitis, stomatitis.
Musculoskeletal and connective tissue disorders: Uncommon: Arthralgia, myalgia.
Rare: Tendon disorder including tendinitis (e.g. Achilles tendon), muscular weakness which may be of importance in patients with myasthenia gravis.
Not known: Rhabdomyolysis, tendon rupture (e.g. Achilles tendon), ligament rupture, muscle rupture, arthritis.
Renal and urinary disorders: Uncommon: Blood creatinine increased.
Rare: Renal failure acute (e.g. due to interstitial nephritis).
General disorders and administration site conditions: Uncommon: Asthenia.
Rare: Pyrexia.
Not known: Pain (including pain in back, chest, and extremities).
a Anaphylactic and anaphylactoid reactions may sometimes occur even after the first dose.
b Mucocutaneous reactions may sometimes occur even after the first dose.
Other undesirable effects which have been associated with fluoroquinolone administration include: attacks of porphyria in patients with porphyria.
Please seek medical attention immediately at the first sign of any adverse drug reaction shall appear.
Drug Interactions
Effect of other medicinal products on Tigeron Tablets: Iron salts, magnesium or aluminum-containing antacids: Levofloxacin absorption is significantly reduced when iron salts, or magnesium- or aluminium-containing antacids are administered concomitantly with Tigeron tablets. It is recommended that preparations containing divalent or trivalent cations such as iron salts, or magnesium- or aluminium-containing antacids should not be taken 2 hours before or after Tigeron tablet administration. No interaction was found with calcium carbonate.
Sucralfate: The bioavailability of Tigeron tablets is significantly reduced when administered together with sucralfate. If the patient is to receive both sucralfate and Tigeron, it is best to administer sucralfate 2 hours after the Tigeron tablet administration.
Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs: No pharmacokinetic interactions of levofloxacin were found with theophylline in a clinical study. However a pronounced lowering of the cerebral seizure threshold may occur when quinolones are given concurrently with theophylline, non-steroidal anti-inflammatory drugs, or other agents which lower the seizure threshold.
Levofloxacin concentrations were about 13% higher in the presence of fenbufen than when administered alone.
Probenecid and cimetidine: Probenecid and cimetidine had a statistically significant effect on the elimination of levofloxacin. The renal clearance of levofloxacin was reduced by cimetidine (24%) and probenecid (34%). This is because both drugs are capable of blocking the renal tubular secretion of levofloxacin. However, at the tested doses in the study, the statistically significant kinetic differences are unlikely to be of clinical relevance.
Caution should be exercised when levofloxacin is coadministered with drugs that affect the tubular renal secretion such as probenecid and cimetidine, especially in renally impaired patients.
Other relevant information: Clinical pharmacology studies have shown that the pharmacokinetics of levofloxacin were not affected to any clinically relevant extent when levofloxacin was administered together with the following drugs: calcium carbonate, digoxin, glibenclamide, ranitidine.
Effect of Tigeron on other medicinal products: Ciclosporin: The half-life of ciclosporin was increased by 33% when coadministered with levofloxacin.
Vitamin K antagonists: Increased coagulation tests (PT/INR) and/or bleeding, which may be severe, have been reported in patients treated with levofloxacin in combination with a vitamin K antagonist (e.g. warfarin). Coagulation tests, therefore, should be monitored in patients treated with vitamin K antagonists.
Drugs known to prolong QT interval: Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides).
Storage
Store at temperatures not exceeding 30°C.
MIMS Class
ATC Classification
J01MA12 - levofloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.
Presentation/Packing
Tigeron 500: FC tab 500 mg (pink colored capsule shaped with 500 engraved on one side and plain on other side) x 5's, 10's, 50's.
Tigeron 750: FC tab 750 mg (pink colored capsule shaped with 750 engraved on one side and plain on other side) x 5's, 10's, 50's.
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