Vietnam Product

Tigeron Tablets

Tigeron Tablets

Why you have been prescribed this medicine?

You have been prescribed this medicine if you have any of the following:
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
• Uncomplicated urinary tract infections
• 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.

When you should consult your doctor?

You should consult your doctor if you experience any of the following:

You should consult your doctor if you experience any of the following:
The adverse reactions are described according to the MedDRA system organ class below. Frequencies are defined using the following convention: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), 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, haemolyticanaemia
Immune system disorders
Rare:
Angioedema, hypersensitivity
Not known:
Anaphylactic shocka, anaphylactoidshocka
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.
ADVERSE DRUG REACTION:
"Inform doctors about unexpected reactions after using drugs"

What to do if you miss a dose?

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.
Otherwise take it as soon as you remember and then go back to taking it as you would normally.

Things you MUST NOT DO while on this medicine?

MethicillinresistantS. aureus are very likely to possess co-resistanceto fluoroquinolones, including levofloxacin.Therefore levofloxacin is not recommended for the treatment of known or suspected MRSA infections unless laboratoryresults have confirmed susceptibility of the organism to levofloxacin (and commonly recommended antibacterial agentsfor the treatment of MRSAinfectionsare considered inappropriate). Levofloxacin may be used in the treatment of Acute Bacterial Sinusitis and Acute Exacerbation of Chronic Bronchitiswhen these infections have been adequately diagnosed. Resistance to fluoroquinolones of E. coli – the most common pathogen involved in urinary tract infections – variesacross the European Union. Prescribers are advised to take into account the local prevalence of resistance in E. coli tofluoroquinolones.

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 consensusdocuments 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. Tendinitisand tendon rupture, sometimes bilateral, may occur within 48 hours of starting treatment with levofloxacin and havebeen reported up to several months after discontinuation of treatment. The risk of tendinitis and tendon rupture isincreased in patients aged over 60 years, in patients receiving daily doses of 1000 mg and in patients usingcorticosteroids. 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 consulttheir physician if they experience symptoms of tendinitis. If tendinitis is suspected, treatment with levofloxacin must behalted 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 severalweeks after treatment), may be symptomatic of Clostridium difficileassociateddisease (CDAD). CDAD may range inseverity from mild to life threatening, the most severe form of which is pseudomembranous colitis. Itis therefore important to consider this diagnosis in patients who develop serious diarrhoea during or after treatment withlevofloxacin. If CDAD is suspected or confirmed, levofloxacin should be stopped immediately and appropriate treatmentinitiated without delay. Antiperistalticmedicinal 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 ahistory of epilepsy and, as with other quinolones, should be used with extreme caution in patientspredisposed to seizures or concomitant treatment with active substances that lower the cerebral seizure threshold, suchas theophylline. In case of convulsive seizures, treatment with levofloxacin shouldbe discontinued.

Patients with G-6-phosphatedehydrogenase deficiency
Patients with latent or actual defects in glucose-6-phosphatedehydrogenase activity may be prone to haemolyticreactions 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 renalimpairment.

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 contacttheir physician or an emergency physician, who will initiate appropriate emergency measures.

Severe bullous reactions
Cases of severe bullous skin reactions such as StevensJohnsonsyndrome or toxic epidermal necrolysis have beenreported with levofloxacin. Patients should be advised to contact their doctor immediately prior tocontinuing treatment if skin and/or mucosal reactions occur.

Dysglycaemia
As with all quinolones, disturbances in blood glucose, including both hypoglycaemia and hyperglycaemia have beenreported, 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, carefulmonitoring of blood glucose is recommended.

Prevention of photosensitisation
Photosensitisation has been reported with levofloxacin. It is recommended that patients should notexpose themselves unnecessarily to strong sunlight or to artificial UV rays (e.g. sunray lamp, solarium), duringtreatment 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 incombination with a vitamin K antagonist (e.g. warfarin), coagulation tests should be monitored when these drugs aregiven concomitantly.

Psychotic reactions
Psychotic reactions have been reported in patients receiving quinolones, including levofloxacin. In very rare casesthese have progressed to suicidal thoughts and selfendangering behavior sometimesafter only a single dose oflevofloxacin. In the event that the patient develops these reactions, levofloxacin should bediscontinued and appropriate measures instituted. Caution is recommended if levofloxacin is to be used in psychoticpatients 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 forprolongation of the QT interval such as, for example:congenitallong QT syndromeconcomitantuse of drugs that are known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclicantidepressants, macrolides, antipsychotics).Uncorrectedelectrolyte imbalance (e.g. hypokalemia, hypomagnesemia)cardiacdisease (e.g. heart failure, myocardial infarction, bradycardia)Elderly patients and women may be more sensitive to QTcprolongingmedications. Therefore, caution should be takenwhen using fluoroquinolones, including levofloxacin, in these populations.

Peripheral neuropathy
Peripheral sensory neuropathy and peripheral sensory motor neuropathy have been reported in patients receivingfluoroquinolones, including levofloxacin, which can be rapid in its onset. Levofloxacin should bediscontinued if the patient experiences symptoms of neuropathy in order to prevent the development of an irreversiblecondition.

Hepatobiliary disorders
Cases of hepatic necrosis up to fatal hepatic failure have been reported with levofloxacin, primarily in patients withsevere underlying diseases, e.g. sepsis. Patients should be advised to stop treatment and contacttheir doctor if signs and symptoms of hepatic disease develop such as anorexia, jaundice, dark urine, pruritus or tenderabdomen.

Exacerbation of myasthenia gravis
Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weaknessin patients with myasthenia gravis. Postmarketing serious adverse reactions, including deaths and the requirement forrespiratory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Levofloxacin isnot 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 consultedimmediately.

Superinfection
The use of levofloxacin, especially if prolonged, may result in overgrowth of nonsusceptibleorganisms. Ifsuperinfection occurs during therapy, appropriate measures should be taken.

Interference with laboratory tests
In patients treated with levofloxacin, determination of opiates in urine may give falsepositiveresults. It may benecessary to confirm positive opiate screens by more specific method.Levofloxacin may inhibit the growth of Mucobacterium tuberculosis and, therefore, may give falsenegativeresults in thebacteriological diagnosis of tuberculosis.

INTERACTIONS WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS:
Effect of other medicinal products on Tigeron Tablets:
Iron salts, magnesium- or aluminium-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).

What to do if you accidentally take too much (overdose) of the medicine?

The most important signs to be expected following acute overdosage of Tigeron tablets arecentral 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.
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. Haemodialysis, including peritoneal dialysis and CAPD, are not effective in removing levofloxacin from the body.

Is it safe in pregnancy and breast-feeding?

Tell your doctor immediately if you become pregnant while taking this medication.
For safety of any drug during pregnancy or breastfeeding – please consult your doctor.

Storage Conditions:

Store in a cool, dry place, below 300C.
Keep all medicines out of reach of children.

Drug Description

General physico-chemical properties:
Pink coloured capsule shaped film coated tablet with 250/500/750 engraved on one side and plain on other side.

Composition:
Each film coated tablet contains:
Levofloxacin Hemihydrate equivalent to Levofloxacin 250/500/750 mg
Additional ingredients:Microcrystalline cellulose, povidone K-30, crospovidone, colloidal silicon dioxide, magnesium stearate, isopropyl alcohol, opadry pink 03B84681 and purified water.
Pharmaceutical Form:
Film coated tablets

Indications and dosage.

INDICATIONS:
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
• Uncomplicated urinary tract infections
• 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 AND ADMINISTRATION:
Recommended doses for adult patients with normal kidney function with creatinine clearance more than 50 ml/min

Indications

Daily dose

Dosing per day

Treatment duration

Acute bacterial sinusitis

500 mg

1 time

10–14 days

750 mg

1 time

5 days

Acute bacterial exacerbation of chronic bronchitis

250–500 mg*

1 time

7-10 days

750 mg

1 time

3-5 days

Community-acquired pneumonia

500 mg

1-2 time

7-14 days

750 mg

1 time

5 days

Uncomplicated urinary tract infection

250 mg

1 time

3 days

Chronic bacterial prostatitis.

500 mg

1 time

28 days

Complicated urinary tract infection, including pyelonephritis

250 mg

1 time

7-10 days

Infections of skin and soft tissues(Uncomplicated)

500

1-2 times

7-10 days

Skin and soft tissue infections(Complicated)

750

1 time

7-14 days

Inhalation Anthrax

500 mg

1 time

8 weeks

* In combination with antibiotics with an action on anaerobic causative agent.
Dosage for patients with kidney function disorders and creatinine clearance less than 50 ml/min:

Creatinine clearance

Dosage regimen (in accordance with infection severity)

50-20 ml/min

initial dose: 250 mg
next doses: 125 mg/24 h

initial dose: 500 mg
next doses: 250 mg/24 h

initial dose: 500 mg
next doses: 250 mg/12 h

19-10 ml/min

initial dose: 250 mg
next doses: 125 mg/48 h

initial dose: 500 mg
next doses: 125 mg/24 h

initial dose: 500 mg
next doses: 125 mg/12 h

<10 ml/min (also in hemodialysis and CAPD1)

initial dose: 250 mg
next doses: 125 mg/48 h

initial dose: 500 mg
next doses: 125 mg/24 h

initial dose: 500 mg
next doses: 125 mg/24 h

1 After hemodialysis or chronic ambulatory peritoneal dialysis (CAPD) additional doses are not required. 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.

Side effects and drug interactions.

ADVERSE REACTIONS: The adverse reactions are described according to the MedDRA system organ class below. Frequencies are defined using the following convention: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), 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, haemolyticanaemia
Immune system disorders
Rare:
Angioedema, hypersensitivity
Not known:
Anaphylactic shocka, anaphylactoidshocka
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.
Drug interactions:
Effect of other medicinal products on Tigeron Tablets:
Iron salts, magnesium- or aluminium-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).

Warnings and precautions

MethicillinresistantS. aureus are very likely to possess co-resistanceto fluoroquinolones, including levofloxacin.Therefore levofloxacin is not recommended for the treatment of known or suspected MRSA infections unless laboratoryresults have confirmed susceptibility of the organism to levofloxacin (and commonly recommended antibacterial agentsfor the treatment of MRSAinfectionsare considered inappropriate). Levofloxacin may be used in the treatment of Acute Bacterial Sinusitis and Acute Exacerbation of Chronic Bronchitiswhen these infections have been adequately diagnosed. Resistance to fluoroquinolones of E. coli – the most common pathogen involved in urinary tract infections – variesacross the European Union. Prescribers are advised to take into account the local prevalence of resistance in E. coli tofluoroquinolones.

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 consensusdocuments 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. Tendinitisand tendon rupture, sometimes bilateral, may occur within 48 hours of starting treatment with levofloxacin and havebeen reported up to several months after discontinuation of treatment. The risk of tendinitis and tendon rupture isincreased in patients aged over 60 years, in patients receiving daily doses of 1000 mg and in patients usingcorticosteroids. 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 consulttheir physician if they experience symptoms of tendinitis. If tendinitis is suspected, treatment with levofloxacin must behalted 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 severalweeks after treatment), may be symptomatic of Clostridium difficileassociateddisease (CDAD). CDAD may range inseverity from mild to life threatening, the most severe form of which is pseudomembranous colitis. Itis therefore important to consider this diagnosis in patients who develop serious diarrhoea during or after treatment withlevofloxacin. If CDAD is suspected or confirmed, levofloxacin should be stopped immediately and appropriate treatmentinitiated without delay. Antiperistalticmedicinal 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 ahistory of epilepsy and, as with other quinolones, should be used with extreme caution in patientspredisposed to seizures or concomitant treatment with active substances that lower the cerebral seizure threshold, suchas theophylline. In case of convulsive seizures, treatment with levofloxacin shouldbe discontinued.

Patients with G-6-phosphatedehydrogenase deficiency Patients with latent or actual defects in glucose-6-phosphatedehydrogenase activity may be prone to haemolyticreactions 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 renalimpairment.

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 contacttheir physician or an emergency physician, who will initiate appropriate emergency measures.

Severe bullous reactions Cases of severe bullous skin reactions such as StevensJohnsonsyndrome or toxic epidermal necrolysis have beenreported with levofloxacin. Patients should be advised to contact their doctor immediately prior tocontinuing treatment if skin and/or mucosal reactions occur.

Dysglycaemia As with all quinolones, disturbances in blood glucose, including both hypoglycaemia and hyperglycaemia have beenreported, 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, carefulmonitoring of blood glucose is recommended.

Prevention of photosensitisation Photosensitisation has been reported with levofloxacin. It is recommended that patients should notexpose themselves unnecessarily to strong sunlight or to artificial UV rays (e.g. sunray lamp, solarium), duringtreatment 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 incombination with a vitamin K antagonist (e.g. warfarin), coagulation tests should be monitored when these drugs aregiven concomitantly.

Psychotic reactions Psychotic reactions have been reported in patients receiving quinolones, including levofloxacin. In very rare casesthese have progressed to suicidal thoughts and selfendangering behavior sometimesafter only a single dose oflevofloxacin. In the event that the patient develops these reactions, levofloxacin should bediscontinued and appropriate measures instituted. Caution is recommended if levofloxacin is to be used in psychoticpatients 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 forprolongation of the QT interval such as, for example:congenitallong QT syndromeconcomitantuse of drugs that are known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclicantidepressants, macrolides, antipsychotics).Uncorrectedelectrolyte imbalance (e.g. hypokalemia, hypomagnesemia)cardiacdisease (e.g. heart failure, myocardial infarction, bradycardia)Elderly patients and women may be more sensitive to QTcprolongingmedications. Therefore, caution should be takenwhen using fluoroquinolones, including levofloxacin, in these populations.

Peripheral neuropathy Peripheral sensory neuropathy and peripheral sensory motor neuropathy have been reported in patients receivingfluoroquinolones, including levofloxacin, which can be rapid in its onset. Levofloxacin should bediscontinued if the patient experiences symptoms of neuropathy in order to prevent the development of an irreversiblecondition.

Hepatobiliary disorders Cases of hepatic necrosis up to fatal hepatic failure have been reported with levofloxacin, primarily in patients withsevere underlying diseases, e.g. sepsis. Patients should be advised to stop treatment and contacttheir doctor if signs and symptoms of hepatic disease develop such as anorexia, jaundice, dark urine, pruritus or tenderabdomen.

Exacerbation of myasthenia gravis Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weaknessin patients with myasthenia gravis. Postmarketing serious adverse reactions, including deaths and the requirement forrespiratory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Levofloxacin isnot 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 consultedimmediately.

Superinfection The use of levofloxacin, especially if prolonged, may result in overgrowth of nonsusceptibleorganisms. Ifsuperinfection occurs during therapy, appropriate measures should be taken.

Interference with laboratory tests In patients treated with levofloxacin, determination of opiates in urine may give falsepositiveresults. It may benecessary to confirm positive opiate screens by more specific method.Levofloxacin may inhibit the growth of Mucobacterium tuberculosis and, therefore, may give falsenegativeresults in thebacteriological diagnosis of tuberculosis.

Overdosage and Contraindications

Overdose:
The most important signs to be expected following acute overdosage of Tigeron tablets arecentral 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. 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. Haemodialysis, 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.

Clinical pharmacology.

PHARMACOLOGICAL PROPERTIES:
Pharmacotherapeutic group:Quinolone antibacterials, fluoroquinolones
ATC code:
J01MA12

Pharmacodynamics:
Levofloxacin is a synthetic antibacterial agent of the fluoroquinolone class and is the S (-)enantiomer of the racemicactive substance ofloxacin.

Mechanism of action
As a fluoroquinolone antibacterial agent, levofloxacin acts on the DNA-DNAgyrasecomplex and topoisomerase IV.

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-Eikenellacorrodens, Haemophilusinfluenza, Haemophilus para-influenzae, Klebsiellaoxytoca, Moraxella catarrhalis, Pasteurellamultocida, Proteus vulgaris, Providencia rettgeri

Anaerobic bacteria- Peptostreptococcus

Others-
Chlamydophilapneumonia, Chlamydophilapsittaci, Chlamydia trachomatis, Legionella pneumophila, Mycoplasma pneumonia, Mycoplasma hominis, Ureaplasmaurealyticum

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. aureusare very likely to possess co-resistance to fluoroquinolones, including levofloxacin.

Aerobic Gram- negative bacteria- Acinetobacter baumannii, Citrobacterfreundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiellapneumonia, Morganellamorganii Proteus mirabilis, Providencia stuartii, Pseudomonas aeruginosa, Serratiamarcescens

Anaerobic bacteria-Bacteroidesfragilis

Inherently Resistant Strains Aerobic Gram-positive bacteria- Enterococcus faecium

Pharmacokinetics:
Absorption
Orally administered levofloxacin is rapidly and almost completely absorbed with peak plasma concentrations being obtained within 1-2h. 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 andmultiple 500 mg or 750 mg doses, indicating widespread distribution into body tissues. Levofloxacinreaches its peak levels in skin tissues and in blister fluid of healthy subjects at approximately 3 hoursafter dosing. Levofloxacin also penetrates wellinto 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 single500 mg oral dose.

Metabolism Levofloxacin is stereochemically stable in plasma and urine and does not invert metabolically to itsenantiomer, D-ofloxacin. Levofloxacin undergoes limited metabolism in humans and is primarilyexcreted as unchanged drug in the urine. Following oral administration, approximately 87% of anadministered dose was recovered as unchanged drug in urine within 48 hours, whereas less than 4% ofthe dose was recovered in feces in 72 hours. Less than 5% of an administered dose was recovered inthe urine as the desmethyl and N-oxide metabolites, the only metabolites identified in humans. Thesemetabolites have little relevant pharmacological activity.

Elimination
Levofloxacin is excreted largely as unchanged drug in the urine. The mean terminal plasma eliminationhalf-life of levofloxacin ranges from approximately 6 to 8 hours following single or multiple doses oflevofloxacin given orally or intravenously. The mean apparent total body clearance and renal clearancerange from approximately 144 to 226 mL/min and 96 to 142 mL/min, respectively. Renal clearance inexcess of the glomerular filtration rate suggests that tubular secretion of levofloxacin occurs inaddition to its glomerular filtration. Concomitant administration of either cimetidine or probenecidresults in approximately 24% and 35% reduction in the levofloxacin renal clearance, respectively,indicating that secretion of levofloxacin occurs in the renal proximal tubule.

PHARMACEUTICAL CHARACTERISTICS:
SHELF-LIFE:
36 months

DOSAGE FORM AND PACKING AVAILABLE:
Clear PVC-PVDC blister of 5 or 10 tablets. Each blister is packed in a carton.

NAME AND ADDRESS OF MANUFACTURER:
Kusum Healthcare Pvt. Ltd.
SP-289(A), RIICO Industrial Area,
Chopanki, Bhiwadi, Distt- Alwar,
Rajasthan, India

CERTIFICATES

KEEP IN TOUCH

Kusum Healthcare Pvt Ltd

Regd. Office: D-158A, Okhla Industrial Area

Phase-1, New Delhi-110020, India

Tel: 011-41005147, 40514919

Fax: +91-11-40527575

Email: kusumhealth@kusumhealthcare.com

CIN: U65929DL1997PTC085780