COMPOSITION:

Active substance:

Levofloxacin;

tablet contains of Levofloxacin hemihydrate equivalent to Levofloxacin 500 mg and 750 mg;

Additional ingredients:

povidon K29/32

microcrystalline cellulose

crospovidon

magnesium stearate

colloidal anhydrous silica

Opadry 03B84681 pink coating.

INDICATIONS:

Acute sinusitis

exacerbation of chronic bronchitis

pneumonia

complicated and non-complicated urinary tract infection (including pyelonephritis)

chronic bacterial prostatitis

infections of skin and soft tissues

septicemia/bacteriemia

intraabdominal infections.

DOSAGE:

Tigeron tablets are used 1 – 2 times per day. Dose depends on type and severity of infection. Treatment duration depends on clinical course and it is not more than 14 days. It is recommended to prolong the treatment at least during 48 – 72 hours after normalization of body temperature or microbiologically proven causative agent elimination.

Tigeron tablets should be swallowed without chewing with enough water. For easy dosage a tablet can be broken using break line. They can be taken both with meal and at any other time.

Recommended doses for adult patients with normal kidney function with creatinin clearance more than 50 ml/min

* 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:

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.

Dosage for elderly patients: If there is no kidney function disorders it is not necessary dose adjustment.

ADVERSE REACTIONS:

Skin and general reactions of hypersensitivity:

in rare cases – itch

skin redness; rare – general reactions of hypersensitivity (anaphylactic and anaphylactoid) with such symptoms as urticaria

bronchus spasms and possible severe asphyxia

very rare – skin and mucous membrane oedema (for example

oedema of face skin and pharynx tunica mucosa); sudden blood pressure decrease and shock; QT-interval lengthening

hypersensitivity to sunlight and UV-light; in single cases – acute skin and mucous membrane rash with wheals formation such as Stevens-Johnson syndrome

toxic epidermal necrolysis (Lyell’s syndrome) and erythema multiforme. More easy skin reactions can precede general reactions of hypersensitivity. These reactions may occur after the first dose and within several minutes or hours after usage.

Gastro-intestinal tract:

often – nausea

diarrhoea; in single cases – loss of appetite

vomiting

abdominal pain

indigestion; rare – blood diarrhoea

which sometimes can be with signs of intestine inflammation

including pseudomembranous colitis; very rare – decreasing of blood sugar content (hypoglycemia)

which probably has a special importance for insular diabetes patients. Symptoms of hypoglycemia may be limosis

nervousness

perspiration

limb tremor.

As for other quinolones it is known that they can cause porphyria attack in patients with porphyria. It may concern Tigeron too.

Central nervous system: in single cases – headache

dizziness/stupor

somnolence

sleep disturbance; rare – disagreeable feeling

for example

hand paraesthesia

tremor

anxiety

apprehensiveness

fits and mental confusion; very rare – disturbance of vision and hearing

disturbance of taste and nose

decreased sense of touch

and psychotic reactions such as hallucination and depressive shifts of mood

psychotic reactions with dangerous behavior for one’s own self

including suicidal idea and action. Movement processes disturbance

also during walking.

Cardiovascular system:

rare – tachycardia

blood pressure reduction; very rare – collapse similar to shock.

Muscular-skeletal system:

rare – tendon lesion

including its inflammation

pain in joint and muscle; very rare – tendon tear (for example

Achilles tendon rupture). This side effect can appear within 48 hours from the treatment start and can affect Achilles tendons of both legs. It is possible muscle weakness

which may have a special importance for patients with severe miastenia; in single cases – musculature affection (rabdomyolisis).

Liver:

often – increased liver enzymes indexes (ALT

AST); in some cases – increased indexes of bilirubin and creatinine of blood serum; very rare – liver reactions such as liver inflammation.

Kidney:

kidney function impairment up to acute kidney insufficiency

for example

due to allergic reactions (interstitial nephritis).

Blood system: in some cases – increase of definite blood cells quantity (eosinophilia)

decrease of leukocyte quantity (leukocytopenia); rare – decrease of quantity of definite leukocyte (neutropenia)

decrease of thrombocyte quantity (thrombocytopenia)

which can cause high inclination toward haemorrhage and bleeding; very rare – rather significant decreasing of quantity of definite leukocyte (agranulocytosis)

which can lead to severe disease symptoms (long-term or recurrent fever

pharyngitis

expressed disease state); in single cases – decrease of erythrocyte quantity due to its destruction (hemolytic anemia)

reduced quantity of all types of blood cells (pancytopenia).

Other: in rare cases – general weakness (asthenia); very rare – fever

allergic reactions of pulmones (allergic pneumonia) or small blood vessel (vasculitis).

Usage of any antibacterial drugs can cause disorders associated with their influence on normal microflora of human organism. As a result of this secondary infection can be developed that will require additional treatment.

Drug interactions:

Levofloxacin absorption is significantly decreases in concurrent usage with antacids

which contain magnesium and aluminium

and with drugs

which contain iron salt. Recommended time period between usages of Tigeron and mentioned above drugs should be not less than 2 hours. Bioavailability of Tigeron tablets is significantly decreased

As far as during clinical trials it was not approved interaction of Levofloxacin and theophylline it was possible a significant decreasing of spastic threshold in concurrent usage of quinolones with theophylline

nonsteroidal anti-inflammatory drugs and other agents

which reduce spastic threshold. Levofloxacin concentration in presence of fenbufen was approximately 13% upper than those one during Levofloxacin usage only. Probenecid and cimetidine statistically reliably influence on Levofloxacin excretion. Kidney clearance of Levofloxacin is decreased in presence of probenecid by 34%

but in presence of cimetidine – by 24%. Due to this both drugs can block tubular excretion of Levofloxacin. Half-life period of cyclosporine is enlarged by 33% in concurrent usage with Levofloxacin.

In concurrent usage with antagonists of K vitamin

for example warfarin

coagulation tests (PT / international normalizing ratio) and/or bleeding

which may be severe

are increased. In consideration to this in patients

who concurrently take antagonists of K vitamin

coagulation indexes should be controlled.

It is not recommended Levofloxacin concomitant usage with alcohol.

Pregnancy and lactation:

Tigeron can not be used during pregnancy and lactation because of absence of studies on human and possible articular cartilage lesion by quinolones in growing organism.

If during Tigeron treatment pregnancy is determined a doctor should be informed about it.

Children:

The preparation is not used in children and adolescences less than 18 years old because of possible articular cartilage lesion.

Overdose:

Symptoms: mental confusion

dizziness

impairment of consciousness and convulsive attacks

nausea

tunica mucous erosion

QT-interval lengthening.

Treatment:

the therapy is symptomatic. In cases of overdose it is necessary to examine properly a patient

including ECG. In cases of evident overdose gastric lavage is administered. Antacids are used for mucous coat of stomach protection.

Hemodialysis

including peritoneal dialysis or CAPD

is non-effective for Levofloxacin excretion from the organism. There are no any specific antidotes.

Influence on velocity reactions while driving motor transport and operating other mechanisms:

Patients

who drive motor transport

operate other machines and mechanisms

should take into account possible unsuspected effects of central nervous system (dizziness

somnolence

mental confusion

visual and hearing impairment

movement disturbance during walking

also while walking).

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamics:

Levofloxacin has a wide spectrum of antibacterial action. Bactericidal effect is provided due to inhibition of bacterial enzyme of DNK-gyrase

which is of topoisomerase type II

by Levofloxacin. The result of this inhibition is impossibility of bacterial DNK transfer from “relaxation” condition to “over involuted condition” that

by-turn

render further bacterial cells division (fissiparity) impossible. Activity spectrum of Levofloxacin includes gram-positive and gram-negative bacteria

including non-fermentative bacteria.

Following microorganisms are sensitive to the preparation:

– gram-positive aerobes:

Staphylococcus aureus methi-S

Staphylococcus haemolyticus methi-S

Staphylococcus saprophyticus

Streptococci group C

G

Streptococcus agalactiae

Streptococcus pneumoniae peni – i/S/R

Streptococcus pyogenes;

– gram-negative aerobes:

Acinetobacter baumannii

Citrobacter freundii

Eikenella corrodens

Enterobacter agglomerans

Enterobacter cloacae

Escherichia coli

Haemophilus influenzae ampi-S/R

Haemophilus para-influenzae

Klebsiella oxytoca

Klebsiella pneumoniae

Moraxella catarrhalis +/-

Morganella morganii

Pasteurella multocida

Proteus mirabilis

Proteus vulgaris

Providencia rettgeri

Providencia stuartii

Pseudomonas aeruginosa

Serratia marcescens;

– anaerobes:

Bacteroides fragilis

Clostridium perfringens

Peptostreptococcus;

– others:

Chlamydia pneumoniae

Chlamydia psittaci

Legionella pneumophila

Mycoplasma pneumoniae

Ureaplasma

H.pylori.

Inconstantly sensitive to the preparation action:

– gram-positive aerobes :

Staphylococcus haemolyticus methi-R;

– gram-negative aerobes:

Burkholderia cepacia;

– anaerobes – Bacteroides ovatus

Bacteroides thetaiotamicron

Bacteroides vulgaris

Clostridium difficile.

Resistant to the preparation action:

gram-positive aerobes:

Staphylococcus aureus methi-R. Like another fluoroquinolones Levofloxacin is non-active about spirochete.

Pharmacokinetics:

Absorption:

In per oral use Levofloxacin is quickly and nearly fully absorbed with plasma concentration peak

which is observed in 1 hour after intake. Absolute bioavailability is nearly 100%. Levofloxacin is liable to liner pharmacokinetics in diapason from 50 to 600 mg. Meal has some influence on its absorption.

Distribution:

Approximately 30-40% of Levofloxacin binds with serum protein. Cumulative effect of Levofloxacin in dosage of 500 mg 1 time per day does not have clinical meaning and can be neglected. There is an insignificant but foreseen its cumulation in dosage of 500 mg 2 times per day. Stable distribution indexes are reached within 3 days.

Distribution in tissues and liquids of organism:

Distribution in bronchial mucosa and liquid secretion from bronchial epithelium: Maximal concentration of Levofloxacin in bronchial mucosa and liquid secretion from bronchial epithelium in dose more than 500 mg per os was 8.3 and 10.8 mg/ml

correspondingly.

Distribution in lungs tissue:

Maximal concentration of Levofloxacin in lungs tissue in dose more than 500 mg per os was 11.3 mg/ml and was reached within 4 – 6 hours after use. Concentration in lungs constantly exceeded those one in plasma.

Distribution in bladder fluid:

Maximal concentration of Levofloxacin in bladder fluid after intake of 500 mf 1 – 2 times per day was 4 and 6.7 mg/ml

correspondingly.

Distribution in cerebrospinal fluid:

Levofloxacin is poorly penetrates into cerebrospinal fluid.

Concentration in urine:

Average Levofloxacin concentration during 8 – 12 hours after 150 mg

300 mg or 500 mg single dose per os was 44 mg/ml

91 mg/ml and 200 mg/ml

correspondingly.

Metabolism: Levofloxacin is insignificanly metabolised

its metabolites are desmethyl-levofloxacin and N-oxide Levofloxacin. These metabolites are less than 5% of the preparation

which is excreted with urine.

Excretion:

After per oral use Levofloxacin is rather slowly excreted from plasma (half-life period is 6-8 h). It is excreted mainly through kidney (more than 85% of injected dose). There is no difference between pharmacokinetics of Levofloxacin in intravenous and per oral administration.

PHARMACEUTICAL CHARACTERISTICS:

General physic-chemical properties:

film coated capsule-shaped pink tablets with etching “500” or “750” on one side.

Shelf-life:

3 years.

Storage:

Store in a dry

protected from light place at a temperature not more than 25° C.

Keep it out of reach of children.

Package:

or 10 tablets are in a blister; 1 blister is in a carton box.

Conditions of supply:

By prescription.