Леволет® P

General characteristics. Structure:

Active agents: a levofloksatsina гемигидрат 256,233 mg or 512,466 mg, 250 mg or 500 mg of a levofloksatsin are equivalent.
Excipients: cellulose microcrystallic (Avicel PH 101), starch corn, silicon dioxide colloid, кросповидон, gipromelloza (15 cps), cellulose microcrystallic (Avicel PH 102), magnesium stearate. Cover: dye of Opadray white OY 58900 (gipromelloza of 5 cP, titanium dioxide, macrogoal 400).

Description

Tablets of 250 mg - white or almost white kapsulovidny biconvex tablets, film coated, with a stamping of "RDY" on one party, on another - "279".

Tablets of 500 mg - white or almost white kapsulovidny biconvex tablets, film coated, with a stamping of "RDY" on one party, on another - "280".

Pharmacological properties:

Pharmacodynamics. Ftorkhinolon, antimicrobic microbicide of a broad spectrum of activity. Blocks DNK-girazu (topoisomerase II) and topoisomerase IV, breaks superspiralling and a stitching of ruptures of DNA, suppresses DNA synthesis, causes profound morphological changes in cytoplasm, a cell wall and membranes.

Levofloxacin is active concerning the following strains of microorganisms, as in the conditions of in vitro, and in vivo. Sensitive microorganisms (MPK2 mg/ml).
Aerobic gram-positive microorganisms: Corynebacterium diphtheriae, Enterococcus faecalis, Enterococcus spp., Listeria monocytogenes, Staphylococcus coagulase-negative methi-S(I) (Methicillinum sensitive / moderately sensitive strains), Staphylococcus aureus methi-S (Methicillinum - sensitive strains), Staphylococcus epidermidis methi-S (Methicillinum - sensitive strains), Staphylococcus spp. (CNs - leykotoksinsoderzhashchy), Streptococci of group C and G (including, Streptococcus agalactiae, Streptococcus pneumoniae peni-S/I/R (penicillin sensitive / moderately sensitive/resistant strains)), Streptococcus pyogenes, Viridans streptococci peni-S/R (penicillin-chuvstvitelnye/resistant strains).

Aerobic gram-negative microorganisms: Acinetobacter baumannil, Acinetobacter spp., Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter spp. (including, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S/R (ампициллино-чувствительные / resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (including, Klebsiella oxytoca, Klebsiella pneumoniae), Moraxela catarrhalis β+/β-(the strains producing and not producing some β-lactamazu), Morganella morganii, Neisseria gonorrhoeae non-PPNG/PPNG (which are producing and not producing a penicillinase strains), Neisseria meningitidis, Pasteurella spp. (including, Pasteurella conis, Pasteurella dagmatis, Pasteurella multocida), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including, Providencia rettgeri, Providencia stuartii), Pseudomonas spp. (including, Pseudomonas aeruginosa), Serratia spp. (including, Salmonella spp., Serratia marcescens). Anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterum spp., Veilonella spp. Other microorganisms: Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Legionella spp., Mycobacterium spp. (including, Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma hominis, Mycoplasma pneumoniae), Ricketsia spp., Ureaplasma urealyticum. Moderately sensitive microorganisms (MPK4 mg/l): Aerobic gram-positive microorganisms: Corynebacterium urealiticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis methi-R (Methicillinum - resistant strains), Staphylococcus haemolyticus methi-R (Methicillinum - resistant strains). Aerobic gram-negative microorganisms: Burkholderia cepacia, Campilobacter jejuni, Campilobacter coli. Anaerobic microorganisms: Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovaius, Prevotella spp., Porphyromonas spp. Steady microorganisms (MPK8 mg/l): Aerobic gram-positive microorganisms: Corynebacterium jeikeium, Staphylococcus aureus methi-R (Methicillinum - resistant strains), Staphylococcus coagulase-negative methi-R (koagulazonegativny Methicillinum - resistant strains). Aerobic gram-negative microorganisms: Alcaligenes xylosoxidans. Other microorganisms: Mycobacterium avium.

Pharmacokinetics. At intake it is quickly and almost completely soaked up (meal influences the speed and completeness of absorption a little).

Bioavailability - 99%. Time of achievement of the maximum concentration (Tmax) - 1-2 h; at reception of 250 and 500 mg the average size of the maximum concentration (Cmax) makes 2,8 and 5,2 mkg/ml, respectively. Communication with proteins of plasma - 30-40%. Well gets into bodies and fabrics: lungs, mucous membrane of bronchial tubes, phlegm, bodies of urinogenital system, polymorphonuclear leukocytes, alveolar macrophages.

In a liver a small part is oxidized and/or dezatsetilirutsya.

It is brought out of an organism, preferential, by kidneys by glomerular filtering and canalicular secretion. An elimination half-life (T1/2) - 6-8 h. The renal clearance makes 70% of the general clearance. Less than 5% of a levofloksatsin are excreted in the form of metabolites. In urine, during 24 h, it is found not changed type of 70%, and for 48 h - 87% of the dose accepted inside. In Calais, during 72 h, 4% of the dose accepted inside come to light.

At a renal failure reduction of clearance of drug and its removal by kidneys depends on extent of decrease in the clearance of creatinine (CC).

Indications to use:

Infectious and inflammatory diseases easy and moderate severity, caused by activators, sensitive to drug: - infections of ENT organs (acute sinusitis); lower respiratory tract infections (exacerbation of chronic bronchitis, community-acquired pneumonia); infections of skin and soft tissues; as a part of complex therapy lekarstvenno steady forms of tuberculosis; the complicated infections of kidneys and urinary tract, including pyelonephritis; uncomplicated infections of urinary tract; prostatitis; the septicaemia / bacteremia connected with the indications stated above; intraabdominal infections.

Route of administration and doses:

Inside, to food or in a break between meals, without chewing, washing down with enough liquid.

Doses are defined by character and weight of an infection, and also sensitivity of the estimated activator.

Patients from normal or insignificantly an impaired renal function (KK> of 50 ml/min.) are recommended to appoint drug in the following doses.

Sinusitis: on 500 mg of 1 times/days. A course of treatment - 10-14 days.

Exacerbation of chronic bronchitis: on 250-500 mg of 1 times/days. A course of treatment - 10-14 days.

Community-acquired pneumonia: on 500 mg of 1-2 times/days. A course of treatment - 7-14 days.

Uncomplicated infections of urinary tract: on 250 mg of 1 times/days. A course of treatment - 3 days.

The complicated infections of urinary tract (including pyelonephritis): on 250 mg of 1 times/days. A course of treatment - 7-10 days.

Prostatitis: on 500 mg of 1 times/days. A course of treatment - 28 days.

Septicaemia / bacteremia: on 500 mg of 1-2 times/days. A course of treatment - 10-14 days.

Intraabdominal infection: on 500 mg of 1 times/days. A course of treatment - 7-14 days, in a combination with the antibacterial drugs operating on anaerobic flora.

Infections of skin and soft tissues: on 250 mg of 1-2 times/days or on 500 mg of 1 times/days. A course of treatment - 7-14 days.

As a part of complex therapy of drug resistant forms of tuberculosis on 500-1000 mg of a levofloksatsin of 1 times/days. A course of treatment - up to 3 months.

Use at renal failures
Patients with a renal failure need correction of the mode of dosing, depending on the size of clearance of creatinine.
Clearance of creatinine
                                                                  Doses for intake *
                                           250 mg / 24 h             500 mg / 24 h                 500 mg / 12 h
                                         first dose of 250 mg   first dose of 500 mg    first dose of 500 mg
50-20 ml/min.                  then 125 mg / 24 h     then 250 mg / 24 h       then 250 mg / 12 h
19-10 ml/min.                  then 125 mg / 48 h     then 125 mg / 24 h       then 125 mg / 12 h
<10 ml/min.                     then 125 mg / 48 h     then 125 mg / 24 h       then 125 mg / 24 h
(including a hemodialysis
and constant
out-patient
peritoneal dialysis)

* Doses are defined by character and weight of an infection, and also sensitivity of the estimated activator.

After a hemodialysis or continuous out-patient peritoneal dialysis introduction of additional doses is not required.

Use at abnormal liver functions
At an abnormal liver function special selection of doses as levofloxacin is metabolized in a liver slightly is not required.

Treatment duration, depending on the course of a disease, makes no more than 14 days. As well as at use of other antibiotics, treatment by the drug Levolet®P is recommended to be continued during at least 48-72 h after normalization of body temperature or after a reliable eradikation of the activator.

Features of use:

Treatment levofloksatsiny is recommended to be continued during at least 48-72 h after normalization of body temperature or after a reliable eradikation of the activator.

During treatment it is necessary to avoid solar and artificial ultra-violet radiation in order to avoid damage of integuments (photosensitization).

At emergence of signs of a tendinitis, pseudomembranous colitis levofloxacin is immediately cancelled.

It must be kept in mind that at patients with damage of a brain in the anamnesis (a stroke, a severe craniocereberal injury) development of spasms is possible, at insufficiency glyukozo-6-fosfatdegidrogenazy - risk of development of hemolysis.

During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Frequency of development of side effects is classified depending on the frequency of occurrence of a case: often (1-10:100), sometimes (less than 1:100), it is rare (less than 1:1000), is very rare (less than 1:10 000), in some cases.

From system of blood and bodies of a hemopoiesis: sometimes - an eosinophilia, a leukopenia; seldom - a neutropenia, thrombocytopenia; very seldom - the expressed agranulocytosis; in some cases - hemolitic anemia, a pancytopenia.

From the alimentary system: often - nausea, diarrhea, increase in activity of alaninaminotranspherase (ALT), aspartate aminotransferase (nuclear heating plant), dysbacteriosis; sometimes - appetite loss, vomiting, abdominal pains, digestion disturbances, increase in level of bilirubin in blood serum; seldom - diarrhea with impurity blood (seldom or never it can be a sign of an inflammation of intestines or pseudomembranous colitis); very seldom - hepatitis.

From cardiovascular system: seldom - tachycardia, decrease in the ABP; very seldom - a vascular collapse; in some cases - lengthening of an interval of QT.

From the central and peripheral nervous system: sometimes - a headache, dizziness, constraint of movements, drowsiness, a sleep disorder; seldom - paresthesias in brushes, a shiver, concern, conditions of fear, a spasm, confusion of consciousness; very seldom - psychotic reactions like hallucinations and depressions, disorders of the movements.

From sense bodys: very seldom - a vision disorder and hearing, sense of smell, flavoring and tactile sensitivity.

From a metabolism: very seldom - the hypoglycemia (which is shown sharp increase in appetite, nervousness, a perspiration, a shiver); in some cases - an aggravation of the available porphyria.

From an urinary system: seldom - increase in level of creatinine in blood serum; very seldom - deterioration in function of kidneys up to an acute renal failure (for example, owing to allergic reactions - intersticial nephrite).

From a musculoskeletal system: seldom - damages of sinews (including a tendinitis), joint and muscular pains; very seldom - a rupture of an Achilles tendon (can have bilateral character and be shown during 48 h after an initiation of treatment), muscular weakness (has special value for patients with a myasthenia); in some cases - рабдомиолиз.

Allergic reactions: sometimes - an itch and erubescence; seldom - anaphylactic and anaphylactoid reactions (the shown such symptoms as a small tortoiseshell, a bronchospasm and possible heavy suffocation, and also - in rare instances - a face edema, throats); very seldom - sudden decrease in the ABP, an acute anaphylaxis; in some cases - Stephens-Johnson's syndrome, a toxic epidermal necrolysis (Lyell's disease) and an exudative multiformny erythema, an allergic pneumonitis, a vasculitis.

From skin and a hypodermic fatty tissue: very seldom - a photosensitization.

Others: sometimes - an adynamy; very seldom - persistent fever, development of superinfection.

Interaction with other medicines:

Increases a cyclosporine elimination half-life.

Completeness of absorption medicines reduce the oppressing motility of intestines, сукральфат, antiacid medicines containing salts of aluminum and magnesium, and also the drugs containing iron salts (the break between reception not less than 2 h is necessary). Non-steroidal anti-inflammatory drugs, theophylline increase convulsive readiness, glucocorticosteroids increase risk of a rupture of sinews. Cimetidinum and medicines blocking canalicular secretion slow down removal.

Contraindications:

Hypersensitivity to a levofloksatsin or to other hinolona;
epilepsy; the damages of sinews connected with reception of hinolon in the anamnesis; children's and teenage age up to 18 years; pregnancy; period of a lactation (breastfeeding).

With care

Advanced age (high probability of existence of the accompanying depression of function of kidneys), deficit glyukozo-6-fosfatdegidrogenazy.

Overdose:

Symptoms: nausea, erosive damages of mucous membranes of digestive tract, lengthening of an interval of QT, confusion of consciousness, dizziness, spasms.

Treatment: symptomatic, dialysis is inefficient.

Storage conditions:

List B. In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children! Period of validity 2 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 250 mg or 500 mg. On 10 tablets in PVC / the aluminum blister. On 1 blister together with the application instruction are packed into a pack cardboard.