Лефлокс 0,5%

General characteristics. Structure:

Active ingredient: 512 mg/ml of a levofloksatsin of a gemigidrat (corresponds to the content of 500 mg/ml of a levofloksatsin). 

Excipients: sodium chloride, Acidum hydrochloricum concentrated water for injections.

Antibacterial agent of a broad spectrum of activity from group of hinolon.

Pharmacological properties:

Pharmacodynamics. Лефлокс – antibacterial agent of a broad spectrum of activity from group of hinolon, the levofloxacin containing in quality of active ingredient - the left rotating isomer of an ofloksatsin. Лефлокс blocks DNK-girazy (type topoisomerases II) and IV-topoisomerase the enzymes necessary for replication of a transcription, a reparation and a recombination of bacterial DNA, breaks superspiralling and a stitching of ruptures of deoxyribonucleic acid, inhibits synthesis of deoxyribonucleic acid, causes profound metabolic changes in cytoplasm of bacteria, their cell wall and membranes.

In the concentration equivalent or a little exceeding overwhelming concentration, most often has bactericidal effect. The following microorganisms are sensitive to drug: gram-positive aerobes — Enterococcus faecalis, Staphylococcus aureus metitsillinchuvstvitelny, Staphylococcus aemolyticus metitsillinchuvstvitelny, Staphylococcus saprophyticus,  Streptococci C, G, Streptococcus agalactiae, Streptococcus pneumoniae, including resistant to penicillin, Streptococcus pyogenes; gram-negative aerobes — Acinetobacter baumannii, Citrobacter freundii, Eikenella corrodens, Enterobacter agglomerans, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, including resistant to ampicillin, Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis including producing β-lactamelements, Morganella morganii, Pasteurella multocida, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Serratia marcescens; anaerobe bacterias — Bacteroides fragilis, Clostridium perfringens, Peptostreptococcus; others — Chlamydia pneumoniae, Chlamydia psittaci, Legionella pneumophila, Mycoplasma pneumoniae.

Are changeably sensitive to drug: gram-positive aerobes: Staphylococcus haemolyticus is metitsillinrezistentny; gramotritsatelnyeaeroba: Burkholderia cepacia; anaerobe bacterias: Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides vulgaris, Clostridium difficile. To rezistentna drug: gram-positive aerobes: Staphylococcus aureus is metitsillinrezistentny.

Besides,  pylori such activators as mycobacteria, N. are sensitive to a levofloksatsin. As well as other ftorkhinolona, levofloxacin it is not active concerning spirochetes. In spite of the fact that between levofloksatsiny and other ftorkhinolona cross resistance takes place, some microorganisms, steady against other ftorkhinolona, can be sensitive to a levofloksatsin. Onmozhet to be effective concerning the microorganisms steady against aminoglycosides, macroleads and beta лактамным to antibiotics (including to penicillin). Concerning the majority (≥90%) of strains of microorganisms of in vitro the minimum overwhelming concentration of a levofloksatsin are established (2 mkg/ml and less),

Pharmacokinetics. Drug is characterized by the optimum pharmacokinetics allowing to accept it once a day is not dependent on age and a sex of the patient. Average peak concentration of a levofloksatsin in plasma makes 6,2 mkg/ml after 60-minute intravenous infusion of 500 mg of a levofloksatsin. Drug is widely distributed in body tissues, well gets into tissue of lungs where concentration in plasma, a mucous membrane of bronchial tubes, a phlegm, bodies of urinogenital system, a bone tissue, cerebrospinal fluid, a prostate, polymorphonuclear leukocytes, alveolar macrophages are 2-5 times higher. In a liver a small part it is oxidized and/or dezatsetilirutsya.

Stereokhimicheski Levofloksatsin is stable in plasma and in urine, does not turn in the enantiomer, D-ofloxacin and in an organism is practically metabolized only for 5%. Kidneys remove 80-85% of drug that creates good conditions for treatment of an uric infection, and also allow to apply it at patients with the broken function of a liver. Communication with proteins of plasma - 30-40%. T1/2 makes 6–8 h after single or repeated introductions inside or in / century. The general Cl makes 144–226 ml/min., renal Cl — 96–142 ml/min., excretion is carried out by glomerular filtering and canalicular secretion. Crystals of a levofloksatsin in fresh-gathered urine are not found. As metabolism of a levofloksatsin is insignificant, damages of a liver have no significant effect on pharmacokinetics. Levofloksatsin is brought, it is preferential in an invariable view with urine (about 87% of a dose during 48 h), insignificant quantities — with excrements (less than 4% for 72 h). Less than 5% are defined in urine in the form of the metabolites (desmetit, nitrogen oxide) having insignificant specific pharmacological activity.

The elimination half-life of a levofloksatsin makes six-seven hours, however thanks to good penetration into body tissues post-antibiotic action of drug proceeds by two-three times longer than an elimination half-life that allows to use it 1 time a day. At a renal failure reduction of clearance of drug and its removal through kidneys depends on extent of decrease in clearance of creatinine. The pharmacokinetics of a levofloksatsin at elderly patients has no significant differences. The pharmacokinetics of a levofloksatsin at детейв the present is studied.

Indications to use:

The infectious and inflammatory diseases at adults caused sensitive to a levofloksatsin by microorganisms:

- respiratory infections (exacerbation of chronic bronchitis, community-acquired pneumonia)

- acute sinusitis

- infections of urinary tract, uncomplicated and complicated: (pyelonephritis, cystitis, urethritis, etc.)

- infections of integuments and soft tissues in t. there are surgical h

- the septicaemia and bacteremia connected with the indications stated above the Intraabdominal infection

- prostatitis

Route of administration and doses:

Doses are defined by character and weight of an infection, and also sensitivity of the estimated activator of a condition of an organism, age, weight and function of kidneys at the patient. The drug is administered intravenously on 250-500 mg of 1-2 times/days. Duration of treatment depends on the course of a disease and should not exceed 28 days. It is recommended to continue treatment for at least 48-72 h after normalization of body temperature or the eradikation confirmed with results of microbiological tests vozbuditelya.vvodit in/in kapelno slowly. Time of administration of drug in a dose of 500 mg (100 ml of infusion solution / 500 mg of a levofloksatsin) has to make not less than 60 min. Duration of treatment makes no more than 14 days.  

Indications the Daily dose (mg) Frequency rate of receptions in days Duration of treatment, (days) Acute sinusitis 500 1 10–14 Chronic bronchitis in an aggravation phase 250–500 1 7–10 Not hospital pneumonia 500–1000 1–2 7–14 Uncomplicated infections of an uric path 250 1 3 the Complicated infections of an uric path, including pyelonephritis 250 1 7–10 Infections of skin and soft tissues 500–1000 1–2 7–14 Septicaemia/bacteremia 500–1000 1–2 10–14

Intra belly infections 500 1 7–14 Prostatitis 500 1 28    

Clearance of creatinine of the Dose for in/in introductions of 250 mg / 24 h 500 mg / 24 h 500 mg / 12 h the first dose of 250 mg the first dose of 500 mg the 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. (including a hemodialysis and PAPD *) then 125 mg / 48 h then 125 mg / 24 h then 125 mg / 24 h  

Use of a levofloksatsin in higher dose, but less long time creates conditions for an effective eradikation of activators and promotes prevention of mutations, growth and resistance of activators to effect of drug.

Features of use:

Prior to therapy by Levofloksatsin it is necessary to carry out the corresponding tests for identification of an infestant and assessment of its sensitivity though treatment can be begun before obtaining results of these tests, and then the corresponding therapy is chosen. During treatment by drug alcohol intake is contraindicated.

At the heavy pneumonia caused by pneumococci, Levofloxacin can not give optimum therapeutic effect. The hospital infections caused by certain activators (R. of aeruginosa), can demand the combined treatment. During treatment by Levofloksatsin development of an attack of spasms in patients with the previous damage of a brain caused, for example, by a stroke or a severe injury is possible. Convulsive readiness can increase also at simultaneous use of a fenbufen, non-steroidal anti-inflammatory drugs or theophylline, similar to it. In spite of the fact that the photosensitization is noted very seldom, in order to avoid its patients are not recommended to be exposed without special need to power solar or artificial ultra-violet irradiation.

It is necessary to cancel immediately Levofloxacin at suspicion of pseudomembranous colitis and to begin the corresponding treatment. In such cases it is impossible to apply the medicines oppressing motility of intestines.

The tendinitis which is seldom observed at drug use (first of all an Achilles tendon inflammation) can lead to a rupture of sinews. Treatment by corticosteroids most likely increases risk of a rupture of sinews. At suspicion it is necessary to stop immediately treatment by drug of Lefloks and to begin the corresponding treatment of the affected sinew. Patients with insufficiency glyukozo-6-fosfatdegidrogenazy (an inherited disorder of a metabolism) can react to ftorkhinolona destruction of erythrocytes (hemolysis).

As well as at reception of other hinolon, there can be changes of level of glucose in blood, including symptomatic hyper - and a gipogilikemiya at the patients with diabetes who are at the same time receiving peroral hypoglycemic means or insulin. If against the background of a levofloksatsin hypoglycemic reaction develops, it is necessary to cancel immediately levofloxacin and to begin the corresponding therapy. Careful monitoring of level of glucose in blood at these patients and periodic control of functions of systems of an organism, including renal, hepatic, hemopoietic, as well as reception of any strong antimicrobic is recommended to HP.

When using drug by Patients, the managing director of vehicles and working with potentially dangerous mechanisms, it is necessary to be careful, considering a possibility of development of side effects — drowsiness, confusion of consciousness, dizziness, lacks of coordination of movements.

Side effects:

In general the level of the side reactions connected with levofloksatsiny, the lowest among FH it has good tolerance and is one of the safest ftorkhinolon. Frequency of side reactions, at monotherapy not above than at other classes of highly active antibacterial drugs, also makes 6,3%. It is shown that increase in a dose of LF up to 1000 mg/days does not lead to growth of number of side effects, and their probability does not depend on age of the patient. 

Action on a GIT. Often: nausea, diarrhea. Sometimes: appetite loss, vomiting, abdominal pain, digestion dysfunctions. Seldom: a bloody diarrhea who seldom or never can be a sign of an inflammation of intestines and even pseudomembranous colitis. Very seldom: the hypoglycemia (falling of level of sugar in blood) having special value for the patients suffering from a diabetes mellitus (possible signs of a hypoglycemia: volchy ″ appetite, nervousness, perspiration, shiver). Experience of use of other hinolon demonstrates that they can cause a porphyria aggravation (very rare disease of a metabolism) in the patients who already have this disease. The similar effect is not excluded also at medicine use Lefloksatsin.

Action on a liver and kidneys. Often: increase in activity of enzymes of a liver (for example, alaninaminotranspherases and aspartate aminotransferases). Sometimes: increase in level of bilirubin and creatinine in blood serum (a sign of restriction of functions of a liver and kidneys). Very seldom: hepatic reactions (for example, a liver inflammation), deterioration in functions of kidneys up to an acute renal failure, for example, owing to allergic reactions (intersticial nephrite).

Under the influence of an Ural federal district beams photodestruction of a molecule of a levofloksatsin and, as a result induction of free radicals and damage of skin structures is possible. The itch and erubescence can sometimes disturb. Seldom: the general reactions of hypersensitivity (anaphylactic and anaphylactoid reactions) with such symptoms as a small tortoiseshell, a bronchospasm and possible heavy suffocation, and also – in rare instances – cutaneous dropsies and mucous membranes (for example, in a face and a throat). Very seldom: sudden falling of arterial pressure and shock; hypersensitivity to solar and ultra-violet radiations; allergic pneumonitis; vasculitis. A heavy enanthesis with formation of bubbles, for example, Stephens-Johnson's syndrome, a toxic epidermal necrolysis (Lyell's disease) and an exudative mnogoformny erythema is in some cases possible. The reactions called above can develop after the first dose of medicine - in a few minutes, or hours after introduction.

Action on a nervous system.  The reaction from TsNS connected with influence on ability of drugs to receptor antagonism since aminobutyric acid (GAMK). This type of antagonism of in vivo can be shown in undesirable side effect of drugs on TsNS. Frequency of undesirable side reactions from TsNS at purpose of ftorkhinolon makes 1–2%, and for a levofloksatsin it makes only 0,2-1,1%. The mechanism of the specified disturbances is connected with the fact that ftorkhinolona compete with GAMK for communication with her specific receptors and thus reduce the braking action of GAMK by neurons. At the same time convulsive reactions, sometimes are possible: headache, dizziness and (or) catalepsy, drowsiness, sleep disorder. Seldom: unpleasant feelings (for example, paresthesias in hands), a shiver, concern, conditions of fear, attacks of spasms as epipripadok and confusion of consciousness. Very seldom: a vision disorder and hearing, disturbances of flavoring sensitivity and sense of smell, decrease in tactile sensitivity, psychotic reactions like hallucinations and depressions, and also disorders of the movements, including when walking.

Influence on the hemopoietic system. Sometimes: increase in number of eosinophils, reduction of number of leukocytes. Seldom: a neutropenia, thrombocytopenia that can be followed by strengthening of bleeding. Very seldom: agranulocytosis and development of heavy infections (resistant and recurrent fervescence, inflammations of a throat and permanent deterioration in health). In certain cases: hemolitic anemia, pancytopenia.

Seldom: damages of sinews (tendovaginitis), joint and muscular hurt. Very seldom: the rupture of sinews (for example, an Achilles tendon), this side effect can be observed within 48 hours after an initiation of treatment and can have bilateral character; the muscular weakness having special value for the patients suffering from myasthenia gravis. In some cases: damage of muscles (рабдомиолиз).

Action on cardiovascular system. Medicines from group of ftorkhinolon have proaritmogenny potential, their use is rare, but can cause heartbeat strengthening, a lowering of arterial pressure. In the researches conducted by supra-therapeutic doses at Levofloksatsin   some lengthening of an interval of QT on the cardiogram was also revealed. However, according to the conducted researches this influence is much less, than at other drugs of group of ftorkhinolon. Nevertheless, it patients should not appoint in the presence lengthening of an interval of QT, for example at a hypopotassemia. Sometimes: general weakness (adynamy). Very seldom: fever. Change of microflora: the strengthened reproduction of the bacteria and mushrooms steady against the applied antibiotic (consecutive infection and superinfection) which in rare instances can demand additional treatment.

Interaction with other medicines:

Ftorkhinolona after absorption from a GIT in different degree biotransformations with formation of conjugates with glucuronic acid or to oxidation with participation of enzymes of system of P450 cytochrome are exposed.

There are messages on the expressed decrease in level of convulsive readiness at simultaneous use of the hinolon and substances capable in turn to reduce a threshold of convulsive readiness.

Equally it concerns also simultaneous use of hinolon and a fenbufen or nonsteroid antiinflammatory medicines, similar to it (the medicines used for treatment of rheumatic diseases).

Reception of glucocorticosteroids along with a left phlox increases risk of a rupture of sinews.

It is necessary to remember possible reduction of the threshold of nervous irritability when using a class of hinolon in combination with theophylline or NPVS.

At simultaneous use of antagonists of vitamin K , control of coagulant system of blood of the patient is necessary. Removal (renal clearance) of a levofloksatsin is slightly slowed down under the influence of Cimetidinums and a probenitsid blocking a certain way of removal (canalicular secretion). It concerns, first of all, patients with bounded function of kidneys. Levofloxacin slightly increases an elimination half-life of cyclosporine it is not necessary to appoint лефлокс to patients against the background of reception of antiarrhythmic means of a class 1A (прокаиномид) or 111 (Amiodaronum).

Levofloksatsin's solution 500 mg100 ml is compatible to the following infusion solutions: 0,9% solution of sodium of chloride, 5% solution of a dextrose, 2,5% Ringer's solution with a dextrose, the combined solutions for parenteral food (amino acids, carbohydrates, electrolytes).

Solution of drug cannot be mixed with heparin or solutions with alkali reaction (for example, with bicarbonate sodium solution). At positive dynamics of a clinical condition of the patient in several days of treatment it is possible to pass from in/in drop introductions to oral administration of drug in the same dose.

Contraindications:

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

With care it is necessary to use drug at patients of advanced age in connection with high probability of existence of the accompanying depression of function of kidneys, at deficit glyukozo-6-fosfatdegidrogenazy. Drug is contraindicated to use at pregnancy and in the period of a lactation (breastfeeding). At an abnormal liver function special selection of doses as Levofloxacin is metabolized in a liver in extremely insignificant measure is not required.

Overdose:

Possible symptoms of overdose of Levofloksatsin are shown at the level of the central nervous system (confusion of consciousness, dizziness, disturbances of consciousness and attacks of spasms as epipripadok). Also gastrointestinal frustration (for example, nausea) and damage of mucous membranes can be noted. Overdose treatment: a gastric lavage, adequate hydration with orientation to the available symptoms. Levofloxacin is not removed by means of dialysis. The specific antidote (counteracting substance) does not exist. Wrong reception of one excess tablet of medicine of 250 mg or 500 mg will not make harmful effects.

Storage conditions:

To store in  the place protected from light at a temperature from +5 to +25 °s.khranit in the place, unavailable to children. Period of validity 2 years.

Issue conditions:

According to the recipe

Packaging:

1 polymeric container of 100 ml in secondary packaging.