Levofloxacin of 250 mg; 500 mg No. 10

General characteristics. Structure:

Active ingredient: levofloxacin; 1 tablet contains 256,23 mg of a levofloksatsin of a gemigidrat that is equivalent to 250 mg of a levofloksatsin;
1 tablet contains 512,46 mg of a levofloksatsin of a gemigidrat that is equivalent to 500 mg of a levofloksatsin; Excipients: a gipromeloza, кросповидон, cellulose microcrystallic, the sodium stearylfumarating polyethyleneglycol 6000, talc, ferrous oxide red E 172, ferrous oxide yellow E 172, titanium E 171 dioxide. Main physical and chemical properties: tablets of a round form, coated, from light pink till light brown color with a pink shade, with a biconvex surface. On a break under a magnifying glass the kernel of light yellow or yellow-white color surrounded with one continuous layer is visible.

Pharmacological properties:

Pharmacodynamics. Levofloxacin is characterized by a wide range of antibacterial action. The bactericidal effect is provided owing to oppression levofloksatsiny bacterial DNK-girazy enzyme which belongs to the II type of topoisomerases. The impossibility of transition of bacterial DNA from a condition of "relaxation" in a "nadskruchenny" state is result of such oppression that, in turn, makes impossible further division (reproduction) of bacterial cells. The range of activity of a levofloksatsin includes gram-positive and gram-negative bacteria together with nonfermentative bacteriums.
The following microorganisms are sensitive to drug:
– gram-positive aerobes: Enterococcus faecalis, Staphylococcus aureus methi-S, Staphylococcus haemolyticus methi-S, 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 b+/b-, 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, Ureaplasma, H.pylori.
Are changeably sensitive to effect of drug:
– gram-positive aerobes: Staphylococcus haemolyticus methi-R;
– gram-negative aerobes: Burkholderia cepacia;
– anaerobe bacterias: Bacteroides ovatus, Bacteroides thetaiiotamicron, Bacteroides vulgaris, Clostridium difficile.
To effect of drug of a rezistentna: gram-positive aerobes: Staphylococcus aureus methi – R.
It is similar to other ftorkhinolona, levofloxacin is inactive in relation to spirochetes.

Pharmacokinetics. Absorption. Levofloxacin at oral administration is quickly and almost entirely soaked up, at the same time peak concentration in a blood plasma are reached within 1 hour. Absolute bioavailability makes about 100%. The food almost does not influence absorption of a levofloksatsin.
Distribution.
About 30-40% of a levofloksatsin contact a blood serum protein. The Kumulyatsionny effect of a levofloksatsin at use of 500 mg of 1 times in days of multiple dose is practically absent. There is an insignificant, but predicted kumulyatsionny effect after reception of doses on 500 mg twice a day. The stable state is reached within 3 days.
Penetration into fabrics and liquids of an organism.
Penetration into a mucous membrane of bronchial tubes, bronchial secret of tissues of lungs (BSTL).
The maximum concentration of a levofloksatsin in a mucous membrane of bronchial tubes and a bronchial secret of lungs after reception of 500 mg orally made 8,3 mkg/g and 10,8 mkg/ml respectively. These indicators were reached within 1 hour after administration of drug.
Penetration into tissues of lungs.
The maximum concentration of a levofloksatsin in tissues of lungs after reception of 500 mg orally made about 11,3 mkg/g and were reached in 4-6 hours after administration of drug. Concentration in lungs exceeds that in a blood plasma.
Penetration into bubble contents.
The maximum concentration of a levofloksatsin of 4,0-6,7 mkg/ml got into contents of a bubble in 2-4 hours after administration of drug in 3 days of administration of drug at doses of 500 mg 1-2 times a day respectively.
Penetration into cerebrospinal (spinal) liquid.
Levofloxacin badly gets into cerebrospinal liquid.
Penetration into prostate tissues.
After oral administration of 500 mg of a levofloksatsin of 1 times a day within 3 days average concentration in tissue of a prostate reached 8,7 mkg/g, 8,2 mkg/g and 2 mkg/g respectively in        2 hours, the 6th hour and 24 hours; the average coefficient of concentration prostate/plasma made 1,84.
Concentration in urine.
Average concentration in urine in 8-12 hours after one-time reception orally doses     of 150 mg, 300 mg or 500 mg of a levofloksatsin made 44 mg/l, 91 mg/l that 200 mg/l respectively.
Biotransformation.
Levofloxacin is metabolized in very insignificant measure, metabolites are dismetil-levofloxacin and N-oxide levofloxacin. These metabolites make less than 5% of amount of the drug which is emitted with urine. Levofloxacin is stereokhimichesk stable and is not subject to inversion of chiral structure.
Removal.
After peroral and intravenous administration levofloxacin is removed from a blood plasma rather slowly (the elimination half-life makes 6-8 hours). Removal happens usually kidneys (over 85% of the entered dose).
There is no essential difference concerning pharmacokinetics of a levofloksatsin after intravenous and oral administration that demonstrates that these ways (peroral and intravenous) are interchangeable.
Linearity.
Levofloxacin corresponds to linear pharmacokinetics in the range of 50-600 mg.
Patients with a renal failure.
The pharmacokinetics of a levofloksatsin is influenced by a renal failure. At depression of function of kidneys renal removal and clearance decreases, and elimination half-lives increase, apparently from table 1:
Table 1.
Clearance of creatinine (ml/min.) < 20 20-40 50-80
Renal clearance (ml/min.)  13 26 57
Elimination half-life (hours)  35 27 9
Patients of advanced age.
There are no considerable differences in pharmacokinetics of a levofloksatsin in young patients and patients of advanced age, except the differences connected with clearance of creatinine.
Gender differences.
The separate analysis concerning patients women's and male showed insignificant differences in pharmacokinetics of a levofloksatsin depending on a floor. There are no proofs that these gender differences are clinically significant.

Indications to use:

At adults with infections of easy or moderate weight of Levofloksatsin appoint for treatment of the following infections caused by microorganisms, sensitive to a levofloksatsin:
– acute sinusitis.
– Exacerbations of chronic bronchitis.
– Pneumonia.
– The complicated and uncomplicated infections of an urinary path (including pyelonephritises).
– Infections of skin and soft tissues.
– Septicaemia/bacteremia.
– Intraabdominal infections.

Route of administration and doses:

Pill of a levofloksatsin is taken by 1-2 times a day. The dose depends on type and weight of an infection. Duration of treatment depends on disease and makes no more than 14 days. It is recommended to continue treatment by drug (solution for in/in introductions or tablets), at least, within 48-72 hours after normalization of body temperature or the destruction of the activator confirmed with microbiological tests.
It is necessary to swallow of tablets of a levofloksatsin, without chewing and to wash down with enough liquid. It is possible to accept them both together with food, and in other time.
Concerning dosing it is necessary to adhere to the following recommendations for adult patients with normal function of kidneys at which the clearance of creatinine makes        over 50 ml/minute:
Indications the Daily dose the Number of introductions in days treatment Duration
Acute sinusitis of 500 mg of 1 times of 10-14 days
Exacerbations of chronic bronchitis of 250-500 mg of 1 times of 7-10 days
Not hospital pneumonia of 500-1000 mg 1-2 times of 7-14 days
Uncomplicated infections of an urinary path of 250 mg of 1 times 3 days
The complicated infections of an urinary path inclusive with pyelonephritis of 250 mg of 1 times of 7-10 days
Infections of skin and soft tissues of 500-1000 mg 1-2 times of 7-14 days
Septicaemia/bacteremia of 500-1000 mg 1-2 times of 10-14 days
Intraabdominal infections * 500 mg of 1 times of 7-14 days
* In a combination with antibiotics with action on anaerobic activators.
 Dosing for patients with an impaired renal function who have a clearance of creatinine          <50 ml/min.:
Clearance of creatinine the dosing Mode (depending on weight of an infection and a nosological form)
50-20 ml/min. first dose:
250 mg
the subsequent:
125 * mg / 24 hours first dose:
500 mg
the subsequent:
250 mg / 24 hours first dose:
500 mg
the subsequent:
250 mg / 12 hours
19-10 ml/min. first dose:
250 mg
the subsequent:
125 * mg / 48 hours first dose:
500 mg
the subsequent:
125 * mg / 24 hours first dose:
500 mg
the subsequent:
125 * mg / 12 hours
<10 ml/min., (and also at a hemodialysis and HAPD 1) the first dose:
250 mg
the subsequent:
125 * mg / 48 hours first dose:
500 mg
the subsequent:
125 * mg / 24 hours first dose:
500 mg
the subsequent:
125 * mg / 24 hours
1 – After a hemodialysis or the chronic out-patient peritoneal dialysis (COPPD) additional doses are not necessary.
* Use of a dosage form with smaller dosing is recommended.
Dosing for patients with the broken function of a liver. Dose adjustment is not necessary as levofloxacin in an insignificant measure is metabolized in a liver.
Dosing for patients of advanced age. If renal function is not broken, there is no need for dose adjustment.

Features of use:

At very heavy course of pneumonia, caused by pneumococci, the drug Levofloxacin can not show optimum therapeutic effect.
The hospital infections caused by P. aeruginosa can demand a combination therapy.
Tendinitis and ruptures of sinews.
Less often tendinitis cases can meet. Most often it touches an Achilles sinew and can lead to a rupture of a sinew. The risk of a tendinitis and rupture of sinews increases at patients of advanced age and patients accepting corticosteroids. Therefore careful observation of such patients if by it appoint the drug Levofloxacin is necessary. Patients should consult with the doctor if they observe symptoms of emergence of a tendinitis. At suspicion on a tendinitis treatment it is necessary to stop and begin with the drug Levofloxacin immediately appropriate treatment (for example, providing an immobilization of sinews).
The diseases caused by Clostridium difficile.
Diarrhea, especially in hard cases, persistent and/or hemorrhagic, in time or after treatment by the tablets Levofloxacin, can be symptoms of the disease caused by Clostridium difficile most of which severe form there is pseudomembranous colitis. If there are suspicions of pseudomembranous colitis, it is necessary to stop immediately reception of the tablets Levofloxacin, and patients specific therapy follows without treatment delay the supporting means ± (for example, oral administration of Vancomycinum). The means oppressing motility of intestines are contraindicated in this clinical situation.
Patients inclined to spasms.
The tablets Levofloxacin are contraindicated to patients with epilepsy in the anamnesis, and as in a case with other hinolona, should apply with extreme care the patients inclined to spasms, such as patients with preliminary injury of the central nervous system, at simultaneous therapy fenbufeny and similar to it the nonsteroid antiinflammatory medicines or drugs increasing convulsive readiness (reduce a convulsive threshold), such as theophylline (see the section "Interaction with Other Medicines and Other Types of Interactions").
In case of convulsions treatment levofloksatsiny should be stopped.
Patients with insufficiency glyukozo-6-fosfatdegidrogenazy.
Patients with latent or explicit defects of activity glyukozo-6-fosfatdegidrogenazy can be antibacterial agents of group of hinolon, inclined to hemolitic reactions at treatment, and, thus, they should apply levofloxacin with care.
Patients with a renal failure.
As levofloxacin is removed generally by kidneys, dose adjustment for patients with an impaired renal function (renal failure), see the section "Route of Administration and Doses" is necessary.
Hypersensitivity reaction (hypersensitivity).
Levofloxacin can cause from time to time serious potentially fatal hypersensitivity reactions (for example, a Quincke's disease up to an acute anaphylaxis), after use of an initial dose (see the section "Side reactions"). In this case patients should stop treatment immediately and to see a doctor.
Hypoglycemia.
As in a case with all hinolona, it was reported about hypoglycemia cases, especially at the patients sick with a diabetes mellitus who received the accompanying therapy by hypoglycemic means orally (for example, Glibenclamidum) or insulin. Careful observation of glucose level in blood at patients with a diabetes mellitus is recommended (see the section "Side reactions").
Prevention of a photosensitization.
Though the photosensitization arises very seldom at reception of a levofloksatsin, for the purpose of its avoiding it is not recommended to patients without special need to give in to action of strong sunshine or artificial UF of radiation (for example, lamps of artificial ultraviolet radiation, a sunbed).
Patients, the receiving antagonists of vitamin K.
Owing to possible increase in indicators of coagulative tests (ON / the international normalizing relation) and/or bleedings at the patients accepting Levofloxacin in combination with the antagonist of vitamin K (for example, warfarin), it is necessary to watch coagulative tests if these medicines are applied at the same time (see the section "Interaction with Other Medicines and Other Types of Interactions").
Mental reactions.
It was reported about mental reactions at the patients accepting hinolona including levofloxacin. Seldom or never they progressed to suicide thoughts and self-destructive behavior, sometimes even after reception of the only dose of a levofloksatsin (see the section "Side reactions"). If the patient has these reactions, reception of a levofloksatsin it is necessary to stop and resort to the relevant activities. It is recommended to apply with care levofloxacin to patients with mental disorders or to patients with mental diseases in the anamnesis.
Lengthening of an interval of QT.
It is necessary to treat with care use of ftorkhinolon, including levofloxacin, to patients with the known risk factors for lengthening of an interval of QT, such as, for example:
– inborn syndrome of lengthening of an interval of QT;
– the accompanying use of the medicines known for the ability to extend QT interval (for example, antiarrhythmic means of a class ІА and ІІІ, tricyclic antidepressants, macroleads);
– not corrected electrolytic imbalance (for example, a hypopotassemia, a hypomagnesiemia);
– at patients of advanced age;
– a heart trouble (for example, heart failure, a myocardial infarction, bradycardia), see the section "Route of Administration and Doses" (Patients of advanced age), the section "Interaction with Other Medicines and Other Types of Interactions", the section "Side reactions", the section "Overdose".
Peripheral neuropathy.
It was reported about touch or sensomotor peripheral neuropathy at the patients accepting ftorkhinolona including levofloxacin which can quickly arise. Reception of a levofloksatsin should be stopped if at the patient neuropathy symptoms are observed to prevent emergence of an irreversible state.
Opiates.
At the patients receiving levofloxacin, detection of opiates in urine can yield a wrong positive take. There can be a need to confirm positive takes on opiates by means of more specific methods.
Gepatobiliarny disturbances.
It was reported about cases of necrotic hepatitis, up to a liver failure that made threat for life at reception of a levofloksatsin preferential at patients with serious basic diseases, for example, of sepsis (see the section "Side reactions"). Patients should recommend to stop treatment and to see the doctor if there are such manifestations and symptoms of a disease of a liver as anorexia, jaundice, black urine, an itch or pain in a stomach.

Ability to influence speed of response at control of motor transport or work with other mechanisms.
At Levofloksatsin's use it is necessary to refrain from management of transport and performance of potentially dangerous types of activity requiring special attention and speed of reaction, considering a possibility of development of side reaction of a nervous system (dizziness, catalepsy, drowsiness, confusion of consciousness, a visual disturbance and hearing, disorder of processes of the movement, also during walking). Block of reactions amplifies in case of alcohol intake.

Children. Do not apply.

Side effects:

The undesirable effects connected using a levofloksatsin are given below.
Allergic reactions:
in certain cases: itch and erubescence.
More rare: the general hypersensitivity reactions (anaphylactic and anaphylactoid) with such signs as a small tortoiseshell, a spasm of bronchial tubes and, perhaps, a heavy asthma.
Very seldom: cutaneous dropsy and mucous membranes (for example, face skin and mucous membrane of a throat); allergic reactions from lungs (an allergic pneumonitis) or small blood vessels (vasculitis), a sudden lowering of arterial pressure and shock; lengthening of a QT interval, hypersensitivity to solar and ultraviolet rays.
Isolated cases: heavy rash on skin and mucous membranes with formation of bubbles, such as Stephens-Johnson's syndrome, toxic epidermal necrolysis (Lyell's disease) and exudative mnogoformny erythema. Easier reactions from skin can sometimes precede the general hypersensitivity reactions. Such reactions can appear after the first dose and within several minutes or hours after reception.
Digestive tract and metabolism:
often: nausea, diarrhea.
In certain cases: lack of appetite, vomiting, abdominal pain, digestive disturbances.
More rare: ponosa with blood impurity which can sometimes be intestines inflammation signs, including pseudomembranous colitis.
Very seldom: decrease in content of sugar in blood (hypoglycemia) that has, perhaps, special value for patients with a diabetes mellitus. Can be signs of a hypoglycemia: the increased appetite, nervousness, sweating, trembling of extremities.
Concerning other hinolon it is known that they, perhaps, are capable to cause porphyria attacks in patients with existence of a porphyria. It can concern as well a levofloksatsin.
Central nervous system:
in isolated cases: headache, dizziness/catalepsy, drowsiness, frustration of a dream.
More rare: unpleasant feeling, for example, paresthesia in brushes, trembling, concern, conditions of fear, attacks of a spasm and confusion of consciousness.
Very seldom: visual disturbance and hearing, disturbance of taste and sense of smell, reduced feeling of touch, and also psychotic reactions, such as hallucinations and depressive changes of mood. Disorder of processes of the movement, also during walking.
Cardiovascular system:
more rare: tachycardia, lowering of arterial pressure.
Very seldom: collapse, similar to shock.
Musculoskeletal system:
More rare: damages of sinews, including their inflammation, joint pain or muscles.
Very seldom: rupture of sinews (for example, rupture of an Achilles sinew). This side effect can be shown within 48 hours from an initiation of treatment and affect an Achilles sinew of both legs. Muscular weakness which can have special value for patients with a heavy myasthenia is possible.
Isolated cases: damages of muscles (рабдомиолиз).
Liver and kidneys:
often: the raised indicators of hepatic enzymes (for example, ALT, nuclear heating plant).
In certain cases: the raised indicators of bilirubin and creatinine of blood serum.
Very seldom: hepatic reactions, such as liver inflammation. Deterioration in function of kidneys, up to an acute renal failure, for example, owing to allergic reactions (intersticial nephrite).
Hemopoietic system:
in certain cases: increase in quantity of certain blood cells (eosinophilia), reduction of quantity of leukocytes (leukopenia).
More rare: decrease in quantity of certain leukocytes (neutropenia), reduction of quantity of thrombocytes (thrombocytopenia) which can cause the increased tendency to hemorrhages or bleedings.
Very seldom: rather considerable reduction of quantity of certain leukocytes (agranulocytosis) that can lead to heavy symptoms of a disease (long or recurrent fever, pharyngitis, the expressed painful health).
Isolated cases: decrease in quantity of erythrocytes owing to their destruction (hemolitic anemia). The reduced number of all types of blood cells (pancytopenia).
Other side reactions:
in some cases: general weakness (adynamy).
Very seldom: fever.
Use of any antibacterial agents can lead to the disturbances connected with their influence on normal microflora of a human body. For this reason the consecutive infection demanding additional treatment can develop.

Interaction with other medicines:

Adsorption of a levofloksatsin significantly decreases at a concomitant use with antacids, containing magnesium and aluminum, and also with drugs, containing iron salts. The recommended period between reception of a levofloksatsin and the called drugs has to make not less than two hours. Bioavailability of tablets of a levofloksatsin considerably decreases at a concomitant use with sukralfaty. The period between reception of these drugs has to make not less than two hours. Though in clinical trials it is not established interactions between levofloksatsiny and theophylline, but perhaps essential decrease in a convulsive threshold at simultaneous use of hinolon with theophylline, non-steroidal anti-inflammatory drugs and other agents reducing a convulsive threshold. Concentration of a levofloksatsin in the presence of a fenbufen was about 13% higher, than at reception only a levofloksatsina. Probenitsid and Cimetidinum statistically authentically influence removal of a levofloksatsin. The renal clearance of a levofloksatsin decreases in the presence of a probenitsid by 34%, and Cimetidinum – for 24%. Thanks to it both drugs are capable to block canalicular excretion of a levofloksatsin. The period of semi-life of cyclosporine increases by 33% at a concomitant use with levofloksatsiny.
At simultaneous use with antagonists of vitamin K, for example – warfarin, coagulative tests (ON / the international normalizing relation) and/or bleedings which can be expressed raise. Considering it, the patients receiving in parallel antagonists of vitamin K need to exercise control of indicators of coagulation.
Use of a levofloksatsin along with alcohol is not recommended.

Contraindications:

– Hypersensitivity to a levofloksatsin or to other hinolona.
– Epilepsy.
– Patients with complaints to side reactions from sinews after the previous use of hinolon. Pregnancy and period of feeding by a breast.
– Children's age.

Overdose:

The most important estimated symptoms of overdose of drug levofloxacin touch the central nervous system (confusion of consciousness, dizziness, disturbances of consciousness and attacks of a spasm); reactions from gastrointestinal system, such as nausea and erosion of mucous membranes. According to results of researches, at use of doses above therapeutic lengthening of a QT interval was observed. In cases of overdose it is necessary to make careful observation of the patient, including an ECG. Treatment – symptomatic. In cases of obvious overdose the gastric lavage is appointed. For protection mucous a stomach antiacid means are used.
The hemodialysis, including peritoneal dialysis or TAPD, is not effective for removal of a levofloksatsin from an organism. There are no specific antidotes.
Use during pregnancy or feeding by a breast. Through lack of researches on the person and possible injury of a joint cartilage by hinolona to the growing organism the pregnant women and women nursing cannot appoint levofloxacin. If during treatment of a levofloksatsin pregnancy is established, it is necessary to report about it to the doctor.

Storage conditions:

To store at a temperature not vyshe30 °C. To store in the place, unavailable to children!

Period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister. On 1 blister in a pack from a cardboard.