Levofloxacin

General characteristics. Structure:

Active ingredient: 250 mg or 500 mg of a levofloksatsin (in terms of a levofloksatsin гемигидрат — 256,23 mg and 512,46 mg).

Excipients: cellulose microcrystallic, gipromelloz (gidroksipropilmetiltsellyuloz), primelloza (croscarmellose sodium), calcium stearate.

Structure of a cover: gipromelloz (gidroksipropilmetiltsellyuloz), macrogoal 4000 (polyethyleneglycol, poly(ethylene oxide)), talc, titanium dioxide, dye ferrous oxide yellow.

Synthetic antibacterial drug of a broad spectrum of activity.

Pharmacological properties:

Pharmacodynamics. Levofloxacin — the synthetic antibacterial drug of a broad spectrum of activity from group of ftorkhinolon containing levofloxacin in quality of active agent — left-handed isomer of an ofloksatsin. Levofloxacin blocks DNK-girazu, breaks superspiralling and a stitching of ruptures of DNA, inhibits DNA synthesis, causes profound morphological changes in cytoplasm, a cell wall and membranes.

Levofloxacin is active concerning the majority of strains of microorganisms as in the conditions of in vitro and in vivo.

Aerobic gram-positive microorganisms: Corynebacterium diphtheriae, Enterococcus faecalis, Enterococcus spp, Listeria monocytogenes, Staphylococcus coagulase-negative methi-S(I), Staphylococcus aureus methi-S, Staphylococcus epidermidis methi-S, Staphylococcus spp (CNS), Streptococci of group C and G, Streptococcus agalactiae, Streptococcus pneumoniae peni I/S/R, Streptococcus pyogenes, Viridans streptococci peni-S/R.

Aerobic gram-negative microorganisms: Acinetobacter baumannil, Acinetobacter spp, Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Enterobacter spp, Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S/R, Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella spp, Moraxela catarrhalis β+/β-, Morganella morganii, Neisseria gonorrhoeae non PPNG/PPNG, Neisseria meningitidis, Pasteurella conis, Pasteurella dagmatis, Pasteurella multocida, Pasteurella spp, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Providencia spp, Pseudomonas aeruginosa, Pseudomonas spp, Salmonella spp, Serratia marcescens, Serratia spp.
Anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp, Clostridium perfringens, Fusobacterium spp, Peptostreptococcus, Propionibacterum spp, Veilonella spp.

Other microorganisms: Bartonella spp, Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Legionella spp, Mycobacterium spp, Mycobacterium leprae, Micobacterium tuberculosis, Mycoplasma hominis, Mycoplasma pneumoniae, Ricketsia spp, Ureaplasma urealyticum.

Pharmacokinetics. Levofloxacin is quickly and almost completely soaked up after oral administration. Meal influences the speed and completeness of absorption a little. Bioavailability of 500 mg of a levofloksatsin after oral administration makes nearly 100%. After reception of a single dose of 500 mg of a levofloksatsin the maximum concentration makes 5,2-6,9 mkg/ml, time of achievement of the maximum concentration - 1,3 h, an elimination half-life - 6-8 h.

Communication with proteins of plasma — 30-40%. Well gets into bodies and fabrics: lungs, mucous membrane of bronchial tubes, phlegm, bodies of urinogenital system, bone tissue, medullispinal liquid, prostate, 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. After oral administration about 87% of the accepted dose less than 4% with a stake during 72 h are allocated with urine in not changed look within 48 hours.

Indications to use:

The infectious and inflammatory diseases caused by sensitive microorganisms: acute sinusitis, an exacerbation of chronic bronchitis, community-acquired pneumonia, the complicated infections of urinary tract (including pyelonephritis), the uncomplicated infections of urinary tract, prostatitis, infections of integuments and soft tissues, septicaemia/bacteremia connected with the indications stated above, an intraabdominal infection.

Route of administration and doses:

Drug accept inside one or twice a day. Not to chew and wash down a tablet sufficient amount of liquid (from 0,5 to 1 glasses), it is possible to accept before food or between meals. Doses are defined by character and weight of an infection, and also sensitivity of the estimated activator.

The patient with normal or moderately reduced function of kidneys (clearance of creatinine> of 50 ml/min.) recommends the following mode of a drug dosing:
Sinusitis: on 500 mg once a day — 10 - 14 days.

Exacerbation of chronic bronchitis: on 250 mg or on 500 mg once a day — 7-10 days.

Community-acquired pneumonia: on 500 mg 1-2 times a day — 7-14 days.

Uncomplicated infections of urinary tract: on 250 mg once a day — 3 days.

Prostatitis: on 500 mg once a day — 28 days.

The complicated infections of urinary tract, including pyelonephritis: on 250 mg once a day — 7-10 days.

Infections of skin and soft tissues: on 250 mg once a day or on 500 mg 1-2 times a day — 7-14 days.

Septicaemia/bacteremia: on 250 mg or on 500 mg 1-2 times a day — 10-14 days.

Intraabdominal infection: on 250 mg or on 500 mg once a day — 7-14 days (in a combination with the antibacterial drugs operating on anaerobic flora).

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

At an abnormal liver function special selection of doses as levofloxacin is metabolized in a liver only in extremely insignificant measure is not required.

As well as at use of other antibiotics, treatment by the drug Tablet Levofloxacin on 250 mg and 500 mg is recommended to continue not less than 48 — 78 hours after normalization of body temperature or after laboratory confirmed recovery.

Features of use:

Levofloxacin cannot be applied to treatment of children and teenagers in view of probability of damage of joint cartilages.

At treatment of patients of senile age it must be kept in mind that patients of this group often suffer from renal failures (see the section "Route of Administration and Doses").

At the heavy pneumonia caused by pneumococci, levofloxacin can not give optimum therapeutic effect. The hospital infections caused by certain activators (P. aeruginosa) can demand the combined treatment.

During treatment by the drug Levofloxacin 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.

In spite of the fact that the photosensitization is noted at use of a levofloksatsin 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.

At suspicion of pseudomembranous colitis it is necessary to cancel immediately levofloxacin 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 Levofloxacin use (first of all an Achilles tendon inflammation) can lead to a rupture of sinews. Patients of advanced age are more inclined to a tendinitis. Treatment by glucocorticosteroids most likely increases risk of a rupture of sinews. At suspicion on a tendinitis it is necessary to stop immediately treatment by the drug Levofloxacin 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). In this regard, treatment of such patients levofloksatsiny should be carried out carefully.

Such side effects of the drug Levofloxacin as dizziness or catalepsy, drowsiness and visual disturbances (see also undressed "Side effect), can worsen reactionary ability and ability to concentration of attention. It can represent a certain risk in situations when these abilities have special value (for example, when driving, at service of cars and mechanisms, when working in unstable situation).

Side effects:

Frequency of this or that side effect is defined by means of the following table:
Frequency Emergence of side effects
often: at 1-10 patients from 100
sometimes: less, than at 1 patient from 100
seldom: less, than at 1 patient from 1 000
very seldom: less, than at 1 patient from 10 000
separate cases less than 0,01%

Allergic reactions: Sometimes: itch and erubescence. Seldom: the general reactions of hypersensitivity (anaphylactic and anaphylactoid reactions) with such symptoms as a small tortoiseshell, narrowing of bronchial tubes and is possible - heavy suffocation. Seldom or never: cutaneous dropsies and mucous membranes (for example, in a face and a throat), sudden falling of arterial pressure and shock; hypersensitivity to solar and ultraviolet radiation (see. "Special instructions"); allergic pneumonitis; vasculitis. In some cases: a heavy enanthesis with blistering, for example, Stephens-Johnson's syndrome, a toxic epidermal necrolysis (Lyell's disease) and an exudative mnogoformny erythema. Easier skin reactions can sometimes precede the general reactions of hypersensitivity. The reactions called above can develop after the first dose in a few minutes or hours after administration of drug.

From the alimentary system: Often: nausea, diarrhea, increase in activity of enzymes of a liver (for example, alaninaminotranspherases and aspartate aminotransferases). Sometimes: appetite loss, vomiting, abdominal pains, digestion disturbances. Seldom: diarrhea with impurity of blood which seldom or never can be a sign of an inflammation of intestines and even pseudomembranous colitis (see. "Special instructions"). Very seldom: hepatic reactions (for example, liver inflammation).

From a metabolism: Very seldom: the decrease in concentration of glucose in blood having special value for the patients suffering from a diabetes mellitus; possible signs of a hypoglycemia: increase in appetite, nervousness, perspiration, shiver. Experience of use of other hinolon demonstrates that they are capable to cause a porphyria aggravation in the patients who already have this disease. The similar effect is not excluded also at drug use levofloxacin.

From a nervous system: Sometimes: headache, dizziness and/or catalepsy, drowsiness, sleep disorders. Seldom: concern, paresthesias in hands, a shiver, psychotic reactions like hallucinations and depressions, the excited state, spasms and confusion of consciousness. Very seldom: vision disorder and hearing, disturbances of flavoring sensitivity and sense of smell, decrease in tactile sensitivity.

From cardiovascular system: Seldom: the strengthened heartbeat, a lowering of arterial pressure. Very seldom: (shocklike) vascular collapse. In some cases: lengthening of an interval of Q-T.

From a musculoskeletal system: Seldom: damages of sinews (including a tendinitis), joint and muscular pains. Very seldom: rupture of sinews (for example, Achilles tendon); this side effect can be observed within 48 hours after an initiation of treatment and can have bilateral character (see. "Special instructions"); the muscular weakness having special value for patients with a bulbar syndrome. In some cases: damages of muscles (рабдомиолиз).

From an urinary system: Seldom: increase in level of bilirubin and creatinine in blood serum. Very seldom: deterioration in function of kidneys up to an acute renal failure, intersticial nephrite.

From bodies of a hemopoiesis: Sometimes: increase in number of eosinophils, reduction of number of leukocytes. Seldom: neutropenia; thrombocytopenia that can be followed by strengthening of bleeding. Very seldom: agranulocytosis and development of heavy infections (resistant or recurrent fervescence, deterioration in health). In some cases: hemolitic anemia; pancytopenia. Other side effects: Sometimes: general weakness. Very seldom: fever.

Any antibioticotherapia can cause changes of microflora which normal is present at the person. For this reason there can be a strengthened reproduction of the bacteria and mushrooms steady against the applied antibiotic which in rare instances can demand additional treatment.

Interaction with other medicines:

There are messages on the expressed reduction of the threshold of convulsive readiness at simultaneous use of the hinolon and substances capable in turn to reduce a cerebral threshold of convulsive readiness. Equally it concerns also simultaneous use of hinolon and theophylline.

Effect of the drug Levofloxacin is considerably weakened at simultaneous use with sukralfaty. The same occurs also at simultaneous use magnesium - or aluminum-bearing antiacid means, and also iron salts. It is necessary to accept levofloxacin not less, than in 2 hours prior to or in 2 hours after reception of these means. With calcium carbonate of interaction it is not revealed.

At simultaneous use of antagonists of vitamin K control of coagulant system of blood is necessary.

Removal (renal clearance) of a levofloksatsin is slightly slowed down under the influence of Cimetidinum and a probenitsid. It should be noted that this interaction has practically no clinical value. Nevertheless, at simultaneous use of medicines like probenitsid and Cimetidinum blocking a certain way of removal (canalicular secretion), treatment levofloksatsiny it is necessary to carry out with care. It concerns first of all patients with bounded function of kidneys.

Levofloxacin slightly increases a cyclosporine elimination half-life.

Reception of glucocorticosteroids increases risk of a rupture of sinews.

Contraindications:

- hypersensitivity to a levofloksatsin or to other hinolona;
- a renal failure (at clearance of creatinine less than 20 ml/min. - in connection with impossibility of dosing of a dosage form);
- epilepsy;
- damages of sinews at earlier carried out treatment of a hinolonama;
- children's and teenage age (up to 18 years);
- pregnancy and period of a lactation.

With care. Drug should be used with care at elderly people in connection with high probability of existence of the accompanying depression of function of kidneys, at deficit glyukozo-6-fosfatdegidrogenazy.

Overdose:

Symptoms of overdose of the drug Levofloxacin are shown at the level of the central nervous system (confusion of consciousness, dizziness, disturbances of consciousness and attacks of spasms as epipripadok). Besides, gastrointestinal frustration (for example, nausea) and erosive damages of mucous membranes, lengthening of an interval of Q-T can be noted.

Treatment has to be symptomatic. Levofloxacin is not removed by means of dialysis (a hemodialysis, peritoneal dialysis and continuous peritoneal dialysis). The specific antidote does not exist.

Storage conditions:

List B. In the dry, protected from light place, at a temperature not over 25 ºС. To store in the place, unavailable to children. Period of validity: 2 years. Not to use after expiry date.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, on 250 mg and 500 mg. On 5 or 10 tablets in a blister strip packaging or to bank polymeric. For a dosage of 250 mg: 1 blister strip packaging or to 1 bank together with the application instruction is placed in a pack from a cardboard. For a dosage of 500 mg: 1 either 2 blister strip packagings or to 1 bank together with the application instruction place in a pack from a cardboard.