Levofloxacin - Teva

General characteristics. Structure:

Contains in 1 tablet: active agent levofloxacin (levofloksatsina гемигадрат) 500,00 (512,46) mg; excipients: silicon dioxide of colloid 12,00 mg, hypro rod of 28,00 mg, sodium carboxymethylstarch, type A of 55,00 mg, talc of 55,20 mg, croscarmellose sodium of 20,60 mg, magnesium stearate of 6,74 mg, cover of Opadray 15B26688 brown (gipromelloza of 2910 3 WEDNESDAY of 4,760 mg, gipromelloza of 2910 6 WEDNESDAY of 4,760 mg, titanium mg E171 3,044 dioxide, macrogoal-400 of 1,120 mg, mg polysorbate-800,140, dye ferrous oxide of yellow E172 0,120 mg, dye ferrous oxide of red E172 0,043 mg, dye ferrous oxide of black E172 0,013 mg).

Description: kapsuloobrazny tablets, light pink with a yellowish shade, film coated, from a tablet, risky on both parties, with an engraving of "LX" and "500" on one party of a tablet.

Pharmacological properties:

Pharmacodynamics. Optically active left-handed isomer of an ofloksatsin - L-ofloxacin (S-(-)-enantiomer). Possesses a wide range of antimicrobic activity. Blocks bacterial topoisomerase IV and DNK-girazu (topoisomerase II). Breaks superspiralling and a stitching of ruptures of DNA, causes profound morphological changes in cytoplasm, a cell wall. In the concentration equivalent or exceeding the minimum overwhelming concentration (MOC), most often has bactericidal effect. The main mechanism of development of resistance is connected with gyr-A gene mutation with possible development of cross resistance between levofloksatsiny and other ftorkhinolona. Cross resistance between levofloksatsiny and antibacterial drugs of other classes usually does not arise.
Sensitive microorganisms: aerobic gram-positive microorganisms - Corynebacterium diphtheriae, Enterococcus spp., including Enterococcus faecalis, Listeria monocytogenes, Staphylococcus spp. (koagulazootritsatelny metitsillinchuvstvitelny / leykotoksinsoderzhashchy / moderately sensitive strains), including Staphylococcus aureus (metitsillinchuvstvitelny strains), Staphylococcus epidermidis (metitsillinchuvstvitelny strains), Streptococcus spp. groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae (penitsillinchuvstvitelny / moderately sensitive / resistant strains), Streptococcus pyogenes, Streptococcus spp. viridans groups (penitsillinchuvstvitelny / resistant strains); aerobic gram-negative microorganisms - Acinetobacter spp., including Acinetobacter baumannii, Acinetobacillus actinomycetecomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter spp., including Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (ampitsillinchuvstvitelny / resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp., including Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis (which are producing and not producing some beta lactamazu strains), Morganella morganii, Neisseria gonorrhoeae (which are producing and not producing a penicillinase strains), Neisseria meningitidis, Pasteurella spp., including Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida, Proteus vulgaris, Providencia spp., including Providencia rettgeri, Providencia stuartii, Pseudomonas spp. including Pseudomonas aeruginosa, Serratia spp., including Serratia marcescens, Salmonella spp.; anaerobic microorganisms - Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterium spp., Veilonella spp.; other microorganisms - Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Legionella spp., Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.
Moderately sensitive microorganisms (MPK more than 4 mg/l): aerobic gram-positive microorganisms - Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis (metitsillinrezistentny strains), Staphylococcus haemolyticus (metitsillinrezistentny strains); aerobic gram-negative microorganisms - Burkhoideria cepacia, Campylobacter jejuni, Campylobacter coli; anaerobic microorganisms - Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp., Porphyromonas spp.
Resistant microorganisms (MPK more than 8 mg/l): aerobic gram-positive microorganisms - Corynebacterium jeikeium, Staphylococcus aureus (metitsillinrezistentny strains), other Staphylococcus spp. (koagulazootritsatelny metitsillinrezistentny strains); aerobic gram-negative microorganisms - Alcaligenes xylosoxidane; other microorganisms - Mycobacterium avium.

Pharmacokinetics. Absorption
At intake levofloxacin is quickly and almost completely soaked up from the digestive tract (DT). At a single dose of 500 mg the maximum concentration (Cmax) in a blood plasma is reached in 1 h. Absolute bioavailability about 100%. Meal slightly influences the speed and completeness of absorption.
Distribution
Communication with proteins of plasma makes 30-40%. Levofloxacin well gets into bodies and fabrics: lungs, a mucous membrane of bronchial tubes, a phlegm, bodies of an urinary system, generative organs, a bone tissue, a prostate, polymorphonuclear leukocytes, alveolar macrophages, in insignificant quantities gets into liquor.
At intake of 500 mg 2 times a day are noted insignificant accumulation of drug in an organism.
Metabolism
In a liver a small part of a levofloksatsin is metabolized with formation of a demetillevofloksatsin and N-oxide of a levofloksatsin. The molecule of a levofloksatsin of a stereokhimicheska is stable and is not subject to chiral inversion.
Removal
After reception in a single dose of 500 mg the elimination half-life (T1/2) makes 6-8 h.
It is removed preferential by kidneys by glomerular filtering and canalicular secretion. More than 85% of a dose are removed by kidneys in not changed look. Less than 5% of a dose cosecrete kidneys in the form of metabolites.
Pharmacokinetics in special clinical cases
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). At KK of 50-80 ml/min. T1/2 makes 9 h, at KK of 20-40 ml/min. T1/2 makes 27 h, at KK less than 20 ml/min. of T1/2 make 35 h.

Indications to use:

The Infektsionnovospalitelny diseases caused by microorganisms, sensitive to a levofloksatsin:
- acute bacterial sinusitis;
- exacerbation of chronic bronchitis;
- community-acquired pneumonia;
- the complicated infectious diseases of kidneys and urinary tract, including pyelonephritis;
- chronic bacterial prostatitis;
- infections of skin and soft tissues.

Route of administration and doses:

In 1-2 times in days. The dose and duration of treatment are defined by character and weight of an infection, and also sensitivity of the estimated activator. A pill should be taken, without chewing and washing down with enough liquid (from ½ to 1 glasses). At selection of doses of a tablet it is possible to break on a dividing groove on equal parts. Drug can be accepted before food or at any time between meals.
Treatment by the drug Levofloxacin - Teva is recommended to continue during at least 48-72 h after normalization of body temperature or after a reliable eradikation of the activator.
Acute bacterial sinusitis: on 1 tablet (500 mg) of 1 times a day within 10-14 days.
Acute bronchitis and exacerbation of chronic bronchitis: on ½-1 to a tablet (250-500 mg) of 1 times a day within 7-10 days.
Community-acquired pneumonia: on 1 tablet (500 mg) 1-2 times a day within 7-14 days.
The complicated infectious diseases of kidneys and urinary tract, including pyelonephritis: on ½ tablet (250 mg) of 1 times a day within 7-10 days.
Chronic bacterial prostatitis: on 1 tablet (500 mg) of 1 times a day within 28 days.
Infections of skin and soft tissues: on 1 tablet (500 mg) 1-2 times a day within 7-14 days.
With an abnormal liver function of correction of the mode of dosing it is not required to patients.
Patients with a renal failure (KK less than 50 ml/min.) need correction of the mode of dosing depending on size KK.

First dose           of KK of 20-49 ml/min.    of KK of 10-19 ml/min.        of KK less than 10 ml/min.
                                                                                            (including a hemodialysis
                                                                                             and peritoneal
                                                                                             dialysis)
500                                                               mg 250 mg 250 mg 250 mg
each 12 hours     each 12 hours    each 24 hours        each 48 hours

500                                                               mg 250 mg 250 mg 250 mg
each 24 hours      each 24 hours        each 48 hours      each 48 hours

250                                                                mg 250 mg 250 mg 250 mg
each 24 hours      each 24 hours     each 48 hours      each 48 hours

After a hemodialysis or peritoneal dialysis introduction of additional doses is not required.
It is not required to patients of advanced age of correction of the mode of dosing.

Features of use:

At use of a levofloksatsin cases of a tendinitis which affects generally an Achilles tendon and can lead to its gap were observed. At patients of advanced age, and also at the accompanying use of GKS, the probability of development of a tendinitis and rupture of a sinew at use of a levofloksatsin increases. At suspicion on a tendinitis it is necessary to cancel immediately levofloxacin and to begin the corresponding treatment, having provided a condition of rest in the field of defeat.
At suspicion of pseudomembranous colitis (emergence of the diarrhea, in particular, expressed and/or with blood) it is necessary to cancel immediately levofloxacin and to begin the corresponding treatment.
During treatment levofloksatsiny development of an attack of spasms in patients with the previous damage of a brain is possible (including with a stroke or a severe injury of a brain).
At use of hinolon for patients with insufficiency glyukozo-6-fosfatdegidrogenazy hemolysis of erythrocytes is possible.
In need of use of a levofloksatsin for patients with a diabetes mellitus it is necessary to control concentration of glucose in blood.
Sometimes after reception of the first dose of a levofloksatsin development of the expressed, potentially dangerous reactions of hypersensitivity (a Quincke's disease, an acute anaphylaxis) is possible.
In spite of the fact that the photosensitization is noted at use of a levofloksatsin very seldom, for prevention of its development patients should avoid stay to the sun or UF-radiations.
At simultaneous use of a levofloksatsin and indirect anticoagulants it is necessary to control a condition of coagulant system of blood.
At reception of ftorkhinolon, including levofloxacin, development of psychotic reactions which very seldom when progressing can lead to suicide thoughts and potentially dangerous behavior is possible. At development of the similar phenomena administration of drug should be stopped.
At use of a levofloksatsin for patients who have the contributing factors to lengthening of an interval of QT it is necessary to conduct an electrocardiogram research to and in time treatments levofloksatsiny.
At reception of ftorkhinolon cases of development of touch or sensomotor peripheral neuropathy were observed. For prevention of development of irreversible effects at development of symptoms of peripheral neuropathy levofloxacin should be cancelled immediately.
At reception of a levofloksatsin at patients false positive results of tests for availability of opiates in urine are possible. For confirmation of a positive take of the test it is necessary to use more specific methods.
There are messages on exceptional cases of development of a liver failure against the background of treatment levofloksatsiny, first of all for patients with a serious illness, such as sepsis. At emergence of symptoms of an abnormal liver function, such as loss of appetite, jaundice, urine darkening, an itch or sensitivity of an abdominal wall at a palpation, levofloxacin should be cancelled.
At purpose of drug patients of advanced age should mean that patients of this group often have renal failures.

Influence on ability to driving of the car and to control of mechanisms
Possible development of side effects from the central nervous system and sense bodys can exert impact on ability to driving of the car, service of cars and mechanisms, when working in unstable situation.

Side effects:

Frequency of development of side reactions is classified according to WHO recommendations: often - not less than 1% and less than 10%; infrequently - not less than 0,1% and less than 1%; seldom - not less than 0,01% and less than 0,1%; very seldom - less than 0,01%, including isolated cases.
Infections and invasions: infrequently - accession of a fungal infection, growth of resistant microorganisms; very seldom - superinfection.
From the hemopoietic and lymphatic systems: infrequently - an eosinophilia, a leukopenia; seldom - a neutropenia, thrombocytopenia; very seldom - an agranulocytosis; isolated cases - hemolitic anemia, a pancytopenia, hemorrhages.
From a metabolism: very seldom - a hyperglycemia (the increased appetite, the increased sweating, a shiver), a hypoglycemia.
From a nervous system: infrequently - sleeplessness, nervousness, dizziness, a headache, drowsiness; seldom - uneasiness, a depression, psychotic reactions, agitation, opacification of consciousness, a spasm, a tremor, paresthesias; very seldom - sensomotor peripheral neuropathy, hallucinations, the psychotic reactions connected with causing harm by the patient to themselves, suicide behavior, extrapyramidal symptoms and disturbances of muscular coordination.
From sense bodys: very seldom - vision disorders, decrease in hearing, a sonitus, disturbance of sense of smell, flavoring and tactile sensitivity.
From cardiovascular system: seldom - a lowering of arterial pressure, a vascular collapse, tachycardia; very seldom - lengthening of an interval of QT, a ciliary arrhythmia.
From the alimentary system: often - nausea, diarrhea, increase in activity of "hepatic" transaminases and an alkaline phosphatase in a blood plasma; infrequently - vomiting, anorexia, an abdominal pain, dyspepsia, dysbacteriosis, a meteorism, a lock, a hyperbilirubinemia; seldom - hemorrhagic diarrhea; very seldom pseudomembranous colitis, jaundice, hepatitis, liver failure.
From an urinary system: infrequently - a hypercreatinemia; very seldom - intersticial nephrite, an acute renal failure.
Allergic reactions: infrequently - rash, an itch; seldom - a small tortoiseshell, a dermahemia; very seldom - anaphylactic and anaphylactoid reactions, including shock, a Quincke's disease, a photosensitization, a malignant exudative erythema (Stephens-Johnson's syndrome), a toxic epidermal necrolysis (Lyell's disease), an exudative multiformny erythema, a vasculitis, a bronchospasm, an allergic intersticial pneumonitis.
From a musculoskeletal system: seldom - disturbances from sinews, including an Achilles tendon tendinitis, an arthralgia, a mialgiya, muscular weakness; very seldom - a rupture of sinews; frequency is not established - рабдомиолиз.
Others: infrequently - an adynamy, weakness; very seldom - persistent fever, a porphyria aggravation.

Interaction with other medicines:

Absorption of a levofloksatsin considerably decreases at simultaneous use with sukralfaty, magnesium - or aluminum-bearing antiacid means, and also with iron salts (the interval between reception of a levofloksatsin and these medicines has to make not less than 2 h). From calcium are not revealed by a carbonate of interaction.
Hinolona can increase ability of drugs (including theophylline) to lower a threshold of convulsive readiness. At a concomitant use with fenbufeny higher concentration of a levofloksatsin (for 13%) were observed, than at monotherapy.
Removal of a levofloksatsin is slowed down under the influence of Cimetidinum (for 24%) and a probenetsida (for 34%).
Levofloxacin causes small increase in T1/2 of cyclosporine.
The concomitant use with glucocorticosteroids (GKS) increases risk of development of a rupture of sinews.
The concomitant use of a levofloksatsin with peroral anticoagulants increases time of coagulation and/or bleeding.
Levofloxacin at simultaneous use with the antiarrhytmic drugs IA and III of classes, tricyclic antidepressants, macroleads can cause lengthening of an interval of QT.

Contraindications:

Hypersensitivity to a levofloksatsin, to other hinolona or other components of drug; epilepsy, including in the anamnesis; the damages of sinews connected with reception of ftorkhinolon in the anamnesis; children's and teenage age up to 18 years; pregnancy; breastfeeding period,

With care
Renal failure (KK less than 50 ml/min.); hemodialysis and peritoneal dialysis; deficit glyukozo-6-fosfatdegidrogenazy; diabetes mellitus; abnormal liver function; the accompanying reception of the antiarrhytmic drugs IA and III of classes, tricyclic antidepressants, macroleads; disturbance of electrolytic balance; advanced age; cardiovascular diseases, including chronic heart failure, myocardial infarction; lengthening of an interval of QT; bradycardia; the brain diseases which are followed by reduction of the threshold of convulsive activity; mental diseases, including in the anamnesis; peripheral neuropathy.

Overdose:

Symptoms: nausea, erosive damages of mucous membranes of a GIT, dizziness, opacification of consciousness and attacks of spasms as epileptic seizures.
Treatment: carry out symptomatic therapy, monitoring of an ECG. The specific antidote does not exist. The hemodialysis is not effective.

Storage conditions:

At a temperature not above 25 °C in the place protected from light. To store in the place, unavailable to children. Period of validity 3 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 500 mg.
On 7 tablets in blisters from PVC/PVDH / aluminum foil;
1 or 2 blisters together with the application instruction in a cardboard pack.