Лефлобакт

General characteristics. Structure:

Solution for infusions of 0.5% of chartreuse color, transparent.

Active ingredient:                         1 ml    1 фл.
levofloxacin (in the form of a gemigidrat)    5   mg 500 mg

Excipients: sodium chloride - 900 mg, water for and - to 100 ml.

Pharmacological properties:

Лефлобакт® – the synthetic antimicrobic bactericidal drug of a broad spectrum of activity from group of ftorkhinolon containing levofloxacin in quality of active agent – left-handed isomer of an ofloksatsin. In comparison with ofloksatsiny levofloxacin has wider range of antibacterial activity which is in addition including various streptococci, including pneumococci.

Levofloxacin blocks bacterial DNK-girazu (topoisomerase II) and topoisomerase IV, breaks superspiralling and a stitching of ruptures of DNA, inhibits DNA synthesis, causes profound morphological changes in cytoplasm, a cell wall and a membrane of microorganisms, but does not influence enzymes of cells of a human body.

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

Are sensitive to a levofloksatsin (MPK <2 mg/ml)

Gram-positive aerobic microorganisms: Corynebacterium diphtheriae, Enterococcus faecalis, Enterococcus spp. (except Enterococcus faecium), Listeria monocytogenes, Staphylococcus spp. koagulazonegativny (the strains sensitive and moderately sensitive to Methicillinum), Staphylococcus aureus (Methicillinum - sensitive strains), Staphylococcus epidermidis (Methicillinum - sensitive strains), Streptococcus spp. the groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae (sensitive, moderately sensitive and resistant to penicillin), Streptococcus pyogenes, Streptococcus of the Viridans group (sensitive and resistant to penicillin).

Gram-negative aerobic microorganisms: Acinetobacter spp. (including Acinetobacter baumannii, Acinetobacter calcoaceticus), Actinobacillus actinomycetemcomitans, Bordetella pertussis, Citrobacter diversus, Citrobacter freundii, Eikenella corrodens, Enterobacter spp. (including Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (the strains sensitive and resistant to ampicillin), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (including Klebsiella pneumoniae, Klebsiella oxytoca), Moraxella catarrhalis (which are producing and not producing some β-lactamazu strains), Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella spp. (including Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas aeruginosa, Pseudomonas spp., Salmonella spp., Serratia spp. (including Serratia marcescens).

Anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterum spp., Veillonella spp.

Other microorganisms: Bartonella spp., Chlamydia (Chlamydophila) pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella spp. (including Legionella pneumophila), Mycobacterium spp. (including Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma pneumoniae, Mycoplasma hominis, Rickettsia spp., Ureaplasma urealyticum.

Are moderately sensitive to a levofloksatsin (MPK of ≥4 mg/l)

Gram-positive aerobic microorganisms: Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis (Methicillinum - resistant strains), Staphylococcus haemolyticus (Methicillinum - resistant strains).

Gram-negative aerobic microorganisms: Burkholderia cepacia, Campylobacter jejuni, Campylobacter coli.

Anaerobic microorganisms: Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp., Porphyromonas spp.

Are steady against a levofloksatsin (MPK ≥ 8 mg/ml)

Gram-positive aerobic microorganisms: Corynebacterium jeikeium, Staphylococcus aureus (Methicillinum - resistant strains), Staphylococcus spp. (koagulazonegativny Methicillinum - resistant strains).

Gram-negative aerobic microorganisms: Alcaligenes xylosoxidans.

Other microorganisms: Mycobacterium avium.

 

Pharmacokinetics. Distribution

The pharmacokinetics of a levofloksatsin has linear character and is predictable at single and multiple administration of drug. The plasma profile of concentration of a levofloksatsin in/in introductions is similar later to that at reception of tablets. Therefore peroral and in/in a way of introduction can be considered as interchangeable.

Linkng with proteins of plasma - 30-40%. Well gets into bodies and fabrics: lungs, mucous membrane of bronchial tubes, phlegm, bodies of an urinary system, generative organs, bone tissue, cerebrospinal fluid, prostate, polymorphonuclear leukocytes, alveolar macrophages.

Average Vd of a levofloksatsin makes from 89 to 112 l after 500 mg, one-time and repeated in/in introductions. Pharmacokinetic characteristics after one-time in/in introductions of a levofloksatsin in a dose of 500 mg, respectively, make: Cmax - 6.2±1 mkg/ml, time necessary for achievement of Cmax - 1±0.1 h.

Metabolism

Levofloxacin is slightly metabolized in a liver (about 5% of the entered dose).

Removal

T1/2 is 6.4±0.7 h. Levofloxacin is preferential emitted with kidneys in not changed look.

Pharmacokinetics in special clinical cases

At a renal failure reduction of clearance of drug and its removal through kidneys depends on extent of decrease in clearance of creatinine.

Indications to use:

The infectious and inflammatory diseases caused by bacteria, sensitive to a levofloksatsin:

— lower respiratory tracts (community-acquired pneumonia);

— urinary tract and kidneys (including acute pyelonephritis);

— chronic bacterial prostatitis;

— skin and soft tissues (the suppurated atheromas, abscess, furuncles);

— intraabdominal infections;

— the septicaemia/bacteremia connected with the indications stated above.

Route of administration and doses:

In/in, kapelno, slowly 1-2 Doses are defined by character and weight of an infection, and also sensitivity of the estimated activator.

Patients with normal function of kidneys (clearance of creatinine> of 50 ml/min.) can recommend the following mode of a drug dosing.

Community-acquired pneumonia: on 500 mg (100 ml of solution) 1-2 within 7-14 days.

Uncomplicated infections of urinary tract: on 250 mg (50 ml of solution) of 1 times / within 3 days.

The complicated infections of urinary tract (including acute pyelonephritis): on 250 mg (50 ml of solution) of 1 times / within 7-10 days.

Infections of skin and soft tissues (the suppurated atheromas, abscess, furuncles): on 500 mg (100 ml of solution) 2 within 7-14 days.

Chronic bacterial prostatitis: 500 mg (100 ml of solution) of 1 times / within 28 days.

Septicaemia/bacteremia: on 500 mg (100 ml of solution) 1-2 within 10-14 days

Intraabdominal infection: on 500 mg (100 ml of solution) of 1 times / within 7-14 days (in a combination with the antibacterial drugs operating on anaerobic flora).

Patients with a renal failure need correction of the mode of dosing depending on the size of clearance of creatinine.

Clearance of creatinine                                           dosing Mode
                                           250 mg / 24 h                   500 mg / 24 h                   500 mg / 12 h
                                     first dose: 250 mg        first dose: 500 mg       first dose: 500 mg
50-20
ml/min.                        then - on 125 mg / 24 h    then - on 250 mg / 24 h     then - on 250 mg / 12 h
19-10
ml/min.                        then - on 125 mg / 48 h    then - on 125 mg / 24 h     then - on 125 mg / 12 h
<10 ml/min.                then - on 125 mg / 48 h    then - on 125 mg / 24 h      then - on 125 mg / 24 h
(including a hemodialysis and DAPD1)

1 - after a hemodialysis or the long out-patient peritoneal dialysis (LOPPD) 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.

Infusion solution of a levofloksatsin of 500 mg (100 ml) is entered in/in kapelno slowly. Duration of infusion of 1 bottle of solution of a levofloksatsin of 500 mg (100 ml) has to make not less than 60 min. Later in/in introductions in several days transition to intake in the same dose is possible.

Treatment levofloksatsiny is recommended to continue not less than 48-72 p after normalization of body temperature or after a reliable eradikation of the activator.

Features of use:

At the heavy pneumonia caused by pneumococci, the therapeutic effect of Leflobakt can be insufficient.

Duration in/in infusion of 500 mg (100 ml of infusion solution) has to make not less than 60 min.

During infusion in some cases can be observed a heart consciousness; tranzitorny decrease in the ABP. At the expressed decrease in the ABP infusion is immediately stopped.

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, allergic reactions 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 injury) development of spasms is possible, at insufficiency glyukozo-6-fosfatdegidrogenazy - risk of development of hemolysis.

As levofloxacin is excreted mainly through kidneys, obligatory control of function of kidneys, and also correction of the mode of dosing is required from patients with a renal failure.

It was reported about very exceptional cases of lengthening of an interval of QT at the patients receiving ftorkhinolona including levofloxacin. At use of ftorkhinolon, including levofloxacin, it is necessary to be careful at patients with the known risk factors of lengthening of an interval of QT: advanced age; disturbance of electrolytic balance (hypopotassemia, hypomagnesiemia); syndrome of inborn lengthening of an interval of QT; heart diseases (heart failure, myocardial infarction, bradycardia); a concomitant use of the medicines capable to extend QT interval.

At the patients receiving ftorkhinolona including levofloxacin, the touch and sensory-motor peripheral neuropathy which beginning can be bystry was noted. If the patient has neuropathy symptoms, use of a levofloksatsin has to be stopped. It minimizes possible risk of development of irreversible changes.

During treatment it is necessary to avoid alcohol intake.

Influence on ability to driving of motor transport and to control of mechanisms

During treatment it is necessary to refuse driving and potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From the alimentary system: nausea, vomiting, diarrhea, a loss of appetite, an abdominal pain, pseudomembranous colitis, increase in activity of hepatic transaminases, a hyperbilirubinemia, hepatitis, dysbacteriosis, a heavy liver failure, including cases of development of an acute liver failure, especially at patients with a serious basic disease (for example, at sepsis).

From cardiovascular system: decrease in the ABP, vascular collapse, tachycardia, lengthening of an interval of QT.

From a metabolism: a hypoglycemia (increase in appetite, the increased sweating, a shiver), porphyria attacks.

From a nervous system: a headache, the dizziness, weakness, drowsiness, sleeplessness, paresthesias, a peripheral touch and sensomotor neuropathy, uneasiness, fear, psychotic reactions self-damaging behavior including suicide thoughts and actions, hallucinations, confusion of consciousness, a depression, motive frustration, spasms, a tremor, extrapyramidal frustration, agitation (excitement), nightmares.

From sense bodys: an ageusia, a dysgeusia (food faddism), loss of flavoring feelings, a parosmiya (frustration of feeling of a smell, especially subjective feeling of the smell which is objectively absent), including loss of sense of smell, вертиго (feeling of a deviation or spinning or own body or surrounding objects), a ring in ears, decrease in hearing.

From a musculoskeletal system: arthralgia, myasthenia, mialgiya, rupture of sinews, tendinitis, рабдомиолиз.

From an urinary system: giperkreatininemiya, intersticial nephrite, acute renal failure.

From bodies of a hemopoiesis: eosinophilia, hemolitic anemia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, pancytopenia, hemorrhages.

Allergic reactions: itch, hyperemia, cutaneous dropsy and mucous membranes, small tortoiseshell, malignant exudative erythema (Stephens-Johnson's syndrome), toxic epidermal necrolysis (Lyell's disease), bronchospasm, suffocation, asthma, acute anaphylaxis, allergic pneumonitis, vasculitis.

Local reactions: phlebitis and periphlebitis.

Others: porphyria aggravation, photosensitization, persistent fever, development of superinfection, adynamy.

Interaction with other medicines:

At the combined treatment fenbufeny and similar to it NPVP, theophylline medicine can raise a threshold of convulsive readiness.

GKS increase risk of a rupture of sinews (especially at advanced age).

Removal of a levofloksatsin is slightly slowed down under the influence of Cimetidinum and a probenetsid.

Levofloxacin causes small increase in T1/2 of cyclosporine from a blood plasma.

At simultaneous use with warfarin the prothrombin time and risk of bleeding increases (careful monitoring of MNO, prothrombin time and other indicators of coagulation, and also monitoring of possible symptoms of bleeding is necessary).

Ethanol can strengthen side effects from TsNS (dizziness, drowsiness).

At the patients with a diabetes mellitus receiving peroral hypoglycemic means or insulin against the background of reception of a levofloksatsin are possible hypo - and hyper glycemic states (careful monitoring of concentration of glucose in blood is recommended).

At simultaneous use with the drugs extending QT interval (antiarrhytmic drugs of classes I A and III, tricyclic and tetracyclic antidepressants, neuroleptics, macroleads, antifungal, derivative an imidazole, some antihistaminic, including астемизол, терфенадин, эбастин) lengthening of an interval of QT is possible.

Solution for infusions is compatible from 0.9% solution of sodium of chloride, 5% solution of a dextrose (glucose), 2.5% Ringer's solution to a dextrose, the combined solutions for parenteral food (amino acids, carbohydrates, electrolytes).

It is impossible to mix with the heparin and solutions having alkali reaction.

Contraindications:

— epilepsy;

— damage of sinews at earlier carried out treatment of a hinolonama;

— pregnancy;

— lactation period;

— children's and teenage age (up to 18 years);

— hypersensitivity (including to other hinolona).

With care

— advanced age, in connection with high probability of existence of the accompanying depression of function of kidneys (deficit glyukozo-6-fosfatdegidrogenazy);

— at patients with damage of a brain in the anamnesis (a stroke or a severe injury) (development of spasms is possible);

— at patients with a pseudoparalytic myasthenia is (myasthenia gravis);

— patients with the known risk factors have lengthenings of an interval of QT;

— at patients with a diabetes mellitus;

— predisposition to convulsive reactions (atherosclerosis of vessels of a brain, disturbance of cerebral circulation (in the anamnesis);

— organic diseases of TsNS;

— renal failure;

— syndrome of inborn lengthening of an interval of QT;

— heart diseases (heart failure, myocardial infarction, bradycardia);

— an electrolytic imbalance (for example, at a hypopotassemia, a hypomagnesiemia);

— psychoses and other mental disturbances in the anamnesis;

— hepatic porphyria;

— a concomitant use of the medicines extending QT interval (antiarrhytmic drugs of classes I A and III, tricyclic and tetracyclic antidepressants, neuroleptics, macroleads, antifungal, derivative an imidazole, some antihistaminic, including астемизол, терфенадин, эбастин) and reducing a threshold of convulsive readiness of a brain (фенбуфен, theophylline).

It is not recommended to appoint levofloxacin along with other means extending QT interval since the risk of development of cardiac arrhythmias increases.

 

Drug LEFLOBAKT® use solution for infusions at pregnancy and feeding by a breast

Contraindicated at pregnancy. For the period of treatment it is necessary to stop breastfeeding.

 

Use at abnormal liver functions

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

 

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               of 250 mg / 24 h                       500 mg / 24 h                  500 mg / 12 h 
                                      first dose: 250 mg           first dose: 500 mg       first dose: 500 mg
50-20 ml/min.               then - on 125 mg / 24 h         then - 250 mg / 24 h        then - 250 mg / 12 h
19-10 ml/min.              then - on 125 mg / 48 h          then - 125 mg / 24 h        then - 125 mg / 12 h
<10 ml/min.                then - on 125 mg / 48 h        then - 125 mg / 24 h        then - 125 mg / 24 h
(including a hemodialysis and DAPD1)
1 = after a hemodialysis or the long out-patient peritoneal dialysis (LOPPD) introduction of additional doses is not required.

Use for elderly patients

With care.

Use for children

It is contraindicated to children aged up to 18 years.

Overdose:

Symptoms: confusion of consciousness, dizziness, spasms, lengthening of an interval of QT.

Treatment: symptomatic, dialysis is inefficient.

Storage conditions:

Drug should be stored in protected from light, the place, unavailable to children, at a temperature from 15 °C to 25 °C.

At room lighting infusion solution can be stored without svetozashchita no more than 3 days. Freezing is inadmissible. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

100 ml - bottles glass (1) - packs cardboard.
100 ml - bottles glass (1) - packs cardboard.