Leflobact - instructions for use, dose, side effects, contraindications

Leflobact is a synthetic antimicrobial bactericidal broad-spectrum drug from the group of fluoroquinolones, containing as an active substance levofloxacin - the left-handed isomer of ofloxacin. In comparison with ofloxacin, levofloxacin has a broader spectrum of antibacterial activity, in addition Including various streptococci, incl. pneumococci.

Levofloxacin blocks bacterial DNA-gyrase (topoisomerase II) and topoisomerase IV, disrupts supercoiling and cross-linking of DNA gaps, inhibits DNA synthesis, causes deep morphological changes in the cytoplasm, cell wall and membrane of microorganisms, but does not affect the enzymes of cells in the human body.

Levofloxacin is active against most strains of microorganisms both in conditions in vitro and in vivo.

In vitro:

Sensitive to levofloxacin (minimal suppressive concentration (MIC) <2 mg / ml):

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

Gram-negative aerobic microorganisms: Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter spp., Actinobacillus actinomycetemcomitans, Bordetella pertussis, Citrobacter diversus, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (strains sensitive and resistant to ampicillin), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella spp., Moraxella catarrhalis (producing and non-producing beta-lactamase strains), Morganella morganii, Neisseria gonorrhoeae, 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 r marcescens, Serratia 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 spp., Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma pneumoniae, Mycoplasma hominis, Rickettsia spp., Ureaplasma urealyticum.

Moderately sensitive to levofloxacin (MIC> 4 mg / l):

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

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

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

Resistant to levofloxacin (MIC> 8 mg / ml):

Gram-positive aerobic microorganisms: Corynebacterium jeikeium: Staphylococcus aureus (methicillin-resistant strains), Staphylococcus spp. Coagulase-negative (methicillin-resistant strains).

Gram-negative aerobic microorganisms: Alcaligenes xylosoxidans.

Other microorganisms: Mycobacterium avium.

Pharmacokinetics:

The pharmacokinetics of levofloxacin are linear in nature and are predictable for single and multiple administration of the drug. The plasma profile of the concentrations of levofloxacin after intravenous administration is similar to that of tablets.

Therefore, oral and intravenous routes of administration may be considered interchangeable.

Binding to plasma proteins - 30-40%. It penetrates well into organs and tissues: lungs, bronchial mucosa, sputum, urinary system organs, genital organs, bone tissue, cerebrospinal fluid, prostate gland, polymorphonuclear leukocytes, alveolar macrophages.

The average volume of distribution of levofloxacin ranges from 89 to 112 liters after a single and multiple injection of 500 mg intravenously.

Pharmacokinetic characteristics after a single intravenous injection of levofloxacin in a dose of 500 mg, respectively, are: maximum concentration (6,2 ±1,0) μg / ml, the time required to reach the maximum concentration - (1,0 7± 0,1) h, half-life - (6.4 ± 0.7) h.

Levofloxacin is predominantly excreted by the kidneys unchanged.

In renal failure, the decrease in clearance of the drug and its excretion through the kidneys depends on the degree of decrease in creatinine clearance.

Indications:

Infectious-inflammatory diseases caused by susceptible to levofloxacin bacteria:

lower respiratory tract (community-acquired pneumonia);

urinary tract and kidneys (including acute pyelonephritis);

chronic bacterial prostatitis;

skin and soft tissues (festering atheromas, abscess, boils);

septicemia / bacteremia associated with the above indications;

intra-abdominal infections.

Contraindications:

hypersensitivity (including to other quinolones);

epilepsy;
the defeat of the tendons during the previous treatment with quinolones;
pregnancy;
lactation period; children and adolescence (up to 18 years).

Carefully:

Elderly, due to the high likelihood of concomitant decline in kidney function (glucose-6phosphate dehydrogenase).

In patients with brain damage; in history (stroke or severe trauma) (possible development of seizures).

In patients with pseudo-paralytic myasthenia gravis (myasthenia gravis); with known risk factors for lengthening the interval QT.

In patients with diabetes mellitus.

It is not recommended to appoint levofloxacin simultaneously with other means, extending the interval QT, as the risk of developing cardiac arrhythmias increases.

Predisposition to convulsive reactions (atherosclerosis of cerebral vessels, cerebral circulatory disorders (in anamnesis), organic diseases of the central nervous system), renal failure, congenital lengthening syndrome QT, heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (eg, hypokalemia, hypomagnesemia), psychoses and other mental disorders in the history, hepatic porphyria / simultaneous use of drugs that extend the interval QT, (antiarrhythmic IA and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal, imidazole derivatives, some antihistamines, including astemizole, terfenadine, ebastine) and lowering the threshold, convulsive readiness of the brain (fenbufen, theophylline).

Pregnancy and lactation:Contraindicated in pregnancy. For the duration of treatment, breastfeeding should be discontinued.

Dosing and Administration:

Intravenous drip slowly 1-2 times a day. Doses are determined by the nature and severity of the infection, as well as the suspected pathogen susceptibility.

Patients with normal renal function (creatinine clearance> 50 ml / min) can be recommended the following dosing regimen:

Community-acquired pneumonia: 500 mg of levofloxacin (100 ml of the preparation) 1-2 times a day, for 7-14 days;

Uncomplicated urinary tract infections: 250 mg of levofloxacin (50 ml of the drug) 1 once a day for 3 days;

Complicated urinary tract infections (including acute pyelonephritis): 250 mg of levofloxacin (50 ml of the drug) once a day for 7-10 days;

infections of the skin and soft tissues (festering atheromas, abscess, boils): 500 each mg (100 ml of the drug) 2 times a day, for 7-14 days.

chronic bacterial prostatitis: 500 mg of levofloxacin (100 ml of the drug) once a day, for 28 days;

septicemia / bacteremia: 500 mg of levofloxacin (100 ml of the drug) 1-2 times a day, for 10-14 days;

intra-abdominal infection: 500 mg of levofloxacin (100 ml of the drug) once a day day, for 7-14 days (in combination with antibacterial drugs acting on anaerobic flora).

Patients with impaired renal function require correction of the dosing regimen depending on the amount of creatinine clearance.

Dosing regimen:

Creatinine clearance	250mg / 24h.	500 mg / 24 hours.	500 mg / 12 hours;
Creatinine clearance	first dose: 250 mg	first dose: 500 mg	first dose: 500 mg
50-20 ml / min.	then: 125 mg to 125 mg / 24 hours.	then: 250 mg / 24 hours.	then: 250 mg / 12 hours.
19-10 ml / min.	Then for 125 mg / 48 hours.	then: 125 mg / 24 hours.	then: 125 mg / 12 hours.
<10 ml / min. (including hemodialysis and DAPD¹)	Then for 125 mg / 48 hours.	then: 125 mg / 24 hours.	then: 125 mg / 24 hours.

¹ - after hemodialysis or long-term outpatient peritoneal dialysis (DAPD) no additional doses are required.

If the liver function is not required, a special dose selection is required, since the leftfloxacin is metabolized in the liver only to a very small extent.

Infusion solution of levofloxacin 500 mg (100 ml) is administered intravenously drip slow.

The duration of infusion of 1 vial of levofloxacin 500 mg (100 ml) should be at least 60 minutes. After intravenous injection after a few days, it is possible to switch to ingestion at the same dose.

Treatment with levofloxacin is recommended to continue no less than 48-72 hours after the normalization of body temperature or after a reliable eradication of the pathogen.

Side effects:

From the digestive system: nausea, vomiting, diarrhea, decreased appetite, abdominal pain, pseudomembranous colitis; increased hepatic activity, transaminases, hyperbilirubinemia, hepatitis, dysbacteriosis, severe hepatic insufficiency, including cases of development of acute liver failure, especially in patients with severe underlying disease (eg, sepsis).

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

From the side of metabolism: hypoglycemia (increased appetite, increased sweating, trembling), attacks of porphyria.

From the side of the nervous system, headache, dizziness, weakness, drowsiness, insomnia, paresthesia, peripheral sensory and sensorimotor neuropathy, anxiety, fear, psychotic reactions, self-damaging behavior, including suicidal thoughts and actions, hallucinations, confusion, depression, motor disorders, convulsions, tremor, extrapyramidal disorders, agitation (agitation), nightmares.

From the sense organs(dysgeusia), loss of taste sensations, parosmia (odor disorder, especially subjective sense of smell, objectively absent), including loss of smell, vertigo (feeling of deflection or twisting or own body or surrounding objects), ringing in the ears, hearing loss.

From the musculoskeletal system: arthralgia, myasthenia gravis, myalgia, tendon rupture, tendonitis, rhabdomyolysis.

From the urinary system: hypercreatininemia, interstitial nephritis, acute renal failure.

From the hematopoiesis: eosinophilia, hemolytic anemia, leukopenia, neutropenia; agranulocytosis, thrombocytopenia, pancytopenia, hemorrhages.

Allergic reactions: itching, hyperemia, swelling of the skin and mucous membranes, urticaria, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis, bronchospasm, suffocation, dyspnea, anaphylactic shock, allergic pneumonitis, vasculitis.

Local Reactions: phlebitis and periphlebitis.

Other: aggravation of porphyria, photosensitivity, persistent fever, development of superinfection, asthenia.

Overdose:Symptoms: confusion, dizziness, convulsions, lengthening of the interval QT.
Treatment: symptomatic, dialysis is ineffective.

Interaction:

When combined with fenbufen and similar non-steroidal anti-inflammatory drugs, theophylline, the drug may increase the threshold of convulsive readiness.

Glucocorticoids increase the risk of rupture of tendons (especially in old age).

Removal of levofloxacin slightly slows down under the action of cimetidine and probenecid. Levofloxacin causes a slight increase in the half-life of cyclosporin from the blood plasma.

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

Alcohol can increase the side effects of the central nervous system (dizziness, drowsiness).

In patients with diabetes mellitus, receiving oral hypoglycemic agents or insulin, against the background of taking levofloxacin hypo- and hyperglycemic conditions are possible (careful monitoring of blood glucose concentration is recommended).

With simultaneous application with drugs that extend the interval QT (antiarrhythmic IA and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal, imidazole derivatives, some antihistamines, including astemizole, terfenadine, ebastine) it is possible to extend the interval QT.

Solution for infusion is compatible with 0.9 % solution of sodium chloride, 5 % solution of dextrose (glucose), 2.5% Ringer's solution with dextrose, combined solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).

Do not mix with heparin and solutions that have an alkaline reaction.

Special instructions:

In severe pneumonia caused by pneumococci, the therapeutic effect of Leflobact may be inadequate.

After normalization of body temperature, it is recommended to continue treatment of at least 48- 72h.

The duration of intravenous infusion of 500 mg (100 ml infusion solution) should be at least 60 minutes.

In the time of infusion in some cases may experience a palpitations; transient decrease in blood pressure. With a marked decrease in blood pressure, the infusion is immediately stopped.

During treatment, sunlight and artificial ultraviolet irradiation should be avoided to avoid damage to the skin (photosensitization).

When there are signs of tendinitis, pseudomembranous colitis, allergic reactions levofloxacin immediately cancel.

It should be borne in mind that in patients with a history of brain damage (stroke,severe trauma) may develop seizures, with insufficiency of glucose-6-fosfatdegidrogenazy - the risk of hemolysis.

As levofloxacin excreted mainly through the kidneys, in patients with. impaired renal function requires mandatory monitoring of renal function, as well as correction of the dosing regimen. Very rare cases of lengthening of the interval have been reported QT in patients who received fluoroquinolones, including levofloxacin. When using fluoroquinolones, including levofloxacin, caution should be exercised in patients with known risk factors for lengthening the interval QT: elderly age; electrolyte imbalance (hypokalemia, hypomagnesemia); congenital syndrome interval lengthening QT; heart disease (heart failure, myocardial infarction, bradycardia); simultaneous reception of drugs that can lengthen the interval QT. In patients receiving fluoroquinolones, including levofloxacin, was noted sensory and sensory-motor peripheral neuropathy, the beginning of which can be rapid. If the patient has symptoms of neuropathy, the use of levofloxacin should be discontinued.This minimizes the possible risk of irreversible changes.

During treatment, alcohol should be avoided.

Effect on the ability to drive transp. cf. and fur:During the treatment period, it is necessary to abandon the management of the car and potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Solution for infusions 5 mg / ml.

Packaging:To 100 ml in bottles of orange or colorless glass with a capacity of 100 ml, hermetically sealed with stoppers rubber, crimped caps.

For 100 ml in bottles of colorless glass with a capacity of 100 ml, hermetically sealed with stoppers rubber, crimped caps.

1 bottle or bottle is placed in a pack of cardboard with instructions for use and suspension polymer or without suspension.

35 bottles or bottles are placed in a box of corrugated cardboard with an equal number of instructions for use and suspension polymer or without suspension, for hospitals.

Storage conditions:

In the dark place at a temperature of 15 to 25 ° C. With room lighting, the infusion solution can be stored without light protection for a maximum of 3 days. Freezing is unacceptable.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:PL-000691

Date of registration:28.09.2011

The owner of the registration certificate:SYNTHESIS, OJSC SYNTHESIS, OJSC Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Information update date: & nbsp03.10.2015

Illustrated instructions

Instructions

Leflobact (Leflobact)