LEFLOBACT 500 mg 10 pcs. film-coated tablets

Leflobact 500 mg 10 pcs. film-coated tablets

pharmachologic effect

Leflobact® is a synthetic broad-spectrum antimicrobial bactericidal drug from the group of fluoroquinolones, containing levofloxacin, a levorotatory isomer of ofloxacin, as an active substance.
Compared to ofloxacin, levofloxacin has a wider spectrum of antibacterial activity, additionally including various streptococci, incl. pneumococci. Levofloxacin blocks bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, disrupts supercoiling and cross-linking of DNA breaks, inhibits DNA synthesis, causes profound morphological changes in the cytoplasm, cell wall and membrane of microorganisms, but does not affect the enzymes of human cells.

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

Sensitive to levofloxacin (MIC less than 2 mg/ml)

Gram-positive aerobic microorganisms: Corynebacterium diphtheriae, Enterococcus faecalis, Enterococcus spp. (except 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. groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae (sensitive, moderately sensitive and resistant to penicillin), Streptococcus pyogenes, Streptococcus 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 (strains sensitive and resistant to ampicillin), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (including Klebsiella pneumoniae, Klebsiella oxytoca), Moraxella catarrhalis (beta-lactamase producing and non-producing 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.

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, Campylobacter coli.

Anaerobic microorganisms: Bacteroides thetaiotaomicron, 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.

Composition and release form Leflobakt 500 mg 10 pcs. film-coated tablets

Tablet - 1 tablet:

Active substance: levofloxacin (in the form of levofloxacin hemihydrate) - 500 mg;
Excipients: calcium stearate - 3.7 mg, 7.4 mg, starch 1500 - 18.5 mg, 37.0 mg, potato starch - 31.8 mg, 63.6 mg, crospovidone (Kollidon CL-M) - 7.4 mg, 14.8 mg, povidone (low molecular weight medical polyvinylpyrrolidone 12600 ± 2700) - 5.8 mg, 11.6 mg, lactose monohydrate (milk sugar) - 26.87 mg, 53.73 mg, talc - 9 .25 mg, 18.5 mg, microcrystalline cellulose - 16.68 mg, 33.36 mg;
shell composition: hypromellose (hydroxypropyl methylcellulose) - 17.7 mg, 35.4 mg, macrogol (polyethylene glycol 4000) - 0.92 mg, 1.84 mg, titanium dioxide - 1.33 mg, 2.66 mg, tropeolin 0 - 0.05 mg, 0.1 mg.

10 pieces. packaged.

Description of the dosage form

The tablets are oval, yellow film-coated.

Directions for use and doses

The drug should be taken at least 2 hours before or 2 hours after taking medications containing magnesium and/or aluminum, iron, zinc, or sucralfate.

If you accidentally miss a dose of the drug, you should take the next dose as soon as possible and continue to take Leflobact according to the recommended dosage regimen.

Acute sinusitis - 500 mg 1 time per day for 10-14 days.

Exacerbation of chronic bronchitis - 500 mg 1 time per day for 7-10 days.

Community-acquired pneumonia - 500 mg 1-2 times a day, for 7-14 days.

Uncomplicated urinary tract infections - 250 mg 1 time per day for 3 days.

Complicated urinary tract infections - 500 mg 1 time per day for 7-14 days.

Pyelonephritis - 500 mg 1 time per day, for 7-10 days.

Chronic bacterial prostatitis - 500 mg 1 time per day for 28 days.

Infections of the skin and soft tissues - 500 mg 1-2 times a day, for 7-14 days.

Complex treatment of drug-resistant forms of tuberculosis - 500 mg 1-2 times a day - up to 3 months.

Prevention and treatment of anthrax through airborne transmission: 500 mg once a day for up to 8 weeks.

Levofloxacin is excreted primarily through the kidneys, therefore, when treating patients with limited renal function, it is necessary to reduce the dose of the drug.

It is possible to prescribe the drug Leflobact in tablets to continue the course of treatment for those patients who were first prescribed intravenous administration of the drug Leflobact solution for infusion and an improvement in their condition was achieved, allowing further administration of levofloxacin orally.

Dosage regimen in patients with impaired liver function.

If liver function is impaired, no dosage adjustment is required, since levofloxacin is only slightly metabolized in the liver.

Dosage regimen in elderly patients.

For elderly patients, no adjustment of the dosage regimen is required, except in cases where the CC is reduced to 50 ml/min or lower.

Orally, before meals or in between meals, without chewing, with a sufficient amount of liquid (from 0.5 to 1 glass).

Pharmacodynamics

Pharmacokinetics

When taken orally, it is quickly and almost completely absorbed (food intake has little effect on the speed and completeness of absorption). Bioavailability - 99%. The time required to achieve maximum concentration is 1-2 hours; when taking 250 mg and 500 mg, the maximum concentration is 2.8 and 5.2 mcg/ml, respectively. Bonding with plasma proteins is 30-40%. Penetrates well into organs and tissues: lungs, bronchial mucosa, sputum, organs of the genitourinary system (including the prostate gland), bone tissue, cerebrospinal fluid, polymorphonuclear leukocytes, alveolar macrophages.

In the liver, a small portion is oxidized and/or deacetylated.

It is excreted from the body primarily through the kidneys and urine through glomerular filtration and tubular secretion unchanged. Renal clearance accounts for 70% of the total clearance. The half-life is 6-8 hours. Less than 5% of levofloxacin is excreted in the form of metabolites. After oral administration unchanged, 70% of the dose is excreted by the kidneys within 24 hours and 87% within 48 hours; in the rectum, 4% are detected within 72 hours.

Indications for use Leflobact 500 mg 10 pcs. film-coated tablets

Infectious and inflammatory diseases caused by sensitive microorganisms: lower respiratory tract (chronic bronchitis, pneumonia); ENT organs (sinusitis, otitis media); genitourinary organs (including acute pyelonephritis, prostatitis, urogenital chlamydia); skin and soft tissues (festering atheromas, abscess, boils); as part of complex therapy of drug-resistant forms of tuberculosis.

Contraindications

Hypersensitivity, epilepsy, tendon damage during previous treatment with quinolones, pregnancy, lactation, childhood and adolescence (up to 18 years), renal dysfunction: with creatinine clearance less than 20 ml/min, while on hemodialysis.

Application Leflobakt 500 mg 10 pcs. film-coated tablets during pregnancy and breastfeeding

The use of the drug during pregnancy is contraindicated. When prescribing the drug during lactation, the issue of stopping breastfeeding should be decided.

special instructions

After normalization of body temperature, it is recommended to continue treatment for at least 48-78 hours.

During treatment, it is necessary to avoid solar and artificial UV irradiation to avoid damage to the skin (photosensitization).

If signs of tendonitis or pseudomembranous colitis appear, levofloxacin is immediately discontinued.

It should be borne in mind that in patients with a history of brain damage (stroke, severe trauma), seizures may develop; in patients with glucose-6-phosphate dehydrogenase deficiency, there is a risk of hemolysis.

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: nausea, erosive lesions of the mucous membranes of the gastrointestinal tract (GIT), prolongation of the QT interval, confusion, dizziness, convulsions.

Treatment: gastric lavage, symptomatic, dialysis is ineffective. There is no specific antidote.

Side effects Leflobakt 500 mg 10 pcs. film-coated tablets

The side effects listed below are presented in accordance with the following gradations of frequency of their occurrence: very often (&le 1/10); often (&le 1/100,< 1/10); uncommon (&le 1/1000,< 1/100); rare (&le 1/10000,< 1/1000); very rare (<1/10000) (including isolated reports); frequency is unknown (it is not possible to determine the frequency of occurrence based on available data).

Cardiac disorders: rarely - sinus tachycardia, palpitations; frequency unknown (post-marketing data) - prolongation of the QT interval, ventricular arrhythmias, ventricular tachycardia, ventricular tachycardia of the “pirouette” type, which can lead to cardiac arrest.

Disorders of the blood and lymphatic system: uncommon - leukopenia (decreased number of leukocytes in peripheral blood), eosinophilia (increased number of eosinophils in peripheral blood); rarely - neutropenia (decreased number of neutrophils in peripheral blood), thrombocytopenia (decreased number of platelets in peripheral blood); frequency unknown (post-marketing data) - pancytopenia (decrease in the number of all formed elements in the peripheral blood), agranulocytosis (absence or sharp decrease in the number of granulocytes in the peripheral blood), hemolytic anemia.

Nervous system disorders: often - headache, dizziness; infrequently - drowsiness, tremor, dysgeusia (taste perversion); rarely - paresthesia, convulsions; frequency unknown (post-marketing data) - peripheral sensory neuropathy, peripheral sensorimotor neuropathy, dyskinesia, extrapyramidal disorders, ageusia (loss of taste), parosmia (disorder of the sense of smell, especially the subjective sensation of an objectively absent smell), including loss of smell, syncope, benign intracranial hypertension.

Violations of the organ of vision: rarely - visual disturbances, such as blurriness of the visible image; frequency unknown (post-marketing data) - transient vision loss, uveitis.

Hearing and labyrinthine disorders: infrequently - vertigo (feeling of deviation or spinning of one’s own body or surrounding objects); rarely - ringing in the ears; frequency unknown (post-marketing data) - hearing loss, hearing loss.

Disorders of the respiratory system, chest and mediastinal organs: infrequently - shortness of breath; frequency unknown (post-marketing data) - bronchospasm, allergic pneumonitis.

Gastrointestinal disorders: often - diarrhea, vomiting, nausea; infrequently - abdominal pain, dyspepsia, flatulence, constipation; frequency unknown (post-marketing data) - hemorrhagic diarrhea, which in very rare cases may be a sign of enterocolitis, including pseudomembranous colitis, pancreatitis.

Renal and urinary tract disorders: uncommon - increased serum creatinine concentration; rarely - acute renal failure (for example, due to the development of interstitial nephritis).

Drug interactions

With preparations containing magnesium, aluminum, iron and zinc, didanosine.

Medicines containing divalent or trivalent cations, such as zinc or iron salts (medicines for the treatment of anemia), magnesium- and/or aluminum-containing drugs (such as antacids), didanosine (only dosage forms containing aluminum or magnesium as a buffer ), it is recommended to take at least 2 hours before or 2 hours after taking Leflobact tablets.

Calcium salts have a minimal effect on the absorption of levofloxacin when taken orally.

With sucralfate.

The effect of Leflobact is significantly weakened by the simultaneous use of sucralfate (a drug for protecting the gastric mucosa). For patients receiving levofloxacin and sucralfate, it is recommended that sucralfate be taken 2 hours after taking levofloxacin.

With theophylline, fenbufen or similar drugs from the group of non-steroidal anti-inflammatory drugs that reduce the threshold of convulsive readiness of the brain.

No pharmacokinetic interaction of levofloxacin with theophylline was detected. However, with the simultaneous use of quinolones and theophylline, non-steroidal anti-inflammatory drugs and other drugs that reduce the threshold of convulsive readiness of the brain, a pronounced decrease in the threshold of convulsive readiness of the brain is possible.

The concentration of levofloxacin while taking fenbufen increases only by 13%.

With indirect anticoagulants (vitamin K antagonists).

In patients treated with levofloxacin in combination with indirect anticoagulants (for example, warfarin), an increase in prothrombin time/international normalized ratio and/or the development of bleeding, including severe bleeding, was observed. Therefore, with the simultaneous use of indirect anticoagulants and levofloxacin, regular monitoring of blood coagulation parameters is necessary.

With probenecid and cimetidine.

When simultaneous use of drugs that interfere with renal tubular secretion, such as probenecid and cimetidine, and levofloxacin, caution should be exercised, especially in patients with renal failure.

The elimination (renal clearance) of levofloxacin is slowed down by cimetidine by 24% and probenecid by 34%. This is unlikely to be of clinical significance if renal function is normal.

With cyclosporine.

Levofloxacin increased the half-life of cyclosporine by 33%. Since this increase is clinically insignificant, no dose adjustment of cyclosporine is required when used concomitantly with levofloxacin.

With glucocorticosteroids.

Concomitant use of glucocorticosteroids increases the risk of tendon rupture.

With drugs that prolong the QT interval.

Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs that prolong the QT interval (for example, class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics).

Leflobact® (Leflobact)

Leflobact® is a synthetic broad-spectrum antimicrobial bactericidal drug from the group of fluoroquinolones.

Levofloxacin is a levorotatory isomer of ofloxacin. Levofloxacin blocks the enzymes DNA gyrase (topoisomerase II) and topoisomerase IV, disrupts supercoiling and cross-linking of DNA breaks, and causes profound morphological changes in the cytoplasm, cell wall and membrane of bacteria.

Levofloxacin is active against

most strains of microorganisms both in vitro and in vivo.

Gram-positive aerobic microorganisms:

Staphylococcus spp. (coagulase-negative, methicillin-sensitive/moderately methicillin-sensitive strains), Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-sensitive/moderately penicillin-sensitive/ penicillin-resistant strains), Streptococcus spp (groups C, G), Streptococcus viridans (penicillin-sensitive and penicillin-resistant strains), Enterococcus faecalis, Corynebacterium diphtheriae, Listeria monocytogenes.

Gram-negative aerobic microorganisms:

Acinetobacter spp. (including Acinetobacter anitratus, Acinetobacter baumannii, Acinetobacter calcoaceticus), Actinobacillus actinomycetemcomitans, Citrobacter freundii, Citrobacter diversus, Eikenella corrodens, Enterobacter spp. (including Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Enterobacter sakazakii), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (ampicillin-sensitive/ampicillin-resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (including Klebsiella oxytoca, Klebsiella pneumoniae), Moraxella catarrhalis, Morganella morganii, Neisseria gonorrhoeae (including penicillinase-producing strains), Neisseria meningitidis, Pasteurella spp. (including Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas spp. (including Pseudomonas aeruginosa, Pseudomonas fluorescens), Salmonella spp., Serratia spp. (including Serratia marcescens).

Anaerobic microorganisms:

Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterium 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 hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

LEFLOBACT

Pharmacodynamics

Aerobic gram-positive microorganisms:

Staphylococcus spp. (coagulase-negative, methicillin-sensitive/moderately methicillin-sensitive strains), Staphylococcus aureus, Staphylococcus epidermidis (methicillin-sensitive strains); Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-sensitive/moderately penicillin-sensitive/penicillin-resistant strains), Streptococcus (groups C, G), Viridans group streptococci (penicillin-sensitive and penicillin-resistant strains); Enterococcus faecalis; Corynebacterium diphtheriae; Listeria monocytogenes;

Aerobic gram-negative microorganisms:

Acinetobacter spp., Acinetobacter anitratus, Acinetobacter baumannii, Acinetobacter calcoaceticus; Actinobacillus actinomycetemcomitans; Citrobacter freundii, Citrobacter diversus; Eikenella corrodens; Enterobacter spp., Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Enterobacter sakazakii; Escherichia coli; Gardnerella vaginalis; Haemophilus ducreyi, Haemophilus influenzae (ampicillin-sensitive/ampicillin-resistant strains), Haemophilus parainfluenzae; Helicobacter pylori; Klebsiella spp., Klebsiella oxytoca, Klebsiella pneumoniae; Moraxella catarrhalis; Morganella morganii; Neisseria gonorrhoeae (including penicillinase-producing strains), Neisseria meningitidis; Pasteurella spp., Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida; Proteus mirabilis, Proteus vulgaris; Providencia spp., Providencia rettgeri, Providencia stuartii; Pseudomonas spp., Pseudomonas aeruginosa, Pseudomonas fluorescens; Salmonella spp.; Serratia spp., Serratia marcescens;

Anaerobic microorganisms:

Bacteroides fragilis; Bifidobacterium spp.; Clostridium perfringens; Fusobacterium spp.; Peptostreptococcus spp.; Propionibacterium spp.; Veillonella spp.;

Other microorganisms:

Bartonella spp.; Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis; Legionella spp., Legionella pneumophila; Mycobacterium spp., Mycobacterium leprae, Mycobacterium tuberculosis; Mycoplasma hominis; Mycoplasma pneumoniae; Rickettsia spp.; Ureaplasma urealyticum.

Possibilities of clinical use of levofloxacin

Antibacterial drugs from the fluoroquinolone group occupy one of the leading positions in the treatment of various bacterial infections, including in outpatient settings. However, the currently popular ciprofloxacin, ofloxacin, lomefloxacin, pefloxacin have high activity against gram-negative pathogens, moderate activity against atypical pathogens and little activity against pneumococci and streptococci, which significantly limits their use, especially for respiratory infections.

In the last decade, new drugs from this group - the so-called - have begun to enter clinical practice. new fluoroquinolones, which retain the high activity against gram-negative pathogens characteristic of their predecessors, and at the same time are significantly more active against gram-positive and atypical microorganisms. One such drug is levofloxacin (Tavanic). According to its chemical structure, it is a levorotatory isomer of ofloxacin. A wide spectrum of antibacterial activity, high safety, and convenient pharmacokinetic properties make it possible for its wide use in various infections.

Mechanism of action

Levofloxacin has a rapid bactericidal effect because it penetrates into the microbial cell and inhibits, like first-generation fluoroquinolones, bacterial DNA gyrase (topoisomerase II), which disrupts the process of bacterial DNA formation. Human cell enzymes are not sensitive to fluoroquinolones, and the latter do not have a toxic effect on the cells of the macroorganism. Unlike drugs of the previous generation, new fluoroquinolones inhibit not only DNA gyrase, but also the second enzyme responsible for DNA synthesis, topoisomerase IV, isolated from some microorganisms, primarily gram-positive ones. It is believed that the high antipneumococcal and antistaphylococcal activity of the new fluoroquinolones is explained by the effect on this enzyme.

Levofloxacin has a clinically significant dose-dependent post-antibiotic effect, significantly longer than ciprofloxacin, as well as a long-term (2-3 hours) subinhibitory effect.

Under the influence of levofloxacin, an increase in the function of polymorphonuclear lymphocytes was noted in healthy volunteers and HIV-infected patients. Its immunomodulatory effect on tonsillar lymphocytes in patients with chronic tonsillitis has been shown. The data obtained allow us to speak not only about antibacterial activity, but also about the synergistic anti-inflammatory and antiallergic effect of levofloxacin.

Spectrum of antimicrobial activity

Levofloxacin is characterized by a broad antimicrobial spectrum, including gram-positive and gram-negative microorganisms, including intracellular pathogens (Table 1).

When comparing the effectiveness of various antibacterial drugs against pathogens of respiratory infections, it was found that levofloxacin is superior to other drugs in terms of antimicrobial activity. All strains of pneumococcus were sensitive to it, including penicillin-resistant ones, with a relatively lower sensitivity of pneumococci to comparison drugs: ofloxacin - 92%, ciprofloxacin - 82%, clarithromycin - 96%, azithromycin - 94%, amoxicillin/clavulanate - 96%, cefuroxime - 80%. All strains of Moraxella catarrhalis, Haemophilus influenzae and methicillin-sensitive Staphylococcus aureus, and 95% of Klebsiella pneumoniae strains were also sensitive to levofloxacin.

Resistance

The possibility of widespread clinical use of levofloxacin and other new fluoroquinolones raises concerns about the danger of developing resistance to them. Chromosomal mutations are the main mechanism providing microbial resistance to fluoroquinolones. In this case, there is a gradual accumulation of mutations in one or two genes and a stepwise decrease in sensitivity. The development of clinically significant pneumococcal resistance to levofloxacin is observed after three mutations and, therefore, seems unlikely. This is confirmed by experimental data: levofloxacin caused spontaneous mutations 100 times less frequently than ciprofloxacin, regardless of the sensitivity of the tested pneumococcal strains to penicillin and macrolides. Widespread use of the drug in recent years in the USA and Japan has not led to an increase in resistance to it. According to K. Yamaguchi et al., 1999, the sensitivity of bacteria to levofloxacin over five years, i.e., since the beginning of its widespread use, has not changed and exceeds 90% for both gram-negative and gram-positive pathogens.

The greater risk of developing antibiotic resistance is associated not with pneumococci, but with gram-negative bacteria. At the same time, according to some data, the use of levofloxacin in intensive care units is not accompanied by a significant increase in the resistance of gram-negative intestinal flora.

Pharmacokinetics

Levofloxacin is well absorbed from the gastrointestinal tract. Its bioavailability is 99% or more. Since levofloxacin is almost not metabolized in the liver, this helps to quickly achieve its maximum concentration in the blood (much higher than that of ciprofloxacin). Thus, when volunteers were prescribed a standard dose of fluoroquinolone, the values of its maximum concentration in the blood when taking levofloxacin were 2.48 μg/ml/70 kg, ciprofloxacin - 1.2 μg/ml/70 kg.

After taking a single dose of levofloxacin (500 mg), its maximum concentration in the blood, equal to 5.1 ± 0.8 mcg/ml, is achieved after 1.3-1.6 hours, while the bactericidal activity of the blood against pneumococci remains up to 6.3 hours, regardless of their sensitivity to penicillins and cephalosporins. For a longer period of time, up to 24 hours, the bactericidal effect of blood on gram-negative bacteria of the Enterobacteriacae family is maintained.

The half-life of levofloxacin is 6-7.3 hours. About 87% of the administered dose of the drug is excreted unchanged in the urine over the next 48 hours.

Levofloxacin penetrates quickly into tissues, with tissue concentrations of the drug being higher than those in the blood. Particularly high concentrations are established in the tissues and fluids of the respiratory tract: alveolar macrophages, bronchial mucosa, bronchial secretions. Levofloxacin also reaches high concentrations inside cells.

The long half-life, the achievement of high tissue and intracellular concentrations, as well as the presence of post-antibiotic action - all this allows levofloxacin to be prescribed once a day.

Drug interactions

The bioavailability of levofloxacin is reduced when taken simultaneously with antacids, sucralfate, and drugs containing iron salts. The interval between taking these medications and levofloxacin should be at least 2 hours. No other clinically significant interactions with levofloxacin were identified.

Clinical effectiveness

There are many publications devoted to the results of clinical studies of the effectiveness of levofloxacin. Below are the most significant of them.

A multicenter randomized trial involving 590 patients compared the efficacy and safety of two treatment regimens: levofloxacin IV and/or orally at a dose of 500 mg per day and ceftriaxone IV 2.0 g per day; and/or cefuroxime 500 mg orally twice daily in combination with erythromycin or doxycycline in patients with community-acquired pneumonia. Duration of therapy is 7–14 days. Clinical efficacy was 96% in the levofloxacin group and 90% in the cephalosporin group. Eradication of pathogens was achieved in 98 and 85% of patients, respectively. The incidence of adverse events in the levofloxacin group was 5.8%, and in the comparison group 8.5%.

Another large randomized trial compared the effectiveness of treating patients with severe pneumonia with levofloxacin 1000 mg per day and ceftriaxone 4 g per day. During the first days, levofloxacin was prescribed intravenously, then orally. The results of treatment in both groups were comparable, but in the ceftriaxone group there was a significantly more frequent change of antibiotic in the first days of treatment due to insufficient clinical effect.

Comparable results were obtained when comparing groups of patients treated with levofloxacin and co-amoxiclav.

The effectiveness of levofloxacin monotherapy was studied in more than 1000 patients with community-acquired pneumonia. Clinical and bacteriological effectiveness here were 94 and 96%, respectively.

Pharmacoeconomic studies have shown that the total costs of treating patients with levofloxacin and the combination of a cephalosporin and a macrolide are comparable or even slightly lower in the levofloxacin group.

In patients with exacerbation of chronic bronchitis, the effectiveness of treatment with levofloxacin at a dose of 500 mg per day orally and cefuroxime axetil orally 500 mg twice a day was compared. At the same time, clinical and bacteriological effectiveness did not differ depending on the groups and amounted to 77–97%.

Thus, at present, the high effectiveness of levofloxacin in respiratory infections of the lower respiratory tract can be considered proven. The results of the studies made it possible to include levofloxacin as a first-line or alternative drug in the treatment regimen for patients with community-acquired pneumonia and exacerbations of chronic bronchitis (Table 2).

In recent years, levofloxacin has become more widely used for other infectious diseases. Thus, reports have appeared regarding its successful use in patients with acute sinusitis. Levofloxacin is active in 100% of cases against the most common bacterial pathogens of this disease; its effectiveness is comparable to amoxicillin/clavulanate in high doses and significantly superior to cephalosporins, cotrimoxazole, macrolides and doxycycline.

Among the causative agents of urological infections, there is an increase in resistance to widely used antibacterial drugs. Thus, during the period from 1992 to 1996, there was an increase in the resistance of E. Coli and S. saprophyticus to cotrimoxazole by 8–16% and to ampicillin by 20%. Resistance to ciprofloxacin, nitrofurans and gentamicin increased by 2% over the same period. The use of levofloxacin in patients with complicated urinary infections at a dose of 250 mg per day was effective in 86.7% of patients.

The pharmacokinetic indicators of high levels of levofloxacin in tissues were given above. This, along with the antimicrobial spectrum of the drug, served as the basis for its use for the prevention of infectious complications during endoscopic methods of treatment and diagnosis, for example, with retrograde cholangiopancreatography and for perioperative prophylaxis in orthopedics.

The use of levofloxacin in these situations appears promising and requires further study.

Safety

Levofloxacin is considered one of the safest antibacterial drugs. However, there are a number of restrictions when prescribing it.

In patients with impaired liver function, there is no need to adjust the dose of the drug, but impaired renal function with a decrease in creatinine clearance (less than 50 ml/min) requires a reduction in the dose of the drug. Additional administration of levofloxacin after hemodialysis or outpatient peritoneal dialysis is not required.

Levofloxacin is not used in pregnant and lactating women, children and adolescents. The drug is contraindicated in patients who have a history of adverse reactions to fluoroquinolone treatment.

In elderly and senile patients, when taking levofloxacin, no increased risk of developing undesirable side reactions was detected and no dose adjustment is required.

Controlled clinical studies have shown that adverse reactions with levofloxacin are rare and mostly not serious. There is a relationship between the dose of the drug and the incidence of ND: at a daily dose of 250 mg, their frequency does not exceed 4.0–4.3%, at a dose of 500 mg/day. - 5.3–26.9%, at a dose of 1000 mg/day. — 22–28.8%. The most frequently observed symptoms of gastrointestinal dyspepsia were nausea and diarrhea (1.1–2.8%). With intravenous administration, redness of the injection site is possible, and the development of phlebitis is sometimes observed (1%).

Dosing

Levofloxacin is available in two forms: for intravenous administration and oral administration. 250-500 mg is used once a day; for severe infections, 500 mg twice a day may be prescribed. For community-acquired pneumonia, the duration of treatment is 10-14 days, for exacerbation of chronic bronchitis - 5-7 days.

Table 1. Spectrum of antimicrobial activity of levofloxacin

Highly active

S. pneumoniae
Streptococci
Staphylococcus
Chlamydia
Mycoplasma
Legionella
H. parainfluenzae
M. catarrhalis
K. pneumoniae
B. pertussis
Yersinia
Salmonella
Citrobacter spp.
E. coli
Enterobacter spp., Acinetobacter spp.
P. mirabilis, vulgaris
Neisseria spp.
C. perfringens
B. urealyticus

Moderately active

Enterococci
Listeria
Peptococcus
Peptostreptococcus
S. spp.
S. marcescens
H. influenzae
P. aeruginosa

Inactive

C. difficile
Pseudomonas spp.
Fusobacteria
Mushrooms
Viruses
M. morgani

Note!

Levofloxacin has a wide spectrum of action, including most gram-positive and gram-negative pathogens, including those located intracellularly
Unlike previously used fluoroquinolones, levofloxacin is highly active against gram-positive cocci, including pneumococci resistant to penicillin and erythromycin. In addition, levofloxacin is more active against atypical pathogens. Levofloxacin has convenient pharmacokinetic properties: high bioavailability, long half-life, which allows it to be used once a day, creates high tissue and intracellular concentrations
The drug is not metabolized in the liver and has no unwanted drug interactions; does not require dose adjustment in elderly patients. Levofloxacin is well tolerated and is one of the safest antibacterial drugs
The use of the drug for infections of the urinary tract, skin and soft tissues, and for the prevention of complications in surgery seems promising.
The presence of two forms of the drug - for parenteral and oral use - allows it to be used in a step-down therapy mode, which, along with the possibility of a single dose, significantly facilitates the work of medical staff and is convenient for the patient

Leflobact tab p/pl/o 500 mg N10 (Synthesis)

Antibacterial drug of the fluoroquinolone group. Levofloxacin is a levorotatory isomer of ofloxacin. Levofloxacin blocks the enzymes DNA gyrase (topoisomerase II) and topoisomerase IV, disrupts supercoiling and cross-linking of DNA breaks, and causes profound morphological changes in the cytoplasm, cell wall and membrane of bacteria. Levofloxacin is active against most strains of microorganisms both in vitro and in vivo: Aerobic gram-positive microorganisms: Staphylococcus spp. (coagulase-negative, methicillin-sensitive/moderately methicillin-sensitive strains), Staphylococcus aureus, Staphylococcus epidermidis (methicillin-sensitive strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-sensitive/moderately penicillin-sensitive/penicillin-resistant strains), Streptococcus ( groups C, G), Viridans group streptococci (penicillin-sensitive and penicillin-resistant strains), Enterococcus faecalis, Corynebacterium diphtheriae, Listeria monocytogenes; Aerobic gram-negative microorganisms: Acinetobacter spp., Acinetobacter anitratus, Acinetobacter baumannii, Acinetobacter calcoaceticus; Actinobacillus actinomycetemcomitans; Citrobacter freundii, Citrobacter diversus, Eikenella corrodens; Enterobacter spp., Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Enterobacter sakazakii; Escherichia coli; Gardnerella vaginalis; Haemophilus ducreyi, Haemophilus influenzae (ampicillin-sensitive/ampicillin-resistant strains), Haemophilus parainfluenzae; Helicobacter pylori, Klebsiella spp., Klebsiella oxytoca, Klebsiella pneumoniae; Moraxella catarrhalis, Morganella morganii, Neisseria gonorrhoeae (including penicillinase-producing strains), Neisseria meningitidis, Pasteurella spp., Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida, Proteus mirabilis, Proteus vulgaris, Providencia spp., Providencia rettgeri, Providencia stuartii; Pseudomonas spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Salmonella spp., Serratia spp., Serratia marcescens, Anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp.; Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterium spp., Ve illonella spp. Other microorganisms: Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella spp., Legionella pneumophila, Mycobacterium spp., Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma hominis, Mycoplasma pneumoniae; Rickettsia spp., Ureaplasma urealyticum.

Leflobact, 5 mg/ml, solution for infusion, 100 ml, 1 pc.

Pharmacotherapeutic group: Antimicrobial agent - fluoroquinolone ATX: J.01.MA Fluoroquinolones

J.01.MA12 Levofloxacin

Pharmacodynamics:

Leflobact is a synthetic broad-spectrum antimicrobial bactericidal drug from the group of fluoroquinolones, containing levofloxacin, a levorotatory isomer of ofloxacin, as an active substance. Compared to ofloxacin, levofloxacin has a wider spectrum of antibacterial activity, additionally including various streptococci, incl. pneumococci.

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

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

In vitro:

Sensitive to levofloxacin (minimum inhibitory concentration (MIC) <2 mg/ml):

Gram-positive aerobic microorganisms: Corynebacterium diphtheriae, Enterococcus faecalis, Enterococcus spp. (except 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. groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae (sensitive, moderately sensitive and resistant to penicillin), Streptococcus pyogenes, Streptococcus group 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 (beta-lactamase producing and non-producing strains), Morganella morganii, Neisseria gonorrhoeae, Neisseria meningiti dis 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-negative aerobic microorganisms: Burkholderia cepacia, Campylobacter jejuni/coli.

Anaerobic microorganisms: Bacteroides thetaiotaomicron, 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 is linear and predictable with single and multiple administrations of the drug. The plasma concentration profile of levofloxacin after intravenous administration is similar to that when taking tablets.

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

Plasma protein binding is 30-40%. Penetrates well into organs and tissues: lungs, bronchial mucosa, sputum, urinary system organs, genitals, bone tissue, cerebrospinal fluid, prostate gland, polymorphonuclear leukocytes, alveolar macrophages.

The mean volume of distribution of levofloxacin ranges from 89 to 112 L after single and multiple doses of 500 mg intravenously.

Pharmacokinetic characteristics after a single intravenous administration of levofloxacin at a dose of 500 mg, respectively, are: maximum concentration (6.2 ± 1.0) mcg/ml, time required to achieve maximum concentration - (1.0 7 ± 0.1) h , half-life - (6.4 ± 0.7) hours.

Levofloxacin is predominantly excreted unchanged by the kidneys.

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