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Active ingredients
Levofloxacin
Release form
Pills
Composition
Active ingredient: levofloxacin Auxiliary substances: crospovidone, hypromellose, microcrystalline cellulose, sodium stearyl fumarate, talc, macrogol 8000, dye based on titanium dioxide and iron oxides. Base volume: tablet Concentration of active ingredient (mg): 250 mg.
Pharmacological effect
Synthetic antimicrobial drug from the group of fluoroquinolones, levorotatory isomer ofloxacin. has a broad spectrum of antimicrobial action. Levofloxacin blocks dna-gyrase (topoisomerase ii) and topoisomerase iv, disrupts superspiration and cross-linking of dna gaps, inhibits dna synthesis, causes profound morphological changes in the cytoplasm, cell wall and membranes of microbial cells. microorganisms both in vitro and in vivo. in vitro sensitive (μP ≤2 mg / ml; inhibition zone ≤17 mm) aerobic gram-positive microorganisms: bacillus anthratis, corynebacterium diphtheriae, corynebact erium jeikeium, enterococcus spp. (including enterococcus faecalis), listeria monocytogenes, staphylococcus spp. (coagulase-negative, methicillin-sensitive / methicillin-moderately sensitive strains), staphylococcus aureus (methicillin-sensitive strains), staphylococcus epidermidis (methicillin-sensitive strains), staphylococcus spp. (coagulase-negative), streptococcus spp. groups c and g (including streptococcus agalactiae, streptococcus pneumoniae (penicillin-sensitive / moderately sensitive / resistant strains), streptococcus pyogenes, streptococcus viridans (penicillin-sensitive / resistant strains); isp, actinobacillus actinimycetemcomitans, citrobacter freundii, eikenella corrodens, ispobacter sv., isobacter sv. helicobacter pylori, klebsiella spp. (including klebsiella oxytoca, klebsiella pneumoniae), moraxella catarrhalis (strains producing and producing no β-lactamase), morganella morganii, neisseria gonnorrhoeae (strains producing and producing no penicillinase), neisseria meningitidis, pasteurella spp. (including pasteurella canis, pasteurella dagmatis, pasteurella multocida), proteus mirabilis, proteus vulgaris, providencia spp. (including providencia rettgeri, providencia stuartii), pseudomonas spp. (nosocomial infections caused by pseudomonas aeruginosa may require combined treatment), salmonella spp., serratia spp. (serratia marcescens); anaerobic microorganisms: bacteroides fragilis, bifidobacterium spp., clostridium perfringens, fusobacterium spp., peptostreptococcus spp., propionibacterum spp., veilonella spp .; other microorganisms: bartonella spp., chlamydia pneumoniae, chlamydia psittaci, chlamydia trachomatis, legionella pneumophila, legionella spp., mycobacterium spp. . (Including mycobacterium leprae, mycobacterium tuberculosis), mycoplasma hominis, mycoplasma pneumoniae, rickettsia spp, ureaplasma urealyticum.levofloksatsin moderately active (MIC = 4 mg / L; 16-14 mm zone of inhibition) against aerobic gram-positive organisms: corynebacterium urealiticum, corynebacterium xerosis, enterococcus faecium, staphylococcus epidermidis (methicillin-resistant strains), staphylococcus haemolyticus (methicillin-resistant strains); aerobic gram-negative microorganisms: campilobacter jejuni, campilobacter coli; anaerobic microorganisms: prevotella spp., porphyromonas spp. for levofolksacin resistant (≥ 8 mg / l; zone of inhibition ≤ 13 mm), aerobic gram-positive microorganisms: staphylococcus aureus (methicillin-resistant strains), staphylococcus spp.(coagulase-negative methicillin-resistant strains); aerobic gram-negative microorganisms: alcaligenes xylosoxidans; anaerobic microorganisms: bacteroides thetaiotaomicron; other microorganisms: mycobacterium avium. clinical efficacy in clinical studies the drug was effective in treating infections caused by the microorganisms listed below , haemophilus influenzae, haemophilus parainfluenzae, klebsiella pneumoniae, moraxela (branhamella) catarrhalis, morganella morganii, proteus mirabilis, pseudomonas aeruginosa, serratia marcescens. other: chaphaus, weparashan, weparashanas, wepango, pediatrics, juvenile levofloxacin develops as a result of a phased process of gene mutations encoding both type ii topoisomerases: dna-gyrase and topoisomerase iv. other mechanisms of resistance, such as the mechanism of influence on the penetration barriers of a microbial cell (a mechanism characteristic of pseudomonas aeruginosa) and the mechanism of efflux (active removal of an antimicrobial agent from a microbial cell), can also reduce the sensitivity of microorganisms to levofloxacin. no cross-resistance between levofloxacin and other antimicrobial agents is observed.
Pharmacokinetics
AbsorptionAfter ingestion, levofloxacin is rapidly and almost completely absorbed from the gastrointestinal tract. Food intake has little effect on its absorption. Absolute bioavailability when administered is 99-100%. After a single dose of levofloxacin in a dose of 500 mg Cmax in plasma is reached within 1-2 hours and is 5.2 ± 1.2 mcg / ml. The pharmacokinetics of levofloxacin is linear in the dose range from 50 to 1000 mg.Css of levofloxacin in plasma while taking 500mg of levofloxacin 1 or 2 times / day is achieved within 48 hours. ml, and Cmin of levofloxacin (concentration before taking the next dose) in PL the snake was 0.5 ± 0.2 mcg / ml. On the 10th day of intake of the drug Tavanic in a dose of 500 mg 2 times / day Cmax of levofloxacin in plasma was 7.8 ± 1.1 mcg / ml, and Cmin of levofloxacin (concentration before taking the next dose) in plasma was 3.0 + 0.9 mcg / ml. Distribution Plasma protein binding is 30-40%. After a single dose and repeated use of levofloxacin at a dose of 500 mg Vd, levofloxacin averages 100 l,indicating a good penetration of levofloxacin into the organs and tissues of the human body. After a single oral administration of levofloxacin at a dose of 500 mg Cmax of levofloxacin in the bronchial mucosa and the epithelial lining fluid was reached within 1-4 hours and amounted to 8.3 mcg / g and 10.8 mcg / ml , respectively, with the coefficients of penetration into the mucous membrane of the bronchi and the fluid of the epithelial lining compared with plasma concentrations of 1.1-1.8 and 0.8-3.0, respectively. After 5 days of receiving levofloxacin orally at a dose of 500 mg, the average The concentration of levofloxacin 4 h after the last administration of the drug in the fluid of the epithelial lining was 9.94 μg / ml and in alveolar macrophages - 97.9 μg / ml.Cmax in the lung tissue after ingestion of levofloxacin orally at a dose of 500 mg was approximately 11.3 μg / g and was reached after 4 -6 hours after taking the drug with penetration coefficients of 2-5 compared to plasma concentrations. After 3 days of taking levofloxacin at a dose of 500 mg 1 time or 2 times / day, Cmax of levofloxacin in the alveolar fluid was reached 2-4 hours after taking the drug and SOS They added 4.0 and 6.7 mcg / ml, respectively, with the penetration coefficient compared to the plasma concentrations of the components 1. Levofloxacin penetrates well into the cortical and spongy bone tissue, both in the proximal and distal femur with the penetration coefficient (bone / plasma ) 0.1-3. Cmax of levofloxacin in the cancellous spongy bone of the proximal femur after ingestion of the drug at a dose of 500 mg was approximately 15.1 mcg / g (2 hours after taking the drug). Levofloxacin does not penetrate into the spinal fluid. After ingestion of levofloxacin at a dose of 500 mg 1 time / day for 3 days, the average concentration of levofloxacin in the tissue of the prostate gland was 8.7 mcg / g, the average concentration ratio of the prostate gland / plasma was 1.84. The average concentration in the urine after 8-12 hours after ingestion Three doses of 150, 300 and 600 mg of levofloxacin were 44 mcg / ml, 91 mcg / ml and 162 mcg / ml, respectively. Metabolism is slightly metabolized in Levofloxacin (5% of the dose taken). Its metabolites are demethyl levofloxacin and levofloxacin N-oxide, which are excreted by the kidneys. Levofloxacin is stereochemically stable and does not undergo chiral transformations. Withdrawal After ingestion, levofloxacin is relatively slowly excreted from the plasma (T1 / 2 - 6-8 h). Excreted mainly in the urine (more than 85% of the dose).The total clearance of levofloxacin after a single dose of 500 mg was 175 ± 29.2 ml / min. There are no significant differences in the pharmacokinetics of levofloxacin when it is in / in the introduction and ingestion, which confirms that the ingestion and in / in the introduction are interchangeable. Pharmacokinetics in Special groups of patients. The pharmacokinetics of levofloxacin in men and women do not differ. The pharmacokinetics in elderly patients does not differ from that in young patients, with the exception of differences in pharmacokinetics associated with differences in CC. In renal failure, the pharmacokinetics of levofloxacin are altered. As renal function decreases, renal clearance and renal clearance decrease, and T1 / 2 increases. Pharmacokinetics in renal failure after a single dose of Tavanic 500 mgKK (ml / min) <20 20-49 50-80 Kidney clearance (ml / min) 13 26 57Т1 / 2 (h) 35 27 9
Indications
Tavanic is widely used for the treatment of the following pathologies: - septicemia; - intraabdominal infection; - urinary tract infections; - community-acquired pneumonia; - bronchopulmonary system infections (chronic bronchitis, pneumonia); - tuberculosis (in complex therapy) otitis, sinusitis, sinusitis); - chlamydia, mycoplasmosis; - infections of the skin, subcutaneous tissue, soft tissues (abscesses, boils, cellulitis); - prostatitis (bacterial origin).
Contraindications
Tavanic under 18 is not appointed. The physician should use the drug with extreme caution in elderly patients (due to the high probability of renal failure). They are not used for: - epilepsy and a tendency to epileptic reactions; - pregnancy; - glucocorticosteroid therapy (because of an increased risk of tendon rupture); - history of tendon lesions after quinolone use; - hypersensitivity to quinolones, fluorine-containing drugs; - lactation.
Precautionary measures
The drug should be stored out of the reach of children at a temperature not higher than 25 ° C.
Use during pregnancy and lactation
The drug is contraindicated for use in pregnancy and in lactating women.
Dosage and administration
Tablets are designed for internal use. If necessary, you can break them at risk to obtain the required dose.Tablets washed down with water. You can consume regardless of the food. Dosage regimen - individual, determined by the doctor. The standard scheme for prescribing Tavanic for various pathologies is given in the table.PathologyMortality of Admission (once a day) Approximate course of treatment (in days) A single dose of the drug (mg) Sinusitis 110-14500 Chronic bronchitis (acute period) 117-10250500 Urinary tract infection 1 13250 Prostat 128500 asp. 21-27-10250500 Infections of the skin, hypodermis, and soft tissues1-21-27-14250500Septemiya10-141-2500Infections of the abdominal area (in combination therapy) 7-141500Resistant forms of tuberculosisUp to 901-2500Excretion of Tavanica occurs by the kidneys, according to this requires a dose reduction in the presence of violations of their functions. Calculation of the dose is carried out depending on the QC (creatinine clearance index). With a clearance of 20-50 ml per minute, a single dose will be 0.125-0.25 g (maximum twice a day), with rates of 10-19 ml / min - half a tablet of Tavanic 0.25 g every 0.5-2 day, with clearance less than 10 - Tavanic pills half a floor of 0.25 g every 1-2 days. Course duration - up to 2 weeks. When you skip taking the drug, you resume the use as soon as you remember and continue according to the treatment regimen. The duration of the course of therapy with Tavanic solution for infusions is no more than 14 days. Intravenous slowly (at the rate of one hour per infusion). In case of positive dynamics, the transition to oral forms of Tavanic with the appropriate dosage is shown.
Side effects
The undesirable effects on taking Tavanic are: - collapse, hypotension, tachycardia; - dyspepsia; - pseudomembranous enterocolitis; - hypoglycemia; - nausea, vomiting; - hepatitis, hyperbilirubinemia; - dysbacteriosis; - increased activity of AST, AlT; insomnia, anxiety, fear; - paresthesia, convulsions, movement disorders; - drowsiness, dizziness; - hallucinations, depression; - disorders of the sensitive sphere (sense of smell, touch, tactile and taste sensations); - arthralgia, myalgia, - myasthenia, - confusion ; - tendin it, tendon rupture; interstitial nephritis; hypercreatininemia; neutropenia, eosinophilia, pancytopenia, leukopenia, thrombocytopenia; Stevens-Johnson syndrome; agranulocytosis; hemolytic anemia; photosensitization reactions; ; - Lyell's syndrome; - phlebitis; - superinfection; - urticaria; - anaphylaxis; - bronchospasm,pneumonitis of allergic genesis; - vasculitis; - rhabdomyolysis; - exacerbation of porphyria. Increasing the dose of Tavanic to 1000 mg does not increase the adverse effects. The severity of adverse effects and age are not related. In general, the tolerability of levofloxacin is good, serious side effects rarely develop.
Overdose
Symptoms: Based on the data obtained in animal studies, the most important expected symptoms of an acute overdose of the drug Tavanic are symptoms of the central nervous system (impaired consciousness, including confusion, dizziness and convulsions). With post-marketing use of the drug in overdose, effects from the CNS were observed, including confusion, convulsions, hallucinations and tremors. Nausea and erosion of the gastrointestinal mucosa are possible. In clinical and pharmacological studies conducted with doses of levofloxacin exceeding therapeutic, prolongation of the QT interval was shown. Treatment: conducting symptomatic therapy, careful monitoring of the patient, including ECG monitoring. In the case of an acute overdose of pills of the drug Tavanic, gastric lavage and the introduction of antacids to protect the gastric mucosa are indicated. Levofloxacin is not cleared by dialysis (hemodialysis, peritoneal dialysis, and permanent peritoneal dialysis). There is no specific antidote.
Interaction with other drugs
Combinations that require caution must be followed. Preparations containing divalent or trivalent cations, such as zinc and iron salts, antacid agents containing magnesium and / or aluminum, didanosine (only dosage forms containing aluminum or magnesium as a buffer) are recommended to take at least 2 hours before or 2 hours after taking the pills Tavanic. Calcium salts have a minimal effect on the absorption of levofloxacin when it is ingested. The effect of the drug Tavanic is significantly weakened while taking Sukralfat. Patients receiving levofloxacin and sucralfate are advised to take sucralfate 2 hours after taking levofloxacin. No pharmacokinetic interaction of levofloxacin with theophylline was detected. The concentration of levofloxacin with simultaneous use of fenbufen increases only by 13%.However, while quinolone and theophylline, NSAIDs and other drugs that reduce the threshold of brain convulsive readiness are given, a marked decrease in the threshold of convulsive readiness of the brain is possible. An increase in prothrombin time was observed in patients who received levofloxacin in combination with indirect anticoagulants (for example, warfarin). INR and / or bleeding, incl. and heavy. Therefore, with the simultaneous use of indirect anticoagulants and levofloxacin, regular monitoring of blood coagulation parameters is necessary. With simultaneous use of levofloxacin and drugs that disturb renal tubular secretion of levofloxacin, such as probenecid and cimetidine, caution should be exercised especially in patients with renal insufficiency. Withdrawal (renal clearance) of levofloxacin is slowed by the action of cimetidine by 24% and probenecid by 34%. It is unlikely that this may have clinical significance in normal renal function. Levofloxacin increased T1 / 2 of cyclosporine by 33%. Since this increase is clinically insignificant; dose adjustment of cyclosporine when used simultaneously with levofloxacin is not required. Simultaneous use of GCS increases the risk of tendon rupture. Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs that prolong the QT interval (for example, antiarrhythmic class IA and III drugs, tricyclic antidepressants, macrolides, antipsychotics). Other combinations. Clinical and pharmacological studies have been conducted for the study. of levofloxacin pharmacokinetic interaction with digoxin, glibenclamide, ranitidine and warfarin have shown that the pharmacokinetics of levofloxacin while the use of these drugs is not changed sufficiently that it had clinical significance.
special instructions
Hospital infections caused by Pseudomonas aeruginosa (Pseudomonas aeruginosa) may require combined treatment. The prevalence of acquired resistance of strains of microorganisms sown may vary depending on the geographic region and over time. In this regard, information on drug resistance in a particular country is required.For the treatment of severe infections or treatment failure, a microbiological diagnosis should be made with the release of the pathogen and its sensitivity to levofloxacin. There is a high probability that methicillin-resistant strains of Staphylococcus aureus will be resistant to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of established or suspected infections caused by methicillin-resistant strains of Staphylococcus aureus, if laboratory studies have not confirmed the sensitivity of this microorganism to levofloxacin. As with other quinolones, levofloxacin should be used with great caution in patients with a predisposition : in patients with previous CNS lesions, such as stroke, severe traumatic brain injury; in patients simultaneously receiving drugs that reduce the threshold of convulsive readiness of the brain, such as fenbufen and other similar NSAIDs, as well as other drugs that lower the threshold of convulsive readiness, such as theophylline. Diarrhea developed during or after treatment with levofloxacin, especially severe, persistent and / or blood may be a symptom of pseudomembranous colitis caused by Clostridium difficile. If pseudomembranous colitis is suspected, treatment with levofloxacin should be stopped immediately and specific antibiotic therapy should start immediately (vancomycin, teicoplanin or metronidazole orally). Drugs that inhibit intestinal peristalsis are contraindicated. Rarely observed tendonitis when using quinolones, including levofloxacin, can lead to tendon rupture, including the Achilles tendon. This side effect may develop within 48 hours after the start of treatment and may be bilateral. Elderly patients are more prone to tendinitis. The risk of tendon rupture may increase with simultaneous use of GCS. If you suspect tendonitis, you should immediately discontinue treatment with Tavanic and begin appropriate treatment of the affected tendon, for example, by ensuring sufficient immobilization. Levofloxacin can cause serious, potentially fatal hypersensitivity reactions (angioedema, anaphylactic shock), even when using the drug in initial doses.Patients should immediately stop taking the drug and consult a doctor. When using levofloxacin, there have been cases of severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis. In the event of any reactions from the skin or mucous membranes, the patient should immediately consult a doctor and not continue treatment before consulting a specialist. He reported cases of necrosis of the liver, including the development of fatal liver failure, when using levofloxacin, mainly in patients with severe major diseases (such as sepsis). The patient should be warned about the need to stop treatment and urgent treatment to the doctor in case of signs and symptoms of liver damage, such as anorexia, jaundice, dark urine, pruritus, abdominal pain. Levofloxacin is excreted mainly by the kidneys, patients with impaired renal function require mandatory monitoring of renal function, as well as correction of the dosage regimen. When treating elderly patients, it should be borne in mind that patients in this group often suffer from impaired renal function. Although photosensitization is very rare when using levofloxacin, patients are not recommended to prevent its development during treatment and undergo 48 hours after treatment with levofloxacin without preventing special need for strong solar or artificial ultraviolet radiation (for example, visiting a tanning bed). As with the use of other antibiotics, the use of levofloxation and, especially for a long time may lead to an increased reproduction insensitive thereto microorganisms (bacteria and fungi), which may cause changes in the microflora, which is normally present in humans, resulting in superinfection may occur. Therefore, in the course of treatment, it is imperative that the patient’s condition be re-evaluated, and if superinfection develops during treatment, appropriate measures should be taken. Very rare cases of prolongation of the QT interval have been reported in patients receiving fluoroquinolones, including levofloxacin. When using fluoroquinolones, including levofloxacin,Care should be taken in patients with known risk factors for prolongation of the QT interval: in patients with uncorrected electrolyte disturbances (with hypokalemia, hypomagnesia); with syndrome of congenital lengthening of the QT interval, with heart disease (heart failure, myocardial infarction, bradycardia), while taking medicines that can prolong the QT interval, such as class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, neuroleptics. Elderly and female patients may be more sensitive to drugs that prolong the QT interval. Therefore, fluoroquinolones, including levofloxacin, should be used with caution in patients. Patients with latent or manifested glucose-6-phosphate dehydrogenase deficiency are prone to hemolytic reactions when treated with quinolones, which should be taken into account when treating with levofloxacin. As with other quinolones, cases of hyperglycemia and hypoglycemia have been observed in the use of levofloxacin, usually in patients with diabetes mellitus who are simultaneously treated with oral hypo likemicheskimi agents (e.g. glibenclamide) or insulin. Cases of hypoglycemic coma have been reported. Patients with diabetes require careful monitoring of blood glucose concentrations. Patients receiving fluoroquinolones, including levofloxacin, have had sensory and sensory-motor peripheral neuropathy, the onset 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. Fluoroquinolones, including levofloxacin, are characterized by neuromuscular blocking activity and can exacerbate muscle weakness in patients with pseudo-paralytic myasthenia. In the post-marketing period, adverse reactions were observed, including pulmonary insufficiency, requiring mechanical ventilation, and death, which were associated with the use of fluoroquinolones in patients with pseudoparalytic myasthenia.The use of levofloxacin in patients with an established diagnosis of pseudo-paralytic myasthenia is not recommended. The use of levofloxacin for the prevention and treatment of anthrax during airborne infection is based on data on the sensitivity of Bacillus anthracis to it obtained in in vitro studies and in experimental studies conducted on animals, as well as on limited data on the use of levofloxacin in humans. Your doctor should refer to national and / or international documents that reflect a common opinion on anthrax treatment. With quinolones, including levofloxacin, psychotic reactions have been reported, which in very rare cases have progressed to the development of suicidal thoughts and behavioral disorders with self-harm (sometimes after taking a single dose of levofloxacin). With the development of such reactions, treatment with levofloxacin should be discontinued and appropriate therapy should be prescribed. Patients with psychosis or a history of mental illness should be prescribed with caution. If any visual impairment develops, an ophthalmologist should be consulted immediately. In patients taking levofloxacin, the determination of opiates in the urine can lead to false-positive results, which should be confirmed by more specific methods. Levofloxacin can inhibit the growth of Mycobacterium tuberculosis and further lead to false-negative bacteriological diagnosis of tuberculosis Influence on the ability to drive vehicles and control mechanisms. Such side effects of the drug Tavanic, such as dizziness or vertigo, drowsiness and visual disturbances, can reduce psychomotor reactions and the ability to concentrate. This may represent a certain risk in situations where these abilities are of particular importance (for example, when driving a car, when servicing machines and mechanisms, when working in an unstable position).