Levofloxacin-Teva tablets 500mg, No. 7

Bacterial infections sensitive to levofloxacin in adults:

• acute sinusitis;

• exacerbation of chronic bronchitis;

• community-acquired pneumonia;

• uncomplicated urinary tract infections;

• complicated urinary tract infections (including pyelonephritis);

• chronic bacterial prostatitis;

• infections of the skin and soft tissues;

• for the complex treatment of drug-resistant forms of tuberculosis;

• prevention and treatment of anthrax with airborne infection.

The dosage regimen is determined by the nature and severity of the infection, as well as the sensitivity of the suspected pathogen. The duration of treatment varies depending on the course of the disease.

Recommended dosing regimen and duration of treatment in patients with normal renal function (CC> 50 ml / min)

Acute sinusitis: 1 tablet of Levofloxacin-Teva 1 time per day (respectively, 500 mg of levofloxacin) - 10-14 days. Х

Exacerbation of chronic bronchitis: 1 tablet of Levofloxacin-Teva 1 time per day (respectively, 500 mg of levofloxacin) - 7-10 days.

Community-acquired pneumonia: 1 tablet of Levofloxacin-Teva 1-2 times a day (respectively, 500-1000 mg of levofloxacin) - 7-14 days.

Uncomplicated urinary tract infections: 1/2 tablet of Levofloxacin-Teva 1 time per day (respectively, 250 mg of levofloxacin) - 3 days.

Complicated urinary tract infections: 1 tablet of Levofloxacin-Teva 1 time per day (respectively, 500 mg of levofloxacin) - 7-14 days.

Pyelonephritis: 1 tablet of Levofloxacin-Teva 1 time per day (respectively, 500 mg of levofloxacin) - 7-10 days.

Chronic bacterial prostatitis: 1 tablet of Levofloxacin-Teva 1 time per day (respectively, 500 mg of levofloxacin) - 28 days.

Skin and soft tissue infections: 1 tablet of Levofloxacin-Teva 1-2 times a day (respectively, 500-1000 mg of levofloxacin) - 7-14 days.

Complex treatment of drug-resistant forms of tuberculosis: 1 tablet of Levofloxacin-Teva 1-2 times a day (respectively, 500-1000 mg of levofloxacin) - up to 3 months.

Prevention and treatment of anthrax with airborne infection: 1 tablet of Levofloxacin-Teva (respectively, 500 mg of levofloxacin) 1 time per day for up to 8 weeks.

Dosage regimen in patients with impaired renal function

Levofloxacin is excreted mainly by the kidneys, therefore, when treating patients with impaired renal function, a decrease in the dose of the drug is required.

Dosage regimen in patients with impaired liver function

If the liver function is impaired, the dosage regimen does not need to be adjusted, since levofloxacin is only slightly metabolized in the liver.

Dosage regimen in elderly patients

For elderly patients, no dosage regimen correction is required, except in cases of a decrease in CC to 50 ml / min and below.

1 tablet contains:

active substance levofloxacin (levofloxacin hemihydrate) 500.00 (512.46) mg;

excipients: colloidal silicon dioxide 12.00 mg, hyprolose 28.00 mg, sodium carboxymethyl starch, type A 55.00 mg, talc 55.20 mg, croscarmellose sodium 20.60 mg, magnesium stearate 6.74 mg, Opadray 15V26688 shell brown (hypromellose 2910 3 CP 4.760 mg, hypromellose 2910 6 CP 4.760 mg, titanium dioxide E171 3.044 mg, macrogol-400 1.120 mg, polysorbate-80 0.140 mg, iron dye yellow oxide E172 0.120 mg, iron dye red oxide E172 0.043 mg, iron dye black oxide E172 0.013 mg).

• Hypersensitivity to levofloxacin or other quinolones, as well as to any of the excipients of Levofloxacin-Teva;

• epilepsy;

• pseudoparalytic myasthenia gravis (myasthenia gravis) (see sections 'Adverse reactions', 'Special instructions'); Х a history of tendon lesions when taking fluoroquinolones;

• children and adolescents up to 18 years of age (due to incomplete growth of the skeleton, since the risk of damage to cartilaginous growth points cannot be completely excluded);

• pregnancy (the risk of damage to the cartilaginous growth points in the fetus cannot be completely ruled out);

• the period of breastfeeding (the risk of damage to the cartilaginous points of bone growth in a child cannot be completely excluded).

  Carefully

• In patients predisposed to the development of seizures [in patients with previous lesions of the central nervous system (CNS), in patients simultaneously receiving drugs that lower the seizure threshold of the brain, such as fenbufen, theophylline] (see the section 'Interaction with other drugs ').

• In patients with latent or manifest deficiency of glucose-6-phosphate dehydrogenase (increased risk of hemolytic reactions during treatment with quinolones).

• In patients with impaired renal function (mandatory monitoring of renal function is required, as well as correction of the dosage regimen, see section 'Dosage and Administration').

• In patients with known risk factors for prolongation of the QT interval: in elderly patients; in female patients, in patients with uncorrected electrolyte disturbances (with hypokalemia, hypomagnesemia); with congenital lengthening of the QT interval; with heart disease (heart failure, myocardial infarction, bradycardia); while taking medications that can lengthen the QT interval (antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, antipsychotics) (see sections 'Overdose', 'Interaction with other drugs', 'Special instructions').

• In patients with diabetes mellitus receiving oral hypoglycemic drugs, such as glibenclamide or insulin preparations (the risk of hypoglycemia increases).

• In patients with severe adverse reactions to other fluoroquinolones, such as severe neurological reactions (increased risk of similar adverse reactions when using levofloxacin).

• In patients with psychosis or in patients with a history of mental illness

Pharmacodynamics

Levofloxacin is a synthetic broad-spectrum antibacterial drug from the group of fluoroquinolones, containing levofloxacin, the levorotatory isomer of ofloxacin, as an active substance. Levofloxacin blocks DNA gyrase and topoisomerase IV, disrupts supercoiling and stitching of DNA breaks, inhibits DNA synthesis, and causes deep morphological changes in the cytoplasm, cell wall and membranes of microbial cells. Levofloxacin is active against most strains of microorganisms both in vitro and in vivo.

Pharmokinetics

Absorption

Levofloxacin is rapidly and almost completely absorbed after oral administration; food intake has little effect on its absorption. Absolute oral bioavailability is 99-100%. After a single dose of 500 mg of levofloxacin, the maximum plasma concentration (Cmax) is reached within 1-2 hours and is 5.2 ± 1.2 ?g / ml. The pharmacokinetics of levofloxacin is linear in the dose range from 50 to 1000 mg. The equilibrium state of the concentration of levofloxacin in the blood plasma when taking 500 mg of levofloxacin 1 or 2 times a day is achieved within 48 hours. On the 10th day of ingestion of levofloxacin 500 mg once a day, Cmax was 5.7 ± 1.4 ?g / ml, and the minimum concentration of levofloxacin (concentration before taking the next dose) (Cmin) in blood plasma was 0.5 ± 0.2 ?g / ml.On the 10th day of oral administration of levofloxacin 500 mg 2 times a day, Cmax was 7.8 ± 1.1 ?g / ml, and Cmin was 3.0 ± 0.9 ?g / ml.

Distribution

The connection with blood serum proteins is 30-40%. After a single and repeated administration of 500 mg of levofloxacin, the volume of distribution of levofloxacin averages 100 liters, which indicates a good penetration of levofloxacin into the organs and tissues of the human body. Penetration into the bronchial mucosa, epithelial lining fluid, alveolar macrophages

After a single oral intake of 500 mg of levofloxacin, the maximum concentrations of levofloxacin in the bronchial mucosa and epithelial lining fluid were reached within 1 hour or 4 hours and were 8.3 ?g / g and 10.8 ?g / ml, respectively, with coefficients of penetration into the mucous membrane bronchi and epithelial lining fluid, compared with plasma concentrations of 1.1-1.8 and 0.8-3, respectively. After 5 days of ingestion of 500 mg of levofloxacin, the average concentrations of levofloxacin 4 hours after the last administration of the drug in the epithelial lining fluid were 9.94 ?g / ml and in alveolar macrophages - 97.9 ?g / ml.

Penetration into lung tissue

The maximum concentrations in the lung tissue after ingestion of 500 mg of levofloxacin were approximately 11.3 ?g / g and were achieved 4-6 hours after taking the drug with penetration coefficients of 2-5, compared with the concentration in the blood plasma.

Penetration into the alveolar fluid

After 3 days of taking 500 mg of levofloxacin 1 or 2 times a day, the maximum concentrations of levofloxacin in the alveolar fluid were reached 2-4 hours after taking the drug and were 4.0 and 6.7 ?g / ml, respectively, with a penetration coefficient of 1 compared with concentrations in blood plasma.

Bone penetration

Levofloxacin penetrates well into the cortical and cancellous bone tissue both in the proximal and distal parts of the femur, with a penetration coefficient (bone tissue / blood plasma) of 0.1-3. The maximum concentrations of levofloxacin in the cancellous bone tissue of the proximal femur after taking 500 mg of the drug orally were approximately 15.1 ?g / g (2 hours after taking the drug).

Penetration into the cerebrospinal fluid

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Penetration into prostate tissue

After oral administration of 500 mg of levofloxacin 1 time per day for 3 days, the average concentration of levofloxacin in the prostate tissue was 8.7 ?g / g, the average ratio of concentrations of the prostate gland / blood plasma was 1.84. Concentrations in urine Average concentrations in urine 8-12 hours after oral administration of doses of 150, 300 and 600 mg of levofloxacin were 44 ?g / ml, 91 ?g / ml and 162 ?g / ml, respectively.

Metabolism

Levofloxacin is metabolized to an insignificant extent (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 oral administration, levofloxacin is relatively slowly excreted from the blood plasma (half-life (T1 / 2) - 6-8 hours). Excretion, mainly through the kidneys (more than 85% of the dose taken). 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 administered intravenously and when taken orally, which confirms that oral and intravenous administration are interchangeable.

Pharmacokinetics in selected patient groups

The pharmacokinetics of levofloxacin do not differ in men and women. Pharmacokinetics in elderly patients does not differ from that in young patients, with the exception of differences in pharmacokinetics associated with differences in creatinine clearance (CC). In renal failure, the pharmacokinetics of levofloxacin changes. As renal function deteriorates, renal excretion and renal clearance (ClR) decrease and T1 / 2 increases.

Overdose

Overdose symptoms

Based on the data obtained in toxicological studies conducted in animals, the most important expected symptoms of an acute overdose of Levofloxacin-Teva are symptoms from the central nervous system (impaired consciousness, including confusion, dizziness and convulsions). With post-marketing use of the drug in overdose, effects from the central nervous system were observed, including confusion, convulsions, hallucinations and tremors. Perhaps the development of nausea and the occurrence of erosions of the mucous membrane of the gastrointestinal tract. In clinical and pharmacological studies carried out with doses of levofloxacin exceeding therapeutic ones, an increase in the QT interval was observed.

Overdose treatment

In case of overdose, careful monitoring of the patient is required, including monitoring of the electrocardiogram. Treatment is symptomatic. In case of an acute overdose of Levofloxacin-Teva tablets, gastric lavage and administration of antacids are indicated to protect the gastric mucosa. Levofloxacin is not excreted by dialysis (hemodialysis, peritoneal dialysis and continuous ambulatory peritoneal dialysis). There is no specific antidote.

Side effects

Infectious and parasitic diseases: infrequently - fungal infections, the growth of resistant pathogenic microorganisms. Data obtained in clinical trials and post-marketing use of the drug

Cardiac disorders Rare: sinus tachycardia, palpitations. The frequency is 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 (see sections 'Overdose', 'Special instructions').

Disorders from the blood and lymphatic system Uncommon: leukopenia (a decrease in the number of leukocytes in the peripheral blood), eosinophilia (an increase in the number of eosinophils in the peripheral blood). Rarely: neutropenia (a decrease in the number of neutrophils in the peripheral blood), thrombocytopenia (a decrease in the number of platelets in the peripheral blood). The frequency is unknown (post-marketing data): pancytopenia (a decrease in the number of all formed elements in the peripheral blood), agranulocytosis (the absence or a sharp decrease in the number of granulocytes in the peripheral blood), hemolytic anemia.

Nervous system disorders Often: headache, dizziness. Uncommon: drowsiness, tremors, dysgeusia (taste perversion). Rarely: paresthesia, convulsions (see section 'Special instructions'). Frequency unknown (post-marketing data): peripheral sensory neuropathy, peripheral sensory-motor neuropathy (see section 'Special instructions'), dyskinesia, extrapyramidal disorders, ageusia (loss of taste), parosmia (disorder of the sense of smell, especially the subjective sense of smell, objectively absent), including loss of smell; fainting, benign intracranial hypertension.

Visual impairment Rare: visual impairment such as blurring of the visible image. Frequency unknown (post-marketing data): transient loss of vision, uveitis.

Hearing disorders and labyrinthine disorders Uncommon: vertigo (a feeling of deflection or spinning or one's own body or surrounding objects). Rare: ringing in the ears. Frequency unknown (post-marketing data): hearing loss, hearing loss.

Respiratory, chest and mediastinal disorders Uncommon: shortness of breath. Frequency unknown (post-marketing data): bronchospasm, allergic pneumonitis.

Disorders from the gastrointestinal tract Often: diarrhea, vomiting, nausea. Uncommon: abdominal pain, indigestion, flatulence, constipation. Frequency unknown (post-marketing data): hemorrhagic diarrhea, which in very rare cases can be a sign of enterocolitis, including pseudomembranous colitis (see section 'Special instructions'), pancreatitis.

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

Skin and subcutaneous tissue disorders Uncommon: rash, pruritus, urticaria, hyperhidrosis. Frequency unknown (post-marketing data): toxic epidermal necrolysis, Stevens-Johnson syndrome, exudative erythema multiforme, photosensitivity reactions (hypersensitivity to solar and ultraviolet radiation) (see the section 'Special instructions'), leukocytoclastic vasculitis, stomatitis. Reactions from the skin and mucous membranes can sometimes develop even after taking the first dose of the drug.

Musculoskeletal and connective tissue disorders Uncommon: arthralgia, myalgia. Rare: Tendon involvement, including tendonitis (eg, Achilles tendon), muscle weakness, which can be especially dangerous in patients with pseudoparalytic myasthenia gravis (see section 'Special instructions'). Frequency unknown (post-marketing data): rhabdomyolysis, tendon rupture (eg, Achilles tendon. This adverse reaction can occur within 48 hours after the start of treatment and can be bilateral (see also the section 'Special instructions')), ligament rupture, rupture muscles, arthritis.

Metabolic and nutritional disorders Uncommon: anorexia. Rarely: hypoglycemia, especially in patients with diabetes mellitus (possible signs of hypoglycemia: 'wolfish' appetite, nervousness, perspiration, tremors). Frequency unknown: hyperglycemia, hypoglycemic coma (see section 'Special instructions').

Infectious and parasitic diseases Uncommon: fungal infections, development of resistance of pathogenic microorganisms. Vascular disorders Rare: decreased blood pressure. General disorders Uncommon: asthenia. Rarely: pyrexia (fever). Frequency not known: pain (including back, chest and limb pain). Immune system disorders Rare: angioedema.

Frequency unknown (post-marketing data): anaphylactic shock, anaphylactoid shock. Anaphylactic and anaphylactoid reactions can sometimes develop even after taking the first dose of the drug. Liver and biliary tract disorders Often: increased activity of 'liver' enzymes in the blood (for example, alanine aminotransferase (ALT), aspartate aminotransferase (AST)), increased activity of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT). Uncommon: an increase in the concentration of bilirubin in the blood. Frequency unknown (post-marketing data): severe liver failure, including cases of acute liver failure, sometimes fatal, especially in patients with severe underlying disease (eg, in patients with sepsis) (see section 'Special instructions'); hepatitis, jaundice.

Mental Disorders Often: insomnia. Uncommon: feeling of anxiety, anxiety, confusion. Rarely: mental disorders (eg, hallucinations, paranoia), depression, agitation (agitation), sleep disturbances, nightmares. Frequency not known (post-marketing data): mental disorders with behavioral disorders with self-harm, including suicidal thoughts and suicidal attempts.

Other possible side effects related to all fluoroquinolones Very rare: attacks of porphyria (a very rare metabolic disease) in patients with porphyria.

Overdose

Overdose symptoms

Based on the data obtained in toxicological studies conducted in animals, the most important expected symptoms of an acute overdose of Levofloxacin-Teva are symptoms from the central nervous system (impaired consciousness, including confusion, dizziness and convulsions). With post-marketing use of the drug in overdose, effects from the central nervous system were observed, including confusion, convulsions, hallucinations and tremors. Perhaps the development of nausea and the occurrence of erosions of the mucous membrane of the gastrointestinal tract. In clinical and pharmacological studies carried out with doses of levofloxacin exceeding therapeutic ones, an increase in the QT interval was observed.

Overdose treatment

¬ случае передозировки требуетс¤ тщательное наблюдение за пациентом, включа¤ мониторирование электрокардиограммы. Ћечение симптоматическое. ¬ случае острой передозировки таблеток Ћевофлоксацин-“ева показано промывание желудка и введение антацидов дл¤ защиты слизистой оболочки желудка. Ћевофлоксацин не выводитс¤ посредством диализа (гемодиализа, перитонеального диализа и посто¤нного амбулаторного перитонеального диализа). —пецифического антидота не существует.

Ћекарственное взаимодействие

¬заимодействи¤, требующие соблюдени¤ осторожности

— препаратами, содержащими магний, алюминий, железо и цинк, диданозином

ѕрепараты, содержащие двухвалентные или трЄхвалентные катионы, такие как соли цинка или железа (лекарственные препараты дл¤ лечени¤ анемии), магний- и/или алюминий-содержащие препараты (такие как антациды), диданозин (только лекарственные формы, содержащие в качестве буфера алюминий или магний) рекомендуетс¤ принимать не менее чем за 2 ч до или через 2 ч после приема таблеток Ћевофлоксацин-“ева. —оли кальци¤ оказывают минимальный эффект на абсорбцию левофлоксацина при его приеме внутрь.

— сукральфатом

?ействие препарата Ћевофлоксацин-“ева значительно ослабл¤етс¤ при одновременном применении сукральфата (средства дл¤ защиты слизистой оболочки желудка). ѕациентам, получающим левофлоксацин и сукральфат, рекомендуетс¤ принимать сукральфат через 2 ч после приема левофлоксацина.

— теофиллином, фенбуфеном или подобными лекарственными препаратами из группы нестероидных противовоспалительных препаратов, снижающими порог судорожной готовности головного мозга ‘армакокинетического взаимодействи¤ левофлоксацина с теофиллином не вы¤влено. ќднако при одновременном применении хинолонов и теофиллина, нестероидных противовоспалительных препаратов и других препаратов, снижающих порог судорожной готовности головного мозга, возможно выраженное снижение порога судорожной готовности головного мозга.  онцентраци¤ левофлоксацина при одновременном приеме фенбуфена повышаетс¤ только на 13%. — непр¤мыми антикоагул¤нтами (антагонисты витамина  ) ” пациентов, получавших лечение левофлоксацином в комбинации с непр¤мыми антикоагул¤нтами (например, варфарином), наблюдалось повышение протромбинового времени/международного нормализованного отношени¤ и/или развитие кровотечени¤, в том числе и т¤желого. ѕоэтому при одновременном применении непр¤мых антикоагул¤нтов и левофлоксацина необходим регул¤рный контроль показателей свертывани¤ крови.

— пробенецидом и циметидином

ѕри одновременном применении лекарственных препаратов, нарушающих почечную канальцевую секрецию, таких как пробенецид и циметидин, и левофлоксацина, следует соблюдать осторожность, особенно у пациентов с почечной недостаточностью. ¬ыведение (почечный клиренс) левофлоксацина замедл¤етс¤ под действием циметидина на 24% и пробенецида на 34%. ћаловеро¤тно, что это может иметь клиническое значение при нормальной функции почек.

— циклоспорином Ћевофлоксацин увеличивал “1/2 циклоспорина на 33%. “ак как это увеличение ¤вл¤етс¤ клинически незначимым, коррекции дозы циклоспорина при его одновременном применении с левофлоксацином не требуетс¤.

— глюкокортикостероидами

ќдновременный прием глюкокортикостероидов повышает риск разрыва сухожилий.

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).

Other

Clinical and pharmacological studies carried out to study the possible pharmacokinetic interactions of levofloxacin with digoxin, glibenclamide, ranitidine and warfarin showed that the pharmacokinetics of levofloxacin when used simultaneously with these drugs does not change sufficiently to be of clinical significance.