Levofloxacin 250 mg 5 pcs. film-coated tablets

Composition per tablet:

Description

Capsule-shaped biconvex tablets, film-coated, white or almost white; on the cross section two layers are visible, the inner layer is light yellow to yellow in color, white inclusions are allowed.

Pharmacotherapeutic group:

antimicrobial agent, fluoroquinolone.

ATX code:

J01MA12.

Pharmacological properties

Pharmacodynamics

Levofloxacin is a synthetic broad-spectrum antibacterial drug from the group of fluoroquinolones, containing the levorotatory isomer of ofloxacin as an active substance.

Levofloxacin blocks DNA gyrase, disrupts supercoiling and cross-linking of DNA breaks, inhibits DNA synthesis, and causes profound morphological changes in the cytoplasm, cell wall and membranes of bacteria.

Levofloxacin has a bactericidal effect and is active against a large number of pathogens of bacterial infections both in vitro

, and
in vivo
.

Sensitive microorganisms (minimum inhibitory concentration (MIC) ≤ 2 mg/l):

• aerobic gram-positive microorganisms: Bacillus anthracis , Corynebacterium diphtheriae , Corynebacterium jeikeium , Enterococcus spp
  ., including
  Enterococcus faecalis, Listeria monocytogenes, Staphylococcus spp.
  ( coagulase-negative, methicillin-sensitive/leukotoxin-containing/moderately sensitive strains), including
  Staphylococcus aureus (
  methicillin-sensitive strains
  ), Staphylococcus epidermidis (
  methicillin-sensitive strains
  ), Streptococcus spp.
  groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae ( penicillin-sensitive / moderately sensitive / resistant strains
  ), Streptococcus pyogenes, Streptococcus spp.
  Viridans group ( penicillin-sensitive/resistant strains
  );
• aerobic gram-negative microorganisms: Acinetobacter spp .
  , including
  Acinetobacter baumannii , Acinetobacillus actinomycetemcomitans , Citrobacter freundii , Eikenella corrodens , Enterobacter spp
  ., including
  Enterobacter aerogenes , Enterobacter cloacae , Escherichia coli , Gardnerella vaginalis , Haemophilus ducreyi , Haemophilus influenzae
  (ampicillin-sensitive/ resistant strains),
  Haemophilus parainfluenzae , Helicobacter pylori , Klebsiella spp
  ., including
  Klebsiella oxytoca , Klebsiella pneumoniae , Moraxella catarrhalis
  (beta-lactamase producing and non-producing strains),
  Morganella morganii , Neisseria gonorrhoeae
  (penicillinase producing and non-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
  (hospital infections caused by
  Pseudomonas aeruginosa
  may require combination treatment),
  Serratia spp
  ., including
  Serratia marcescens , Salmonella spp
  .;
• 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 pneumophila , Legionella spp ., Mycobacterium spp .
  , including
  Mycobacterium leprae , Mycobacterium tuberculosis , Mycoplasma hominis , Mycoplasma pneumoniae , Rickettsia spp ., Ureaplasma urealyticum
  .

Moderately sensitive microorganisms (MIC = 4 mg/l):

• aerobic gram-positive microorganisms: Corynebacterium urealyticum , Corynebacterium xerosis , Enterococcus faecium , Staphylococcus epidermidis
  (methicillin-resistant strains),
  Staphylococcus haemolyticus
  (methicillin-resistant strains);
• aerobic gram-negative microorganisms: Campylobacter jejuni , Campylobacter coli
  ;
• anaerobic microorganisms: Prevotella spp ., Porphyromonas spp
  .

Resistant microorganisms (MIC more than 8 mg/l):

• aerobic gram-positive microorganisms: Staphylococcus aureus
  (methicillin-resistant strains), other
  Staphylococcus spp
  . (coagulase-negative methicillin-resistant strains);
• aerobic gram-negative microorganisms: Alcaligenes xylosoxidans
  ;
• anaerobic microorganisms: Bacteroides thetaiotaomicron
• other microorganisms: Mycobacterium avium
  .

Clinical efficacy (effectiveness in clinical studies against infections caused by the following microorganisms):

• aerobic gram-positive microorganisms: Enterococcus faecalis , Staphylococcus aureus , Streptococcus pneumoniae , Streptococcus pyogenes
  ;
• aerobic gram-negative microorganisms: Citrobacter freundii , Enterobacter cloacae , Escherichia coli , Haemophilus influenzae , Haemophilus parainfluenzae , Klebsiella pneumoniae , Moraxella catarrhalis , Morganella morganii , Proteus mirabilis , Pseudomonas aeruginosa , Serratia marcescens
  ;
• other microorganisms: Chlamydia pneumoniae , Legionella pneumophila , Mycoplasma pneumoniae
  .

Resistance to levofloxacin develops as a result of a stepwise process of mutations in the genes encoding both type II topoisomerases: DNA gyrase and topoisomerase IV. Other resistance mechanisms, such as the mechanism of influencing the penetration barriers of the microbial cell (a mechanism characteristic of Pseudomonas
aeruginosa
) and the mechanism of efflux (active removal of the antimicrobial agent from the microbial cell), may also reduce the sensitivity of microorganisms to levofloxacin.

Due to the peculiarities of the mechanism of action of levofloxacin, cross-resistance between levofloxacin and other antimicrobial agents is not usually observed.

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Absorption

Levofloxacin is rapidly and almost completely absorbed after oral administration; food intake has little effect on its absorption. Absolute bioavailability when taken orally is 99-100%. After a single dose of 500 mg of levofloxacin, the maximum concentration in blood plasma (Cmax) is reached within 1-2 hours and is 5.2 ± 1.2 μg/ml. The pharmacokinetics of levofloxacin is linear in the dose range from 50 to 1000 mg. The equilibrium state of levofloxacin concentration in blood plasma when taking 500 mg of levofloxacin 1 or 2 times a day is achieved within 48 hours.

On the 10th day of oral administration of the drug Levofloxacin Ecolevid® 500 mg 1 time per day, the Cmax of levofloxacin was 5.7 ± 1.4 mcg/ml, and the minimum concentration of levofloxacin (concentration before taking the next dose) (Cmin) in the blood plasma was 0.5 ±0.2 µg/ml.

On the 10th day of oral administration of the drug Levofloxacin Ecolevid® 500 mg 2 times a day, Cmax was 7.8 ± 1.1 μg/ml, and C min was 3.0 ± 0.9 μg/ml.

Distribution

The connection with serum proteins is 30-40%. After a single and repeated dose of 500 mg of levofloxacin, the volume of distribution of levofloxacin is, on average, 100 l, which indicates good penetration of levofloxacin into organs and tissues of the human body.

Penetration into the bronchial mucosa, epithelial lining fluid, alveolar macrophages

After a single oral dose 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 μg/g and 10.8 μg/ml, respectively, with penetration coefficients into the mucosa bronchi and epithelial lining fluid, compared with plasma concentrations of 1.1-1.8 and 0.8-3, respectively.

After 5 days of oral administration of 500 mg levofloxacin, the mean concentrations of levofloxacin 4 hours after the last dose in the epithelial lining fluid were 9.94 μg/ml and in alveolar macrophages - 97.9 μg/ml.

Penetration into lung tissue

Maximum concentrations in lung tissue after oral administration of 500 mg of levofloxacin were approximately 11.3 mcg/g and were achieved 4-6 hours after dosing with penetration coefficients of 2-5, compared with plasma concentrations.

Penetration into 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 μg/ml, respectively, with a penetration coefficient of 1. compared to plasma concentrations.

Penetration into bone tissue

Levofloxacin penetrates well into cortical and cancellous bone tissue in both 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 oral administration of 500 mg of the drug were approximately 15.1 mcg/g (2 hours after dosing).

Penetration into the cerebrospinal fluid

Levofloxacin penetrates poorly into the cerebrospinal fluid.

Penetration into prostate tissue

After oral administration of 500 mg of levofloxacin once daily for 3 days, the average concentration of levofloxacin in prostate tissue was 8.7 mcg/g, the average prostate/blood plasma concentration ratio was 1.84.

Concentrations in urine

Mean urinary concentrations 8 to 12 hours after oral doses of 150, 300, and 600 mg of levofloxacin were 44 mcg/mL, 91 mcg/mL, and 162 mcg/mL, respectively.

Metabolism

Levofloxacin is metabolized to a small extent (5% of the dose taken). Its metabolites are demethyllevofloxacin and levofloxacin N-oxide, which are excreted by the kidneys. Levofloxacin is stereochemically stable and does not undergo chiral transformations.

Removal

After oral administration, levofloxacin is relatively slowly eliminated from the blood plasma (half-life (T1/2) - 6-8 hours). Excretion is 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 orally, which confirms that oral and intravenous administration are interchangeable.

Pharmacokinetics in selected patient groups

The pharmacokinetics of levofloxacin do not differ between men and women.

Pharmacokinetics in elderly patients do not differ from those in younger 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 (CIR) decrease and T1/2 increases.

Pharmacokinetics in renal failure after a single oral dose of 500 mg of Levofloxacin Ecolevid®.

Indications for use

Treatment of infectious and inflammatory diseases caused by microorganisms sensitive to levofloxacin:

• community-acquired pneumonia;
• complicated urinary tract infections and pyelonephritis;
• chronic bacterial prostatitis;
• infections of the skin and soft tissues;
• for complex treatment of drug-resistant forms of tuberculosis;
• prevention and treatment of anthrax through airborne transmission.

For the treatment of the following infectious and inflammatory diseases, levofloxacin can be used as an alternative to other antimicrobial drugs:

• acute sinusitis;
• exacerbation of chronic bronchitis;
• uncomplicated cystitis.

When using the drug Levofloxacin Ecolevid®, official national recommendations on the proper use of antibacterial drugs, as well as the sensitivity of pathogenic microorganisms in a particular country should be taken into account (see section "Special instructions").

Contraindications

Hypersensitivity to levofloxacin, other fluoroquinolones or components of the drug, epilepsy, tendon damage during previous treatment with quinolones, pregnancy, lactation, childhood and adolescence (up to 18 years), myasthenia gravis.

Lactose intolerance or lactase deficiency, as well as glucose-galactose malabsorption.

Due to the inability to split the tablet in two, the use of the drug is contraindicated in patients with impaired renal function:

• in patients with creatinine clearance less than 50 ml/min, it is impossible to use a dosage regimen with an initial dosage of 250 mg/24 hours;
• in patients with creatinine clearance less than 20 ml/min, it is impossible to use the dosage regimen with an initial dosage of 500 mg/24 hours and 500 mg/12 hours;
• when creatinine clearance is less than 10 ml/min (including during hemodialysis and continuous ambulatory peritoneal dialysis), it is impossible to use it for all dosage regimens.

Overdose

Symptoms of an overdose of Levofloxacin appear at the level of the central nervous system (confusion, dizziness, disturbances of consciousness and seizures of the epileptic type). In addition, gastrointestinal disorders (for example, nausea) and erosive lesions of the mucous membranes, prolongation of the QT interval may occur.

Treatment should be symptomatic. Levofloxacin is not eliminated by dialysis (hemodialysis, peritoneal dialysis and continuous peritoneal dialysis). There is no specific antidote.

Carefully

• In patients predisposed to the development of seizures [in patients with previous lesions of the central nervous system (CNS); in patients simultaneously taking drugs that lower the threshold of convulsive activity of the brain, such as fenbufen, theophylline] (see 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 QT interval prolongation: in elderly patients; in female patients; in patients with uncorrected electrolyte disturbances (with hypokalemia, hypomagnesemia); with congenital long QT syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); while taking medications that can prolong the QT interval (class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics) (see sections “Overdose”, “Interaction with other drugs”, “Special instructions”);
• In patients with diabetes mellitus receiving oral hypoglycemic drugs (for example, glibenclamide) or insulin drugs (the risk of hypoglycemia increases);
• In patients with severe adverse reactions to other fluoroquinolones, such as severe neurological reactions (increased risk of developing similar adverse reactions when using levofloxacin);
• In patients with psychosis or in patients with a history of mental illness (see section "Special instructions");
• In elderly patients, in patients after transplantation, as well as with concomitant use of glucocorticosteroids (increased risk of tendinitis and tendon rupture) (see section "Special instructions").

Side effects of Levofloxacin

Allergic reactions: sometimes – itching and redness of the skin; rarely - general hypersensitivity reactions (anaphylactic and anaphylactoid reactions) with symptoms such as urticaria, constriction of the bronchi and possibly severe suffocation; very rarely - swelling of the skin and mucous membranes (for example, in the face and throat), sudden drop in blood pressure and shock, increased sensitivity to solar and ultraviolet radiation, allergic pneumonitis, vasculitis; in some cases - severe skin rashes with blistering, for example, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome) and exudative erythema multiforme. General hypersensitivity reactions may sometimes be preceded by milder skin reactions. The above reactions can develop after the first dose, a few minutes or hours after administration of the drug.

From the digestive system: often - nausea, diarrhea, increased activity of liver enzymes (for example, alanine aminotransferase and aspartate aminotransferase); sometimes - loss of appetite, vomiting, abdominal pain, digestive disorders; rarely - diarrhea mixed with blood, which in very rare cases can be a sign of intestinal inflammation and even pseudomembranous colitis.

On the metabolic side: very rarely - a decrease in the concentration of glucose in the blood, which is of particular importance for patients with diabetes (possible signs of hypoglycemia: increased appetite, nervousness, perspiration, trembling). Experience with the use of other quinolones suggests that they can cause exacerbation of porphyria in patients already suffering from this disease. A similar effect cannot be excluded when using the drug levofloxacin.

From the nervous system: sometimes - headache, dizziness and/or stupor, drowsiness, sleep disturbances; rarely - anxiety, paresthesia in the hands, trembling, psychotic reactions such as hallucinations and depression, agitation, convulsions and confusion; very rarely - impaired vision and hearing, impaired taste and smell, decreased tactile sensitivity.

From the cardiovascular system: rarely - increased heartbeat, decreased blood pressure; very rarely - vascular (shock-like) collapse; in some cases - prolongation of the QT interval.

From the musculoskeletal system: rarely - tendon damage (including tendinitis), joint and muscle pain; very rarely - tendon rupture (for example, Achilles tendon); this side effect can be observed within 48 hours after the start of treatment and can be bilateral in nature, muscle weakness, which is of particular importance for patients with bulbar syndrome; in some cases - muscle damage (rhabdomyolysis).

From the urinary system: rarely - increased levels of bilirubin and creatinine in the blood serum; very rarely - deterioration of kidney function up to acute renal failure, interstitial nephritis.

From the hematopoietic organs: sometimes - an increase in the number of eosinophils, a decrease in the number of leukocytes; rarely - neutropenia, thrombocytopenia, which may be accompanied by increased bleeding; very rarely - agranulocytosis and the development of severe infections (persistent or recurrent increase in body temperature, deterioration in health); in some cases - hemolytic anemia; pancytopenia.

Other: sometimes - general weakness; very rarely - fever.

Any antibiotic therapy can cause changes in the microflora that is normally present in humans. For this reason, increased proliferation of bacteria and fungi resistant to the antibiotic used may occur, which in rare cases may require additional treatment.

Directions for use and doses

Inside. Once or twice a day. The tablets should be swallowed without chewing and washed down with a sufficient amount of liquid (0.5 to 1 glass).

The drug can be taken before meals or at any time between meals, since food intake does not affect the absorption of the drug (see section "Pharmacokinetics").

The drug should be taken at least 2 hours before or 2 hours after taking drugs containing magnesium and/or aluminum, iron, zinc, or sucralfate (see section “Interaction with other drugs”).

Considering that the bioavailability of levofloxacin when taking Levofloxacin Ecolevid® tablets is 99-100%, if the patient is transferred from intravenous infusion with other levofloxacin drugs, taking Levofloxacin Ecolevid® tablets should be continued at the same dose that was used for intravenous infusion of levofloxacin drugs (see section "Pharmacokinetics").

Skipping one or more doses of the drug

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

special instructions

Levofloxacin eye drops can only be used topically. The solution cannot be injected into the anterior chamber of the eye or subconjunctivally.

The solution contains benzalkonium chloride, which is a preservative. In this regard, there is no need to use the drug when wearing hydrophilic contact lenses, because in this case eye irritation may occur. If there are signs of bacterial conjunctivitis, then contact methods of refractive correction should be completely abandoned.

Due to the fact that after instillation of the medicine, a temporary decrease in vision may occur, it is not recommended to engage in potentially hazardous activities during this period, in particular, driving a car.

Due to the fact that systemic fluoroquinolols can lead to serious allergic reactions even after a single dose, Levofloxacin eye drops should be discontinued if signs of allergy and hypersensitivity occur.

If you use the drug for a long time, there is a high probability of resistance developing in microorganisms, as well as the growth of fungal flora. If there is a decrease in the effectiveness of Levofloxacin eye drops or an increase in clinical symptoms, then it is necessary to change the medicine to another antibiotic.