Levofloxacin Ecolevid, 500 mg 5 pcs

Pharmacotherapeutic group: Antimicrobial agent, fluoroquinolone.

ATX code: J01MA12.

Pharmacological properties

Pharmacodnamca

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

Levofloxacin blocks DNA-giase, disrupts superspiralization and cross-linking of DNA breaks, inhibits DNA synthesis and causes deep morphological changes in cytoplasm, cell wall and membranes of bacteria.

Levofloxacin acts bactericidally and is active against a large number of pathogens of bacterial infections both in vitro and in vivo.

Sensitive microorganisms (minimum suppressive concentration (MDC) ≤ 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 nonproducing strains), Morganella morganii, Neisseria gonorrhoeae (penicillinase-producing and nonproducing 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 combined 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 (MPC = 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 (MPC greater 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 trials for infections caused by the microorganisms listed below):

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.

Levofloxacin resistance develops as a result of a stepwise process of mutations in the genes 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 the microbial cell (a mechanism characteristic of Pseudomonas aeruginosa) and the mechanism of efflux (active elimination of the antimicrobial agent from the microbial cell), may also reduce the sensitivity of microorganisms to levofloxacin.

Because of the nature of the mechanism of action of levofloxacin there is usually no cross-resistance between levofloxacin and other antimicrobial agents.

Pharmacoknetzka

Absorption

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

On the 10th day of oral administration of Levofloxacin Ecolevid^® 500 mg once daily, the Cmax of levofloxacin was 5.7±1.4 µg/ml, and the minimum plasma concentration of levofloxacin (concentration before the next dose) (Cmin) was 0.5±0.2 µg/ml.

On day 10 of oral administration of Levofloxacin Ecolevid^® 500 mg twice daily, Cmax was 7.8±1.1 µg/ml and C min was 3.0±0.9 µg/ml.

Distribution

The binding to serum proteins is 30-40%. After single and repeated administration of 500 mg of levofloxacin the volume of distribution of levofloxacin averaged 100 l, indicating good penetration of levofloxacin into human organs and tissues.

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

. After a single oral dose of 500 mg of levofloxacin, maximum concentrations of levofloxacin in bronchial mucosa and epithelial lining fluid were reached within 1 h or 4 h and were 8.3 µg/g and 10.8 µg/mL, respectively, with rates of penetration into bronchial mucosa 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 of levofloxacin, mean concentrations of levofloxacin 4 hours after the last drug administration in the epithelial lining fluid were 9.94 µg/mL and in alveolar macrophages were 97.9 µg/mL.

Prevalence in pulmonary tissue

The maximum pulmonary tissue concentrations after oral administration of 500 mg of levofloxacin were approximately 11.3 µg/g and were reached 4-6 h after drug administration with penetration ratios of 2-5, compared with plasma concentrations.

Alveolar fluid penetration

After 3 days of administration of 500 mg of levofloxacin 1 or 2 times daily, maximum concentrations of levofloxacin in alveolar fluid were reached 2-4 h after drug administration and were
4.0 and 6.7 µg/mL, respectively, with a penetration coefficient of 1, compared to plasma concentrations.

Bone penetration

Levofloxacin penetrates well into cortical and cancellous bone tissue in both the proximal and distal femur, with a penetration ratio (bone tissue/plasma) of 0.1-3. Maximum levofloxacin concentrations in the cancellous bone tissue of the proximal femur following oral administration of 500 mg of the drug were approximately 15.1 µg/g (2 hours after drug administration).

Infiltration into the cerebrospinal fluid

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Infiltration into prostate tissue

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

Urinary concentrations

The mean urinary concentrations 8-12 h after oral doses of 150, 300, and 600 mg of levofloxacin were 44 µg/mL, 91 µg/mL, and 162 µg/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.

Elimation

Levofloxacin is relatively slowly eliminated from the blood plasma after oral administration (half-life (T1/2) is 6-8 hours). Excretion is mainly through the kidneys (more than 85% of the dose taken). Total clearance of levofloxacin after a single dose of 500 mg was 175±29.2 ml/minute.

There are no significant differences in the pharmacokinetics of levofloxacin when administered intravenously and when administered orally, confirming 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 younger patients, except for differences in pharmacokinetics associated with differences in creatinine clearance (CK).

In renal failure, the pharmacokinetics of levofloxacin are altered. As renal function deteriorates, renal excretion and renal clearance (CIR) decreases and T1/2 increases.

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

Indications

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®, you should take into account official national recommendations for the proper use of antibacterial drugs, as well as the sensitivity of pathogenic microorganisms in a particular country (see section “Special instructions”).

Pharmacological effect

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 (producing and non-producing penicillinase 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.

Pharmacokinetics

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 Levofloxacin Ecolevid® 500 mg 1 time per day, Cmax of levofloxacin was 5.7 ± 1.4 μg/ml, and the minimum concentration of levofloxacin (concentration before taking the next dose) (Cmin) in 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 binding to 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 achieved within 1 hour or 4 hours and were 8.3 μg/g and 10.8 μg/ml, respectively, with penetration coefficients into the bronchial mucosa and epithelial lining fluid, compared with plasma concentrations blood, amounting to 1.1-1.8 and 0.8-3, respectively.

After 5 days of oral administration of 500 mg of levofloxacin, the average 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 with 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.

Special instructions

Hospital-acquired infections caused by Pseudomonas aeruginosa may require combination treatment.

Risk of developing resistance

The prevalence of acquired resistance in cultured strains of microorganisms may vary by geographic region and over time. In this regard, information on drug resistance in a specific country is required. For the treatment of severe infections or if treatment is ineffective, a microbiological diagnosis must be established with the isolation of the pathogen and determination of its sensitivity to levofloxacin.

Methicillin-resistant Staphylococcus aureus

There is a high likelihood that methicillin-resistant Staphylococcus aureus will be resistant to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of known or suspected infections caused by methicillin-resistant Staphylococcus aureus unless laboratory tests have confirmed the sensitivity of this microorganism to levofloxacin.

Disability and Potential Irreversible Serious Adverse Reactions Associated with Fluoroquinolones

The use of fluoroquinolones, including levofloxacin, has been associated with disability and the development of irreversible serious adverse reactions from various body systems that can occur simultaneously in the same patient. Adverse reactions caused by fluoroquinolones include tendonitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and nervous system side effects (hallucinations, anxiety, depression, insomnia, headaches, and confusion). These reactions may develop from several hours to several weeks after starting levofloxacin therapy.

The development of these adverse reactions was observed in patients of any age or without the presence of previous risk factors. If the first signs or symptoms of any serious adverse reactions occur, use of levofloxacin should be discontinued immediately. Fluoroquinolones, including levofloxacin, should be avoided in patients who have experienced any of these serious adverse reactions.

Patients predisposed to developing seizures

Like other quinolones, levofloxacin should be used with great caution in patients with a predisposition to seizures. Such patients include patients with previous lesions of the central nervous system, such as stroke, severe traumatic brain injury; patients simultaneously taking drugs that lower the seizure threshold of the brain, such as fenbufen and other similar non-steroidal anti-inflammatory drugs, or other drugs that lower the seizure threshold, such as theophylline (see section “Interaction with other drugs”).

If seizures develop, treatment with levofloxacin should be discontinued.

Pseudomembranous colitis

Diarrhea that develops during or after treatment with levofloxacin, especially severe, persistent and/or bloody, 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 (vancomycin, teicoplanin or oral metronidazole) should be started immediately. Drugs that inhibit intestinal motility are contraindicated.

Tendonitis and tendon rupture

Tendinitis has been reported rarely with quinolones, including levofloxacin, and can sometimes lead to rupture of tendons, including the Achilles tendon, and may be bilateral.

This side effect may occur within 48 hours of starting treatment or several months after completion of fluoroquinolone therapy.

Elderly patients are more prone to developing tendinitis; In patients taking fluoroquinolones, the risk of tendon rupture may be increased with concomitant use of corticosteroids. In addition, post-transplant patients have an increased risk of developing tendonitis, so it is recommended to be careful when prescribing fluoroquinolones to this category of patients. In patients with impaired renal function, the daily dose should be adjusted based on creatinine clearance. Patients should be advised to remain quiet at the first sign of tendonitis or tendon rupture and to contact their healthcare provider. If you suspect the development of tendinitis or tendon rupture, you should immediately stop treatment with Levofloxacin Ecolevid® and begin appropriate treatment of the affected tendon, for example, providing it with sufficient immobilization (see sections “Contraindications” and “Side effects”).

Hypersensitivity reactions

Levofloxacin can cause serious, potentially fatal, hypersensitivity reactions (angioedema, anaphylactic shock), even with initial doses (see section “Side effects”). Patients should immediately stop taking the drug and consult a doctor.

Severe bullous reactions

When using levofloxacin, cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been observed (see section “Side effects”). In case of development of any reactions from the skin or mucous membranes, the patient should immediately consult a doctor and not continue treatment until his consultation.

Disorders of the liver and biliary tract

Cases of hepatic necrosis, including fatal liver failure, have been reported with the use of levofloxacin, mainly in patients with severe underlying diseases, such as sepsis (see section “Side effects”). Patients should be warned to stop treatment and seek immediate medical attention if signs and symptoms of liver damage occur, such as anorexia, jaundice, dark urine, itching and abdominal pain.

Patients with impaired renal function

Since levofloxacin is excreted mainly through the kidneys, patients with impaired renal function require mandatory monitoring of renal function, as well as adjustment of the dosage regimen (see section “Dosage and Administration”). When treating elderly patients, it should be taken into account that patients in this group often have impaired renal function (see section “Dosage and Administration”).

Preventing the development of photosensitivity reactions

Although photosensitivity develops very rarely with the use of levofloxacin, to prevent its development, patients are not recommended to be unnecessarily exposed to strong solar or artificial ultraviolet irradiation (for example, visiting a solarium) during treatment and for 48 hours after the end of treatment with levofloxacin.

Superinfection

As with the use of other antibiotics, the use of levofloxacin, especially for a long time, can lead to increased proliferation of microorganisms (bacteria and fungi) that are insensitive to it, which can cause changes in the microflora that is normally present in humans. As a result, superinfection may develop. Therefore, during treatment, it is imperative to re-evaluate the patient’s condition, and, if superinfection develops during treatment, appropriate measures should be taken.

QT prolongation

Very rare cases of QT prolongation have been reported in patients taking fluoroquinolones, including levofloxacin.

When using fluoroquinolones, including levofloxacin, caution should be exercised in patients with known risk factors for prolongation of the QT interval: 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, such as class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics.

Elderly and female patients may be more sensitive to drugs that prolong the QT interval. Therefore, fluoroquinolones, including levofloxacin, should be used with caution (see sections “With caution”, “Dosage and administration”, “Side effects”, “Overdose” and “Interaction with other drugs”).

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency are predisposed to developing hemolytic reactions when treated with quinolones, which should be taken into account when treating with levofloxacin.

Hypo- and hyperglycemia (dysglycemia)

As with the use of other quinolones, cases of hyperglycemia and hypoglycemia have been observed with the use of levofloxacin, usually in patients with diabetes mellitus receiving concomitant treatment with oral hypoglycemic drugs (for example, glibenclamide) or insulin preparations. Cases of hypoglycemic coma have been reported. In patients with diabetes mellitus, monitoring of blood glucose concentrations is required (see section “Side effects”).

Peripheral neuropathy

Sensory and sensorimotor peripheral neuropathy, which may have a rapid onset, has been reported in patients taking fluoroquinolones, including levofloxacin. If the patient develops symptoms of neuropathy, levofloxacin should be discontinued. This minimizes the possible risk of developing irreversible changes.

Patients should be informed to report any symptoms of neuropathy to their healthcare provider. Fluoroquinolones should not be prescribed to patients with a history of peripheral neuropathy.

Exacerbation of pseudoparalytic myasthenia gravis (myasthenia gravis)

Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may increase muscle weakness in patients with myasthenia gravis. Post-marketing adverse reactions, including pulmonary failure requiring mechanical ventilation and death, have been associated with the use of fluoroquinolones in patients with myasthenia gravis. The use of levofloxacin in a patient with an established diagnosis of pseudoparalytic myasthenia gravis is not recommended (see section “Side Effects”).

Use for airborne anthrax infection

The use of levofloxacin in humans for this indication is based on susceptibility data from Bacillus anthracis obtained from in vitro and experimental animal studies, as well as limited data from the use of levofloxacin in humans. Treating physicians should refer to national and/or international documents that reflect the collectively developed point of view on the treatment of anthrax.

Psychotic reactions

Psychotic reactions, including suicidal ideation/attempts, have been reported in patients taking fluoroquinolones, including levofloxacin, sometimes after a single dose. If such reactions develop, treatment with levofloxacin should be discontinued and appropriate therapy should be prescribed. The drug should be prescribed with caution to patients with psychosis or patients with a history of mental illness (see section “With caution”).

Visual impairment

If any visual impairment develops, immediate consultation with an ophthalmologist is necessary (see section “Side Effects”).

Effect on laboratory tests

In patients taking levofloxacin, the determination of opiates in urine may lead to false-positive results, which should be confirmed by more specific methods.

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and subsequently lead to false-negative results of the bacteriological diagnosis of tuberculosis.

Impact on the ability to drive vehicles and machinery

During treatment, you should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Active ingredient

Levofloxacin

Composition

One tablet contains:

Active substance:

levofloxacin hemihydrate (in terms of levofloxacin) 500 mg;

Excipients: lactitol, lactose monohydrate, low molecular weight povidone, croscarmellose sodium, sodium lauryl sulfate, talc, magnesium stearate, microcrystalline cellulose;

Excipients of the shell: hypromellose, talc, titanium dioxide, macrogol-4000.

Pregnancy

Levofloxacin is contraindicated for use in pregnant and breastfeeding women.

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.

Congenital intolerance to fructose, galactose, galactosemia, 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.

With caution

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

The frequency of adverse reactions is classified according to WHO recommendations: very often ≥1/10, often from ≥1/100 to <1/10, infrequently from ≥1/1000 to <1/100, rarely from ≥1/10000 to <1/1000, very rarely from <1/10000, including isolated cases, frequency unknown - determine the frequency based on available data occurrence was not possible.

From the cardiovascular system

Rarely: sinus tachycardia, palpitations.

Not known: QT prolongation, ventricular arrhythmias, ventricular tachycardia, torsade de pointes (TdP), which may lead to cardiac arrest.

From 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: pancytopenia (decrease in the number of all formed elements in the peripheral blood), agranulocytosis (absence and/or sharp decrease in the number of granulocytes in the peripheral blood), hemolytic anemia.

From the nervous system

Common: headache, dizziness.

Uncommon: drowsiness, tremor, dysgeusia (taste perversion).

Rarely: paresthesia, convulsions (see section “Special instructions”).

Frequency unknown: peripheral sensory neuropathy, peripheral sensorimotor neuropathy (see section “Special Instructions”), 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.

From the side of the organ of vision

Very rare: visual disturbances such as blurred vision.

Frequency unknown: uveitis, transient vision loss.

Hearing and labyrinth disorders

Uncommon: vertigo (a feeling of deviation or spinning of one’s own body or surrounding objects).

Rarely: ringing in the ears.

Frequency unknown: hearing loss, hearing loss.

From the respiratory system, chest organs and mediastinum

Uncommon: shortness of breath.

Frequency unknown: bronchospasm, allergic pneumonitis.

From the gastrointestinal tract

Common: diarrhea, nausea, vomiting.

Uncommon: abdominal pain, flatulence, constipation, dyspepsia.

Frequency unknown: hemorrhagic diarrhea, which in very rare cases may be a sign of enterocolitis, including pseudomembranous colitis (see section “Special instructions”), pancreatitis.

From the kidneys and urinary tract

Uncommon: hypercreatininemia (increased serum creatinine concentration).

Rarely: acute renal failure (for example, due to the development of interstitial nephritis).

From the skin and subcutaneous tissues

Uncommon: rash, itching, urticaria, hyperhidrosis.

Frequency unknown: Stevens-Johnson syndrome, toxic epidermal necrolysis, exudative erythema multiforme, photosensitivity reactions (increased sensitivity to solar and ultraviolet radiation) (see 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.

From the musculoskeletal system and connective tissue

Uncommon: arthralgia, myalgia.

Rarely: tendon lesions, including tendinitis (eg, Achilles tendon), muscle weakness, which can be especially dangerous in patients with myasthenia gravis (see section “Special instructions”).

Not known: rhabdomyolysis, tendon rupture (for example, Achilles tendon. This side effect can be observed within 48 hours after the start of treatment and can be bilateral (see also section “Special instructions”)), ligament rupture, muscle rupture, arthritis.

Metabolism and nutrition

Uncommon: anorexia.

Rarely: hypoglycemia, especially in patients with diabetes mellitus (possible signs of hypoglycemia: voracious appetite, nervousness, perspiration, trembling).

Frequency unknown: severe hypoglycemia, up to the development of hypoglycemic coma, especially in elderly patients, patients with diabetes mellitus, taking oral hypoglycemic drugs or insulin (see section “Special Instructions”).

Infectious and parasitic diseases

Uncommon: fungal infections, development of resistance of pathogenic microorganisms.

From the side of blood vessels

Rarely: decreased blood pressure.

General disorders

Uncommon: asthenia.

Rarely: pyrexia (fever).

Not known: pain (including pain in the back, chest and limbs).

From the immune system

Rarely: angioedema.

Frequency unknown: anaphylactic shock, anaphylactoid shock.

Anaphylactic and anaphylactoid reactions can sometimes develop even after taking the first dose of the drug.

From the liver and biliary tract

Often: increased activity of liver enzymes in the blood (for example, alanine aminotransferase (ALAT), aspartate aminotransferase (AST)), increased activity of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT).

Uncommon: increased concentration of bilirubin in the blood.

Not known: severe liver failure, including cases of acute liver failure, sometimes fatal, especially in patients with severe underlying disease (eg, patients with sepsis); hepatitis, jaundice.

Mental disorders

Common: insomnia.

Uncommon: feeling of restlessness, anxiety, confusion.

Rare: mental disorders (eg, hallucinations, paranoia), depression, agitation (excitement), sleep disturbances, nightmares.

Frequency unknown: mental disorders with behavioral disorders with self-harm, including suicidal thoughts and suicide attempts, attention problems, disorientation, agitation, nervousness, memory impairment, delirium.

Other possible adverse effects that apply to all fluoroquinolones

Very rare: attacks of porphyria (a very rare metabolic disease) in patients with porphyria.

Interaction

There are reports of a pronounced decrease in the seizure threshold with the simultaneous use of quinolones and substances that reduce the cerebral seizure threshold. This also applies to the simultaneous use of quinolones and theophylline, as well as non-steroidal anti-inflammatory drugs – propionic acid derivatives.

No pharmacokinetic interaction of levofloxacin with theophylline was detected.

Oral administration with drugs containing divalent and 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), leads to reduced absorption and a weakening of the effect of levofloxacin, so it should be prescribed after 2 hours before or 2 hours after taking the above medications.

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

The effect of levofloxacin 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.

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

When using vitamin K antagonists simultaneously, monitoring of blood coagulation parameters is necessary.

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

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.

Levofloxacin, when used simultaneously with class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, and antipsychotics, may cause a prolongation of the QT interval.

Levofloxacin increases 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.

Taking glucocorticosteroids increases the risk of tendon rupture.

The pharmacokinetics of levofloxacin when used simultaneously with digoxin, glibenclamide, ranitidine, warfarin does not change sufficiently for it to be of clinical significance.

Overdose

Overdose symptoms:

Based on data obtained from toxicological studies conducted in animals, the most important expected symptoms of acute overdose with levofloxacin are central nervous system symptoms (impaired consciousness, including confusion, dizziness and convulsions).

During post-marketing use of levofloxacin in overdose, central nervous system effects have been observed, including confusion, convulsions, hallucinations and tremor.

Nausea and erosions of the gastrointestinal mucosa may develop.

In clinical pharmacological studies conducted with doses of levofloxacin exceeding therapeutic doses, prolongation of the QT interval was observed.

Treatment of overdose:

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

Storage conditions

In a place protected from moisture and light at a temperature not exceeding 25 ° C.
Keep out of the reach of children.

Shelf life

2 years.
Do not use after expiration date.

Manufacturer

ABVA RUS, Russia