Levofloxacin, 500 mg 10 pcs

Pharmacodynamics

Levofloxacin is a synthetic broad-spectrum antibacterial drug from the group of fluoroquinolones, containing levofloxacin, the left-handed isomer ofloxacin, as the active substance. It blocks DNA-enzyme (topoisomerase II) and topoisomerase IV, breaks supercoiling and cross-linking of DNA breaks, inhibits DNA synthesis, causes deep morphological changes in cytoplasm, cell wall and membranes of sensitive microorganisms.

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

In vitro

Sensitive microorganisms (MAC ≤ 2 mg/l; zone of inhibition ≥ 17 mm)

Aerobic Gram-positive microorganisms:

Corynebacterium diphtheriae, Corynebacterium striatum, Enterococcus spp, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus coagulase-negative methi-S(I) (coagulase-negative methicillin-sensitive/moderately sensitive strains, including methicillin-sensitive strains of Staphylococcus aureus methi-S (methicillin-sensitive), Staphylococcus epidermidis methi-S (methicillin-sensitive), Staphylococcus spp. CNS (coagulazonegative), Streptococci groups C and G, Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus pneumonia peni I/S/R (penicillin-sensitive/moderately sensitive/resistant), penicillin-sensitive/resistant strains Viridans streptococci peni-S/R).

Aerobic Gram-negative microorganisms:

Acinetobacter spp. (including Acinetobacter baumanii), Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter spp. (including Enterobacter aerogenes, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus spp. (including Haemophilus ducreyi, Haemophilus parainfluenzae, ampicillin sensitive/resistant strains of Haemophilus influenza ampi-S/R), Helicobacter pylori, Klebsiella spp. Klebsiella oxytoca, Klebsiella pneumoniae), Moraxela catarrhalis β+/β- (beta-lactamase producing and non-producing strains), Morganella morganii, Neisseria meningitides, Neisseria gonorrhoeae non PPNG/PPNG (non-producing and penicillinase producing), Pasteurella spp. Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas spp. 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.,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.

Moderately susceptible microorganisms (MPC = 4 mg/L; inhibition zone = 16-14 mm)

Aerobic Gram-positive microorganisms:

Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis methi-R (methicillin-resistant strains), Staphylococcus haemolyticus methi-R (methicillin-resistant strains).

Aerobic Gram-negative microorganisms: Campylobacter jejuni/coli.

Anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

Resistant microorganisms (MPC ≥ 8 mg/L; inhibition zone ≤ 13 mm)

Aerobic Gram-positive microorganisms:

Staphylococcus spp. (coagulase-negative methicillin-resistant strains, including methicillin-resistant strains of Staphylococcus aureus).

Aerobic Gram-negative microorganisms: Alcaligenes xylosoxidans.

Anaerobic microorganisms: Bacteroides thetaiotaomicron.

Other microorganisms: Mycobacterium avium.

Resistance

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 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), can also reduce the sensitivity of microorganisms to levofloxacin.

In connection with the specific mechanism of action of levofloxacin there is usually no cross-resistance between levofloxacin and other antimicrobial agents.

Clinical efficacy (effectiveness in clinical studies in the treatment of 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 (Branhamella) catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens.

Others

Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae.

Pharmacokinetics

Absorption

After oral administration levofloxacin is quickly and almost completely absorbed from the gastrointestinal tract. Food intake has little effect on the speed and completeness of absorption. Absolute bioavailability when administered orally is 99-100%. Maximal concentration in plasma is reached after 1-2 hours and for levofloxacin 250 mg, 500 mg and 750 mg doses it is 2.8 µg/ml, 5.2 µg/ml and 8.0 µg/ml, respectively.

The pharmacokinetics of levofloxacin are linear between 50 and 1000 mg. After a single, multiple dose, the amount of the drug absorbed is directly proportional to the dose taken. The equilibrium plasma concentration with 500 mg of levofloxacin 1, 2 times a day is reached after 48 hours.

Distribution

The average volume of distribution of levofloxacin varies from 74 to 112 liters. Binding to plasma proteins is 30-40%. Good penetration into organs and tissues: bronchial mucosa, epithelial lining fluid, alveolar macrophages (concentration in lung tissue is 2-5 times higher than in plasma), lung tissue, bone tissue, urogenital organs, polymorphonuclear leukocytes.

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 excreted from the plasma after oral administration (half-life 6-8 hours). It is excreted mainly by the kidneys through glomerular filtration and tubular secretion. The kidneys excrete unchanged 70% of the dose taken orally within 24 hours and 87% – within 48 hours. 4% of the oral dose is excreted in the intestine within 72 hours.

Pharmacokinetics in selected groups of patients

Pharmacokinetics of levofloxacin does not differ in men and women.

In renal insufficiency the pharmacokinetics of levofloxacin changes. As renal function decreases, renal excretion and renal clearance decrease and the elimination half-life increases.

The pharmacokinetics in elderly patients do not differ from that in younger patients, except for differences related to creatinine clearance.

Indications

Levofloxacin:

– acute bacterial sinusitis;
– exacerbation of chronic bronchitis;
– community-acquired pneumonia;
– uncomplicated urinary tract infections;
– complicated urinary tract infections (including acute pyelonephritis);
– chronic bacterial prostatitis;
– infections of the skin and soft tissues (including suppurating atheromas, abscess, furunculosis);
– tuberculosis (as part of complex therapy of drug-resistant forms).
– prevention and treatment of anthrax through airborne droplets.

Pharmacological effect

Pharmacodynamics

Levofloxacin is a synthetic broad-spectrum antibacterial drug from the group of fluoroquinolones, containing levofloxacin, the levorotatory isomer of ofloxacin, as the active substance. Blocks DNA gyrase (topoisomerase II) and topoisomerase IV, disrupts supercoiling and cross-linking of DNA breaks, inhibits DNA synthesis, causes profound morphological changes in the cytoplasm, cell wall and membranes of sensitive microorganisms.

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

In vitro

Sensitive microorganisms (MIC ≤ 2 mg/l; inhibition zone ≥ 17 mm)

Aerobic gram-positive microorganisms:

Corynebacterium diphtheriae, Corynebacterium striatum, Enterococcus spp., Enterococcus faecalis, Listeria monocytogenes, Staphylococcus coagulase-negative methi-S(I) (coagulase-negative methicillin-sensitive/moderately sensitive strains, including methicillin-sensitive strains of Staphylococcus aureus methi-S (methicillin-sensitive), Staphylococcus epidermidis methi-S (methicillin-sensitive), Staphylococcus spp. CNS (coagulase-negative), Streptococci groups C and G, Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus pneumonia peni I/S/R (penicillin-sensitive/moderately sensitive/resistant), penicillin-sensitive/resistant strains of Viridans streptococci peni-S/R).

Aerobic gram-negative microorganisms:

Acinetobacter spp. (including Acinetobacter baumanii), Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter spp. (including Enterobacter aerogenes, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus spp. (including Haemophilus ducreyi, Haemophilus parainfluenzae, ampicillin sensitive/resistant strains of Haemophilus influenza ampi-S/R), Helicobacter pylori, Klebsiella spp. (including Klebsiella oxytoca, Klebsiella pneumoniae), Moraxela catarrhalis β+/β- (strains producing and not producing beta-lactamase), Morganella morganii, Neisseria meningitides, Neisseria gonorrhoeae non PPNG/PPNG (non-producing and producing penicillinase), 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., 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.

Moderately sensitive microorganisms (MIC = 4 mg/l; inhibition zone = 16-14 mm)

Aerobic gram-positive microorganisms:

Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis methi-R (methicillin-resistant strains), Staphylococcus haemolyticus methi-R (methicillin-resistant strains).

Aerobic gram-negative microorganisms: Campylobacter jejuni/coli.

Anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

Resistant microorganisms (MIC ≥ 8 mg/l; inhibition zone ≤ 13 mm)

Aerobic gram-positive microorganisms:

Staphylococcus spp. (coagulase-negative methicillin-resistant strains, including methicillin-resistant strains of Staphylococcus aureus).

Aerobic gram-negative microorganisms: Alcaligenes xylosoxidans.

Anaerobic microorganisms: Bacteroides thetaiotaomicron.

Other microorganisms: Mycobacterium avium.

Resistance

Resistance to levofloxacin develops as a result of a stepwise process of mutations in the genes encoding both type II topoisomerases: DNA gyrase and toponsomerase 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.

Clinical efficacy (effectiveness in clinical studies in the treatment of 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 (Branhamella) catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens.

Other

Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae.

Pharmacokinetics

Absorption

After oral administration, levofloxacin is rapidly and almost completely absorbed from the gastrointestinal tract. Food intake has little effect on the speed and completeness of absorption. Absolute bioavailability when taken orally is 99-100%. The maximum plasma concentration is reached after 1-2 hours and for a dose of levofloxacin 250 mg, 500 mg and 750 mg is equal to 2.8 μg/ml, 5.2 μg/ml and 8.0 μg/ml, respectively.

The pharmacokinetics of levofloxacin is linear in the range from 50 to 1000 mg. After taking a single, multiple dose, the amount of absorbed drug is directly proportional to the dose taken. Equilibrium concentration in plasma when taking 500 mg of levofloxacin 1.2 times a day is achieved after 48 hours.

Distribution

The mean volume of distribution of levofloxacin varies from 74 to 112 L. Plasma protein binding 30-40%. Penetrates well into organs and tissues: bronchial mucosa, epithelial lining fluid, alveolar macrophages (the concentration in lung tissue is 2-5 times higher than the concentration in plasma), lung tissue, bone tissue, organs of the genitourinary system, polymorphonuclear leukocytes.

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 eliminated from plasma relatively slowly (half-life 6-8 hours). It is excreted from the body primarily by the kidneys by glomerular filtration and tubular secretion. 70% of the dose taken orally is excreted unchanged by the kidneys within 24 hours and 87% within 48 hours. 4% of the dose taken orally is excreted by the intestines within 72 hours.

Pharmacokinetics in selected patient groups

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

In renal failure, the pharmacokinetics of levofloxacin changes. As renal function declines, renal excretion and renal clearance are reduced and the half-life is prolonged.

Pharmacokinetics in elderly patients does not differ from those in young patients, with the exception of differences associated with creatinine clearance.

Special instructions

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

The prevalence of acquired resistance in absorbed strains of microorganisms may vary depending on the geographical 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 streptococcus aureus

There is a high likelihood that methicillin-resistant Streptococcus 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 Streptococcus aureus unless laboratory tests have confirmed the sensitivity of this organism to levofloxacin.

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 CNS lesions, such as stroke, severe traumatic brain injury; patients simultaneously receiving 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”).

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 diffieile. If the development of pseudomembranous coli is suspected, treatment with levofloxacin should be stopped immediately and specific antibiotic therapy (vancomycin, teicoplanin or metronidazole orally) should be started immediately. Drugs that inhibit intestinal motility are contraindicated.

Tendinitis

Rarely observed, tendonitis with quinolones, including levofloxacin, can lead to rupture of tendons, including the Achilles tendon. This side effect may develop within 48 hours of starting treatment and may be bilateral. Elderly patients are more prone to developing tendonitis. The risk of tendon rupture may be increased when taking corticosteroids concomitantly. If tendinitis is suspected, treatment with Levofloxacin should be stopped immediately and appropriate treatment of the affected tendon should be initiated, for example by providing adequate immobilization (see sections “Contraindications” and “Side effects”).

Hypersensitivity reactions

Levofloxacin may 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

Cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been observed while taking levofloxacin (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 the development of 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 kidney failure

Since levofloxacin is excreted mainly by 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 borne in mind that patients in this group often suffer from impaired renal function.

Preventing the development of photosensitivity reactions

Although photosensitivity with levofloxacin is very rare, to prevent its development, patients are not recommended to undergo unnecessary exposure to strong sunlight or artificial ultraviolet radiation (for example, visiting a solarium) during treatment and for 48 hours after the end of treatment with levofloxacin.

Superinfection

Like the use of other antibiotics, the use of levofloxacn, 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, which can lead to the development of superinfection. 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 receiving 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”, “Interaction with other drugs”).

Patients with glucose-6-phosphate dehydrogenase deficiency

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

Hypo- and hyperglycemia (dysglycemia)

As with the treatment of other quinolones, cases of hypo- and hyperglycemia have been observed with the use of lefloxacin, 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, careful 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 receiving fluoroquinolones, including levofloxacin. If the patient develops symptoms of neuropathy, levofloxacin should be discontinued. This minimizes the possible risk of developing irreversible changes.

Exacerbation of pseudoparalytic myasthenia gravis

Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may increase muscle weakness in patients with myasthenia gravis. In the postmarketing period, adverse reactions, including pulmonary failure requiring mechanical ventilation and death, have been observed 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 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 have been reported with quinolones, including levofloxacin, which in very rare cases have progressed to suicidal ideation and self-harming behavior (sometimes after a single dose of levofloxacin (see Adverse Reactions section)). 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.

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

Caution should be exercised when driving and engaging in other potentially hazardous activities, as some side effects of levofloxacin, such as dizziness, drowsiness and visual disturbances, may adversely affect the ability to drive and perform potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Active ingredient

Levofloxacin

Composition

Active substance: levofloxacin hemihydrate, which is equivalent to levofloxacin – 512.46 mg (500.00 mg).

Excipients: microcrystalline cellulose – 44.69 mg; crospovidone – 7.85 mg; sodium stearyl fumarate – 1.41 mg; croscarmellose sodium – 6.15 mg; colloidal silicon dioxide – 15.38 mg; maltodextrin – 24.60 mg; magnesium stearate – 2.46 mg.

Shell: Opadry orange 20А230018 (OPADRY Orange 20А230018) – 15,000 mg [hydroxypropyl methylcellulose 2910/hypromellose 6 cP (E464) – 6,600 mg; titanium dioxide (E171) – 1.375 mg; talc – 3.150 mg; hyprolose (hydroxypropylcellulose, lucel EF) (E463) – 3.851 mg; sunset yellow dye (E 110) – 0.024 mg].

Pregnancy

Levofloxacin is contraindicated for use in pregnant women and women during breastfeeding.

Contraindications

– History of hypersensitivity to levofloxacin, other fluoroquinolones or other components of the drug;

– epilepsy;

– pseudoparalytic myasthenia (myasthenia gravis);

– tendon lesions associated with a history of taking fluoroquinolones;

– childhood and adolescence 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 eliminated);

– pregnancy (the risk of damage to the cartilaginous growth points of the fetus cannot be completely excluded);

– lactation period (the risk of damage to the cartilaginous growth points of bones in a child cannot be completely excluded).

With caution

– predisposition to convulsive reactions (in patients with previous lesions of the central nervous system (CNS), in patients simultaneously receiving drugs that reduce the threshold of convulsive readiness of the brain (fenbufen, theophylline));

– latent, manifested deficiency of glucose-6-phosphate dehydrogenase (increased risk of hemolytic reactions during treatment with quinolones);

– impaired renal function (monitoring of renal function is required, as well as correction of the dosage regimen, see “Dosage and Administration”;

– in patients with known risk factors for prolongation of the QT interval: in elderly patients (over 65 years), in female patients, in patients with uncorrected electrolyte disturbances (hypokalemia, hypomagnesemia); with congenital long QT syndrome; in patients with heart failure, myocardial infarction, bradycardia; while taking medications that prolong the QT interval (class IA and III antiarrhythmics, tricyclic antidepressants, antipsychotics, macrolides);

– in patients with diabetes mellitus receiving oral hypoglycemic drugs (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.

Side Effects

The side effects listed below are presented in accordance with the following gradations of the frequency of their occurrence: very often (≥ 1/10), often (≥ 1/100 to < 1/10), infrequently (≥ 1/1000 to < 1/100), rarely (≥ 1/10000 to < 1/1000), very rarely (< 1/10000), unspecified frequency (according to It is not possible to determine the frequency of occurrence based on the available data).

From the nervous system: often – headache, dizziness; infrequently – drowsiness, tremor, dysgeusia (taste perversion); rarely – paresthesia, convulsions (see section “Special instructions”); unspecified frequency – peripheral sensory neuropathy, peripheral sensorimotor neuropathy, dyskinesia, extrapyramidal disorders, 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.

Mental disorders: often – insomnia; infrequently – feelings of restlessness, anxiety, confusion; rarely – mental disorders (for example, hallucinations, paranoia), depression, agitation, sleep disturbances, nightmares; unspecified frequency – mental disorder with behavioral disorder with self-harm, including suicidal thoughts and suicide attempts.

On the part of the organ of vision: very rarely – visual disturbances, such as blurriness of the visible image; unspecified frequency – transient loss of vision.

From the organ of hearing and labyrinthine disorders: infrequently – vertigo (feeling of deviation, spinning, one’s own body, surrounding objects); rarely – ringing in the ears; unspecified frequency – hearing loss, hearing loss.

From the cardiovascular system: rarely – sinus tachycardia, palpitations, decreased blood pressure; unspecified frequency – 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”).

From the blood and lymphatic system: infrequently – eosinophilia, leukopenia; rarely – neutropenia, thrombocytopenia; unspecified frequency – pancytopenia, agranulocytosis, hemolytic anemia.

From the gastrointestinal tract: often – nausea, vomiting, diarrhea; uncommon – abdominal pain, dyspepsia, flatulence, constipation; unspecified frequency – hemorrhagic diarrhea, which in very rare cases may be a sign of enterocolitis, including pseudomembranous colitis (see section “Special instructions”).

From the liver and biliary tract: often – increased activity of alanine aminotransferase; uncommon – increased bilirubin levels; unspecified frequency – severe liver failure, including cases of acute acute liver failure, sometimes fatal, especially in patients with sepsis); hepatitis, jaundice. hepatitis.

From the respiratory system, chest and mediastinal organs: infrequently – shortness of breath; unspecified frequency – bronchospasm, allergic pneumonitis.

From the side of metabolism and nutrition: infrequently – anorexia; rarely – hypoglycemia (increased appetite, increased sweating, trembling, nervousness); unspecified frequency – hyperglycemia, hypoglycemic coma (see section “Special instructions”).

From the musculoskeletal system and connective tissue: infrequently – arthralgia, myalgia; rarely – tendon damage (for example, Achilles tendon), including tendonitis, muscle weakness, which can be dangerous in patients with pseudoparalytic myasthenia gravis (see section “With caution”); unspecified frequency – 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), ligament rupture, muscle rupture, arthritis (see section “Special Instructions”).

From the kidneys and urinary tract: infrequently – hypercreatininemia; rarely – acute renal failure (for example, due to the development of interstitial nephritis).

From the blood and lymphatic system: infrequently – eosinophilia, leukopenia; rarely – neutropenia, thrombocytopenia; unknown frequency – pancytopenia, agranulocytosis, hemolytic anemia.

From the skin and subcutaneous tissues: infrequently – rash, itching, urticaria, hyperhidrosis; unspecified frequency – malignant exudative erythema (Stevens-Jobs syndrome), toxic epidermal necrolysis (Lyell’s syndrome), photosenenbilization reaction, leukocytoclastic vasculi, stomatitis, exudative erythema multiforme. Reactions from the skin and mucous membranes, anaphylactic and anaphylactoid reactions can sometimes develop even after taking the first dose of the drug.

Infectious and parasitic diseases: infrequently – fungal infections, development of resistance of pathogenic microorganisms.

From the immune system: rarely – angioedema; unspecified frequency – anaphylactic shock, anaphylactoid shock.

General disorders: infrequently – asthenia; rarely – pyrexia (increased body temperature); unspecified frequency – pain (including pain in the back, chest and limbs).

Other possible undesirable effects that apply to all fluoroquinolones: very rarely – attacks of porphyria in patients with porphyria.

Interaction

Interactions requiring caution

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

Drugs containing divalent or trivalent cations, such as zinc and 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) are recommended to be taken at least 2 hours before or 2 hours after taking the drug Levofloxacin.

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

With sucralfate

The effect of levofloxacin is significantly weakened by simultaneous use of sucralfate. For patients receiving levofloxacin and sucralfate, it is recommended that sucralfate be taken 2 hours after taking levofloxacin.

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

No pharmacokinetic interaction of levofloxacin with theophylline was detected. However, with the simultaneous use of quinolones and theophylline, non-steroidal anti-inflammatory drugs and other drugs that reduce the threshold of convulsive readiness of the brain, a pronounced decrease in the threshold of convulsive readiness of the brain is possible. The concentration of levofloxacin with simultaneous administration of fenbufen increases only by 13%.

With indirect coagulants

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

With probenecid and cimetidine

When simultaneous use of drugs that interfere with the renal tubular secretion of levofloxacin, such as probenecid and cimetidine, caution should be exercised, especially in patients with renal failure. Cimetidine and probenecid slow down the elimination of levofloxacin by 24% and 34%, respectively. This is unlikely to be of clinical significance if renal function is normal.

With cyclosporine

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.

With glucocorticosteroids

Concomitant use of glucocorticosteroids increases the risk of tendon rupture.

With drugs that prolong the QT interval

Levofloxacin, like other deuteroquinolones, 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).

Others

The results of clinical and pharmacological studies to study possible pharmacokinetic interactions of levofloxacin with digoxin, glibenclamide, ranitidine, and warfarin were shown. That the pharmacokinetics of levofloxacin when used concomitantly with these drugs does not change sufficiently to be of clinical significance.

Overdose

Symptoms: disturbances of consciousness, including confusion, dizziness, convulsions, possible development of nausea, erosive lesions of the mucous membranes of the gastrointestinal tract, prolongation of the QT interval, hallucinations, tremor.

In case of overdose, careful monitoring of the patient is required, including ECG monitoring.

Treatment: symptomatic. In case of acute overdose, gastric lavage and administration of antacids are indicated to protect the gastric mucosa. There is no specific antidote, dialysis is ineffective.

Short product description

Levofloxacin is a broad-spectrum antibacterial drug. It disrupts the synthesis of microbial DNA and causes profound structural changes in the cells of sensitive microorganisms.

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

Storage conditions

At a temperature not exceeding 25 ºС.

Keep out of the reach of children.

Shelf life

2 years.
Do not use after expiration date.

Manufacturer

Pharmstandard-Leksredstva, Russia