Levasept tablets 500 mg No. 5

Instructions for Levasept tablets 500 mg No. 5

Composition

active ingredient: levofloxacin;

1 film-coated tablet contains levofloxacin hemihydrate equivalent to levofloxacin 500 mg;

excipients: microcrystalline cellulose, crospovidone, povidone, colloidal anhydrous silica, talc, magnesium stearate; shell – Opadry 03B565038 (sorbic acid, hydroxypropylcellulose, titanium dioxide (E 171), hypromellose, vanillin, quinoline yellow aluminum lake (E 104), polysorbates, propylene glycol).

Dosage form

Film-coated tablets.

Main physicochemical properties: brown, oblong, biconvex tablets, film-coated, imprinted with "B500" on one side and smooth on the other side.

Pharmacotherapeutic group

Antibacterials of the quinolone group. Fluoroquinolones. Levofloxacin. ATX code J01M A12.

Pharmacological properties

Pharmacodynamics

Levofloxacin is characterized by a broad spectrum of antibacterial activity. The bactericidal effect is provided by the inhibition by levofloxacin of the bacterial enzyme DNA gyrase, which belongs to type II topoisomerases. The result of such inhibition is the inability of bacterial DNA to transition from a relaxed state to a supercoiled state, which, in turn, makes further division (reproduction) of bacterial cells impossible. The spectrum of activity of the drug Levasept includes gram-positive, gram-negative bacteria, along with non-fermenting bacteria.

Typically sensitive species

Gram-positive aerobes: Bacillus anthracis, methicillin-sensitive Staphylococcus aureus, Staphylococcus saprophyticus, Streptococci groups C and G, Streptococcus agalactiae, Streptococcus pneumonia, Streptococcus pyogenes.

Gram-negative aerobes: Eikenella corrodens, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella oxytoca, Moraxella catarrhalis, Pasteurella multocida, Proteus vulgaris, Providencia rettgeri.

Anaerobes: Peptostreptococcus.

Others: Chlamydophila pneumonia, Chlamydophila psittaci, Chlamydia trachomatis, Legionella pneumophila, Mycoplasma pneumonia, Mycoplasma hominis, Ureaplasma urealyticum.

Species with possible acquired resistance

Gram-positive aerobes: Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, Staphylococcus coagulase spp.

Gram-negative aerobes: Acinetobacter baumannii, Citrobacter freundii, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Providencia stuartii, Pseudomonas aeruginosa, Serratia marcescens.

Anaerobes: Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides vulgaris, Clostridium difficile.

Naturally resistant strains

Gram-positive aerobes: Enterococcus faecium.

Mechanism of resistance development

Resistance to levofloxacin develops as a stepwise mutation of the target site in both types of topoisomerase II, DNA gyrase and topoisomerase IV. Other mechanisms of resistance, such as permeability (characteristic of Pseudomonas aeruginosa) and efflux mechanisms, may also influence susceptibility to levofloxacin.

Cross-resistance between levofloxacin and other fluoroquinolones has been observed. Given the mechanism of action, there is no cross-resistance between levofloxacin and other classes of antibacterial agents.

Breakpoint concentrations of the antibiotic (or the limit values of the diameter of the zone of inhibition of the growth of the microorganism).

EUCAST (European Committee on Antimicrobial Susceptibility Testing) recommends the minimum inhibitory concentration (MIC) of levofloxacin for determining susceptibility from intermediately susceptible organisms and intermediately resistant microorganisms, presented in Table 1 according to MIC test data (mg/L).

Clinically determined EUCAST MICs for levofloxacin (version 2.0, 2012-01-01)

Table 1

The MIC breakpoints for levofloxacin are relevant for high-dose treatment. Low-level resistance to fluoroquinolones occurs (ciprofloxacin MIC 0.12–0.5 mg/L), but there is no evidence of clinically relevant resistance in respiratory tract infections caused by H. influenzae. Strains with MICs above the breakpoints are very rare or have not been reported. Identification and antibiotic susceptibility testing of any isolate should be repeated twice and, if confirmed, the isolate should be referred to a reference laboratory. In the absence of clinical response, confirmed isolates with MICs above the current resistance breakpoint should be considered resistant. The breakpoints are for oral doses of 500 mg x 1 to 500 mg x 2 and intravenous doses of 500 mg x 1 to 500 mg x 2.

The prevalence of resistance may vary geographically and over time for individual species, so local information on resistance is important, particularly in the treatment of severe infections. Expert advice should be sought when the local prevalence of resistance is such that the usefulness of the agent, at least for some types of infection, is questionable.

Absorption. Levofloxacin is rapidly and almost completely absorbed after oral administration, with peak plasma concentrations occurring 1–2 hours after dosing. Absolute bioavailability is 99–100%. Absorption is slightly affected by food intake. Steady-state values are reached within 48 hours after administration of 500 mg 1–2 times daily.

Distribution: Approximately 30–40% of levofloxacin is bound to serum proteins. The mean volume of distribution of levofloxacin is approximately 100 L after single and repeated doses of 500 mg, indicating good distribution into body tissues.

The cumulative effect of levofloxacin at a dosage of 500 mg once a day is not clinically significant and can be neglected. There is a slight but predictable accumulation at a dosage of 500 mg twice a day. Steady state is reached within 3 days.

Distribution in bronchial mucosa and bronchial epithelial secretions. The maximum concentration of levofloxacin in bronchial mucosa and bronchial epithelial secretions after oral administration of 500 mg is 8.3 and 10.8 μg/ml, respectively.

Distribution in lung tissue: The maximum concentration of levofloxacin in lung tissue after oral administration of 500 mg is approximately 11.3 μg/ml and is reached within 4-6 hours after administration of the drug. The concentration in the lungs exceeds the concentration in blood plasma.

Distribution in blister fluid: The maximum concentration of levofloxacin in blister fluid after administration of 500 mg 1 and 2 times a day is 4.0 and 6.7 μg/ml, respectively.

Distribution in cerebrospinal fluid: Levofloxacin penetrates poorly into the cerebrospinal fluid.

Distribution in prostate tissue: After oral administration of 500 mg levofloxacin once daily for 3 days, mean concentrations in prostate tissue are 8.7 μg/mL, 8.2 μg/mL, and 2 μg/mL at 2, 6, and 24 hours, respectively; the mean prostate/plasma concentration ratio is 1.84.

Urine concentration: The mean concentration of levofloxacin within 8–12 hours after administration of a single oral dose of 150 mg, 300 mg, or 500 mg is 44 μg/mL, 91 μg/mL, and 200 μg/mL, respectively.

Metabolism: Levofloxacin is metabolized to a minor extent, its metabolites are desmethyl-levofloxacin and levofloxacin N-oxide. These metabolites account for less than 5% of the amount of drug excreted in the urine. Levofloxacin is stereochemically stable and is not subject to inversion of the chiral structure.

Elimination: After oral administration, levofloxacin is eliminated from plasma very slowly (half-life 6–8 hours). Elimination is mainly renal (more than 85% of the dose). There is no significant difference in the pharmacokinetics of levofloxacin after intravenous and oral administration.

Linearity: Levofloxacin has linear pharmacokinetics over the dose range of 50 to 600 mg.

Patients with renal insufficiency

The pharmacokinetics of levofloxacin are affected by renal insufficiency. Renal excretion and clearance are reduced and half-lives are prolonged with decreased renal function, as shown in Table 2.

Table 2

Elderly patients

There are no significant differences in the pharmacokinetics of levofloxacin between young and elderly patients, except for differences related to creatinine clearance.

Gender differences

Separate analyses of male and female patients have shown slight gender differences in the pharmacokinetics of levofloxacin. There is no evidence that these gender differences in pharmacokinetics are clinically relevant.

Indication

Levacept is indicated for the treatment of infections in adults caused by levofloxacin-sensitive microorganisms:

Acute bacterial rhinosinusitis; exacerbation of chronic obstructive pulmonary disease, including bronchitis; community-acquired pneumonia; complicated skin and soft tissue infections; uncomplicated cystitis.

In the treatment of the above infections, the drug should be used only when the use of other antibacterial agents, which are usually prescribed for the initial treatment of these infections, is not possible.

Acute pyelonephritis and complicated urinary tract infections; chronic bacterial prostatitis; pulmonary anthrax: post-exposure prophylaxis and treatment.

Levasept in this dosage form (tablets) can be used to complete the course of therapy in patients who have demonstrated improvement during the initial treatment with Levoflox, solution for infusion.

Official recommendations on the appropriate use of antibacterial agents should be considered.

Contraindication

Hypersensitivity to levofloxacin, to other fluoroquinolones or to any component of the drug. Epilepsy. Tendon damage associated with previous use of fluoroquinolones. Children's age. Pregnancy or breastfeeding.

Interaction with other medicinal products and other types of interactions

Effects of other medicinal products on levofloxacin

The absorption of levofloxacin is significantly reduced when taken simultaneously with iron salts and antacids containing magnesium or aluminum, or didanosine (only for forms containing aluminum or magnesium buffering agents). The simultaneous use of fluoroquinolones with multivitamins containing zinc leads to a decrease in their absorption when taken orally.

The tablets should be taken at least 2 hours after taking drugs containing divalent or trivalent cations, such as iron salts or antacids containing magnesium or aluminum. Calcium carbonate had a minimal effect on the absorption of levofloxacin when administered orally.

Sucralfate

The bioavailability of levofloxacin is significantly reduced when the drug is used simultaneously with sucralfate. If the patient needs to receive both sucralfate and levofloxacin, it is better to take sucralfate 2 hours after taking Levacept tablets.

Theophylline, fenbufen, or similar nonsteroidal anti-inflammatory drugs (NSAIDs)

No pharmacokinetic interaction of levofloxacin with theophylline has been identified. However, a significant decrease in the seizure threshold may occur with the simultaneous use of quinolones with theophylline, nonsteroidal anti-inflammatory drugs and other drugs that reduce the seizure threshold.

Levofloxacin concentrations in the presence of fenbufen were approximately 13% higher than when levofloxacin was administered alone.

Probenecid and cimetidine

Probenecid and cimetidine have a statistically significant effect on the excretion of levofloxacin.

Renal clearance of levofloxacin with simultaneous use of cimetidine is reduced by 24%, probenecid - by 34%. This is explained by the fact that both drugs are able to block the tubular secretion of levofloxacin. However, in the study, statistically significant kinetic differences were not clinically significant.

Levofloxacin should be administered with caution simultaneously with drugs that affect tubular secretion, such as probenecid and cimetidine, especially in patients with renal insufficiency.

Other drugs

It is known that no clinically significant effect was caused on the pharmacokinetics of levofloxacin when levofloxacin was used together with calcium carbonate, digoxin, glibenclamide, ranitidine.

Effect of levofloxacin on other drugs

Cyclosporine

The half-life of cyclosporine increases by 33% when co-administered with levofloxacin.

Vitamin K antagonists

Co-administration with vitamin K antagonists (e.g. warfarin) has been associated with increased international normalized ratio (INR) and/or bleeding, which may be severe. Therefore, coagulation parameters should be monitored in patients receiving concomitant vitamin K antagonists.

QT-prolonging drugs

Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving medicinal products known to prolong the QT interval (e.g. class IA and III antiarrhythmics, tricyclic antidepressants, macrolides and antipsychotics), see section 4.4.

Other significant information

No clinically significant effect on the pharmacokinetics of levofloxacin was detected with the simultaneous use of the following drugs: calcium carbonate, digoxin, glibenclamide, ranitidine.

It is not recommended to use levofloxacin simultaneously with alcohol.

Concomitant use with glucocorticoids increases the risk of tendon rupture.

Levofloxacin has not been shown to have any effect on the pharmacokinetics of theophylline (which is a marker substrate for the CYP1A2 enzyme), indicating that levofloxacin is not a CYP1A2 inhibitor.

Eating

No clinically significant interaction with food has been observed. Thus, Levacept tablets can be taken regardless of food intake.

Application features

The drug should be avoided in patients who have had serious adverse reactions to quinolones and fluoroquinolones in the past. Treatment of these patients with levofloxacin should only be initiated if there are no alternative treatment options and after a careful benefit/risk assessment.

Methicillin-resistant S. aureus

Methicillin-resistant S. aureus (MRSA) has a very high probability of being co-resistant to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of infections known or suspected to be caused by MRSA, unless laboratory tests have confirmed that the pathogen is susceptible to levofloxacin.

Levofloxacin can be used to treat acute bacterial sinusitis and exacerbation of chronic bronchitis, if these infections have been appropriately diagnosed.

Fluoroquinolone resistance in E. coli (a common cause of urinary tract infections) varies between countries. When prescribing fluoroquinolones, especially for urinary tract infections, the local prevalence of fluoroquinolone resistance in E. coli should be taken into account.

Use in pulmonary anthrax is based on in vitro and animal susceptibility data of Bacillus anthracis and limited human data. Physicians should follow national and/or international consensus statements on the treatment of anthrax.

Prolonged, disabling and potentially irreversible serious adverse reactions.

In very rare cases, prolonged (months or years), disabling and potentially irreversible adverse reactions affecting various, and sometimes multiple, body systems (including musculoskeletal, nervous, mental and sensory) have been reported in patients receiving quinolones and fluoroquinolones, regardless of age and existing risk factors. The drug should be discontinued immediately at the first signs or symptoms of any adverse reaction and a doctor should be consulted.

Tendinitis and tendon ruptures

Tendinitis, which may lead to tendon rupture, including but not limited to the Achilles tendon, has been reported rarely with quinolone therapy. Tendinitis and tendon rupture, sometimes bilateral, may occur within 48 hours of levofloxacin administration and even several months after discontinuation of levofloxacin.

Patients over 60 years of age, patients receiving a daily dose of 1000 mg of levofloxacin, patients with impaired renal function, patients with solid organ transplants and patients receiving concomitant corticosteroids are most susceptible to tendinitis and tendon rupture. Therefore, concomitant use of corticosteroids should be avoided. The daily dose should be adjusted for elderly patients, taking into account creatinine clearance.

Such patients should be closely monitored and a physician should be consulted if symptoms of tendinitis (e.g. painful swelling, inflammation) occur. If tendinitis is suspected, levofloxacin should be discontinued immediately and appropriate treatment should be initiated (e.g. immobilization of the tendon) (see sections 4.3 and 4.8).

Diseases caused by Clostridium difficile

Diarrhea, particularly severe, persistent and/or hemorrhagic, during or after treatment (up to several weeks after the end of treatment) with the drug may be a symptom of Clostridium difficile-associated disease, the most severe form of which is pseudomembranous colitis. If pseudomembranous colitis is suspected, the drug should be discontinued immediately and supportive therapy and, if necessary, specific therapy (e.g., oral vancomycin) should be initiated as soon as possible.

Agents that inhibit intestinal motility are contraindicated in this clinical situation.

Patients prone to seizures

Quinolones may lower the seizure threshold and induce seizures. Levofloxacin is contraindicated in patients with a history of epilepsy. As with other quinolones, Levacept should be used with caution in patients prone to seizures, such as those with central nervous system (CNS) lesions, concomitant treatment with fenbufen and similar NSAIDs or drugs that increase seizure susceptibility (lower the seizure threshold), such as theophylline (see section "Interaction with other medicinal products and other forms of interaction"). If seizures occur, levofloxacin treatment should be discontinued.

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with latent or present defects in glucose-6-phosphate dehydrogenase activity may be predisposed to hemolytic reactions when treated with quinolone antibacterial agents, therefore levofloxacin should be used with caution in such patients and monitored for possible hemolysis.

Patients with renal failure

Since levofloxacin is excreted mainly by the kidneys, dose adjustment is required for patients with impaired renal function (renal failure), see section "Method of administration and dosage".

Hypersensitivity reactions

Levofloxacin may occasionally cause serious, potentially fatal hypersensitivity reactions (e.g. angioedema up to and including anaphylactic shock) after the initial dose of the drug (see section 4.8). In such cases, patients should discontinue treatment immediately and consult a doctor.

Severe skin reactions

Severe cutaneous adverse reactions (SCARs), including toxic epidermal necrolysis (TEN), also known as Lyell syndrome, Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported and can be life-threatening or fatal. Patients should be advised of the signs and symptoms of severe skin reactions and monitored closely. If such signs and symptoms occur, levofloxacin should be discontinued immediately and alternative treatment should be considered. If a patient has developed a serious reaction such as SJS, TEN or DRESS with levofloxacin, levofloxacin should never be restarted in that patient. Patients should be advised to seek immediate medical attention before continuing treatment if skin and/or mucous membrane reactions occur.

Changes in blood glucose levels (both hyperglycemia and hypoglycemia) have been reported with the use of quinolones, especially in diabetic patients receiving concomitant oral hypoglycemic agents (including glibenclamide) or insulin. Cases of hypoglycemic coma have been reported. Blood sugar levels should be monitored in diabetic patients.

Prevention of photosensitivity

Photosensitivity has been reported with levofloxacin. To avoid this, patients are advised not to be exposed to strong sunlight or artificial UV radiation (e.g. artificial UV lamps, solariums) while taking levofloxacin and for 48 hours after stopping the drug.

Patients receiving vitamin K antagonists

Due to the potential risk of increased coagulation tests (prothrombin time/INR) and/or bleeding in patients receiving levofloxacin in combination with a vitamin K antagonist (e.g. warfarin), blood coagulation tests should be monitored during concomitant use (see section 4.5).

Psychotic reactions

Psychotic reactions have been reported in patients taking quinolones, including levofloxacin.

In very rare cases, they have progressed to suicidal ideation and self-harm, sometimes after taking a single dose of levofloxacin (see section 4.8). If a patient experiences these reactions, levofloxacin should be discontinued and appropriate measures should be taken.

It is recommended that levofloxacin be used with caution in patients with psychotic disorders or patients with a history of mental illness.

QT prolongation

Levacept should be used with caution in patients with known risk factors for QT prolongation, such as:

Congenital or acquired long QT syndrome; Concomitant use of medicinal products known to prolong the QT interval (e.g. class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics); Uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia); Cardiac disease (e.g. heart failure, myocardial infarction, bradycardia).

Elderly patients and younger women may be more sensitive to drugs that prolong the QT interval, therefore caution should be exercised when administering levofloxacin to these categories of patients (see sections “Interaction with other medicinal products and other types of interactions”, “Method of administration and dosage”; “Elderly patients”; “Overdose”, “Adverse reactions”).

Aortic aneurysm and aortic dissection.

According to epidemiological studies, there is an increased risk of developing aortic aneurysm and dissection after taking fluoroquinolones, especially in elderly patients.

Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other possible treatments in patients with a family history of aneurysm or in patients diagnosed with aortic aneurysm and/or aortic dissection, or in the presence of other risk factors or conditions predisposing to aortic aneurysm and dissection (e.g. Marfan syndrome, Ehlers-Danlos vascular syndrome, Takayasu syndrome, giant cell arteritis, Behçet's disease, hypertension, atherosclerosis).

Patients should be advised to seek immediate emergency medical attention if they experience sudden abdominal, chest, or back pain.

Peripheral neuropathy

Cases of sensory or sensorimotor peripheral neuropathy, which may be rapid in onset, have been reported in patients receiving fluoroquinolones, including levofloxacin, resulting in paresthesia, hypoesthesia, dysesthesia, or weakness. Patients treated with levofloxacin should be advised to inform their physician if symptoms of neuropathy, such as pain, burning, tingling, numbness, or weakness, occur in order to prevent the development of a potentially irreversible condition. Levofloxacin should be discontinued if a patient develops symptoms of neuropathy in order to prevent the development of an irreversible condition.

Genitobiliary disorders

Cases of necrotizing hepatitis up to life-threatening hepatic failure have been reported with levofloxacin, predominantly in patients with severe underlying diseases such as sepsis (see section 4.8). Patients should be advised to discontinue treatment and seek medical advice if signs and symptoms of liver disease such as anorexia, jaundice, dark urine, pruritus or abdominal pain occur.

Exacerbation of myasthenia gravis

Fluoroquinolones, including levofloxacin, block neuromuscular transmission and may cause muscle weakness in patients with myasthenia gravis. Serious adverse reactions, including fatalities and the need for respiratory support, have been reported post-marketing with fluoroquinolones in patients with myasthenia gravis. Levofloxacin is not recommended for use in patients with a history of myasthenia gravis.

There are reports (22 reports worldwide) of the development of retinal detachment with the use of fluoroquinolone antibiotics.

If visual impairment or other effects on the eyes are observed, an ophthalmologist should be consulted immediately (see sections “Ability to influence the reaction speed when driving vehicles or other mechanisms”, “Adverse reactions”).

Superinfection

When using levofloxacin, especially long-term, the growth of resistant microorganisms is possible. If superinfection develops during therapy, appropriate measures should be taken.

Impact on laboratory tests

In patients treated with levofloxacin, urine opiates may give false-positive results. It may be necessary to confirm positive opiates with more specific methods.

Levofloxacin inhibits the growth of Mycobacterium tuberculosis, therefore a false-negative result is possible when conducting a bacteriological study in patients with tuberculosis.

When prescribing, official guidelines on the appropriate use of antibacterial agents should be taken into account.

Ability to influence reaction speed when driving vehicles or other mechanisms

Patients who drive vehicles, work with machines and mechanisms should take into account possible adverse reactions from the nervous system (dizziness/vertigo, numbness, drowsiness, confusion, impaired vision and hearing, impaired movement processes, including when walking).

Use during pregnancy or breastfeeding

Pregnancy: There are limited data from the use of levofloxacin in pregnant women.

Due to the lack of human studies and the potential for quinolones to damage articular cartilage in the growing body, Levasept is contraindicated for use in pregnant women. If pregnancy is established during treatment with Levasept, the doctor should be informed.

Breastfeeding. Levasept is contraindicated for use during breastfeeding.

There is insufficient information on the excretion of levofloxacin into breast milk, although other fluoroquinolones are excreted in breast milk. Due to the lack of human studies and the potential for fluoroquinolones to damage articular cartilage in the growing body, Levacept should not be administered to breastfeeding women.

Fertility

Levofloxacin did not cause impairment of fertility and reproductive function in rats.

Method of administration and doses

Take Levasept tablets 1–2 times a day. The dose depends on the type, severity of the infection, and the sensitivity of the probable pathogen.

Levasept in this dosage form (tablets) can be used to complete the course of therapy in patients who have demonstrated improvement during initial treatment with levofloxacin, solution for infusion, using the same doses.

The duration of treatment depends on the course of the disease and is no more than 14 days. It is recommended to continue using the drug for at least 48–72 hours after normalization of body temperature or confirmed destruction of pathogens by microbiological tests.

Levacept tablets should be swallowed without chewing, with sufficient liquid. The tablets can be taken regardless of food intake.

The drug should be administered at least 2 hours before or 2 hours after the administration of iron salts, zinc salts, antacids containing magnesium or aluminum, didanosine (only for forms containing aluminum or magnesium in buffering agents) and sucralfate, since these drugs may reduce absorption (see section "Interaction with other medicinal products and other types of interactions").

Recommended dosage for adult patients with normal renal function, with creatinine clearance above 50 ml/min

Table 3

Indication

Special populations

Dosage for patients with renal impairment with creatinine clearance less than 50 mL/min

Table 4

1 - After hemodialysis or chronic ambulatory peritoneal dialysis (CHAPD), additional doses are not required.

*- Since the tablet is not divisible, if a dose of less than 500 mg is prescribed, levofloxacin preparations in the appropriate dosage should be used.

Dosage for patients with hepatic impairment: No dosage adjustment is required since levofloxacin is only slightly metabolized in the liver and is excreted primarily by the kidneys.

Dosage for elderly patients: If renal function is not impaired, no dose adjustment is necessary (see section "Special instructions").

Children

Levasept is contraindicated for use in children and adolescents (under 18 years of age) due to the risk of damage to articular cartilage.

Overdose

Symptoms of levofloxacin overdose include central nervous system disorders (confusion, dizziness, impaired consciousness, convulsions); gastrointestinal reactions such as nausea and erosion of the mucous membranes; possible prolongation of the QT interval. Hallucinations and tremor are possible.

Treatment: symptomatic. ECG monitoring is recommended as QT prolongation may occur. Antacids should be used to protect the gastric mucosa. Hemodialysis, including peritoneal dialysis or HAPD, is not effective in removing levofloxacin from the body. There are no specific antidotes.

Adverse reactions

The frequency of side effects was determined using the following criteria: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1000 to <1/100), rare (>1/10000 to <1/1000), very rare (>1/10000), frequency unknown (cannot be estimated from the available data).

Infections and infestations:

uncommon: fungal infections, including Candida fungi, proliferation of other resistant microorganisms, disruption of the normal intestinal microflora and development of secondary infection.

From the blood and lymphatic system:

infrequently: leukopenia, eosinophilia;

rarely: thrombocytopenia, neutropenia;

frequency unknown: agranulocytosis, pancytopenia, hemolytic anemia.

On the part of the immune system:

Rare: angioedema, hypersensitivity;

frequency unknown: anaphylactic shock, anaphylactoid shock.

Anaphylactic and anaphylactoid reactions may occasionally occur even after the first dose.

Metabolism and nutrition:

uncommon: anorexia;

Rare: hypoglycemia, especially in patients with diabetes;

frequency unknown: hyperglycemia, hypoglycemic coma.

Signs of hypoglycemia may include increased appetite, nervousness, sweating, and trembling of the limbs.

From the endocrine system:

Rare: syndrome of inappropriate antidiuretic hormone secretion (SIADH).

From the psyche*:

common: insomnia;

infrequently: nervousness; confusion, anxiety, restlessness, states of fear;

rarely: psychotic disorders (including hallucinations, paranoia), depression, agitation, unusual dreams, nightmares;

frequency unknown: psychotic reactions with self-destructive behavior, including suicidal thoughts or actions.

Nervous system*:

common: headache, dizziness;

uncommon: drowsiness, tremor, dysgeusia (subject