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

Urinary tract infections, Respiratory tract infections, Skin infections, Tuberculosis, Lung inflammation (pneumonia), Inflammation of the female reproductive organs, Bronchitis, Boils, Sinusitis, Gymorrhoid, Prostatitis, Infectious diseases:

– acute bacterial sinusitis;
– exacerbation of chronic bronchitis;
– community-acquired pneumonia;
– uncomplicated urinary tract infections;
– complicated urinary tract infections (including acute pyelonephritis);
– Chronic bacterial prostatitis;
– Skin and soft tissue infections (including suppurated atheromas, abscesses, furunculosis);
– Tuberculosis (as a part of complex therapy of drug-resistant forms).
– anthrax prevention and treatment in case of airborne infection.

Active ingredient

Levofloxacin

Composition

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

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

The shell: OPADRY Orange 20A230018 – 15,000 mg [hydroxypropyl methylcellulose 2910/hypromellose 6 cP (E464) – 6,600 mg; titanium dioxide (E171) – 1,375 mg; talc, 3.150 mg; hyprolose (hydroxypropyl cellulose, clucel EF) (E463), 3.851 mg; sunset yellow dye (E 110), 0.024 mg].

How to take, the dosage

To be taken orally once or twice daily (every 24, 12 hours). The tablets should be taken without chewing and with plenty of water (0.5 to 1 cup).

The drug can be taken before meals, at any time between meals, since eating does not affect absorption of the drug.

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

Given that the bioavailability of levofloxacin when receiving levofloxacin in tablets is 99-100%, if the patient is transferred from intravenous infusion of levofloxacin to receiving tablets, treatment should continue at the same dose that was used for intravenous infusion (see section “Pharmacokinetics”).

If one or more doses of the medication are missed, the next dose should be taken as soon as possible and the medication should be continued according to the recommended dosing regimen.

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

Adult patients with normal to moderately reduced renal function (creatinine clearance greater than 50 ml/min) use according to the regimen presented in the table:

Infection Dose, mg Frequency of administration per day Duration of treatment, days

Acute bacterial sinusitis 500 1 10-14

750 1 5

Acute chronic bronchitis 500 1 7

Out-of-hospital pneumonia 500 1-2 7-14

750 1 5*

Uncomplicated urinary tract infections 250 1 3/p>

Complicated urinary tract infections 500 1 7-14

Complicated urinary tract infections including ч. Acute pyelonephritis 750 1 5**

Pyelonephritis 500 1 7-10

Chronic bacterial prostatitis 500 1 28

Uncomplicated skin and subcutaneous tissue infections 500 1 7-10/p>

Complicated skin and subcutaneous tissue infections 750 1 7-14

Tuberculosis (as part of complex therapy of drug-resistant forms) 500 1-2 Up to 3 months

/p>

The prevention and treatment of anthrax in the airborne route of infection 500 1 Up to 8 weeks

* This regimen is indicated for the treatment of community-acquired pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae.

** This regimen is indicated for the treatment of urinary tract infections caused by Enterococcus faecalis, Klebsiella pneumoniae, Proteus mirabilis and acute pyelonephritis caused by Escherichia coli, including cases with associated bacteremia.

Adjust the dose of levofloxacin in adult patients with impaired renal function (creatinine clearance less than 50 ml/min).

Dose in normal renal function every 24 h Creatinine clearance from

20 to 49 ml/min Creatinine clearance from 10 to 19 ml/min Creatinine clearance

less than 10 mL/min (including hemodialysis, continuous ambulatory peritoneal dialysis)

750 mg 750 mg every 48 hours Initial dose 750 mg, then 500 mg every 48 hours Initial dose 750 mg, then 500 mg every 48 hours

500 mg Initial dose 500 mg, then 250 mg every 24 hours Initial dose 500 mg, then 250 mg every 48 hours Initial dose 500 mg, then 250 mg every 48 hours

250 mg No dose adjustment required 250 mg every 48 hours No dose adjustment is required for uncomplicated urinary tract infections No dose adjustment information is required

No additional doses are required after hemodialysis, continuous ambulatory peritoneal dialysis.

Dose adjustment is not necessary in patients with hepatic impairment because the metabolism volume of levofloxacin in the liver is limited.

In elderly patients no dosing adjustment is required unless creatinine clearance drops to 50 ml/min or lower.

Interaction

Cautious interactions

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

Compounds containing bivalent or trivalent cations, such as zinc and iron salts (anemic products), magnesium and/or aluminum-containing products (such as antacids), and didanosine (only forms containing aluminum or magnesium as a buffer) should be taken at least two hours before or two hours after starting Levofloxacin.

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

With sucralfate

The effect of levofloxacin is significantly impaired with concomitant use of sucralfate. Patients receiving levofloxacin and sucralfate are recommended to take sucralfate 2 hours after taking levofloxacin.

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

Pharmacokinetic interaction of levofloxacin with theophylline has not been revealed. However, with concomitant administration of quinolones and theophylline, nonsteroidal anti-inflammatory drugs and other drugs that reduce cerebral seizure threshold, a pronounced decrease in cerebral seizure threshold is possible. Concentration of levofloxacin is increased by only 13% when concomitant administration of fenbufen.

With indirect coagulants

In patients treated with levofloxacin in combination with indirect anticoagulants (e.g., warfarin) an increase in prothrombin time/normalized international ratio and/or development of bleeding has been observed, including severe bleeding. Therefore, when concomitant use of indirect anticoagulants and levofloxacin, regular monitoring of blood clotting parameters is necessary.

With probenicidin and cimetidine

When concomitant use of drugs that interfere with renal tubular secretion of levofloxacin, such as probenicid and cimetidine, caution should be exercised especially in patients with renal insufficiency. Cimetidine and probenicidin retard excretion of levofloxacin by 24% and 34%, respectively. This is unlikely to be clinically relevant in normal renal function.

With cyclosporine

Levofloxacin increases the half-life of cyclosporine by 33%. Since this increase is clinically insignificant, there is no need to adjust the dose of cyclosporine when using it concomitantly with levofloxacin.

With glucocorticosteroids

The concomitant use of glucocorticosteroids increases the risk of tendon rupture.

With drugs that prolong the QT interval

Levofloxacin, like other intraquinolones, should be used with caution in patients receiving drugs that prolong the QT interval (e.g., Class IA and III antiarrhythmic agents, tricyclic antidepressants, macrolides, neuroleptics).

Other

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

Special Instructions

Hospital infections caused by Pseudomjnas aeruginosa may require combination therapy.

The prevalence of acquired resistance of absorbable strains of microorganisms may vary by geographic region and over time. Therefore, information on resistance to the drug in a particular country is required. For therapy of severe infections or in case of ineffective treatment it is necessary to establish microbiological diagnosis with pathogen isolation and determination of its sensitivity to levofloxacin.

Methicillin-resistant streptococcus aureus

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

Patients susceptible to seizures

Levofloxacin, like other quinolones, should be used with great caution in patients with a predisposition to seizures. This includes patients with previous CNS lesions such as stroke or severe traumatic brain injury, patients receiving concomitant medications which lower the seizure threshold such as phenbufen and other similar non-steroidal anti-inflammatory drugs or other drugs which lower the seizure threshold such as theophylline (see section “Interaction with other medicinal products”).

Pseudomembranous colitis

Diarrhea during or after treatment with levofloxacin, especially severe, persistent and/or with blood may be a symptom of pseudomembranous colitis caused by Clostridium diffieile. If pseudomembranous colitis is suspected, treatment with levofloxacin should be stopped immediately and specific antibiotic therapy (oral vancomycin, teicoplanin or metronidazole) started immediately. Drugs that inhibit intestinal peristalsis are contraindicated.

Tendinitis

Rarely observed tendinitis with quinolones, including levofloxacin, can lead to tendon rupture, 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 develop tendonitis. The risk of tendon rupture may be increased by concomitant administration of glucocorticosteroids. If tendinitis is suspected, treatment with Levofloxacin should be stopped immediately and appropriate treatment of the tendon affected should be initiated, e.g. sufficient immobilization (see contraindications and side effects).

Hypersensitivity reactions

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

Serious bullous reactions

There have been cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis when taking levofloxacin (see section “Adverse effects”). If any reactions of the skin or mucous membranes develop, the patient should immediately consult a physician and should not continue treatment until he or she has been consulted.

Hepatic and biliary tract disorders

Hepatic necrosis, including fatal hepatic failure, has been reported with levofloxacin, mainly in patients with severe underlying diseases such as sepsis (see section “Adverse effects”). Patients should be warned to discontinue treatment and seek prompt medical attention if signs and symptoms of liver damage, such as anorexia, jaundice, darkened urine, itching and abdominal pain appear.

Patients with renal impairment

Because levofloxacin is mainly excreted by the kidneys, patients with renal impairment require mandatory renal function monitoring as well as dosage adjustment (see section “Dosage and administration”). When treating elderly patients it should be borne in mind that patients of this group often have impaired renal function.

Preventing photosensitization reactions

While photosensitization by levofloxacin is very rare, to prevent its development patients are not recommended to be exposed to strong sunlight or artificial ultraviolet light without an urgent need during treatment and within 48 hours after treatment with levofloxacin (e.g., visiting a solarium).

Superinfection

As with other antibiotics, the use of levofloxacin, especially over a long period of time, can lead to increased proliferation of microorganisms (bacteria and fungi) that are not sensitive to it, which can cause changes in the microflora that are normally present in humans, which may lead to superinfection. Therefore, it is imperative that the patient is reassessed during treatment and if superinfections develop during treatment, appropriate measures should be taken.

Long QT interval

Very rare cases of QT interval prolongation have been reported in patients treated with fluoroquinolones, including levofloxacin. Caution should be exercised when using fluoroquinolones, including levofloxacin, in patients with known risk factors for QT interval prolongation: In patients with uncorrected electrolyte abnormalities (with hypokalemia, hypomagnesemia); with congenital QT interval prolongation syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); with concurrent administration of drugs that can prolong the QT interval, such as antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, neuroleptics.

The elderly and female patients may be more sensitive to QT interval prolonging drugs. Therefore fluoroquinolones including levofloxacin should be used with caution in these patients (see sections: Caution, Dosage and administration, Side effects, Overdose, Interaction with other medicinal products.)

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency have a predisposition to hemolytic reactions when treated with quinolones and this must be considered when treating with levofloxacin.

Hypo- and hyperglycemia (dysglycemia)

As with treatment with other quinolones, cases of hypo- and hyperglycemia have been observed with lefloxacin, usually in patients with diabetes who are simultaneously treated with oral hypoglycemic agents (e.g., glibenclamide) or insulin drugs. Cases of hypoglycemic coma have been reported. Close monitoring of blood glucose concentration is required in patients with diabetes mellitus. (see section “Side effects”).

Peripheral neuropathy

Patients receiving fluoroquinolones, including levofloxacin, have reported sensory and sensory-motor peripheral neuropathy, which may have a rapid onset. If a patient develops symptoms of neuropathy, the use of levofloxacin should be discontinued. This minimizes the possible risk of irreversible changes.

Pseudoparalytic myasthenia gravis exacerbation

Fluoroquinolones, including levofloxacin, are characterized by blocking neuromuscular conduction activity and may increase muscle weakness in patients with pseudoparalytic myasthenia gravis. In the post-registration period, adverse reactions, including pulmonary failure requiring artificial ventilation, and death have been observed that have been associated with fluoroquinolone use in patients with pseudoparalytic myasthenia gravis. The use of levofloxacin in a patient with a confirmed diagnosis of pseudoparalytic myasthenia gravis is not recommended (see section “Side effects”).

The use of levofloxacin in humans for this indication is based on the data of Bacillus anthracis sensitivity obtained in in vitro studies and in experimental studies conducted on animals, as well as on limited data on the use of levofloxacin in humans. Treating physicians should refer to national and/or international documents that reflect a consensus view on the treatment of anthrax.

Psychotic reactions

When using quinolones, including levofloxacin, psychotic reactions have been reported, which in very rare cases have progressed to suicidal ideation and self-injurious behavior (sometimes after a single dose of levofloxacin (see section “Adverse effects”)). If such reactions develop, treatment with levofloxacin should be stopped and appropriate therapy should be prescribed. Caution should be exercised when prescribing the drug in patients with psychosis or patients with a history of mental illness.

VIight impairment

If any visual impairment develops, immediate consultation with an ophthalmologist is necessary (see section on side effects).

Impact on laboratory tests

In patients taking levofloxacin, urinary opioid determination may lead to false-positive results that must be confirmed by more specific methods.

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and further lead to false negatives in the bacteriological diagnosis of tuberculosis.

Impact on the ability to drive vehicles and mechanisms

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

Synopsis

Filmed film-coated, pinkish-orange, oval biconvex tablets. On cut, they are white to light yellow in color.

Contraindications

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

– epilepsy;

– pseudoparalytic myasthenia gravis;

– tendon affections associated with fluoroquinolones in the anamnesis;

– Children and adolescents before 18 years of age (due to the incomplete skeleton growth as it is impossible to completely exclude the risk of cartilaginous growth points affection);

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

– lactation period (the risk of cartilaginous bone points affection in baby cannot be completely excluded).

With caution

– susceptibility to seizure reactions (in patients with previous damage of the central nervous system (CNS), in patients simultaneously receiving drugs that reduce the threshold of seizure readiness of the brain (phenbufen, theophylline);

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

– renal function disorder (renal function monitoring is required as well as dosage regimen correction, see “Dosage regimen. “

– in patients with known risk factors for QT interval prolongation: in elderly patients (over 65 years), in female patients, in patients with unadjusted electrolyte abnormalities (hypokalemia, hypomagnesemia); with congenital QT interval prolongation syndrome; In patients with heart failure, myocardial infarction, bradycardia, concomitant use of drugs that prolong the QT interval (antiarrhythmic drugs of classes IA and III, tricyclic antidepressants, neuroleptics, macrolides);

Side effects

The side effects indicated below are presented according to the following gradations of frequency of occurrence: very frequently (≥ 1/10), frequently (≥ 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 available data it is impossible to determine the frequency of occurrence).

Nervous system disorders: frequently – headache, dizziness; infrequently – somnolence, tremor, dysgeusia (perversion of taste); rarely – paresthesia, seizures (see section “Indications”). Unspecified frequency – peripheral sensory neuropathy, peripheral sensory-motor neuropathy, dyskinesia, extrapyramidal disorders, loss of sense of taste, parosmia (disorder of sense of smell, especially subjective sense of smell that is objectively absent), including loss of smell, syncope, benign intracranial hypertension.

Mental disorders: frequent – insomnia; infrequent – feelings of restlessness, anxiety, confusion; rare – mental disorders (e.g., hallucinations, paranoia), depression, agitation, sleep disorders, nightmares; unspecified frequency – mental disorders with conduct disorder with self-harm, including suicidal thoughts and suicide attempts.

VIight: very rare – visual disturbances such as blurred vision; unspecified frequency – transient loss of vision.

Hearing organ and labyrinth disorders: infrequent – vertigo (feeling of deviation, spinning, own body, surrounding objects); rare – ringing in the ears; unspecified frequency – hearing loss, hearing loss.

The cardiovascular system: rare – sinus tachycardia, palpitations, decreased blood pressure; unspecified frequency – prolonged QT interval, ventricular arrhythmias, ventricular tachycardia type “pirouette”, which can lead to cardiac arrest (see sections “Overdose” and “Special Precautions”).

The blood and lymphatic system: infrequent – eosinophilia, leukopenia; rare – neutropenia, thrombocytopenia; unspecified frequency – pancytopenia, agranulocytosis, hemolytic anemia.

Gastro-intestinal tract: frequently – nausea, vomiting, diarrhea; infrequently – 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 “Indications”).

Hepatic and biliary tract disorders: frequently – increased alanine aminotransferase activity; infrequently – increased bilirubin level; unspecified frequency – severe liver failure, including cases of acute liver failure, sometimes with fatal outcome, especially in patients with sepsis); hepatitis, jaundice.

Respiratory system, thoracic and mediastinal organs: infrequent – dyspnea; unspecified frequency – bronchospasm, allergic pneumonitis.

Metabolism and nutrition: infrequent – anorexia; rare – hypoglycemia (increased appetite, increased sweating, trembling, nervousness); unspecified frequency – hyperglycemia, hypoglycemic coma (see section “Special Indications”).

Musculoskeletal and connective tissue disorders: infrequent – arthralgia, myalgia; rare – tendon lesions (e.g., Achilles tendon), including tendinitis, muscle weakness, which may be dangerous in patients with pseudoparalytic myasthenia gravis (see section “Caution. section “Caution”); unspecified frequency – rhabdomyolysis, tendon rupture (e.g., Achilles tendon). This side effect may occur within 48 hours of treatment start and may be bilateral), ligament tears, muscle tears, arthritis (see section “Special Precautions”).

Renal and urinary tract disorders: infrequent hypercreatininemia; rarely – acute renal failure (e.g., due to the development of interstitial nephritis).

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

Skin and subcutaneous tissue disorders: infrequent – rash, pruritus, urticaria, hyperhidrosis; unspecified frequency – malignant erythema exudatum (Stevens-Job’s syndrome), toxic epidermal necrolysis (Lyell’s syndrome), photosenenobilization reaction, leukocytoclastic vasculitis, stomatitis, erythema exudative multiforme. Skin and mucous membrane reactions, anaphylactic and anaphylactoid reactions may sometimes develop even after the first dose of the drug.

Infectious and parasitic diseases: infrequent fungal infections, development of resistance of pathogens.

Immune system disorders: rare – angioedema; unspecified frequency – anaphylactic shock, anaphylactoid shock.

General disorders: infrequent – asthenia; rare – pyrexia (increase in body temperature); unspecified frequency – pain (including pain in the back, chest and extremities).

Other possible adverse effects relevant to all fluoroquinolones: very rare – episodes of porphyria in patients with porphyria.