Leflok-darnitsa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LEFLOCK-DARNITSA (LEFLOCK-DARNITSA)

Composition:

Active substance: levofloxacin;

1 ml of solution contains 5 mg of levofloxacin (calculated as levofloxacin from levofloxacin hemihydrate);

Excipients: sodium chloride, diluted hydrochloric acid, sodium hydroxide, water for injections.

Pharmaceutical form. Infusion solution.

Main physico-chemical properties: clear yellow to yellowish-greenish tinted liquid.

Pharmacotherapeutic group.

Antibacterial agents of the quinolone group. Fluoroquinolones. ATC code J01MA12.

Pharmacological properties.

Pharmacodynamics.

Levofloxacin is a synthetic antibacterial agent from the fluoroquinolone group, the S-enantiomer of the racemic mixture of the drug ofloxacin. As an antibacterial agent from the fluoroquinolone group, levofloxacin acts on the DNA complex with DNA gyrase and topoisomerase IV. The primary mechanism of resistance is due to mutations in the gyr-A genes.

Cross-resistance.

In vitro, cross-resistance exists between levofloxacin and other fluoroquinolones.

Breakpoints.

The breakpoints for MIC values of levofloxacin, as recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), which distinguish susceptible microorganisms from those with intermediate susceptibility (moderately resistant), and intermediate from resistant organisms, are presented in Table 1 of MIC testing (mg/l).

EUCAST clinical breakpoints for levofloxacin MIC:

Table 1

1 Breakpoint values for levofloxacin apply to high-dose therapy.

2 Low-level resistance to fluoroquinolones (MIC of ciprofloxacin 0.12–0.5 mg/L) may occur, but there is no evidence that such resistance has clinical significance in respiratory tract infections caused by H. influenzae.

3 Isolates with MIC values above the breakpoint between susceptible and intermediate (moderately resistant) strains are very rare or have not yet been reported. Susceptibility testing on any such isolate should be repeated, and if resistance is confirmed, the isolate should be sent to a reference laboratory. As long as data indicate clinical response for confirmed isolates with MIC above the current resistant breakpoint, they should be reported as resistant.

4 Breakpoint values for oral doses ranging from 500 mg once daily to 500 mg twice daily and intravenous doses ranging from 500 mg once daily to 500 mg twice daily.

Antibacterial spectrum

Resistance prevalence for selected organisms may vary geographically and over time. Local information on resistance patterns is desirable, especially when treating severe infections.

Organisms usually susceptible.

Aerobic Gram-positive bacteria: Bacillus anthracis, Staphylococcus aureus* (methicillin-susceptible), Staphylococcus saprophyticus, Streptococci – Groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae*, Streptococcus pyogenes*.

Aerobic Gram-negative bacteria: Burkholderia cepacia**, Eikenella corrodens, Haemophilus influenzae*, Haemophilus para-influenzae*, Klebsiella oxytoca, Moraxella catarrhalis*, Pasteurella multocida, Proteus vulgaris, Providencia rettgeri.

Anaerobic bacteria: Peptostreptococcus.

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

Organisms for which acquired (secondary) resistance may be a problem.

Aerobic Gram-positive bacteria: Enterococcus faecalis*, Staphylococcus aureus (methicillin-resistant), Staphylococcus coagulase spp.

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

Anaerobic bacteria: Bacteroides fragilis, Bacteroides ovatus**, Bacteroides thetaiotaomicron**, Bacteroides vulgatus**, Clostridium difficile**.

Naturally resistant organisms.

Aerobic Gram-positive bacteria: Enterococcus faecium.

* Clinical efficacy has been demonstrated for susceptible isolates in approved clinical indications.

** Natural moderate susceptibility.

Other data.

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

Pharmacokinetics.

Absorption

There is no significant difference in the pharmacokinetics of levofloxacin after intravenous and oral administration. After intravenous administration, the drug accumulates in bronchial mucosa, lung tissue, and bronchial secretions (concentrations in lung tissue exceed those in plasma), and in urine. Levofloxacin penetrates poorly into cerebrospinal fluid.

Distribution

Approximately 30–40% of levofloxacin is protein-bound in plasma. There is practically no accumulation effect after multiple doses of 500 mg once daily. A slight but predictable accumulation occurs after 500 mg twice daily. Steady state is reached within 3 days.

Tissue and fluid penetration

Penetration into bronchial mucosa and bronchial secretions of lung tissue

Maximum concentrations of levofloxacin in bronchial mucosa and bronchial secretions of lung tissue after oral administration of 500 mg were 8.3 and 10.8 µg/mL, respectively. These concentrations were achieved within 1 hour after drug administration.

Penetration into lung tissue

Maximum concentration of levofloxacin in lung tissue after oral administration of 500 mg was approximately 11.3 µg/g, reached 4–6 hours after administration. Concentrations in lung tissue exceed those in plasma.

Penetration into blister fluid (skin)

Maximum concentration of levofloxacin (4.0–6.7 µg/mL) in blister fluid was achieved 2–4 hours after drug administration during 3 days of treatment at doses of 500 mg once or twice daily, respectively.

Penetration into cerebrospinal (spinal) fluid

Levofloxacin penetrates poorly into cerebrospinal fluid.

Penetration into prostate tissue

After administration of 500 mg levofloxacin once daily for 3 days, mean concentrations in prostate tissue were 8.7 µg/g, 8.2 µg/g, and 2 µg/g at 2, 6, and 24 hours, respectively. The mean prostate/plasma concentration ratio was 1.84.

Concentration in urine

Mean urinary concentrations 8–12 hours after single oral doses of 150 mg, 300 mg, and 500 mg of levofloxacin were 44 mg/L, 91 mg/L, and 200 mg/L, respectively.

Biotransformation

Levofloxacin undergoes minimal metabolism, with metabolites including desmethyl-levofloxacin and levofloxacin N-oxide. These metabolites account for less than 5% of the total drug excreted in urine. Levofloxacin is stereochemically stable and does not undergo chiral inversion.

Elimination

After both oral and intravenous administration, levofloxacin is eliminated from plasma relatively slowly (elimination half-life is 6–8 hours). It is primarily excreted by the kidneys (over 85% of the administered dose).

There is no significant difference in the pharmacokinetics of levofloxacin after intravenous and oral administration, indicating that these routes of administration are interchangeable.

Linearity

Levofloxacin exhibits linear pharmacokinetics in the range of 50–600 mg.

Patients with renal impairment

Renal impairment affects the pharmacokinetics of levofloxacin. With reduced renal function, renal excretion and clearance decrease, and elimination half-life increases, as shown in Table 2.

Table 2

Geriatric patients

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

Gender differences

Separate analysis of female and male patient groups demonstrated minor differences in the pharmacokinetics of levofloxacin depending on gender. There is no evidence that these gender-related pharmacokinetic differences are clinically significant.

Clinical characteristics.

Indications.

Levoflox, infusion solution, is indicated in adults for the treatment of the following infectious diseases caused by microorganisms sensitive to levofloxacin:

− community-acquired pneumonia*;

− complicated skin and soft tissue infections*;

− acute pyelonephritis and complicated urinary tract infections;

− chronic bacterial prostatitis;

− pulmonary form of anthrax: post-exposure prophylaxis and definitive treatment.

*For the above-mentioned infectious diseases, levofloxacin should be prescribed only when other antibacterial agents, primarily used for initial treatment of these infections, have shown insufficient efficacy.

Official recommendations regarding appropriate use of antibacterial agents should be taken into account.

Contraindications.

− Hypersensitivity to levofloxacin, to other quinolones, or to any component of the medicinal product.

− Tendon-related adverse reactions following prior use of quinolones.

− Epilepsy.

− Pediatric age (under 18 years).

− Pregnancy or breastfeeding.

Interaction with other medicinal products and other types of interactions.

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

Concomitant use of quinolones with theophylline, NSAIDs, or other substances that lower the seizure threshold may substantially reduce the seizure threshold. The concentration of levofloxacin is approximately 13% higher in the presence of fenbufen than when levofloxacin is administered alone.

Probenecid and cimetidine

Probenecid and cimetidine have a statistically significant effect on the elimination of levofloxacin. Renal clearance of levofloxacin is reduced by 34% in the presence of probenecid and by 24% in the presence of cimetidine. Therefore, both agents can block the tubular excretion of levofloxacin. They should be used with caution in patients with renal impairment.

Cyclosporine

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

Vitamin K antagonists

When used concomitantly with vitamin K antagonists (e.g., warfarin), coagulation test parameters (PT/INR) may increase. Severe bleeding may occur. Therefore, coagulation parameters should be monitored in patients receiving vitamin K antagonists concurrently.

Medicinal products that prolong the QT interval

Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving medicinal products that prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotic agents).

Theophylline

Levofloxacin does not affect the pharmacokinetics of theophylline, which is primarily metabolized via CYP1A2; therefore, levofloxacin is not considered to be an inhibitor of CYP1A2.

Glucocorticoids

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

Other

No clinically significant effect on the pharmacokinetics of levofloxacin has been observed when administered concomitantly with calcium carbonate, digoxin, glyburide, or ranitidine.

The concomitant use of levofloxacin with alcohol is not recommended.

Special precautions for use

The use of the medicinal product should be avoided in patients who have previously experienced serious adverse reactions to quinolones or fluoroquinolones. Treatment of such patients with levofloxacin should only be initiated if there are no alternative treatment options and after careful assessment of the benefit/risk ratio.

Prolonged, disabling and potentially irreversible serious adverse reactions

In very rare cases, patients receiving fluoroquinolones, regardless of age and existing risk factors, have reported prolonged (lasting months or years), disabling and potentially irreversible serious adverse reactions affecting various, and sometimes multiple simultaneously, body systems (musculoskeletal, nervous, psychiatric, and sensory organs). The medicinal product must be discontinued immediately at the first signs or symptoms of any serious adverse reaction, and medical advice should be sought.

Caution is advised when administering the medicinal product to patients with severe renal impairment, significant cerebral atherosclerosis, or cerebrovascular disorders.

Renal and hepatic function should be monitored throughout the entire treatment course.

Alcohol consumption should be avoided during treatment with this medicinal product.

In very severe pneumonia caused by pneumococci, levofloxacin may not provide optimal therapeutic efficacy.

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

Duration of infusion

The recommended duration of infusion for the 500 mg levofloxacin infusion solution is at least 60 minutes. With ofloxacin, tachycardia and transient increases in blood pressure have been observed during infusion. In rare cases, sudden hypotension and circulatory collapse may occur. If marked hypotension occurs during levofloxacin infusion, administration should be immediately discontinued.

An aneurysm and aortic dissection

Epidemiological studies indicate an increased risk of aortic aneurysm and aortic dissection following fluoroquinolone use, particularly in elderly patients.

Therefore, fluoroquinolones should be used only after careful benefit/risk assessment and consideration of alternative therapies in patients with a significant family history of aneurysmal disease, or in patients diagnosed with aortic aneurysm and/or aortic dissection, or in those with risk factors or conditions predisposing to aneurysm and aortic dissection (e.g., Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behçet’s disease, arterial hypertension, established atherosclerosis).

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

Methicillin-resistant Staphylococcus aureus (MRSA)

Methicillin-resistant Staphylococcus aureus (MRSA) is likely to exhibit cross-resistance to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of known or suspected MRSA infections, except when laboratory testing confirms susceptibility of the pathogen to levofloxacin.

Resistance of E. coli

Resistance of E. coli, the most common pathogen causing urinary tract infections, to fluoroquinolones varies across different countries of the European Union. Prescribers should take into account local prevalence of E. coli resistance to fluoroquinolones when prescribing levofloxacin.

Pulmonary anthrax

Clinical experience is based on in vitro susceptibility studies of Bacillus anthracis, experimental animal data, and limited human data. Physicians should refer to nationally and/or internationally agreed guidelines for the treatment of anthrax.

Tendinitis and tendon rupture

Tendinitis and tendon ruptures (not limited to the Achilles tendon), sometimes bilateral, may occur within 48 hours of starting quinolone or fluoroquinolone therapy and, as reported, even several months after discontinuation of treatment in patients receiving daily doses of 1000 mg levofloxacin. The risk of tendinitis and tendon rupture is increased in elderly patients, patients with renal impairment, patients who have undergone solid organ transplantation, and patients receiving concomitant corticosteroid therapy. Therefore, concomitant use of this medicinal product with corticosteroids should be avoided.

Treatment should be discontinued at the first signs of tendinitis (e.g., painful swelling, inflammation), and alternative therapy should be considered. The affected limb(s) should be appropriately managed (e.g., immobilization). Corticosteroids should not be used if signs of tendinopathy occur.

Myoclonus

Cases of myoclonus have been reported in patients receiving levofloxacin (see section "Adverse reactions"). The risk of myoclonus is increased in elderly patients and in patients with renal impairment if the levofloxacin dose is not adjusted according to creatinine clearance. Levofloxacin should be discontinued immediately upon the first occurrence of myoclonus, and appropriate treatment initiated.

Clostridium difficile-associated disease

Diarrhea, especially severe, persistent, or with blood, during or after treatment with levofloxacin may be a symptom of disease caused by Clostridium difficile, the most severe form of which is pseudomembranous colitis. If pseudomembranous colitis is suspected, levofloxacin should be immediately discontinued and appropriate treatment (e.g., vancomycin) initiated promptly. Antiperistaltic agents are contraindicated in this clinical situation.

Patients predisposed to seizures

Quinolones may lower the seizure threshold and provoke seizures. Levofloxacin is contraindicated in patients with a history of epilepsy.

As with other quinolones, the medicinal product should be used with extreme caution in patients predisposed to seizures, such as those with central nervous system disorders, concomitant therapy with fenbufen or similar medicinal products, 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.

Glucose-6-phosphate dehydrogenase deficiency

Patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency are prone to hemolytic reactions when treated with quinolone antibacterial agents. Therefore, levofloxacin should be used with caution in such patients due to the potential risk of hemolysis.

Renal impairment

Since levofloxacin is primarily eliminated via the kidneys, dose adjustment is required in patients with renal impairment (see section "Method of administration and dosage").

Hypersensitivity reactions

Levofloxacin may occasionally cause serious, potentially fatal hypersensitivity reactions (e.g., angioedema, anaphylactic shock), even after the first dose. If hypersensitivity reactions occur, levofloxacin should be discontinued, medical advice sought, and appropriate treatment initiated.

Severe bullous reactions

Severe bullous reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with levofloxacin use. If bullous reactions occur, levofloxacin should be immediately discontinued, medical advice sought, and appropriate treatment initiated.

Blood glucose alterations

Alterations in blood glucose levels (hyperglycemia and hypoglycemia) have been reported with quinolone use, particularly in diabetic patients receiving concomitant oral hypoglycemic agents (e.g., glyburide) or insulin. Cases of hypoglycemic coma have occurred. Diabetic patients should monitor their blood glucose levels.

Prevention of photosensitivity reactions

Photosensitivity reactions have been reported during treatment with levofloxacin. To prevent photosensitivity reactions, patients taking levofloxacin should avoid exposure to sunlight and UV radiation (e.g., artificial UV lamps, tanning beds) during treatment and for 48 hours after discontinuation of levofloxacin.

In patients taking vitamin K antagonists, coagulation parameters should be monitored during concomitant use of levofloxacin and vitamin K antagonists (e.g., warfarin) due to the potential risk of increased coagulation parameters (prothrombin time/INR) and/or bleeding.

Psychotic reactions

Psychotic reactions have been reported in patients receiving quinolones, including levofloxacin. In very rare cases, these progressed to suicidal thoughts and self-destructive behavior, sometimes after only a single dose of levofloxacin. If such reactions occur, levofloxacin should be discontinued and appropriate measures taken. Levofloxacin should be used cautiously in patients with a history of psychotic disorders or psychiatric illness.

QT interval prolongation

Cases of QT interval prolongation have been reported with fluoroquinolone use. Caution should be exercised when using fluoroquinolones, including levofloxacin, in patients with known risk factors for QT prolongation:

− congenital or acquired QT prolongation syndrome;

− concomitant use of medicinal products that prolong the QT interval (including class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics);

− electrolyte imbalances (particularly hypokalemia, hypomagnesemia);

− cardiac conditions (heart failure, myocardial infarction, bradycardia).

Elderly patients are more sensitive to medicinal products that prolong the QT interval. Therefore, fluoroquinolones, including levofloxacin, should be used with caution in this patient group.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy, leading to paresthesia, hypoesthesia, dysesthesia, or weakness, have been reported in patients receiving quinolones and fluoroquinolones. If symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness occur, patients should be instructed to inform their physician to prevent progression to potentially irreversible conditions.

Hepatobiliary disorders

Cases of hepatic necrosis up to life-threatening liver failure have been reported with levofloxacin use, primarily in patients with severe underlying conditions such as sepsis (see section "Adverse reactions"). Patients should be advised to discontinue treatment and consult a physician if symptoms of liver disease occur, such as anorexia, jaundice, dark urine, pruritus, or abdominal pain.

Exacerbation of myasthenia gravis

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

Visual disturbances

If visual disturbances or other ocular effects occur, patients should immediately consult an ophthalmologist.

Superinfection

The use of levofloxacin, particularly over prolonged periods, may lead to overgrowth of microorganisms not susceptible to the medicinal product. If superinfection develops during therapy, appropriate measures should be taken.

Effect on laboratory tests

In patients receiving levofloxacin, opioid screening in urine may yield false-positive results. Confirmation of positive opioid results using more specific methods may be necessary.

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis, potentially leading to false-negative results in bacteriological testing of patients with tuberculosis.

Blood disorders

During treatment with levofloxacin, bone marrow dysfunction may develop, including leukopenia, neutropenia, pancytopenia, hemolytic anemia, thrombocytopenia, aplastic anemia, or agranulocytosis (see section "Adverse reactions"). If any of these disorders are suspected, blood counts should be monitored. If abnormal results are obtained, discontinuation of levofloxacin therapy should be considered.

Important information on excipients

This medicinal product contains 860 mg of sodium per dose. Caution is advised when administering this product to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding

Due to the lack of studies and the potential for quinolones to damage developing joint cartilage, the medicinal product is contraindicated during pregnancy and breastfeeding. If pregnancy occurs during treatment, this should be reported to the physician.

Levofloxacin did not cause impairment of fertility or reproductive function in animal studies.

Ability to affect reaction speed when driving or operating machinery

Some adverse reactions (e.g., dizziness/vertigo, somnolence, visual disturbances) may impair a patient's ability to concentrate and reaction speed, thereby increasing the risk in situations where these abilities are particularly important (e.g., driving or operating machinery).

Dosage and Administration

The dosage depends on the type and severity of the infection, as well as the susceptibility of the likely pathogen to the drug.

The medicinal product should be administered slowly intravenously once or twice daily by intravenous infusion. The infusion of one vial of levofloxacin (100 mL of solution for intravenous administration containing 500 mg of levofloxacin) should last no less than 60 minutes.

Mixing with infusion solutions.

The medicinal product is compatible with the following infusion solutions:

0.9% sodium chloride solution, 5% glucose monohydrate solution, 2.5% dextrose in Ringer's solution, multi-component parenteral nutrition solutions (amino acids, carbohydrates, electrolytes).

The solution should be used within 3 hours after vial perforation.

Treatment with levofloxacin, after initial intravenous administration, may be completed with the oral formulation, provided such a switch is appropriate for the individual patient. Due to the bioequivalence of parenteral and oral formulations, the same dosage may be used.

The duration of treatment depends on the course of the disease. As with other antibacterial agents, it is recommended to continue administration of the drug for at least 48–72 hours after normalization of body temperature or confirmed microbiological eradication of the pathogen.

Dosage for adult patients with normal renal function, in whom creatinine clearance is over 50 mL/min, is shown in Table 3.

Table 3

1 Depending on the patient's condition, a switch from initial intravenous administration of levofloxacin to oral administration at the same dosage may be possible after a few days.

Since levofloxacin is primarily eliminated via the kidneys, the dose should be reduced in patients with impaired renal function.

Dosage recommendations for adult patients with impaired renal function, in whom creatinine clearance is less than 50 ml/min, are provided in Table 4.

Table 4

1 After hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), additional doses are not required.

Dosing in patients with hepatic impairment.

Dose adjustment is not necessary, since levofloxacin is minimally metabolized in the liver and is predominantly eliminated via the kidneys.

Dosing in elderly patients.

If renal function is normal, there is no need for dose adjustment.

Do not insert needle(s) into non-designated areas of the polymer bottle, only into sterile ports!

For infusion therapy, follow the procedure below:

1. Remove the protective plastic cap with tamper-evident seal (if present).
2. Remove protective closure(s) No. 1 as shown in Fig. 1 and Fig. 2 (manufacturer may use different types and materials for protective closures).
3. Remove the cap from the needle and insert it into any of the designated ports No. 2 of the infusion vial (see Fig. 1 and Fig. 2).
4. The other sterile port may be used for introducing other medicinal products into the infusion vial (No. 4, see Fig. 3), or, in case of insufficient flow rate, for a venting needle (No. 4, see Fig. 3).
5. Hang the solution vial using the dedicated ring No. 3 located at the bottom of the vial (see Fig. 3).

Children.

The medicinal product is contraindicated in children, as damage to joint cartilage cannot be excluded.

Overdose.

Symptoms: dizziness, disturbance/confusion of consciousness, seizures, myoclonus, tremor, QT interval prolongation.

Treatment. In case of overdose, careful monitoring of the patient, including ECG, is required. Treatment is symptomatic. Hemodialysis, including peritoneal dialysis and continuous ambulatory peritoneal dialysis (CAPD), is not effective in removing levofloxacin from the body. No specific antidotes exist.

Adverse Reactions

Adverse reactions are listed by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100, <1/10), uncommon (≥ 1/1000, <1/100), rare (≥ 1/10,000, <1/1000), very rare (<1/10,000), frequency not known (cannot be estimated from available data).

Within each group, adverse reactions are listed in order of decreasing severity.

Eye disorders*: rare – visual disturbances such as blurred vision; frequency not known – transient loss of vision, uveitis.

Ear and labyrinth disorders*: uncommon – vertigo; rare – tinnitus; frequency not known – hearing disturbances, hearing loss.

Respiratory, thoracic and mediastinal disorders: uncommon – dyspnea; frequency not known – bronchospasm, allergic pneumonitis.

Gastrointestinal disorders: common – diarrhea, vomiting, nausea; uncommon – abdominal pain, dyspepsia, flatulence, constipation; frequency not known – hemorrhagic diarrhea, which may indicate enterocolitis, including pseudomembranous colitis; pancreatitis.

Hepatobiliary disorders: common – increased liver enzyme levels (ALT/AST, alkaline phosphatase, GGT); uncommon – increased blood bilirubin; frequency not known – jaundice and severe hepatic damage, including cases of acute liver failure, mainly in patients with severe underlying diseases, hepatitis.

Renal and urinary disorders: uncommon – increased serum creatinine levels; frequency not known – acute renal failure (e.g., due to interstitial nephritis).

Metabolism and nutrition disorders: uncommon – anorexia; rare – hypoglycemia, especially in patients with diabetes; frequency not known – hyperglycemia, hypoglycemic coma. Signs of hypoglycemia may include increased appetite, nervousness, excessive sweating, and limb tremor.

Nervous system disorders*: common – headache, dizziness; uncommon – somnolence, tremor, dysgeusia; rare – seizures, paresthesia; frequency not known – peripheral sensory or sensorimotor neuropathy, tactile disturbances, parosmia including anosmia, dyskinesia, extrapyramidal disorders, other movement coordination disorders including gait disturbances, ataxia, ageusia, loss of consciousness, benign intracranial hypertension, myoclonus.

Psychiatric disorders*: common – insomnia; uncommon – anxiety, confusion, irritability, restlessness; rare – psychotic disorders (including hallucinations, paranoia), depression, agitation, pathological dreams, nightmares, fear; frequency not known – psychotic disorders with self-destructive behavior, including suicidal ideation or actions, mania.

Cardiac disorders: rare – tachycardia, palpitations; frequency not known – ventricular tachycardia, which may lead to cardiac arrest; ventricular arrhythmia and torsade de pointes arrhythmia (mainly in patients with risk factors for QT interval prolongation), QT interval prolongation on ECG, arterial hypotension, collapse, vasculitis, phlebitis.

Blood and lymphatic system disorders: uncommon – leukopenia, eosinophilia; rare – neutropenia, thrombocytopenia leading to increased tendency to hemorrhage or bleeding; frequency not known – bone marrow dysfunction, including aplastic anemia, pancytopenia, agranulocytosis, hemolytic anemia.

Immune system disorders: rare – angioneurotic edema, hypersensitivity reactions, including anaphylactic shock, anaphylactoid shock (anaphylactic and anaphylactoid reactions may sometimes occur even after the first dose).

Skin and subcutaneous tissue disorders: uncommon – rash, pruritus, urticaria, skin redness, hyperhidrosis; frequency not known – toxic epidermal necrolysis, Stevens-Johnson syndrome, exudative multiform erythema, photosensitivity reactions, increased sensitivity to sunlight and ultraviolet radiation, leukocytoclastic vasculitis, stomatitis, skin hyperpigmentation.

Musculoskeletal and connective tissue disorders*: uncommon – arthralgia, myalgia; rare – tendon disorders, including tendinitis (e.g., Achilles tendon), muscle weakness, which may be particularly significant in patients with severe myasthenia gravis; frequency not known – rhabdomyolysis, rupture of tendons, ligaments, muscles, arthritis.

Infections and infestations: uncommon – fungal infections, including Candida species, resistance of pathogenic microorganisms.

General disorders and administration site conditions*: common – injection site reaction, including redness and pain; uncommon – asthenia; rare – increased body temperature; frequency not known – general weakness, pain (including back, chest, and limb pain); as with other fluoroquinolones, porphyria attacks may occur in patients with porphyria.

* In very rare cases, patients receiving quinolones and fluoroquinolones, regardless of risk factors, have reported prolonged (lasting months or years), disabling, and potentially irreversible serious adverse reactions affecting various, and sometimes multiple simultaneously, organ systems and sensory organs (including reactions such as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbances, neuropathy associated with paresthesia, depression, fatigue, memory impairment, sleep disturbances, hearing, vision, taste, and smell disorders).

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions via the national reporting system.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze.

Keep out of the reach of children.

Incompatibilities.

The solution should not be mixed with heparin or alkaline solutions (e.g., sodium bicarbonate), or with other medicinal products.

Packaging.

100 ml in a vial; 1 vial in a carton; 100 ml in vials.

Prescription status.

Prescription only.

Manufacturer.
JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and location of business activity.

13, Borispilska Street, Kyiv, 02093, Ukraine.