Rhinoloxin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT RINOLAKSIN

Composition:

Active substance: levofloxacin;

100 ml of solution contains levofloxacin hemihydrate equivalent to levofloxacin 500 mg;
Excipients: sodium chloride, disodium edetate, hydrochloric acid diluted, sodium hydroxide, water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical properties: clear solution ranging in color from yellow to greenish-yellow.

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

Pharmacological properties.

Pharmacodynamics.

Levofloxacin is a synthetic antibacterial agent from the group of fluoroquinolones, the S-enantiomer of the racemic mixture of ofloxacin.

Mechanism of action. As an antibacterial agent from the fluoroquinolone group, levofloxacin acts on the DNA-DNA gyrase and topoisomerase IV complex.

Pharmacokinetic/pharmacodynamic relationship. The degree of antibacterial activity of levofloxacin depends on the ratio of the maximum serum concentration (Cmax) or the area under the pharmacokinetic curve (AUC) to the minimum inhibitory concentration (MIC).

Mechanism of resistance. The primary mechanism of resistance results from mutations in the gyr-A genes. In vitro, cross-resistance exists between levofloxacin and other fluoroquinolones. Due to its mechanism of action, cross-resistance between levofloxacin and other classes of antibacterial agents is generally not observed.

Clinical breakpoints. The recommended breakpoints for levofloxacin MIC values, as defined 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 listed in Table 1 of MIC testing (mg/L).

Clinical breakpoints for levofloxacin MIC.

Table 1

1 Only uncomplicated urinary tract infections.

2 Susceptibility can be inferred based on sensitivity to ciprofloxacin.

The prevalence of resistance may vary geographically and over time for individual species. Local information on resistance should be obtained, especially when treating severe infections. Advice from a specialist should be sought when local resistance prevalence renders the utility of the medicinal product at least questionable for certain types of infections.

Typically susceptible species.

Aerobic Gram-positive bacteria:

Bacillus anthracis

Staphylococcus aureus methicillin-susceptible

Staphylococcus saprophyticus

Streptococci, group C and G

Streptococcus agalactiae

Streptococcus pneumoniae

Streptococcus pyogenes

Aerobic Gram-negative bacteria:

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

Species with potential for developing resistance

Aerobic Gram-positive bacteria:

Enterococcus faecalis

Staphylococcus aureus methicillin-resistant*

Coagulase-negative Staphylococcus spp.

Aerobic Gram-negative bacteria:

Acinetobacter baumannii

Citrobacter freundii

Enterobacter aerogenes

Enterobacter cloacae

Escherichia coli

Klebsiella pneumoniae

Morganella morganii

Proteus mirabilis

Providencia stuartii

Pseudomonas aeruginosa

Serratia marcescens

Anaerobic bacteria:

Bacteroides fragilis

Naturally resistant strains

Aerobic Gram-positive bacteria:

Enterococcus faecium

*Methicillin-resistant S. aureus is highly likely to also be resistant to fluoroquinolones, including levofloxacin.

Pharmacokinetics.

Steady-state conditions are achieved within 48 hours with a dosing regimen of 500 mg once or twice daily.

The mean volume of distribution of levofloxacin is approximately 100 L after single and repeated 500 mg doses, indicating extensive distribution into body tissues. Tissue and body fluid penetration. Levofloxacin penetrates effectively into bronchial mucosa, alveolar epithelial lining fluid, alveolar macrophages, lung tissue, skin (vesicle fluid), prostate tissue, and urine. However, penetration into cerebrospinal fluid is poor.

Biotransformation. Levofloxacin undergoes minimal metabolism, with metabolites being desmethyl-levofloxacin and levofloxacin N-oxide. These metabolites account for less than 5% of the 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), primarily via the kidneys (over 85% of the administered dose).

Mean total systemic clearance of levofloxacin after a single 500 mg dose was 175 ± 29.2 mL/min. There is no significant difference in the pharmacokinetics of levofloxacin after intravenous and oral administration, indicating that these routes (oral and intravenous) are interchangeable.

Linearity. Levofloxacin exhibits linear pharmacokinetics over the range of 50–1000 mg. Patients with renal impairment. The pharmacokinetics of levofloxacin are affected by renal impairment. With reduced renal function, renal excretion and clearance decrease, and elimination half-lives increase, as shown in Table 2.

Table 2

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

Gender differences. Separate analysis of male and female patients demonstrated minor differences in the pharmacokinetics of levofloxacin depending on gender. There is no evidence that these gender differences are clinically significant.

Clinical characteristics.

Indications.

Rhinoloxin, infusion solution, is indicated for the treatment of the following infectious diseases in adults:

• Community-acquired pneumonia*;
• Acute pyelonephritis and complicated urinary tract infections;
• Complicated skin and soft tissue 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 are insufficiently effective.

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

Contraindications.

Hypersensitivity to levofloxacin, other fluoroquinolones, or to any component of the medicinal product. Epilepsy. Tendon-related adverse reactions following prior use of quinolones. Pregnancy or breastfeeding. Pediatric age (under 18 years).

Interaction with other medicinal products and other forms of interaction.

Effect of other medicinal products on levofloxacin.

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

No pharmacokinetic interaction between levofloxacin and theophylline has been demonstrated. However, a significant reduction in seizure threshold may occur with concomitant administration of quinolones and theophylline, nonsteroidal anti-inflammatory drugs, or other agents that lower the seizure threshold. Levofloxacin concentrations were approximately 13% higher in the presence of fenbufen compared to administration of levofloxacin alone.

Probenecid and cimetidine.

Probenecid and cimetidine have a statistically significant effect on levofloxacin elimination. Renal clearance of levofloxacin is reduced by 24% in the presence of cimetidine and by 34% with probenecid. This is because both agents can block tubular secretion of levofloxacin. However, at the doses tested in clinical studies, it is unlikely that these statistically significant kinetic differences would have clinical relevance. Concomitant administration of levofloxacin with medicinal products affecting tubular secretion, such as probenecid and cimetidine, should be approached with caution, especially in patients with renal impairment.

Other information.

The following medicinal products do not exert any clinically significant effect on the pharmacokinetics of levofloxacin when administered concomitantly: calcium carbonate, digoxin, glyburide, ranitidine.

Effect of levofloxacin on other medicinal products.

Cyclosporine.

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

Vitamin K antagonists.

When administered concomitantly with vitamin K antagonists (e.g., warfarin), increased values in coagulation tests (prothrombin time/international normalized ratio) and/or bleeding events, which may be severe, have been reported. Therefore, coagulation parameters should be monitored in patients receiving concomitant vitamin K antagonists (see section "Special precautions").

Medicinal products that prolong the QT interval.

Levofloxacin, as with 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 antipsychotic agents) (see section "Special precautions. QT interval prolongation").

Theophylline.

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

Glucocorticoids.

The risk of tendon rupture is increased when levofloxacin is administered concomitantly with glucocorticoids.

Other.

No clinically significant effect on the pharmacokinetics of levofloxacin was observed when administered with the following medicinal products: calcium carbonate, digoxin, glyburide, ranitidine. 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 (see section "Adverse reactions"). Treatment of these patients with levofloxacin should be initiated only if there are no alternative treatment options and after careful assessment of benefit/risk (see also section "Contraindications").

Long-term, disabling and potentially irreversible serious adverse reactions.

Very rarely, in patients receiving quinolones and fluoroquinolones, regardless of age and presence of risk factors, long-term (lasting several months or years), disabling and potentially irreversible serious adverse reactions affecting various body systems, and sometimes multiple systems simultaneously (musculoskeletal, nervous, psychiatric and sensory organs), have occurred. The medicinal product should be discontinued immediately upon the first signs or symptoms of any serious adverse reaction, and medical advice should be sought. Methicillin-resistant S. aureus.

For methicillin-resistant S. aureus (MRSA), there is a very high likelihood of co-resistance to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of infections known or suspected to be caused by MRSA, except in cases where laboratory test results have confirmed susceptibility of the pathogen to levofloxacin.

Resistance to fluoroquinolones in E. coli (the most common cause of urinary tract infections) varies across countries. When prescribing fluoroquinolones, local prevalence of fluoroquinolone resistance in E. coli should be taken into account.

Duration of infusion.

The recommended duration of infusion should be at least 30 minutes for 250 mg or 60 minutes for 500 mg of levofloxacin infusion solution. Tachycardia and transient decrease in blood pressure have been reported during ofloxacin infusion. Rarely, severe hypotension may lead to cardiovascular collapse. If a marked decrease in blood pressure occurs during levofloxacin infusion (L-isomer of ofloxacin), administration of the medicinal product should be stopped immediately.

Tendinitis and tendon rupture.

Tendinitis and tendon rupture (particularly of the Achilles tendon), sometimes bilateral, may occur within the first 48 hours of initiating therapy with quinolones or fluoroquinolones, and cases have also been reported several months after discontinuation of the drug. The risk of tendinitis and tendon rupture is increased in elderly patients, patients with impaired renal function, patients who have undergone solid organ transplantation, patients receiving a daily dose of 1000 mg levofloxacin, and patients receiving concomitant corticosteroid therapy. Therefore, concomitant use of corticosteroids should be avoided. At the first signs of tendinitis (e.g., painful swelling, inflammation), levofloxacin therapy should be discontinued immediately and alternative treatment options considered. Affected limbs should be appropriately managed (e.g., immobilization). Corticosteroids are not recommended in cases of tendonopathy.

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 has not been adjusted according to creatinine clearance. Levofloxacin should be discontinued immediately at the first occurrence of myoclonus, and appropriate treatment initiated.

Clostridium difficile-associated disease.

Diarrhea, especially severe, persistent and/or bloody, occurring during or after treatment with levofloxacin (including several weeks after treatment), may be a symptom of Clostridium difficile-associated disease. The most severe form of this condition is pseudomembranous colitis (see section "Adverse reactions"). The severity of Clostridium difficile-associated diseases ranges from mild to life-threatening, with pseudomembranous colitis being the most severe form (see section "Adverse reactions"). It is therefore important to consider this diagnosis in patients who develop severe diarrhea during or after treatment with levofloxacin. If Clostridium difficile-associated disease is suspected, levofloxacin should be discontinued immediately and appropriate treatment initiated urgently. Medicinal products that inhibit intestinal motility are contraindicated in this case.

Patients with predisposition to seizures.

Quinolones may lower the seizure threshold and provoke seizures. Levofloxacin is contraindicated in patients with a history of epilepsy (see section "Contraindications"). As with other quinolones, it should be used with extreme caution in patients predisposed to seizures and in those receiving concomitant medicinal products that lower the seizure threshold, such as theophylline (see section "Interaction with other medicinal products and other forms of interaction"). If a seizure occurs (see section "Adverse reactions"), levofloxacin should be discontinued.

Patients with glucose-6-phosphate dehydrogenase deficiency.

Patients with latent or manifest impairment of glucose-6-phosphate dehydrogenase activity may be predisposed to hemolytic reactions when treated with quinolone antibiotics. Therefore, if levofloxacin must be used in such patients, monitoring for possible hemolysis should be performed.

Patients with renal impairment.

Since levofloxacin is primarily eliminated via the kidneys, dose adjustment is required for patients with impaired renal function (renal insufficiency) (see section "Dosage and method of administration").

Hypersensitivity reactions.

Levofloxacin may cause serious, potentially fatal hypersensitivity reactions (ranging from angioneurotic edema to anaphylactic shock), sometimes after the first dose of the medicinal product. If hypersensitivity reactions occur, levofloxacin should be discontinued, medical advice sought, and appropriate treatment initiated.

Severe skin reactions.

Severe skin adverse reactions, including toxic epidermal necrolysis (also known as Lyell's syndrome), Stevens-Johnson syndrome, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), have been reported with levofloxacin use, which may be life-threatening or fatal (see section "Adverse reactions").

Patients should be informed about signs and symptoms of severe skin reactions that may occur after administration of the medicinal product and monitored closely. If signs and symptoms suggestive of these reactions appear, levofloxacin should be discontinued immediately and alternative treatment considered.

If a serious reaction such as toxic epidermal necrolysis, Stevens-Johnson syndrome, or DRESS syndrome develops in a patient during levofloxacin treatment, levofloxacin therapy should never be resumed in that patient.

Blood glucose alterations.

Alterations in blood glucose levels, including both hypoglycemia and hyperglycemia, have been reported with all quinolones, usually in patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic agents (e.g., glyburide) or insulin. Cases of hypoglycemic coma have been reported. In patients with diabetes mellitus, careful monitoring of blood glucose levels is recommended (see section "Adverse reactions").

Phototoxicity prevention.

Cases of phototoxicity have been reported with levofloxacin (see section "Adverse reactions"). To prevent phototoxicity, patients should avoid unnecessary exposure to strong sunlight or artificial UV sources (e.g., UV lamps, sunbeds) during treatment and for 48 hours after discontinuation of levofloxacin.

Patients receiving vitamin K antagonists.

Due to the possible increase in coagulation parameters (prothrombin time/international normalized ratio) and/or increased frequency of hemorrhagic complications in patients receiving levofloxacin in combination with a vitamin K antagonist (e.g., warfarin), coagulation parameters should be monitored when these agents are used concomitantly (see section "Interaction with other medicinal products and other forms of interaction"). Psychotic reactions.

Psychotic reactions have been reported in patients taking quinolones, including levofloxacin. Very rarely, these progressed to suicidal thoughts and self-harming behavior, sometimes after only a single dose of levofloxacin (see section "Adverse reactions"). If such reactions occur, levofloxacin should be discontinued and appropriate measures taken. Levofloxacin should be used with caution in patients with psychotic disorders or a history of psychiatric illness.

QT interval prolongation.

Fluoroquinolones, including levofloxacin, should be used with caution in patients with risk factors for QT interval prolongation, such as:

• congenital or acquired QT prolongation syndrome;
• concomitant use of medicinal products capable of prolonging the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics);
• electrolyte imbalance (e.g., hypokalemia, hypomagnesemia);
• cardiac diseases (e.g., heart failure, myocardial infarction, bradycardia) (see sections "Dosage and method of administration. Dosing in elderly patients", "Interaction with other medicinal products and other forms of interaction", "Adverse reactions", "Overdose"). Elderly patients and women may be more sensitive to medicinal products that prolong the QT interval. Therefore, fluoroquinolones, including levofloxacin, should be used with caution in these patient groups.

Aortic aneurysm and dissection, and valvular regurgitation/insufficiency. Epidemiological studies have shown an increased risk of aortic aneurysm and dissection, particularly in elderly patients, and of aortic and mitral valve regurgitation following fluoroquinolone use. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and of regurgitation/insufficiency of any cardiac valve have been reported in patients receiving fluoroquinolones (see section "Adverse reactions"). Therefore, fluoroquinolones should be used only after careful benefit-risk assessment and consideration of alternative therapeutic options in patients with a family history of aneurysm or congenital heart valve defect, patients with a confirmed diagnosis of aneurysm and/or aortic dissection, or with heart valve disease, or in the presence of other risk factors, namely:

• risk factors for both aortic aneurysm/dissection and valvular regurgitation/insufficiency: connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, hypertension, rheumatoid arthritis;
• risk factors for aortic aneurysm and dissection: vascular disorders such as Takayasu arteritis or giant cell arteritis, atherosclerosis, or Sjögren's syndrome;
• risk factors for valvular regurgitation/insufficiency: infective endocarditis.

The risk of aortic aneurysm, dissection, and rupture is increased in patients receiving systemic corticosteroids concomitantly.

Patients should be advised to seek immediate medical attention in case of sudden abdominal, chest, or back pain.

Patients should be advised to seek immediate medical help in case of acute dyspnea, new-onset palpitations, or development of abdominal or lower limb edema.

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 inform their physician immediately to prevent progression to a potentially irreversible condition (see section "Adverse reactions").

Hepatobiliary disorders.

Cases of hepatic necrosis up to liver failure with fatal outcome 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 or signs of liver disease such as anorexia, jaundice, dark urine, pruritus, or abdominal pain occur.

Exacerbation of myasthenia gravis.

Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. In the post-marketing period, serious adverse reactions, including fatal cases and conditions requiring respiratory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Levofloxacin is not recommended for use in patients with a history of myasthenia gravis.

Visual disturbances.

If any visual disturbances or adverse reactions affecting the eyes occur during levofloxacin intake, immediate consultation with an ophthalmologist is required (see sections "Adverse reactions" and "Effect on ability to drive and use machines").

Superinfection.

The use of levofloxacin, especially prolonged, may lead to overgrowth of organisms resistant to the drug. If superinfection develops during therapy, appropriate measures should be taken.

Acute pancreatitis.

Acute pancreatitis may occur in patients taking levofloxacin. Patients should be informed about the characteristic symptoms of acute pancreatitis. Patients experiencing nausea, malaise, abdominal discomfort, acute abdominal pain, or vomiting should undergo immediate medical evaluation. If acute pancreatitis is suspected, levofloxacin should be discontinued, and if confirmed, treatment with levofloxacin should not be resumed. Caution is required when administering to patients with a history of pancreatitis.

Blood disorders

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

Effect on laboratory test results.

In patients receiving levofloxacin, urine opiate screening may yield false-positive results. Confirmation of positive opiate screening results by more specific methods may be necessary. Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and thus lead to false-negative results in bacteriological diagnosis of tuberculosis.

Important information about excipients.

The medicinal product contains sodium — caution is advised when administering to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Pregnancy. Data on the use of levofloxacin in pregnant women are limited. Animal studies do not indicate direct or indirect reproductive toxicity. However, in the absence of human data and in view of experimental data indicating a risk of cartilage damage in the developing organism due to fluoroquinolones, the medicinal product is contraindicated during pregnancy (see section "Contraindications").

Period of breastfeeding. Levofloxacin is contraindicated in women who are breastfeeding. There is insufficient information on the excretion of levofloxacin into breast milk. However, other fluoroquinolones are excreted into human milk. In the absence of human data and in view of experimental data indicating a risk of cartilage damage in the developing organism due to fluoroquinolones, levofloxacin is contraindicated in women who are breastfeeding (see section "Contraindications").

Fertility. Levofloxacin does not impair fertility or reproductive function in animals.

Effect on ability to drive and use machines.

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).

Administration and Dosage

Levofloxacin solution must be administered by slow intravenous infusion once or twice daily. The dosage depends on the type and severity of infection and on the susceptibility of the causative organism. Usually, after several days of treatment, if the patient's condition permits, the initial intravenous administration may be switched to oral intake (levofloxacin tablets 250 mg or 500 mg). The duration of treatment depends on the course of the disease.

The recommended dosage of levofloxacin is given below.

Table 3

Dosage for patients with normal renal function (creatinine clearance > 50 mL/min)

* Depending on the patient's clinical condition, a switch from initial intravenous to oral administration at the same dosage may be possible after a few days (usually within 2–4 days).

Table 4

Dosing for adult patients with impaired renal function in whom creatinine clearance < 50 mL/min

1 After hemodialysis or chronic 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 primarily excreted by the kidneys.

Dosing in elderly patients.

If renal function is not impaired, dose adjustment is not required (see section "Special precautions": "Tendonitis and tendon rupture", "QT interval prolongation"). Levofloxacin is administered intravenously slowly by infusion. The duration of administration should be at least 30 minutes for a 250 mg dose or at least 60 minutes for a 500 mg dose. Depending on the patient's condition, after several days it may be possible to switch from intravenous administration to oral levofloxacin at the same dosage.

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

Administration method.

The medicinal product should be used immediately (within 3 hours) after perforation of the rubber stopper to prevent bacterial contamination. Protection from light during infusion is not required. The medicinal product is intended for single use only. The solution should be inspected before use. Only clear solution free of particles should be used.

Mixing with other infusion solutions.

Levofloxacin is compatible with the following infusion solutions:

0.9% sodium chloride solution, 5% glucose injection solution, 2.5% glucose in Ringer's solution, multi-component parenteral nutrition solutions (amino acids, carbohydrates, electrolytes). See also section "Incompatibilities".

Any unused medicinal product should be disposed of according to local regulations.

Children.

The medicinal product is contraindicated in children (under 18 years of age) due to the potential risk of damage to joint cartilage.

Overdose.

Symptoms. The most significant expected symptoms of levofloxacin overdose involve the central nervous system (CNS): confusion, myoclonus, dizziness, altered consciousness, seizures, tremor, and QT interval prolongation. In the post-marketing period of levofloxacin use, CNS effects have been observed, including confusion, convulsions, hallucinations, and tremor.

Treatment. Symptomatic and supportive. ECG monitoring should be considered due to the potential for QT interval prolongation. Levofloxacin is not removed by hemodialysis, peritoneal dialysis, or continuous ambulatory peritoneal dialysis (CAPD); there is no specific antidote.

Adverse reactions.

The adverse reactions listed below are classified by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), frequency not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are listed in order of decreasing severity.

Table 5

1 Anaphylactic and anaphylactoid reactions may sometimes occur even after administration of the first dose of the medicinal product.

2 Mucous membrane reactions may sometimes occur even after administration of the first dose of the medicinal product. * Very rare cases of prolonged (several months or years), disabling and potentially irreversible serious reactions affecting various organ systems and sensory organs (including such reactions as tendinitis, tendon rupture, arthralgia, pain in extremities, gait disturbances; in some cases, neuropathies associated with paresthesia, depression, fatigue, memory impairment, sleep disorders, and disturbances of hearing, vision, taste, and smell) have been associated with the use of quinolones and fluoroquinolones, regardless of the presence of risk factors (see section "Special precautions for use").

** In patients receiving fluoroquinolones, cases of aneurysm and aortic dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any cardiac valve have been observed (see section "Special precautions for use").

Other adverse effects associated with fluoroquinolone use include acute attacks of porphyria in patients with porphyria.

Reporting of suspected adverse reactions.

Reporting of adverse reactions after medicinal product registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua

Shelf life. 2 years.

Storage conditions.

Store at temperatures not exceeding 25 °C in the original packaging, protected from light. Do not freeze. Keep out of reach of children.

Incompatibility.

The medicinal product should not be mixed with infusion solutions and injections that are physically and chemically unstable at pH 3–4 (such as sodium bicarbonate, penicillin, heparin). The medicinal product should not be mixed with other medicinal products in the same container, except as specified in the section "Method of administration and dosage."

Packaging.

100 ml in a polyvinyl chloride container, 1 container in a polyethylene bag within a cardboard package.

Prescription status. Prescription only.

Manufacturer.

Subsidiary enterprise "Farmatreyd".

Manufacturer's address and place of business.

85 Sambirska Street, Drohobych, Lviv Oblast, Ukraine