Zoilev

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ZOILEV

Composition:

Active substance: levofloxacin;

100 ml of solution contains levofloxacin 500 mg (as levofloxacin hemihydrate);

Excipients: anhydrous glucose, disodium edetate, diluted hydrochloric acid, water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical properties: clear solution ranging from yellow to yellowish-green in color, free from foreign particles.

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.

Mechanism of action

As a fluoroquinolone-class antibacterial agent, levofloxacin acts on the DNA-DNA gyrase complex and topoisomerase IV.

Pharmacokinetic/pharmacodynamic relationship

The degree of antibacterial activity of levofloxacin depends on the ratio of the maximum serum concentration (C_max) 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 gyrA gene. 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 minimum inhibitory concentration (MIC) breakpoints for levofloxacin, 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 (MIC testing, mg/L).

Clinical MIC breakpoints for levofloxacin

Table 1

1 Only uncomplicated urinary tract infections.

2 Susceptibility can be inferred based on sensitivity to ciprofloxacin.

Resistance prevalence may vary geographically and over time for selected species. Local information on resistance is desirable, especially when treating severe infections. When necessary, advice from a specialist should be sought if local resistance prevalence renders the utility of the agent at least questionable for certain types of infections.

*Methicillin-resistant S. aureus is highly likely to exhibit co-resistance to fluoroquinolones, including levofloxacin.

Pharmacokinetics.

Steady-state concentrations 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 both single and repeated 500 mg doses, indicating extensive distribution into body tissues.

Penetration into tissues and body fluids

Levofloxacin penetrates well into bronchial mucosa, epithelial lining fluid, alveolar macrophages, lung tissue, skin (vesicular fluid), prostate tissue, and urine. However, penetration into cerebrospinal fluid is poor.

Metabolism

Levofloxacin undergoes minimal metabolism. The metabolites identified are desmethyl-levofloxacin and levofloxacin N-oxide. These metabolites account for less than 5% of the administered dose excreted in urine. Levofloxacin is stereochemically stable and does not undergo chiral inversion.

Elimination

Following both oral and intravenous administration, levofloxacin is eliminated from plasma relatively slowly (elimination half-life is 6–8 hours), primarily via the kidneys (more than 85% of the administered dose is excreted unchanged in urine).

The 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 between intravenous and oral administration, indicating that these routes are interchangeable.

Linearity

Levofloxacin exhibits linear pharmacokinetics over the dose range of 50–1000 mg.

Patients with renal impairment

Renal impairment affects the pharmacokinetics of levofloxacin. With decreased renal function, renal excretion and clearance are reduced, and elimination half-life is prolonged (see 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 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.

The medicinal product Zolev, solution for infusion, is indicated for the treatment of the following infectious diseases in adults:

1. community-acquired pneumonia*;
2. acute pyelonephritis and complicated urinary tract infections;
3. complicated skin and soft tissue infections*;
4. chronic bacterial prostatitis;
5. pulmonary form of anthrax: post-exposure prophylaxis and definitive treatment.

*Regarding 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 regarding appropriate use of antibacterial agents should be taken into account.

Contraindications.

Hypersensitivity to levofloxacin, other fluoroquinolones, or any component of the medicinal product. Epilepsy. Patients with history of tendon-related adverse reactions following previous administration of quinolones. Pregnancy or breastfeeding. Pediatric age (under 18 years).

Safety precautions.

The solution 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 must be inspected before use. Only clear solution free from particles should be used.

As with all other medicinal products, any unused medicinal product should be disposed of according to local regulations.

Mixing with other infusion solutions

The product is compatible with the following infusion solutions:

• 0.9% sodium chloride solution;
• 5% glucose solution for injection;
• 2.5% glucose in Ringer's solution;
• combined parenteral nutrition solutions (amino acids, glucose, electrolytes).

Issues related to incompatibility are discussed in the section "Incompatibilities".

Interaction with other medicinal products and other types of interactions.

Effect of other medicinal products on levofloxacin

Theophylline, fenbufen or similar non-steroidal 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, NSAIDs, or other agents that lower the seizure threshold. The concentration of levofloxacin in the presence of fenbufen was approximately 13% higher than when levofloxacin was 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 24% in the presence of cimetidine and by 34% in the presence of probenecid. This is because both drugs are capable of blocking tubular secretion of levofloxacin. However, at the doses tested in clinical studies, it is unlikely that statistically significant kinetic differences would have clinical relevance. Levofloxacin should be used with caution concomitantly with medicinal products affecting tubular secretion, such as probenecid and cimetidine, especially in patients with renal impairment.

Other information

The following medicinal products have no 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 coagulation parameters (prothrombin time/international normalized ratio) and/or bleeding, which may be severe, have been reported. Therefore, in patients receiving concomitant vitamin K antagonists, coagulation parameters should be monitored (see section "Special precautions for use").

MEDICINAL PRODUCTS THAT PROLONG THE QТ INTERVAL

Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving medicinal products known to prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, and antipsychotic medicinal products) (see section "Special precautions for use" ("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 concomitant use of glucocorticoids increases the risk of tendon rupture.

Other

No clinically significant effect on the pharmacokinetics of levofloxacin was observed when administered concomitantly 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 drug 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 no alternative treatment options are available and after careful benefit/risk assessment (see also section "Contraindications").

Methicillin-resistant S. aureus

There is a very high likelihood of co-resistance to fluoroquinolones, including levofloxacin, in methicillin-resistant S. aureus (MRSA). Therefore, levofloxacin is not recommended for the treatment of infections known or suspected to be caused by MRSA, except when laboratory testing has confirmed susceptibility of the pathogen to levofloxacin.

Resistance to fluoroquinolones in E. coli (the most common causative agent of urinary tract infections) varies across countries. Local prevalence of fluoroquinolone resistance in E. coli should be taken into account when prescribing fluoroquinolones.

Pulmonary form of anthrax

Use in humans is based on data regarding Bacillus anthracis susceptibility in vitro and experimental animal data, together with limited human data. Physicians should refer to national and/or international consensus guidelines on the treatment of anthrax.

Prolonged, disabling and potentially irreversible serious adverse reactions

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

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 failure. If a marked decrease in blood pressure occurs during levofloxacin (L-isomer of ofloxacin) infusion, administration of the drug should be stopped immediately.

Tendinitis and tendon rupture

Tendinitis and tendon rupture (particularly, but not limited to, Achilles tendon), sometimes bilateral, may occur within the first 48 hours of starting treatment 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 managed appropriately (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 upon the first occurrence of myoclonus, and appropriate treatment initiated.

Clostridium difficile-associated disease

Diarrhea, especially severe, persistent and/or with blood, 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 condition 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 without delay. Medicinal products that inhibit intestinal motility are contraindicated in this case.

Patients with seizure predisposition

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 deficiency in glucose-6-phosphate dehydrogenase activity may be prone 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 excreted by the kidneys, dose adjustment is required in patients with impaired renal function (renal insufficiency) (see section "Dosage and administration").

Hypersensitivity reactions

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

Severe bullous 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), have been reported with levofloxacin use, which may be life-threatening or fatal (see section "Adverse reactions").

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

If a patient develops a serious reaction such as toxic epidermal necrolysis, Stevens-Johnson syndrome, or DRESS with levofloxacin, levofloxacin therapy should not be resumed in this patient at any time.

Blood glucose alterations

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

Levofloxacin treatment should be discontinued immediately if the patient reports disturbances in blood glucose levels, and alternative non-fluoroquinolone antibacterial therapy should be considered.

Phototoxicity prevention

Cases of photosensitization have been reported with levofloxacin (see section "Adverse reactions"). To prevent photosensitization, patients should be advised to avoid unnecessary exposure to intense sunlight or artificial UV radiation (e.g., UV lamps, sunlamps, tanning beds) 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 medicinal products 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 psychiatric disorders or a history of psychiatric illness.

QT interval prolongation

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

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

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

Hepatobiliary disorders

Cases of liver necrosis up to hepatic failure with fatal outcome have been reported with levofloxacin use (mainly 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 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 ocular adverse reactions occur during levofloxacin therapy, patients should seek immediate ophthalmological consultation (see sections "Ability to influence driving and use of machines" and "Adverse reactions").

Superinfection

The use of levofloxacin, particularly prolonged use, may lead to overgrowth of microorganisms not susceptible (resistant) to the drug. If superinfection develops during therapy, appropriate measures should be taken.

Effect on laboratory test results

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

Aortic aneurysm and dissection, and cardiac valve regurgitation/insufficiency

Epidemiological studies have shown an increased risk of aortic aneurysm and dissection, particularly in elderly patients, and regurgitation of aortic and mitral valves following fluoroquinolone use. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and 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 positive family history of aneurysm or congenital heart valve defect, or in patients with existing diagnosis of aneurysm and/or aortic dissection, or heart valve disease, or in the presence of other risk factors or predisposing conditions:

• for both aortic aneurysm and dissection, and cardiac valve regurgitation/insufficiency (e.g., connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, arterial hypertension, rheumatoid arthritis), or additionally
• for aortic aneurysm and dissection (e.g., vascular disorders such as Takayasu arteritis or giant cell arteritis, known atherosclerosis, or Sjögren's syndrome), or additionally
• for cardiac valve regurgitation/insufficiency (e.g., infective endocarditis). The risk of aortic aneurysm, dissection, and rupture may be increased in patients receiving systemic corticosteroids concomitantly.

In case of sudden abdominal, chest, or back pain, patients should seek immediate medical attention at an emergency department.

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

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, severe abdominal pain, or vomiting should undergo immediate medical evaluation. Levofloxacin should be discontinued if acute pancreatitis is suspected. Levofloxacin should not be restarted if acute pancreatitis is confirmed. Caution should be exercised in patients with a history of pancreatitis (see section "Special precautions for use").

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 is suspected, blood test results should be monitored. If abnormal results are obtained, discontinuation of levofloxacin therapy should be considered.

Excipients

The drug contains 5 g of glucose per dose (100 ml vial). Therefore, the drug should be used with caution in patients with diabetes mellitus.

This medicinal product contains less than 1 mmol (23 mg) of sodium per dose (100 ml vial), i.e., essentially "sodium-free".

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 growing organism due to fluoroquinolone action, the drug is contraindicated during pregnancy (see section "Contraindications").

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 growing organism due to fluoroquinolone action, levofloxacin is contraindicated in women who are breastfeeding (see section "Contraindications").

Fertility

Levofloxacin does not impair fertility or reproductive function in animals.

Ability to influence driving and use of machines

Levofloxacin has a minor or moderate effect on the ability to drive and use machines. Some adverse reactions (e.g., dizziness/vertigo, somnolence, visual disturbances) may impair the patient's ability to concentrate and react, and therefore may pose a risk in situations where such ability is particularly important (e.g., driving a car or operating machinery).

Method of administration and dosage.

The levofloxacin solution must be administered by slow intravenous infusion once or twice daily. The dose 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 administration (levofloxacin tablets 250 mg or 500 mg). The duration of treatment depends on the course of the disease.

The following dosage regimens are recommended for administration of levofloxacin:

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 administration to oral administration at the same dosage may be possible after a few days (usually within 2–4 days).

Table 4

Dosage for adult patients with renal impairment (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 eliminated via the kidneys.

Dosing in elderly patients

If renal function is not impaired, dose adjustment is not required (see section "Special precautions": tendinitis and tendon rupture; QT interval prolongation).

Levofloxacin is administered intravenously slowly by infusion. The infusion duration 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 administration of 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 testing has confirmed eradication of the causative pathogens.

Mixing with other infusion solutions

Levofloxacin is compatible with the following infusion solutions:

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

For information on incompatibility of levofloxacin with other infusion solutions, see section "Incompatibilities", and for compatibility, see section "Special precautions".

Children.

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

Overdose.

Symptoms. The most important expected symptoms of levofloxacin overdose involve the central nervous system (CNS): confusion, dizziness, altered consciousness, seizures, tremor, QT interval prolongation. In the post-marketing period of levofloxacin use, CNS effects have been observed, including confusion, convulsions, myoclonus, 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 information below is based on data from clinical trials involving over 8,300 patients and extensive post-marketing experience.

The frequency in this table is defined as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), frequency not known (cannot be estimated based on available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

Table 5

Adverse reactions

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

2 Mucosal reactions may sometimes occur even after administration of the first dose of the drug.

Other adverse reactions associated with the use of fluoroquinolones include attacks of porphyria in patients with porphyria.

* Very rare cases of prolonged (up to months or years), disabling and potentially irreversible serious adverse drug reactions affecting several, sometimes multiple, organ systems and sensory organs (including such reactions as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbance; in some cases, neuropathy 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 previously existing risk factors (see section "Special precautions for use").

** Cases of aneurysm and dissection of the aorta, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any of the heart valves have been reported in patients receiving fluoroquinolones (see section "Special precautions for use").

Reporting suspected adverse reactions

Reporting suspected adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk ratio of the drug. Healthcare professionals and patients or their legal representatives should 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.

Incompatibilities.

The drug 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 drug should not be mixed with other medicinal products in the same container, except as specified in the section "Special precautions for safety".

Storage conditions.

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

Keep out of reach of children.

Packaging.

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

Prescription status. Prescription only.

Manufacturer.

Subsidiary enterprise "Farmatreyd".

Manufacturer's location and address of business activity.

85 Sambirska Street, Drohobych, Lviv region, Ukraine.