INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LOXOF (LOXOF)

Composition:

Active substance: levofloxacin;

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

Excipients: microcrystalline cellulose, hypromellose, polysorbate 80, crospovidone, magnesium stearate, Opadry Yellow 03B52874 (hypromellose, titanium dioxide (E 171), polyethylene glycol 400, iron oxide yellow (E 172), iron oxide red (E 172)).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: elongated, biconvex, film-coated tablets of light orange color with the imprint "500" on one side.

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 and is the S-enantiomer of the racemic mixture of the drug ofloxacin.

Mechanism of action

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

Pharmacokinetic/pharmacodynamic relationship

The extent of bactericidal activity of levofloxacin depends on the ratio between the maximum serum concentration (Cmax) or the area under the pharmacokinetic curve (AUC) and the minimum inhibitory concentration (MIC).

Mechanism of resistance

Resistance to levofloxacin develops due to sequential mutations in the binding sites of two types of type II topoisomerases: DNA gyrase and topoisomerase IV. Other resistance mechanisms such as membrane impermeability mechanisms (common in Pseudomonas aeruginosa) and efflux may also affect susceptibility to levofloxacin.

Cross-resistance has been observed between levofloxacin and other fluoroquinolones.

Due to its mechanism of action, cross-resistance between levofloxacin and other classes of antibacterial agents is usually not present.

Antibacterial spectrum

The EUCAST (European Committee on Antimicrobial Susceptibility Testing) defined MIC breakpoints for levofloxacin that distinguish susceptible strains from intermediate-susceptible strains and intermediate-susceptible strains from resistant strains are listed in the table below.

EUCAST-defined MIC breakpoints for levofloxacin (version 10.0, 01.01.2020)

1 Only uncomplicated urinary tract infections.

2 Susceptibility can be inferred based on susceptibility to ciprofloxacin.

The prevalence of resistance in certain microbial species may vary geographically and over time. Local information on resistance should be obtained, especially when treating severe infections. If necessary, when local resistance prevalence renders the efficacy of the drug at least questionable for certain types of infections, advice from a specialist should be sought.

Generally susceptible species

Gram-positive aerobic bacteria

Bacillus anthracis, Staphylococcus aureus methicillin-susceptible, Staphylococcus saprophyticus, Streptococci groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes

Gram-negative aerobic bacteria

Burkholderia cepacia, Eikenella corrodens, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, 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 for which acquired (secondary) resistance may be problematic

Gram-positive aerobic bacteria

Enterococcus faecalis, Staphylococcus aureus methicillin-resistant#, Staphylococcus coagulase spp.

Gram-negative aerobic bacteria

Acinetobacter baumannii, Citrobacter freundii, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Escherichia coli, Morganella morganii, Proteus mirabilis, Providencia stuartii, Pseudomonas aeruginosa, Serratia marcescens

Anaerobic bacteria

Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Clostridium difficile

Resistant species

Gram-positive aerobic bacteria

Enterococcus faecium

Methicillin-resistant S. aureus (MRSA) often also exhibits resistance to fluoroquinolones, including levofloxacin.

Pharmacokinetics

Absorption

After oral administration, levofloxacin is rapidly and almost completely absorbed, with peak plasma concentrations reached within 1–2 hours. Absolute bioavailability is 99–100%.

Food has practically no effect on the absorption of levofloxacin.

Steady state is achieved within 48 hours after administration of 500 mg once or twice daily.

Distribution

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

Metabolism

Levofloxacin is only minimally metabolized, with metabolites being 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

After oral administration and intravenous infusion, levofloxacin is eliminated from plasma relatively slowly (elimination half-life is 6–8 hours). Elimination occurs primarily via the kidneys (over 85% of the dose).

The mean apparent total clearance of levofloxacin after a single 500 mg dose was 175 ± 29.2 mL/min.

The lack of significant difference between the pharmacokinetics of levofloxacin after intravenous and oral administration indicates that these routes (oral and intravenous) are interchangeable.

Linearity

Levofloxacin exhibits linear pharmacokinetics over the range of 50–1,000 mg.

Pharmacokinetics in special patient groups

Patients with renal impairment

Renal impairment affects the pharmacokinetics of levofloxacin. With decreased renal function, renal elimination and clearance are reduced, and elimination half-lives are prolonged, as shown in the table below:

Elderly patients

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

Gender differences

Separate analysis of patients revealed minor differences in levofloxacin pharmacokinetics depending on gender. There is no evidence that these gender differences are clinically significant.

Clinical characteristics.

Indications.

Loxof is indicated for the treatment in adults of the following infections caused by microorganisms sensitive to levofloxacin:

• acute bacterial sinusitis*;
• exacerbation of chronic bacterial bronchitis*;
• community-acquired pneumonia;
• complicated skin and soft tissue infections*.

The drug should be used for the treatment of the above-mentioned infections only when other antibacterial agents typically prescribed for initial treatment of these infections are not feasible:

• complicated urinary tract infections (including pyelonephritis);
• chronic bacterial prostatitis;
• uncomplicated cystitis;
• pulmonary form of anthrax: post-exposure prophylaxis and treatment.

Loxof in this pharmaceutical form (tablets) may be used to complete the course of therapy in patients who have shown clinical improvement during initial treatment with levofloxacin intravenous infusion.

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

*Only when the use of other antibacterial agents typically prescribed for treatment of this infection has been considered ineffective or inappropriate.

Contraindications.

Levofloxacin should not be prescribed in the following cases:

• hypersensitivity to levofloxacin or to other quinolones or to any other component of the medicinal product;
• tendon-related adverse reactions following previous use of quinolones;
• epilepsy;
• pediatric age (under 18 years);
• pregnancy or breastfeeding.

Interaction with other medicinal products and other forms of interaction.

Effect of other medicinal products on levofloxacin

Iron salts, zinc salts, antacids containing magnesium and aluminium, didanosine.

Absorption of levofloxacin is significantly reduced when administered concomitantly with iron salts, antacids containing magnesium or aluminium, or didanosine (only for formulations containing buffering agents of aluminium or magnesium). Concurrent administration of fluoroquinolones with multivitamins containing zinc leads to reduced oral absorption. Tablets should be taken at least 2 hours after administration of products containing divalent or trivalent cations, such as iron salts or antacids containing magnesium or aluminium. Calcium carbonate had minimal effect on the oral absorption of levofloxacin.

Sucralfate

Bioavailability of the drug is significantly reduced when administered concomitantly with sucralfate. If a patient needs to receive both sucralfate and levofloxacin, sucralfate should preferably be taken 2 hours after levofloxacin administration (see section "Dosage and administration").

Theophylline, fenbufen or similar nonsteroidal anti-inflammatory drugs

No pharmacokinetic interaction between levofloxacin and theophylline has been observed. However, a significant reduction in seizure threshold may occur when quinolones are used concomitantly with theophylline, nonsteroidal anti-inflammatory drugs, or other agents that lower the seizure threshold. Levofloxacin concentrations were approximately 13% higher in the presence of fenbufen than when levofloxacin was administered alone.

Probenecid and cimetidine

Probenecid and cimetidine statistically significantly affect the elimination of levofloxacin. Renal clearance of levofloxacin is reduced by 24% in the presence of cimetidine and by 34% with probenecid. This is due to the fact that both drugs can block tubular secretion of levofloxacin. However, in studies, statistically significant kinetic differences did not have clinical relevance. Concomitant use of levofloxacin with medicinal products affecting tubular secretion, such as probenecid and cimetidine, should be done with caution, especially in patients with renal impairment.

Other drugs

Clinical pharmacology studies have demonstrated that no clinically significant effect on the pharmacokinetics of levofloxacin occurred when levofloxacin was administered with calcium carbonate, digoxin, glyburide, or ranitidine.

Effect of levofloxacin on other medicinal products

Cyclosporines

The elimination 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), increased coagulation parameters (INR/international normalized ratio) and/or bleeding, which may be severe, have been reported. Therefore, patients receiving vitamin K antagonists concurrently should be monitored for coagulation parameters (see section "Special precautions for use").

Medicinal products that prolong the QT interval

Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving medicinal products that may prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, and antipsychotics) (see section "Special precautions for use. QT interval prolongation").

Other significant information.

No effect of levofloxacin on the pharmacokinetics of theophylline (a marker substrate for the CYP1A2 enzyme) has been observed, indicating that levofloxacin is not an inhibitor of CYP1A2.

The risk of tendon rupture is increased when levofloxacin is used concomitantly with corticosteroids.

Food intake

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

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. Treatment of these patients with levofloxacin should be initiated only if no alternative treatment options are available and after careful assessment of benefit/risk.

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 testing has confirmed susceptibility of the pathogen to levofloxacin (and antibiotics typically recommended for MRSA infections are considered ineffective).

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

Anthrax. For the pulmonary form of anthrax, use is based on in vitro susceptibility data for Bacillus anthracis, experimental animal data, and limited human use data. Physicians should consider national and/or international consensus guidelines on the treatment of anthrax.

Prolonged, disabling and potentially irreversible serious adverse reactions

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

Tendinitis and tendon rupture

Tendinitis, which may lead to tendon rupture including of the Achilles tendon, may occur during treatment with quinolones. Tendinitis and tendon ruptures, sometimes bilateral, may occur within 48 hours of starting levofloxacin or even several months after discontinuation of levofloxacin. Elderly patients, patients with impaired renal function, patients receiving a daily dose of 1,000 mg levofloxacin, patients after organ transplantation, and patients receiving corticosteroids are most susceptible to tendinitis and tendon ruptures. Elderly patients receiving levofloxacin require close monitoring. If tendinitis is suspected (e.g., painful swelling, inflammation), levofloxacin should be discontinued immediately and appropriate treatment initiated (e.g., immobilization of the tendon) (see section "Contraindications" and "Adverse reactions"). Corticosteroids should not be used if signs of tendinopathy appear.

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 appearance of myoclonus, and appropriate treatment initiated.

Clostridium difficile-associated disease

Diarrhea, especially severe, persistent and/or hemorrhagic, during or after treatment with Loxof tablets may be symptoms of disease caused by Clostridium difficile, the most severe form of which is pseudomembranous colitis. If pseudomembranous colitis is suspected, Loxof tablets should be discontinued immediately, and patients should be treated promptly with supportive measures and specific therapy (e.g., oral vancomycin). 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 (see section "Contraindications"). As with other quinolones, it should be used with extreme caution in patients predisposed to seizures and in those receiving concomitant therapy with drugs that increase seizure susceptibility (lower the seizure threshold) (see section "Interaction with other medicinal products and other forms of interaction"). If seizures occur, levofloxacin treatment should be discontinued.

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with latent or manifest deficiency in glucose-6-phosphate dehydrogenase activity may be predisposed to hemolytic reactions when treated with quinolone antibacterial agents; therefore, levofloxacin should be used with caution in such patients.

Patients with renal impairment

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

Hypersensitivity reactions

Levofloxacin may cause serious, potentially fatal hypersensitivity reactions (e.g., angioedema up to anaphylactic shock) after administration of the initial dose (see section "Adverse reactions"). In such cases, patients should discontinue treatment immediately and seek medical advice.

Serious skin reactions

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

Patients should be informed about the signs and symptoms of serious skin reactions and closely monitored during treatment.

Levofloxacin should be discontinued immediately at the first signs of such reactions, and alternative therapy considered. If a patient experiences a serious skin reaction such as toxic epidermal necrolysis (TEN; also known as Lyell's syndrome), Stevens-Johnson syndrome (SJS), or drug reaction with eosinophilia and systemic symptoms (DRESS) during levofloxacin treatment, the drug must not be prescribed under any circumstances in the future.

Alterations in blood glucose levels

As with all quinolones, disturbances in blood glucose levels, including hyperglycemia and hypoglycemia, have been reported, particularly in elderly patients and diabetic patients receiving concomitant therapy with oral hypoglycemic agents (e.g., glyburide) or insulin. Close monitoring of blood glucose levels is recommended in diabetic patients (see section "Adverse reactions").

If a patient reports abnormal blood glucose levels, levofloxacin treatment should be discontinued immediately and alternative non-fluoroquinolone antibacterial therapy considered.

Phototoxicity prevention

Although phototoxicity is very rare with levofloxacin, to avoid it, patients should avoid excessive exposure to sunlight or artificial UV radiation (e.g., UV lamps, sunbeds) during Loxof treatment and for 48 hours after discontinuation of the drug.

Patients receiving vitamin K antagonists

Due to possible increases in coagulation test parameters (PT/INR) and/or bleeding in patients taking Loxof in combination with a vitamin K antagonist (e.g., warfarin), coagulation tests should be monitored when these drugs 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. In very rare cases, these progressed to suicidal thoughts and self-destructive 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. Alternative non-fluoroquinolone antibacterial therapy should be considered. Levofloxacin should be used with caution in patients with a history of psychotic disorders or 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 long QT syndrome;
• concomitant use of drugs known to prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics);
• uncorrected electrolyte imbalance (e.g., hypokalemia, hypomagnesemia);
• heart disease (e.g., heart failure, myocardial infarction, bradycardia).

Elderly patients and women may be more sensitive to drugs that prolong the QT interval; therefore, caution is required when using fluoroquinolones, including levofloxacin, in these patient groups (see sections "Posology and method of administration", "Elderly patients", "Interaction with other medicinal products and other forms of interaction", "Adverse reactions", "Overdose").

Peripheral neuropathy

Rapid onset sensory or sensorimotor peripheral polyneuropathy leading to paresthesia, hypoesthesia, dysesthesia, or muscle weakness has been reported in patients receiving fluoroquinolones, including levofloxacin. Levofloxacin should be discontinued if patients experience neuropathic symptoms such as pain, burning, tingling, numbness, or muscle weakness to prevent irreversible damage.

Hepatobiliary disorders

Cases of necrotic hepatitis up to life-threatening liver failure have been reported with levofloxacin, primarily in patients with severe underlying conditions such as sepsis (see section "Adverse reactions"). Patients should be advised to discontinue treatment and seek medical advice if signs or symptoms of liver disease occur, such as anorexia, jaundice, dark-colored 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. 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 seek immediate ophthalmological evaluation (see sections "Adverse reactions", "Effect on ability to drive and use machines").

Superinfection

With the use of levofloxacin, particularly prolonged use, development of opportunistic infections and overgrowth of resistant microorganisms is possible. If superinfection develops during therapy, appropriate measures should be taken.

Effect on laboratory tests

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

Levofloxacin inhibits the growth of Mycobacterium tuberculosis, so false-negative results may occur in bacteriological testing of patients with tuberculosis.

Aortic aneurysm / aortic dissection

Epidemiological data suggest an increased risk of aortic aneurysm or dissection with fluoroquinolone use, particularly in elderly patients, as well as aortic and mitral valve regurgitation. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal outcomes), and cases of regurgitation/insufficiency of one of the heart valves have been reported in patients receiving fluoroquinolones. Therefore, fluoroquinolone antibiotics should be used only after careful benefit/risk assessment and consideration of alternative treatment options in patients with a personal or family history of aortic aneurysm/dissection or congenital heart valve defects; in patients with existing aortic aneurysm/dissection or heart valve disease; and in patients with risk factors for aortic regurgitation or heart valve regurgitation/insufficiency (e.g., Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, Turner syndrome, giant cell arteritis, Behçet's disease, hypertension, rheumatoid arthritis, atherosclerosis, Sjögren's syndrome, infectious endocarditis).

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

If sudden abdominal pain, chest or back pain, sudden onset of dyspnea, rapid heartbeat, or development of abdominal or lower limb edema occurs, patients should seek immediate emergency medical assistance.

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. If the diagnosis is confirmed, levofloxacin treatment should not be resumed. Caution should be exercised in patients with a history of pancreatitis (see section "Adverse reactions").

Blood disorders

During treatment with levofloxacin, bone marrow suppression 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 parameters should be monitored. If abnormal results are obtained, discontinuation of levofloxacin treatment should be considered.

Use during pregnancy or breastfeeding

Pregnancy. Data on the use of levofloxacin in pregnant women are limited.

Due to the lack of human studies and the potential for quinolones to damage the articular cartilage in the growing organism, levofloxacin is contraindicated in pregnant women and women who are breastfeeding. If pregnancy occurs during treatment, the patient should inform her physician.

Breastfeeding. Levofloxacin is contraindicated during breastfeeding. Information on the excretion of levofloxacin in breast milk is insufficient, although other fluoroquinolones are excreted in breast milk. Due to the lack of human studies and the potential for fluoroquinolones to damage articular cartilage in the growing organism, levofloxacin should not be administered to women who are breastfeeding.

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

Effect on ability to drive and use machines

Patients who drive vehicles or operate machinery should exercise caution during treatment due to possible undesirable nervous system adverse reactions (dizziness, somnolence, visual disturbances) that may impair concentration and reaction ability, creating a risk in situations where these abilities are particularly important.

Method of Administration and Dosage

Loxof tablets should be taken once or twice daily. The dosage and duration of treatment depend on the type, severity of the infection, and the susceptibility of the likely pathogen. It is recommended to continue Loxof treatment for at least 48–72 hours after normalization of body temperature or until microbiological tests confirm the absence of pathogens.

The drug may be used to complete the treatment course in patients who have shown improvement during initial therapy with levofloxacin in the form of an infusion solution, using the same dosage regimen.

Loxof tablets should be swallowed whole, without chewing, with an adequate amount of liquid. They may be taken either with food or between meals.

The drug must be administered at least 2 hours before or after the administration of iron salts, zinc salts, antacids containing magnesium or aluminum, didanosine (only formulations containing aluminum or magnesium in buffering agents), and sucralfate (see section "Interaction with other medicinal products and other types of interactions").

If a dose lower than 500 mg is required, the drug should be administered in another pharmaceutical form or with a different active ingredient content.

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

Table 3

Dosage for patients with impaired renal function, in whom creatinine clearance is less than 50 ml/min

Table 4

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

Dosage in patients with hepatic impairment. Dose adjustment is not necessary, since levofloxacin is minimally metabolized in the liver and is primarily excreted via the kidneys.

Dosage in elderly patients. If renal function is not impaired, there is no need for dose adjustment (see section "Special precautions": Tendinitis and tendon rupture. QT interval prolongation).

Children. Loxof is contraindicated in children, as damage to articular cartilage cannot be excluded (see section "Contraindications").

Overdose.

Symptoms. The most important symptoms of overdose are those related to the central nervous system (confusion, dizziness, disturbances of consciousness, seizures, myoclonus, hallucinations, and tremor); gastrointestinal reactions such as nausea and mucosal erosions; QT interval prolongation is also possible.

Treatment. Treatment is symptomatic. ECG monitoring should be considered due to the possibility of QT interval prolongation. Antacids should be administered to protect gastric mucosa. Hemodialysis, including peritoneal dialysis or CAPD, is not effective for removing levofloxacin from the body. There are no specific antidotes.

Adverse Reactions

The frequency of adverse effects listed in Table 5 was determined according to the following criteria: very common (>1/10), common (from ≥1/100 to <1/10), uncommon (from >1/1000 to <1/100), rare (from >1/10000 to <1/1000), very rare (<1/10000), not known (cannot be estimated from available data).

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

Table 5

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

2 Skin and mucous membrane reactions may sometimes occur even after administration of the first dose.

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

** In patients receiving fluoroquinolones, cases of aneurysm and aortic dissection have been reported, sometimes complicated by rupture (including fatal outcomes), as well as regurgitation/insufficiency of one of the heart valves (see section "Special precautions").

Description of selected adverse reactions

During the post-marketing period of fluoroquinolone use, patients have experienced neuropsychiatric symptoms, including anxiety, suicidal thoughts, panic attacks, neuralgia, and impaired concentration. These events may represent manifestations of prolonged, disabling adverse reactions caused by fluoroquinolones, leading to loss of work capacity.

Reporting of adverse reactions after drug registration is of great importance. It allows continuous monitoring of the benefit-risk balance of the drug. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

Store in a place protected from light and moisture, out of reach of children, at a temperature not exceeding 25 °C.

Packaging.

5 tablets per blister; 1 blister per cardboard pack.

Prescription status. Prescription only.

Manufacturer.

San Pharmaceutical Industries Limited.

Sun Pharmaceutical Industries Limited.

Manufacturer's address and location of its business operations.

Industrial Area 3, Dewas - 455001, India.

Industrial Area 3, Dewas, 455001, India.