Levasect

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

Composition:

Active substance: levofloxacin;

100 ml of solution contain levofloxacin hemihydrate equivalent to 500 mg of levofloxacin;

Excipients: anhydrous glucose, concentrated hydrochloric acid, sodium hydroxide, water for injections.

Pharmaceutical form. Infusion solution.

Main physico-chemical properties: clear greenish-yellow solution.

Pharmacotherapeutic group.
Antibacterials for systemic use. Quinolone antibiotics. Fluoroquinolones. ATC code J01MA12.

Pharmacological properties.

Pharmacodynamics.

Levofloxacin is a broad-spectrum antibiotic from the group of quinolones containing the active substance levofloxacin. Like other fluoroquinolones, levofloxacin inhibits bacterial DNA gyrase, thereby disrupting bacterial DNA function. Levofloxacin is active against both Gram-positive and Gram-negative pathogenic microorganisms, including strains resistant to penicillins, cephalosporins, and/or aminoglycosides. The development of resistance may significantly affect the susceptibility of local strains to the drug; therefore, this information should be taken into account when prescribing the drug, especially in the treatment of severe infections. Levofloxacin has a broad spectrum of activity against microorganisms both in vitro and in vivo: Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Viridans group streptococci, Enterobacter cloacae, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter sakazakii, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Klebsiella oxytoca, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, Pseudomonas aeruginosa, Pseudomonas fluorescens, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Acinetobacter anitratus, Acinetobacter baumannii, Acinetobacter calcoaceticus, Bordetella pertussis, Citrobacter diversus, Citrobacter freundii, Morganella morganii, Proteus vulgaris, Providencia rettgeri et stuartii, Serratia marcescens, Clostridium perfringens.

Like other fluoroquinolones, levofloxacin is inactive against spirochetes.

Pharmacokinetics.

There is no significant difference in the pharmacokinetics of levofloxacin after intravenous and oral administration.

Absorption. After oral administration, levofloxacin is rapidly and almost completely absorbed. Peak plasma concentrations are observed within 1 hour after dosing. Absolute bioavailability is nearly 100%. Levofloxacin exhibits linear pharmacokinetics within the dose range of 50–600 mg. Food intake slightly affects drug absorption.

Distribution. Approximately 30–40% of levofloxacin is protein-bound in serum. Accumulation of levofloxacin with a dosage regimen of 500 mg once daily is practically negligible. There is a slight but predictable accumulation with a dosage regimen of 500 mg twice daily. Steady-state distribution is achieved within 3 days.

• Distribution in tissues and body fluids. Distribution in bronchial mucosa and bronchial epithelial secretions. Maximum concentrations of levofloxacin in bronchial mucosa and bronchial epithelial secretions after an oral dose exceeding 500 mg were 8.3 and 10.8 mg/mL, respectively.
• Distribution in lung tissue. Maximum concentration of levofloxacin in lung tissue after an oral dose exceeding 500 mg was approximately 11.3 mg/mL, reached within 4–6 hours after administration. Concentrations in lung tissue consistently exceeded those in plasma.
• Distribution in cerebrospinal fluid. Levofloxacin penetrates poorly into cerebrospinal fluid.
• Distribution in prostate tissue. After oral administration of 500 mg levofloxacin once daily for 3 days, mean concentrations in prostate tissue were 8.7 mg/g, 8.2 mg/g, and 2 mg/g at 2, 6, and 24 hours, respectively; the mean prostate/plasma concentration ratio was 1.84.

Concentration in urine. Mean concentrations of levofloxacin in urine over 8–12 hours after a single oral dose of 150 mg, 300 mg, or 500 mg were 44 mg/mL, 91 mg/mL, and 200 mg/mL, respectively.

Metabolism. Levofloxacin undergoes minimal metabolism, with metabolites being demethyl-levofloxacin and levofloxacin N-oxide. These metabolites account for less than 5% of the total amount of drug excreted in urine.

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

Clinical characteristics.

Indications.

Bacterial inflammatory processes caused by bacteria sensitive to the drug:

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.

*For the above-mentioned infectious diseases, levofloxacin should be prescribed only when other antibacterial medicinal products 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 to any component of the drug. Epilepsy. Patients with history of tendon-related adverse reactions following previous use of quinolones. Pediatric age (under 18 years). Pregnancy or breastfeeding.

Interaction with other medicinal products and other forms of interaction.

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

Levofloxacin did not show any pharmacokinetic interactions with theophylline in one clinical study. A marked reduction in the cerebral seizure threshold may occur when quinolones are used concomitantly with theophylline, NSAIDs, or other drugs that lower the seizure threshold. The concentration of levofloxacin is approximately 13% higher in the presence of fenbufen than when levofloxacin is administered alone.

Probenecid and cimetidine have a statistically significant effect on the elimination of levofloxacin; renal clearance of the drug was reduced by cimetidine (24%) and probenecid (34%). Levofloxacin should be used with caution when administered concomitantly with drugs affecting renal tubular secretion (probenecid and cimetidine), especially in patients with impaired renal function.

Cyclosporine

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

Vitamin K antagonists

Due to the potential risk of bleeding in patients taking levofloxacin in combination with any vitamin K antagonist (e.g., warfarin), coagulation parameters should be monitored if these drugs are used together.

The pharmacokinetics of levofloxacin were not altered when coadministered with the following agents: calcium carbonate, digoxin, glyburide, ranitidine, warfarin.

Medicinal products that prolong the QT interval

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

Theophylline

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

Glucocorticoids

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

Other

No clinically significant effect on the pharmacokinetics of levofloxacin 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 with levofloxacin in these patients should be initiated only if no alternative treatment options are available and after careful benefit/risk assessment (see also section "Contraindications").

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 for months or years), disabling and potentially irreversible serious adverse reactions affecting various body 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.

Caution should be exercised when administering the drug to patients with severe renal impairment, severe cerebral atherosclerosis, or cerebrovascular disorders.

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

Alcohol consumption should be avoided during treatment with this drug.

In very severe cases of pneumonia caused by pneumococci, levofloxacin may not provide optimal therapeutic effect.

For nosocomial infections caused by Ps. aeruginosa and in severe cases of pneumococcal pneumonia, combination therapy may be required.

Duration of infusion

The recommended duration of administration of the medicinal product is at least 60 minutes for the 500 mg infusion solution. With ofloxacin, tachycardia and transient increases in blood pressure may occur during infusion. In rare cases, this may lead to sudden drop in blood pressure or circulatory collapse. If a marked decrease in blood pressure occurs during administration of levofloxacin (the S-isomer of ofloxacin), the infusion should be stopped immediately.

For methicillin-resistant S. aureus (MRSA), there is a very high likelihood of concomitant resistance to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of known or suspected infections caused by MRSA, except when laboratory results confirm susceptibility of the microorganism to levofloxacin (when antibacterial agents typically recommended for MRSA infections cannot be used).

Infections caused by Escherichia coli

Resistance of E. coli—the most common causative agent of urinary tract infections—to fluoroquinolones varies across countries of the European Union. Prescribers are advised to consider local prevalence of E. coli resistance to fluoroquinolones.

Pulmonary form of anthrax

Recommendations for human use are based on in vitro susceptibility data of Bacillus anthracis, experimental animal studies, and limited human data. Physicians should refer to national and/or international consensus guidelines for the treatment of anthrax.

Tendinitis and tendon rupture

Tendinitis and tendon rupture (not limited to the Achilles tendon), sometimes bilateral, may occur within 48 hours of starting treatment with quinolones or fluoroquinolones, and even several months after discontinuation of treatment, particularly in patients receiving 1000 mg daily doses of levofloxacin. The risk of tendinitis and tendon rupture is increased in elderly patients, patients with renal impairment, organ transplant recipients, and patients receiving concomitant corticosteroid therapy. Therefore, concomitant use of corticosteroids should be avoided.

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

Myoclonus

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

Blood disorders

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

Clostridium difficile-associated disease

Diarrhea, particularly severe, persistent, and/or bloody diarrhea during or after treatment (including several weeks after treatment), may indicate Clostridium difficile-associated disease, the most severe form of which is pseudomembranous colitis. 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 pseudomembranous colitis is suspected, the drug should be discontinued immediately and symptomatic and specific treatment should be initiated without delay. In this clinical situation, drugs that inhibit peristalsis are contraindicated.

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 medications that lower the seizure threshold, such as theophylline (see section "Interaction with other medicinal products and other forms of interaction"). If seizures occur, levofloxacin should be discontinued.

Patients receiving vitamin K antagonists

Due to the potential for increased coagulation test parameters (prothrombin time/international normalized ratio (INR)) and/or bleeding in patients receiving fluoroquinolones, including levofloxacin, in combination with vitamin K antagonists (e.g., warfarin), monitoring of coagulation parameters is recommended when these two drug groups are used concomitantly (see section "Interaction with other medicinal products and other forms of interaction").

Glucose-6-phosphate dehydrogenase deficiency

Patients with latent or manifest deficiency of glucose-6-phosphate dehydrogenase activity may be prone to hemolytic reactions when treated with quinolone antibacterial agents. In such cases, levofloxacin should be used with caution, with monitoring for potential hemolysis.

Prevention of photosensitivity reactions

Cases of photosensitivity have been reported with levofloxacin (see section "Adverse reactions"). Patients taking levofloxacin should avoid exposure to intense sunlight and ultraviolet radiation (UV lamps, tanning beds) during treatment and for 48 hours after discontinuation of the drug to prevent photosensitivity.

Psychotic reactions

Psychotic reactions have been observed in patients receiving quinolones, including levofloxacin. Very rarely, these have led to suicidal thoughts and self-harming behavior, sometimes even after a single dose of levofloxacin.

If psychotic reactions develop, the drug should be discontinued. Levofloxacin should be prescribed with caution to patients with psychiatric disorders, including those with a history of such disorders.

Renal impairment

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

Hypersensitivity reactions

Levofloxacin may occasionally cause serious, potentially life-threatening hypersensitivity reactions (including angioedema, anaphylactic shock), even after the first dose. If hypersensitivity reactions occur, levofloxacin should be discontinued, medical attention should be sought, and appropriate treatment initiated.

Severe skin reactions

Severe skin 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; these reactions may be life-threatening or fatal. Patients should be informed about the signs and symptoms of severe skin reactions and closely monitored. If signs or symptoms suggestive of such reactions occur, levofloxacin treatment should be discontinued immediately and alternative therapy considered. Patients who have experienced Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS during levofloxacin therapy should never be re-exposed to levofloxacin.

Alterations in blood glucose levels

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

QT interval prolongation

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

• congenital or acquired QT prolongation syndrome;
• concomitant use of medicinal products that prolong the QT interval (including class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics);
• electrolyte imbalances (e.g., hypokalemia, hypomagnesemia);
• cardiac diseases (heart failure, myocardial infarction, bradycardia).

Elderly patients and younger women may be more sensitive to drugs that prolong the QT interval. Therefore, fluoroquinolones, including levofloxacin, should be used with caution in these patient groups.

Aortic aneurysm and dissection, and cardiac valve regurgitation/insufficiency

Epidemiological studies suggest an increased risk of aortic aneurysm and dissection, particularly in elderly patients, and regurgitation/insufficiency 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 therapies in patients with:

• a positive family history of aneurysmal disease or congenital heart valve disorders;
• diagnosed aortic aneurysm and/or dissection or heart valve disease;
• risk factors or conditions predisposing to:
  • aortic aneurysm, dissection, and/or 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:
  • aortic aneurysm and dissection (e.g., vascular disorders such as Takayasu arteritis or giant cell arteritis, known atherosclerosis, or Sjögren's syndrome); or additionally:
  • cardiac valve regurgitation/insufficiency (e.g., infective endocarditis).

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

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

Patients should be advised to seek immediate medical attention if they develop acute shortness of breath, new onset of rapid heartbeat, or develop abdominal or lower limb swelling.

Peripheral neuropathy

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

Effect on laboratory tests

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

Hepatobiliary disorders

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

Exacerbation of myasthenia gravis

Fluoroquinolones, including levofloxacin, have neuromuscular blocking effects and may exacerbate muscle weakness in patients with myasthenia gravis. In the post-marketing period, serious adverse reactions, including fatalities 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 visual disturbances or other ocular effects occur, patients should seek immediate ophthalmological evaluation (see sections "Ability to influence reaction rate when driving or operating machinery" and "Adverse reactions").

Superinfection

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

Excipients

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

This medicinal product contains less than 1 mmol (23 mg)/dose (100 ml vial) of sodium, i.e., it is practically 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 evidence indicating a risk of cartilage damage in the developing organism due to fluoroquinolones, the drug is contraindicated in 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 evidence 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.

Ability to influence reaction rate when driving or operating machinery.

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

Administration and Dosage

Prior to administration, a skin sensitivity test must be performed.

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, transition from initial intravenous administration to oral intake may be made (levofloxacin tablets 250 mg or 500 mg). The duration of treatment depends on the course of the disease. Administration of the drug should be continued for at least 48–72 hours after the disappearance of clinical signs of infection. Levofloxacin for infusion solution is intended for slow intravenous administration only and should be given once or twice daily. The infusion time should be no less than 30 minutes for the 250 mg dose and no less than 60 minutes for the 500 mg dose.

Dosing for patients with normal renal function (creatinine clearance (CLCR) ≥50 mL/min)

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

Since levofloxacin is primarily eliminated via the kidneys, dosage adjustment is required for patients with impaired renal function.

Dosing for patients with renal function impairment (CLCR <50 mL/min)

1 No additional doses are required after hemodialysis or chronic ambulatory peritoneal dialysis.

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

Dose adjustment is not required in elderly patients with normal renal function.

When administering levofloxacin consecutively with other medicinal products, they must not be infused through the same intravenous line.

After opening the vial, any unused portion of the medicinal product should be discarded.

Levofloxacin is administered slowly intravenously by drip infusion. The infusion time for one vial (100 ml of solution for intravenous infusion containing 500 mg of levofloxacin) should be at least 60 minutes for the 500 mg dose; the recommended infusion rate for the 250 mg dose is 30 minutes.

Depending on the patient's clinical condition, a switch from intravenous to oral administration of a comparable dose may be considered after several days (usually within 2–4 days).

The duration of treatment depends on the course of the disease. As with other antibacterial agents, it is recommended to continue treatment with this medicinal product for at least 48–72 hours after normalization of body temperature or until microbiological tests confirm 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 solution;

2.5% glucose in Ringer’s solution;

• multi-component parenteral nutrition solutions (amino acids, carbohydrates, electrolytes).

Children.

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

Overdose.

Symptoms: confusion, dizziness, tremor, disturbances of consciousness, seizures, myoclonus, QT interval prolongation, or exacerbation of other adverse reactions. In the post-marketing period of levofloxacin use, central nervous system (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 organ systems and frequency of occurrence. Frequency of occurrence is categorized as follows: very common (≥ 1/10), common (≥1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), frequency not known (cannot be estimated from available data).

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

Infections and infestations: uncommon – fungal infections, including Candida species, overgrowth of other resistant microorganisms.

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

Immune system disorders: rare – angioedema, hypersensitivity (see section "Special warnings and precautions for use"); frequency not known – anaphylactic shock, anaphylactoid reactions, which may occasionally occur even after administration of the first dose (see section "Special warnings and precautions for use").

Endocrine system disorders: rare – syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Gastrointestinal and metabolic disorders: uncommon – anorexia; rare – hypoglycemia, particularly in patients with diabetes mellitus; frequency not known – hyperglycemia, hypoglycemic coma (see section "Special warnings and precautions for use").

Psychiatric disorders*: common – insomnia; uncommon – anxiety, confusion, restlessness; rare – psychotic reactions (including hallucinations, paranoia), depression, agitation, pathological dreams, nightmares; frequency not known – psychotic disorders with self-destructive behavior, including suicidal ideation or actions (see section "Special warnings and precautions for use"), mania.

Nervous system disorders*: common – headache, dizziness; uncommon – somnolence, tremor, dysgeusia; rare – seizures (see sections "Contraindications" and "Special warnings and precautions for use"), paresthesia; frequency not known – peripheral sensory neuropathy (see section "Special warnings and precautions for use"), peripheral sensorimotor neuropathy (see section "Special warnings and precautions for use"), parosmia including anosmia, dyskinesia, extrapyramidal disorders, ageusia, loss of consciousness, benign intracranial hypertension, myoclonus.

Eye disorders*: rare – visual disturbances such as blurred vision (see section "Special warnings and precautions for use"); frequency not known – transient loss of vision (see section "Special warnings and precautions for use").

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

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

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

Gastrointestinal disorders: common – diarrhea, vomiting, nausea; uncommon – abdominal pain, dyspepsia, flatulence, constipation; frequency not known – hemorrhagic diarrhea, which may indicate enterocolitis, including pseudomembranous colitis (see section "Special warnings and precautions for use"), pancreatitis.

Hepatobiliary disorders: common – elevated liver enzymes (ALT/AST, alkaline phosphatase, GGT); uncommon – increased bilirubin in blood; frequency not known – jaundice and severe hepatic injury, including cases of acute liver failure, mainly in patients with severe underlying conditions (see section "Special warnings and precautions for use"), hepatitis.

Skin and subcutaneous tissue disorders: uncommon – rash, pruritus, urticaria, skin redness, hyperhidrosis; rare – drug reaction with eosinophilia and systemic symptoms (DRESS), localized drug eruption; frequency not known – toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, photosensitivity reactions, increased sensitivity to sunlight and ultraviolet radiation (see section "Special warnings and precautions for use"), leukocytoclastic vasculitis, stomatitis, skin hyperpigmentation.

Musculoskeletal and connective tissue disorders*: uncommon – arthralgia, myalgia; rare – tendon disorders (see sections "Contraindications" and "Special warnings and precautions for use"), including tendinitis (e.g., Achilles tendon), muscle weakness, which may be particularly significant in patients with severe myasthenia gravis; frequency not known – rhabdomyolysis, tendon rupture (see sections "Contraindications" and "Special warnings and precautions for use"), ligament rupture, muscle rupture, arthritis.

Renal and urinary disorders: uncommon – increased serum creatinine levels; rare – acute renal failure (e.g., due to interstitial nephritis).

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

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

** 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 reported (see section "Special warnings and precautions for use").

Description of selected adverse reactions

With the use of fluoroquinolones, anxiety, suicidal thoughts, panic attacks, neuralgia, and disturbances in concentration have been reported as potential aspects of prolonged and disabling adverse reactions that may lead to loss of work capacity.

Reporting suspected adverse reactions

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

Shelf life.

3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C. Keep out of reach of children. Unused medicinal product and waste material should be disposed of in accordance with local requirements.

Incompatibilities.

Levofloxacin must not be mixed with heparin or with solutions having an alkaline reaction (e.g., sodium bicarbonate solution), or with other medicinal products except those specified in the section "Dosage and administration".

Packaging. 100 ml of the product in containers. One container in a polyvinyl chloride film, together with the instruction for medical use, in a carton.

Prescription status. Prescription only.

Manufacturer.

Eurolife Healthcare Pvt. Ltd.

Manufacturer's address and place of business.

Plot No. 520, Bhagwanpur, Roorkee, Haridwar, Uttarakhand, India.

Marketing Authorization Holder.

Ananta Medikare Ltd.

Address of the Marketing Authorization Holder and/or its representative.

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, United Kingdom.