Levofloxacin

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

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 physicochemical properties: clear greenish-yellow solution.

Pharmacotherapeutic group.

Antibacterials for systemic use. Antibacterials of the quinolone group. Fluoroquinolones. ATC code J01MA12.

Pharmacological Properties

Pharmacodynamics.

Levofloxacin is a broad-spectrum antibiotic belonging to the quinolone group. 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 local strain susceptibility to the drug; therefore, this information should be taken into account when prescribing the drug, particularly in the treatment of severe infections. Levofloxacin demonstrates broad-spectrum 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 and 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. When administered orally, levofloxacin is rapidly and almost completely absorbed. Peak plasma concentrations are observed within 1 hour after administration. 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 bound to serum proteins. 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 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, achieved within 4–6 hours after administration. Concentrations in lung tissue consistently exceeded those in plasma.
• Distribution in cerebrospinal fluid. Levofloxacin poorly penetrates 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.

Urine concentration. 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 including desmethyl-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 relatively 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 other component of the drug. Epilepsy. Patients with history of tendon reactions after previous use of quinolones. Children and adolescents under 18 years of age. Pregnancy or breastfeeding.

Interaction with other medicinal products and other forms of interaction

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

Levofloxacin showed no pharmacokinetic interactions with theophylline in one clinical study. A marked reduction in the central nervous system seizure threshold may occur when quinolones are administered 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 levofloxacin was reduced by cimetidine (24%) and probenecid (34%). Levofloxacin should be used with caution in combination with drugs affecting 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 when these drugs are used together.

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

Drugs that prolong the QT interval

Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs that prolong the QT interval (including class IA and class 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 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 together 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 there are no alternative treatment options and after careful assessment of benefit/risk (see also section "Contraindications").

Long-term, disabling and potentially irreversible serious adverse reactions

Very rarely, in patients receiving quinolones or fluoroquinolones, regardless of age and existing risk factors, long-term (lasting months or years), disabling and potentially irreversible serious adverse reactions affecting various systems, and sometimes several 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 pronounced cerebral atherosclerosis or impaired cerebral circulation. In case of development of adverse effects, particularly those affecting the central nervous system (CNS) and allergic reactions, which may occur even after the first dose, levofloxacin therapy should be discontinued.

Duration of infusion

The recommended duration of infusion for the 500 mg solution for infusion is at least 60 minutes. With ofloxacin, tachycardia and transient increase in blood pressure may occur during infusion. In rare cases, sudden drop in blood pressure and circulatory collapse may subsequently occur. If a marked decrease in blood pressure is observed during levofloxacin (S-isomer of ofloxacin) administration, 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 in cases where 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 pathogen in urinary tract infections—to fluoroquinolones varies across different countries of the European Union. Prescribers are advised to consider local prevalence of E. coli resistance to fluoroquinolones.

Pulmonary anthrax

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

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 required when these two groups of drugs are used concomitantly (see section "Interaction with other medicinal products and other forms of interaction").

Caution should be exercised when administering the drug to patients with severe renal impairment and those with pronounced cerebral atherosclerosis or impaired cerebral circulation.

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

Alcohol consumption should be avoided during treatment with the drug.

In very severe cases of pneumococcal pneumonia, 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.

Tendinitis and tendon rupture

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

At the first signs of tendinitis (e.g., painful swelling, inflammation), 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 levofloxacin dose 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 test results should be monitored. If abnormal results are obtained, discontinuation of levofloxacin therapy should be considered.

Clostridium difficile-associated disease

Diarrhea, especially severe, persistent, and/or with blood, during or after treatment (including several weeks after treatment) may indicate Clostridium difficile-associated disease. 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 pseudomembranous colitis is suspected, therapy 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 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 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.

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. Therefore, levofloxacin should be prescribed with caution in such patients, with monitoring for potential hemolysis.

Prevention of photosensitivity reactions

Cases of photosensitivity have been reported with levofloxacin use (see section "Adverse reactions"). Patients receiving 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-destructive 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 in their history.

Renal impairment

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

Hypersensitivity reactions

Levofloxacin may occasionally cause serious, potentially fatal hypersensitivity reactions (including angioedema, anaphylactic shock), even after the first dose. If hypersensitivity reactions occur, levofloxacin should be discontinued, medical advice 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), which may be life-threatening or fatal, have been reported with levofloxacin use. Patients should be informed about the signs and symptoms of severe skin reactions and closely monitored. If signs or symptoms indicating such reactions occur, levofloxacin treatment should be discontinued immediately and alternative therapy considered. Patients who have experienced such reactions as Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS during levofloxacin therapy should never be re-exposed to levofloxacin.

Blood glucose alterations

Alterations in blood glucose levels (hyperglycemia and hypoglycemia) have been reported with quinolone use, particularly in diabetic patients receiving concomitant oral hypoglycemic agents (including glibenclamide) or insulin. Cases of hypoglycemic coma have been observed. 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 interval prolongation:

• congenital or acquired long QT 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 conditions (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 indicate an increased risk of aortic aneurysm and dissection, particularly in elderly patients, and aortic and mitral valve regurgitation 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 disease, or in patients diagnosed with aortic aneurysm and/or aortic dissection or heart valve disease, or in those with risk factors or conditions predisposing to:

• aortic aneurysm, 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:
• 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 and dissection and their 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 sudden abdominal, chest, or back pain occurs.

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

Peripheral neuropathy

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

Hepatobiliary disorders

Cases of liver necrosis up to life-threatening liver failure have been reported with levofloxacin use, primarily in patients with severe underlying conditions such as sepsis (see section "Adverse reactions"). Patients should be advised to discontinue treatment and consult a physician if signs 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 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 visual disturbances or other ocular effects occur, immediate consultation with an ophthalmologist is required (see sections "Effect on ability to drive or operate machinery" and "Adverse reactions").

Superinfection

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

Effect on laboratory tests

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

Excipients

The drug contains 5 g of glucose per dose (100 ml vial) and should therefore be used with caution in diabetic patients.

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 effects, the drug is contraindicated during pregnancy (see section "Contraindications").

Breastfeeding. Levofloxacin is contraindicated in women who are breastfeeding. There is insufficient information on the passage of levofloxacin into breast milk. However, other fluoroquinolones are known to pass into maternal 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 effects, levofloxacin is contraindicated in women who are breastfeeding (see section "Contraindications").

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

Effect on ability to drive or operate 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).

Method of Administration and Dosage

Prior to administration, a 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 the infection and on the susceptibility of the causative organism. Usually, after several days of treatment, if the patient's condition permits, transition can be made from initial intravenous administration to oral intake (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 solely for slow intravenous administration 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 may be necessary 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 for patients with hepatic impairment, since levofloxacin is minimally metabolized by the liver and is primarily excreted by the kidneys.

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

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

Depending on the patient's condition, after a few days it may be possible to switch from intravenous administration to oral administration with 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 with the drug for at least 48–72 hours after normalization of body temperature or after microbiological confirmation of pathogen eradication.

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).

When administering sequential infusions of levofloxacin and other medicinal products, they must not be administered into the same vein.

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

Children.

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

Overdose.

Symptoms: confusion, dizziness, tremor, impaired consciousness, seizures, myoclonus, QT interval prolongation, or exacerbation of other adverse reactions. In the post-marketing period of levofloxacin use, CNS effects have been observed, including confusion, convulsions, hallucinations, and tremor.

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

Adverse Reactions

The adverse reactions listed below are classified by organ systems and frequency of occurrence. Frequency of occurrence is categorized as follows: very common (≥ 1/10), common (≥1/100 – < 1/10), uncommon (≥ 1/1000 – < 1/100), rare (≥ 1/10,000 – < 1/1000), very rare (< 1/10,000), frequency not known (cannot be estimated from the available data).

Within each group, adverse reactions are listed in order of decreasing 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 a tendency for 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 precautions for use"); frequency not known – anaphylactic shock, anaphylactoid reactions, which may occasionally occur even after administration of the first dose (see section "Special precautions for use").

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

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

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

CNS disorders*: common – headache, dizziness; uncommon – somnolence, tremor, dysgeusia; rare – seizures (see sections "Contraindications" and "Special precautions for use"), paresthesia; frequency not known – peripheral sensory neuropathy (see section "Special precautions for use"), peripheral sensorimotor neuropathy (see section "Special 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 precautions for use"); frequency not known – transient loss of vision (see section "Special precautions for use").

Ear and labyrinth disorders*: uncommon – vertigo; rare – tinnitus; frequency not known – hearing disturbances, 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 precautions for use"), pancreatitis.

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

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

Musculoskeletal and connective tissue disorders*: uncommon – arthralgia, myalgia; rare – tendon disorders (see sections "Contraindications" and "Special 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 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 – injection site reaction, including erythema and pain; uncommon – asthenia; rare – increased body temperature; frequency not known – general weakness, pain (including back, chest, and limb pain); as with other fluoroquinolones, porphyria attacks are possible 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, organ systems and sensory organs (including reactions such as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbances, neuropathies associated with paresthesia, depression, fatigue, memory impairment, sleep disturbances, hearing, vision, taste, and smell disturbances).

** 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 precautions for use").

Description of selected adverse reactions

With the use of fluoroquinolones, anxiety, suicidal thoughts, panic attacks, neuralgia, and attention disturbances have been reported as potential aspects of prolonged and disabling adverse reactions.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after medicinal product authorization is an important procedure. 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 the reach of children. Unused medicinal product and waste material must be disposed of in accordance with local requirements.

Incompatibilities.

Levofloxacin must not be mixed with heparin or solutions with 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 preparation in containers. One container in a polyvinyl chloride film, together with the instructions for medical use, in a carton.

Prescription status. Prescription only.

Manufacturer.

EuroLife Healthcare Pvt. Ltd.

Manufacturer's address and place of business.

H.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.