Levokilz

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT LEVOKILZ (LEVOKILZ)

Composition:

Active substance: levofloxacin;

1 film-coated tablet contains 250 mg or 500 mg of levofloxacin hemihydrate (equivalent to levofloxacin);

Excipients: sodium croscarmellose, microcrystalline cellulose, hypromellose (hydroxypropylmethylcellulose), magnesium stearate, titanium dioxide (E 171), polyethylene glycol 400, talc, yellow iron oxide (E 172), red iron oxide (E 172).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties:

250 mg film-coated tablets: pink, capsule-shaped, biconvex film-coated tablets with markings “1” and “5” and a break line on one side and marking “T” on the other side;

500 mg film-coated tablets: pink, capsule-shaped, biconvex film-coated tablets with markings “1” and “4” and a break line on one side and marking “T” on the other 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 antibacterial activity of levofloxacin depends on the ratio of maximum serum concentration (C_max) or area under the pharmacokinetic curve (AUC) to minimum inhibitory concentration (MIC).

Mechanism of resistance. Resistance to levofloxacin develops through a stepwise process of mutations in the target sites of both types of topoisomerase II: DNA gyrase and topoisomerase IV. Other resistance mechanisms, such as reduced permeability (common in Pseudomonas aeruginosa) and efflux mechanisms, may also affect susceptibility to levofloxacin.

Cross-resistance has been established between levofloxacin and other fluoroquinolones. Due to its mechanism of action, cross-resistance between levofloxacin and other classes of antibacterial agents is usually not observed.

Breakpoints. The breakpoints for MIC of levofloxacin recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), which differentiate susceptible microorganisms from those with intermediate susceptibility, and microorganisms with intermediate susceptibility from resistant ones, are presented in the table below for MIC testing (mg/L).

Clinical MIC breakpoints for levofloxacin (version 10.0, 2020-01-01)

1 Uncomplicated urinary tract infections only.

2 Susceptibility depends on sensitivity to ciprofloxacin.

The prevalence of resistance may vary geographically and over time for individual species; therefore, it is desirable to obtain local information on microbial resistance, especially when treating severe infections. When necessary, advice from a specialist should be sought if local resistance prevalence is such that the benefit of the drug is at least questionable for certain types of infections.

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

Pharmacokinetics.

Absorption. When administered orally, levofloxacin is rapidly and almost completely absorbed; peak plasma concentrations (Cmax) are reached within 1–2 hours. Absolute bioavailability is 99–100%.

Food has minimal effect on the absorption of levofloxacin.

Steady-state concentrations are achieved within 48 hours with dosing regimens 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 both single and repeated 500 mg doses, indicating extensive distribution into body tissues.

Penetration into tissues and body fluids. Levofloxacin has been shown to penetrate into bronchial mucosa, bronchial secretions, lung tissue, alveolar macrophages, skin (blister fluid), prostate tissue, and urine. However, levofloxacin penetrates poorly into cerebrospinal fluid.

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

Elimination. Following both oral and intravenous administration, levofloxacin is eliminated from plasma relatively slowly (elimination half-life (T½) is 6–8 hours). It is primarily excreted by the kidneys (> 85% of the administered dose).

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

Linearity. Levofloxacin exhibits linear pharmacokinetics over the range of 50 to 1000 mg.

Patients with renal impairment. The pharmacokinetics of levofloxacin are affected by the degree of renal impairment. With declining renal function, renal excretion and clearance decrease, and elimination half-life increases, as shown in the table below.

Pharmacokinetics in renal impairment after a single oral 500 mg dose:

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

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

Clinical characteristics.

Indications.

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

• acute pyelonephritis and complicated urinary tract infections (see section "Special precautions");
• chronic bacterial prostatitis;
• pulmonary form of anthrax: post-exposure prophylaxis and treatment (see section "Special precautions").

For the treatment of the following infections, Levokilz should be used only when it is considered inappropriate to use antibacterial agents usually recommended for the treatment of such infections:

• acute bacterial sinusitis;
• exacerbation of chronic obstructive pulmonary disease, including bronchitis;
• community-acquired pneumonia;
• complicated skin and soft tissue infections;
• uncomplicated cystitis (see section "Special precautions").

Levokilz may also be prescribed to complete a course of therapy in patients who have shown improvement during initial intravenous administration of levofloxacin.

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.

Tendon damage associated with prior use of fluoroquinolones.

Paediatric age.

Pregnancy and lactation.

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 iron salts or antacids containing magnesium or aluminium, or didanosine (only formulations containing buffering agents of aluminium or magnesium) are taken concomitantly. Concomitant administration of fluoroquinolones with multivitamins containing zinc results in reduced oral absorption. It is not recommended to take products containing divalent or trivalent cations, such as iron salts, zinc salts, antacids containing magnesium or aluminium, or didanosine (only formulations of didanosine containing buffering agents of aluminium or magnesium), within 2 hours before/after administration of levofloxacin (see section "Dosage and administration"). Calcium salts had minimal effect on the oral absorption of levofloxacin.

Sucralfate. The bioavailability of levofloxacin is significantly reduced when administered concomitantly with sucralfate. If a patient needs to receive both sucralfate and levofloxacin, it is preferable to take sucralfate 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 was observed. However, a significant reduction in seizure threshold may occur when quinolones are used concomitantly with theophylline, nonsteroidal anti-inflammatory drugs, and other agents that lower the seizure threshold. The concentration of levofloxacin was approximately 13% higher when fenbufen was administered compared to administration of levofloxacin alone.

Probenecid and cimetidine. Probenecid and cimetidine have a statistically significant effect on the elimination of levofloxacin. Renal clearance of levofloxacin is reduced by cimetidine (24%) and probenecid (34%). This occurs because both drugs can block tubular secretion of levofloxacin. Despite this, statistically significant kinetic differences are unlikely to have clinical significance. Levofloxacin should be prescribed with caution concomitantly with drugs affecting tubular secretion, such as probenecid and cimetidine, especially in patients with renal impairment.

Other significant information. No clinically significant effect on the pharmacokinetics of levofloxacin has been observed when administered concomitantly with calcium carbonate, digoxin, glyburide, or ranitidine.

Effect of levofloxacin on other medicinal products

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

Vitamin K antagonists. Increased values of coagulation tests (INR/PT) and/or bleeding, which may be severe, have been reported when levofloxacin is used concomitantly with vitamin K antagonists (e.g., warfarin). Therefore, in patients receiving concomitant vitamin K antagonists, monitoring of coagulation parameters is necessary (see section "Special precautions").

Medicinal products that prolong the QT interval. Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving medicinal products known to prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, and antipsychotics) (see section "Special precautions. 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 a CYP1A2 inhibitor.

Other forms of interaction

Food. No clinically significant interaction with food has been observed. Therefore, the drug can be administered independently 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 (see section "Adverse reactions").

Treatment of these patients with levofloxacin should be initiated only if there are no alternative treatment options and after careful assessment of benefit/risk (see section "Contraindications").

Risk of resistance.

For methicillin-resistant Staphylococcus aureus (MRSA), there is a very high likelihood of cross-resistance to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of infections known or suspected to be caused by MRSA, except when laboratory test results confirm susceptibility of the pathogen to levofloxacin.

Levofloxacin may be used for the treatment of acute bacterial sinusitis and acute exacerbation of chronic bronchitis, provided these infections have been appropriately diagnosed.

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

Anthrax.

For pulmonary anthrax, use is based on in vitro susceptibility data of Bacillus anthracis, experimental animal data, and limited human use. Physicians should refer to national and/or international consensus documents on the treatment of anthrax.

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

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

Tendinitis and tendon rupture.

Tendon inflammation and tendon rupture (most commonly of the Achilles tendon), sometimes bilateral, may occur during levofloxacin therapy. These events have occurred within 48 hours of starting treatment and even several months after discontinuation of therapy. The risk of tendinitis and tendon rupture is increased in elderly patients, patients with impaired renal function, organ transplant recipients, patients receiving daily doses of levofloxacin 1000 mg, and those receiving concomitant corticosteroids. Therefore, concomitant use of the drug with 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 taking levofloxacin (see section "Adverse reactions"). The risk of developing myoclonus is increased in elderly patients and in patients with renal insufficiency if the levofloxacin dose has not been adjusted according to creatinine clearance. Levofloxacin should be discontinued immediately upon the first occurrence of myoclonus, and appropriate treatment should be initiated.

Clostridium difficile-associated disease.

Diarrhea, particularly severe, persistent, and/or bloody diarrhea occurring during or after treatment with levofloxacin (including several weeks after treatment) may be a symptom of Clostridium difficile-associated disease (CDAD). CDAD may range in severity from mild to life-threatening; the most severe form being pseudomembranous colitis (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 CDAD is suspected or confirmed, the drug should be immediately discontinued and appropriate therapy initiated without delay. Antiperistaltic agents are contraindicated in this clinical situation.

Patients predisposed to seizures.

Quinolones may lower the seizure threshold and may induce 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 or when used concomitantly with active substances that lower the cerebral seizure threshold, such as theophylline (see section "Interaction with other medicinal products and other forms of interaction"). In case of seizures, treatment with levofloxacin should be discontinued (see section "Adverse reactions").

Patients with glucose-6-phosphate dehydrogenase deficiency.

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

Patients with renal impairment.

Since levofloxacin is primarily excreted by the kidneys, the dose should be adjusted in patients with impaired renal function (see section "Dosage and administration").

Hypersensitivity reactions.

Levofloxacin may cause serious, potentially fatal hypersensitivity reactions (e.g., angioedema up to anaphylactic shock), sometimes after the first dose (see section "Adverse reactions"). In such cases, patients should immediately discontinue treatment and seek medical advice or emergency assistance for appropriate emergency measures.

Severe skin reactions.

Severe skin reactions such as toxic epidermal necrolysis (also known as Lyell's syndrome), Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), which may be life-threatening or fatal, have been reported during treatment with levofloxacin (see section "Adverse reactions"). Patients should be informed about the signs and symptoms of severe skin reactions, and close monitoring should be established. If symptoms suggestive of these reactions occur, levofloxacin should be immediately discontinued and alternative therapy considered. If a patient develops such serious reactions as Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome while receiving levofloxacin, re-administration of levofloxacin to this patient is contraindicated.

Blood glucose alterations.

Alterations in blood glucose levels (including both hyperglycemia and hypoglycemia) have been reported during treatment with quinolones, particularly in diabetic patients receiving concomitant oral hypoglycemic agents (e.g., glyburide) or insulin. Cases of hypoglycemic coma have been documented. Blood glucose levels should be monitored in diabetic patients (see section "Adverse reactions").

If a patient reports disturbances in blood glucose levels, treatment should be immediately discontinued and alternative antibacterial therapy with non-fluoroquinolone agents considered.

Prevention of photosensitization.

Cases of photosensitivity have been reported with levofloxacin (see section "Adverse reactions"). To prevent photosensitization, patients are advised to avoid exposure to strong sunlight or artificial UV radiation sources (e.g., UV lamps, tanning beds) during treatment and for 48 hours after discontinuation of levofloxacin.

Patients receiving vitamin K antagonists.

Due to the possible increase in coagulation test results (INR/PT) and/or bleeding in patients taking levofloxacin 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"). Levofloxacin should be immediately discontinued at the first sign of psychotic reactions. Patients should be informed about the symptoms of such reactions and the need to seek immediate medical attention. In such cases, alternative antibacterial therapy with non-fluoroquinolone agents should be considered, along with appropriate measures. Levofloxacin should be used with caution in patients with psychotic disorders or a history of psychiatric illness.

QT interval prolongation.

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

• congenital QT prolongation syndrome;
• concomitant use of medicinal products known to prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics);
• uncorrected electrolyte imbalances (e.g., hypokalemia, hypomagnesemia);
• cardiac 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 populations (see sections "Interaction with other medicinal products and other forms of interaction", "Dosage and administration. Dosage in elderly patients", "Overdose", and "Adverse reactions").

Peripheral neuropathy.

Sensory or sensorimotor neuropathy leading to paresthesia, hypoesthesia, dysesthesia, or weakness has been reported in patients receiving quinolones or fluoroquinolones. If symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness occur, patients should inform their physician immediately to prevent potentially irreversible damage (see section "Adverse reactions").

Hepatobiliary disorders.

Cases of non-necrotizing hepatitis up to fatal hepatic 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 consult a physician if symptoms or signs of liver disease occur, such as anorexia, jaundice, dark urine, pruritus, or abdominal pain.

Exacerbation of myasthenia gravis.

Fluoroquinolones, including levofloxacin, block neuromuscular transmission and may trigger muscle weakness in patients with myasthenia gravis. Serious adverse reactions reported in the post-marketing period, including fatal cases and the need for 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 vision is impaired or any ocular effects occur, patients should immediately consult an ophthalmologist (see sections "Ability to influence reaction rate when driving or operating machinery" and "Adverse reactions").

Superinfection.

The use of levofloxacin, especially prolonged use, may lead to the growth of resistant microorganisms. 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 test results using more specific methods may be necessary.

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis, thereby leading to false-negative results in bacteriological diagnosis of tuberculosis.

Aortic aneurysm and aortic dissection, and cardiac valve regurgitation/insufficiency.

Epidemiological studies report an increased risk of aortic aneurysm and aortic dissection, particularly in elderly patients, and regurgitation of aortic and mitral valves following fluoroquinolone use.

Cases of aortic aneurysm and aortic dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any cardiac valve have been reported in patients receiving fluoroquinolones (see section "Adverse reactions").

Therefore, fluoroquinolones should be used only after careful benefit/risk assessment and consideration of alternative therapeutic options in patients with a positive family history of aneurysm or congenital heart valve defect, or in patients with an existing diagnosis of aortic aneurysm and/or dissection, or heart valve disease, or in the presence of other risk factors or predisposing conditions

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

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

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

Acute pancreatitis.

Acute pancreatitis may occur in patients taking levofloxacin. Patients should be informed about the characteristic symptoms of acute pancreatitis. Patients experiencing nausea, malaise, abdominal discomfort, severe abdominal pain, or vomiting should undergo immediate medical evaluation. If acute pancreatitis is suspected, levofloxacin should be discontinued; if confirmed, levofloxacin should not be restarted. Caution should be exercised in patients with a history of pancreatitis (see section "Adverse reactions").

Blood disorders.

Bone marrow suppression, including leukopenia, neutropenia, pancytopenia, hemolytic anemia, thrombocytopenia, aplastic anemia, or agranulocytosis, may develop during treatment with levofloxacin (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.

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 harmful effects with regard to reproductive toxicity. However, due to the lack of human studies and experimental data indicating a risk of cartilage damage in the growing organism by fluoroquinolones, levofloxacin should not be administered to pregnant women.

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

Fertility. It is known that levofloxacin did not cause disorders of fertility or reproductive function in rats.

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 a car or operating machinery).

Dosage and administration.

Levokilz tablets should be taken once or twice daily. The dosage depends on the type and severity of infection and the susceptibility of the likely pathogen.

The medicinal product may also be used to complete the course of therapy in patients who have shown improvement during initial intravenous treatment with levofloxacin; considering the bioequivalence of parenteral and oral forms, the same dosage may be used.

Dosage.

The following dosage recommendations may be provided for the medicinal product:

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

Special populations

Dosing for patients with renal impairment in whom creatinine clearance is < 50 ml/min:

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

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

Dosing in elderly patients. If renal function is not impaired, dose adjustment is not required (see section "Special precautions", subsections "Tendinitis and tendon rupture" and "QT interval prolongation").

Method of administration.

Tablets should be swallowed whole without chewing, with sufficient fluid. For ease of dosing, the tablet may be divided along the break line. Tablets may be taken during or between meals. The medicinal product should be administered at least 2 hours before or after administration of iron salts, zinc salts, antacids containing magnesium or aluminum, or didanosine (only for didanosine formulations containing aluminum or magnesium buffering agents) and sucralfate, as absorption may be reduced.

Children.

The medicinal product is contraindicated in children (under 18 years of age)—see section "Contraindications".

Overdose.

According to toxicity studies in animals or clinical pharmacological studies conducted with doses higher than therapeutic ones, the most important signs expected after acute levofloxacin overdose are central nervous system symptoms such as confusion, dizziness, disturbances of consciousness, and seizures, QT interval prolongation, as well as gastrointestinal reactions such as nausea and mucosal erosions.

During post-marketing use of levofloxacin, central nervous system effects including confusion, convulsions, myoclonus, hallucinations, and tremor have been observed.

In case of overdose, symptomatic treatment should be initiated. ECG monitoring is necessary due to the potential for QT interval prolongation. Antacids may be used to protect the gastric mucosa. Hemodialysis, including peritoneal dialysis and CAPD, is not effective in removing levofloxacin from the body. There are no specific antidotes.

Adverse reactions.

The information below is based on data from clinical trials in over 8300 patients and extensive post-marketing experience with levofloxacin.

Frequency is defined according to the following categories: 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 frequency group, adverse reactions are listed in order of decreasing severity of manifestations.

a Anaphylactic and anaphylactoid reactions may sometimes occur even after the first dose.

b Skin and mucous membrane reactions may sometimes occur even after the first dose.

* Very rare cases of prolonged (up to months or years), disabling and potentially irreversible serious adverse reactions affecting multiple organ systems and sensory organs (including such reactions as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbance; in some cases, neuropathies associated with paresthesia, depression, fatigue, memory impairment, sleep disorders, and disturbances of hearing, vision, taste, and smell) have been associated with the use of quinolones and fluoroquinolones, regardless of previously existing risk factors (see section "Special warnings and precautions for use").

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

Other adverse reactions associated with the use of fluoroquinolones:

• porphyria attacks in patients with porphyria;
• anxiety, suicidal thoughts, panic attacks, neuralgia, and difficulty concentrating, which may be manifestations of prolonged and disabling fluoroquinolone-associated adverse reactions.

Shelf life.

3 years.

Storage conditions.

Keep out of reach and sight of children. Store at a temperature not exceeding 30 °C.

Packaging. 5 tablets in a blister; 1 blister per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Aurobindo Pharma Limited - Unit VII / Aurobindo Pharma Limited - Unit VII.

Manufacturer's address and location of operations. Special Economic Zone, TSIIC, Plot No. S1, Sy. Nos. 411/P, 425/P, 434/P, 435/P and 458/P, Green Industrial Park, Polepally Village, Jedcherla Mandal, Mahabubnagar District, Telangana State, 509302, India / Special Economic Zone, TSIIC, Plot No. S1, Sy. Nos. 411/P, 425/P, 434/P, 435/P and 458/P, Green Industrial Park, Polepally Village, Jedcherla Mandal, Mahabubnagar District, Telangana State, 509302, India.