Novox-500

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT NOVOX®-500, NOVOX®-750 (NOVOX®-500, NOVOX®-750)

Composition:

Active substance: levofloxacin;

1 tablet contains levofloxacin hemihydrate equivalent to levofloxacin 500 mg or 750 mg;

Excipients: microcrystalline cellulose, maize starch, colloidal anhydrous silicon dioxide, povidone, sodium starch glycolate (type A), magnesium stearate, talc, titanium dioxide (E 171), iron oxide red (E 172), polyethylene glycol 6000, hypromellose, purified water.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: oval, biconvex film-coated tablets ranging in color from light pink to pink, with a break line on one side and smooth on the other.

Pharmacotherapeutic group. ATC code.

Antibacterials for systemic use. Fluoroquinolones.

ATC code J01MA12.

Pharmacological Properties.

Pharmacodynamics. Levofloxacin is a broad-spectrum antibiotic from the group of quinolones. 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.

Absorption. After oral administration, levofloxacin is rapidly and almost completely absorbed. Peak plasma concentrations are reached within 1 hour after intake. Absolute bioavailability is nearly 100%. The pharmacokinetics of levofloxacin are linear 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. There is no clinically significant accumulation effect of levofloxacin when dosed at 500 mg once daily. A minor but predictable accumulation occurs with dosing at 500 mg twice daily. Steady-state distribution parameters are 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 the lungs consistently exceeded those in plasma.

Distribution in blister fluid. Maximum concentration of levofloxacin in blister fluid after administration of 500 mg once or twice daily was 6.7 mg/mL.

Distribution in cerebrospinal fluid. Levofloxacin is excreted in small amounts 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; 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. Metabolites include desmethyl-levofloxacin and levofloxacin N-oxide. These metabolites account for less than 5% of the total amount of drug excreted in urine.

Excretion. 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). The pharmacokinetics of levofloxacin after intravenous and oral administration do not differ significantly.

Clinical characteristics.

Indications.

Infections caused by microorganisms sensitive to the drug:

• acute sinusitis;
• exacerbation of chronic obstructive pulmonary disease, including bronchitis;
• community-acquired pneumonia;
• uncomplicated cystitis;
• complicated skin and soft tissue infections;

Levofloxacin should be used to treat the above-mentioned infections only when the use of antibacterial agents usually recommended for initial treatment of these infections is considered inappropriate.

• acute pyelonephritis and complicated urinary tract infections;
• chronic bacterial prostatitis.

Contraindications.

Hypersensitivity to levofloxacin, other fluoroquinolones, or to any component of the drug. Epilepsy. Tendon damage associated with fluoroquinolone use. Pediatric age (under 18 years). Pregnancy and breastfeeding.

Interaction with other medicinal products and other forms of interaction.

Effect of other medicinal products on levofloxacin.

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

Absorption of levofloxacin is significantly reduced when iron salts, magnesium- or aluminium-containing antacids, or didanosine (this applies only to medicinal forms of didanosine with aluminium- or magnesium-containing buffering agents) are administered simultaneously with the drug. Concomitant administration of fluoroquinolones and multivitamin preparations containing zinc reduces their oral absorption. It is not recommended to use products containing divalent or trivalent cations, such as iron salts, zinc salts, magnesium- or aluminium-containing antacids, or didanosine (this applies only to medicinal forms of didanosine with aluminium- or magnesium-containing buffering agents) within 2 hours before or after taking the drug. Calcium salts have minimal effect on the absorption of levofloxacin after oral administration.

Sucralfate.

The bioavailability of levofloxacin tablets 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 taking the drug.

Theophylline, fenbufen, or similar nonsteroidal anti-inflammatory drugs.

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

Probenecid and cimetidine.

Probenecid and cimetidine statistically significantly affect the elimination of levofloxacin. Renal clearance of levofloxacin decreases by 24% in the presence of cimetidine and by 34% in the presence of probenecid. This is because both drugs can block tubular secretion of levofloxacin. However, at the doses tested in the study, it is unlikely that statistically significant kinetic differences would have clinical significance. Concomitant administration of levofloxacin with medicinal products affecting tubular secretion, such as probenecid and cimetidine, should be used with caution, especially in patients with renal impairment.

Other information.

The following medicinal products do not cause any clinically significant effect on the pharmacokinetics of levofloxacin when administered concomitantly: calcium carbonate, digoxin, glyburide, ranitidine.

Effect of levofloxacin on other medicinal products.

Cyclosporine.

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

Vitamin K antagonists.

When used concomitantly with vitamin K antagonists (e.g., warfarin), increased coagulation test results (prothrombin time, international normalized ratio) and/or bleeding, which may be severe, have been reported. Therefore, coagulation parameters should be monitored in patients receiving vitamin K antagonists concurrently.

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 antipsychotic medicinal products).

Other significant information.

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

Other forms of interaction.

Food intake.

No clinically significant interaction with food has been observed. The drug may be taken regardless of food intake.

Special precautions for use.

The use of the drug should be avoided in patients who have previously experienced serious adverse reactions to quinolones or fluoroquinolones. Treatment with levofloxacin in these patients should only be initiated if there are no alternative treatment options and after careful benefit-risk assessment.

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 of the body, sometimes multiple systems simultaneously (including 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.

Methicillin-resistant S. aureus (MRSA).

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

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 E. coli (the most common cause of urinary tract infections) varies across different countries. Local prevalence of fluoroquinolone resistance in E. coli should be considered when prescribing fluoroquinolones.

Hospital-acquired infections caused by P. aeruginosa may require combination therapy.

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 have been reported even several months after discontinuation of treatment in patients who received daily doses of 1000 mg levofloxacin. The risk of tendinitis and tendon rupture is increased in elderly patients, patients with impaired renal function, patients who have undergone solid organ transplantation, 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 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. The risk of myoclonus is increased in elderly patients and in patients with impaired renal function if the levofloxacin dose is not adjusted according to creatinine clearance. If myoclonus occurs, levofloxacin should be discontinued immediately and appropriate treatment initiated.

Clostridium difficile-associated disease.

Diarrhea, especially severe, persistent, and/or with blood, occurring during or after treatment with levofloxacin (including several weeks after treatment) may be a symptom of Clostridium difficile-associated disease. The most severe form of this disease is pseudomembranous colitis. Therefore, physicians should consider the possibility of Clostridium difficile-associated disease in patients who develop severe diarrhea during or after treatment with levofloxacin. If Clostridium difficile-associated disease is suspected, levofloxacin should be discontinued immediately and appropriate treatment initiated urgently. Medicinal products that inhibit intestinal peristalsis are contraindicated in this case.

Patients with predisposition to seizures.

Quinolones may lower the seizure threshold and provoke seizures. Levofloxacin is contraindicated in patients with a history of epilepsy. 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. If a seizure occurs, levofloxacin should be discontinued.

Patients with glucose-6-phosphate dehydrogenase deficiency.

Patients with latent or manifest deficiency in glucose-6-phosphate dehydrogenase activity may be predisposed to hemolytic reactions when treated with quinolone antibiotics. Therefore, if levofloxacin must be used in such patients, monitoring for possible hemolysis should be performed.

Patients with renal impairment.

Since levofloxacin is primarily eliminated via the kidneys, dose adjustment is required for patients with impaired renal function (renal insufficiency).

Hypersensitivity reactions.

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

Severe skin adverse reactions.

Severe skin adverse reactions, including toxic epidermal necrolysis (TEN, also known as Lyell's syndrome), Stevens-Johnson syndrome (SJS), and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), have been reported with levofloxacin use and may be fatal (see section "Adverse reactions").

Patients should be informed about the signs and symptoms of severe skin reactions and closely monitored. If signs or symptoms suggestive of these reactions occur, levofloxacin should be discontinued immediately and alternative therapy considered.

If a serious reaction such as SJS, TEN, or DRESS syndrome occurs during levofloxacin treatment, the patient should never be treated with levofloxacin again.

Glucose level alterations.

As with all quinolones, changes in blood glucose levels, including both hypoglycemia and hyperglycemia, have been reported, typically in diabetic patients receiving concomitant therapy with oral hypoglycemic agents (e.g., glibenclamide) or insulin. Cases of hypoglycemic coma have been reported. Close monitoring of blood glucose levels is recommended in diabetic patients.

Phototoxicity prevention.

Cases of photosensitization have been reported during levofloxacin treatment. To prevent photosensitization, patients should avoid unnecessary exposure to strong sunlight or artificial UV radiation sources (e.g., UV lamps, sunbeds) during treatment and for 48 hours after discontinuation of levofloxacin.

Patients receiving vitamin K antagonists.

Due to possible increases in coagulation parameters (prothrombin time, international normalized ratio) and/or increased frequency of hemorrhagic complications in patients receiving levofloxacin in combination with a vitamin K antagonist (e.g., warfarin), coagulation parameters should be monitored when these agents are used concomitantly.

Psychotic reactions.

Psychotic reactions have been reported in patients taking quinolones, including levofloxacin. Very rarely, these progressed to suicidal thoughts and self-harming behavior, sometimes after only a single dose of levofloxacin. If such reactions occur, levofloxacin should be discontinued and appropriate measures taken. Caution is recommended when prescribing levofloxacin to patients with a history of psychotic disorders or psychiatric illness.

QT interval prolongation.

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

• congenital or acquired 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);
• electrolyte imbalances (e.g., hypokalemia, hypomagnesemia);
• cardiac diseases (e.g., heart failure, myocardial infarction, bradycardia).

Elderly patients and 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.

Peripheral neuropathy.

Cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hypoesthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. If symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness occur, patients should be advised to inform their physician promptly to prevent potentially irreversible damage.

Hepatobiliary disorders.

Cases of liver necrosis up to liver failure with fatal outcome have been reported during levofloxacin use (mainly in patients with severe underlying conditions, e.g., sepsis). 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.

Acute pancreatitis.

Acute pancreatitis may occur in patients taking levofloxacin. Patients should be informed about the typical symptoms of acute pancreatitis. Patients experiencing nausea, malaise, abdominal discomfort, severe abdominal pain, or vomiting should be examined by a physician immediately. 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.

During treatment with levofloxacin, bone marrow suppression may develop, including leukopenia, neutropenia, pancytopenia, hemolytic anemia, thrombocytopenia, aplastic anemia, or agranulocytosis. If any of these blood disorders are suspected, blood parameters should be monitored. If abnormalities occur, discontinuation of levofloxacin should be considered.

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 any visual disturbances or adverse reactions affecting the eyes occur during levofloxacin treatment, immediate consultation with an ophthalmologist is recommended.

Superinfection.

The use of levofloxacin, especially prolonged use, may lead to overgrowth of microorganisms resistant to the drug. If superinfection develops during therapy, appropriate measures should be taken.

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 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 only be used after careful benefit-risk assessment and consideration of alternative treatment options in patients with a family history of aneurysm or congenital heart valve defects, and in patients diagnosed with aortic aneurysm and/or dissection or cardiac valve disease, or in the presence of other risk factors for:

• both aortic aneurysm and dissection and cardiac valve regurgitation/insufficiency: connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, hypertension, rheumatoid arthritis;
• aortic aneurysm and dissection: vascular disorders such as Takayasu arteritis or giant cell arteritis, atherosclerosis, Sjögren's syndrome;
• cardiac valve regurgitation/insufficiency: infective endocarditis.

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

Patients should seek immediate medical attention if sudden abdominal, chest, or back pain occurs.

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

Effect on laboratory test results.

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

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and thus lead to false-negative results in bacteriological diagnosis of tuberculosis.

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

Sodium.

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, i.e., essentially "sodium-free."

Use during pregnancy or breastfeeding.

Pregnancy.

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

Animal studies do not indicate direct or indirect harmful effects with respect 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 during pregnancy.

If pregnancy is diagnosed during treatment, this should be reported to the physician.

Breastfeeding.

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

Fertility.

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

Ability to drive and use machines.

Levofloxacin has a minor or moderate effect on the ability to drive and use machinery. In some patients, the drug may cause headache, dizziness/vertigo, somnolence, insomnia, visual disturbances, or confusion. Therefore, during treatment, patients should refrain from driving and operating complex machinery requiring heightened attention and psychomotor speed.

Method of administration and dosage.

The drug is taken 1-2 times daily. The dosage depends on the type and severity of the infection. The duration of treatment depends on the course of the disease and should not exceed 14 days. It is recommended to continue treatment for at least 48–72 hours after normalization of body temperature or until microbiological tests confirm eradication of the causative agent.

Tablets should be swallowed whole, without chewing, with sufficient amount of liquid. Administer independently of food intake. Each tablet has a score line to facilitate division into parts if necessary.

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

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

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

** If a dose of 125 mg is required, levofloxacin formulations with appropriate dosing should be used.

Dosing in patients with hepatic impairment.

Dosage adjustment is not necessary, as levofloxacin is minimally metabolized in the liver and is primarily excreted via the kidneys.

Dosing in elderly patients.

If renal function is normal, there is no need for dose adjustment.

Pediatric use.

Levofloxacin should not be used in children (under 18 years of age), as damage to joint cartilage cannot be excluded.

Overdose.

Symptoms: confusion, dizziness, disturbances of consciousness, seizures, myoclonus, hallucinations, tremor, nausea, erosion of mucous membranes, QT interval prolongation.

Treatment: symptomatic therapy. Due to the potential for QT interval prolongation, ECG monitoring is required. In cases of clear overdose, gastric lavage should be performed. Antacids may be used to protect the gastric mucosa. Hemodialysis, including peritoneal dialysis and chronic ambulatory peritoneal dialysis (CAPD), is ineffective for removing levofloxacin from the body. There is no specific antidote.

Adverse Reactions

The information below is based on clinical trial data involving over 8,300 patients and extensive post-marketing experience.

The frequency of adverse effects was defined using the following criteria: very common (>1/10), common (from >1/100 to <1/10), uncommon (from >1/1,000 to <1/100), rare (from >1/10,000 to <1/1,000), very rare (>1/10,000), frequency not known (cannot be estimated from 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, disruption of normal intestinal flora, and development of secondary infections.

Allergic reactions: sometimes – pruritus, rash, hyperhidrosis; rare – urticaria, bronchospasm/dyspnea; very rare – angioneurotic edema, arterial hypotension, anaphylactic shock, photosensitization; in isolated cases – severe bullous eruptions such as Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), exudative polymorphic erythema, leukocytoclastic vasculitis, stomatitis.

Such reactions may sometimes occur even after the first dose, within minutes or hours of administration.

Gastrointestinal system, metabolism: common – nausea, diarrhea; sometimes – anorexia, vomiting, abdominal pain, dyspepsia, flatulence, constipation; rare – bloody diarrhea, which in isolated cases may indicate enterocolitis, including pseudomembranous colitis; very rare – hyperglycemia, hypoglycemia (possibly hypoglycemic coma), especially in patients with diabetes mellitus, pancreatitis.

Central nervous system*: sometimes – headache, dizziness/vertigo, syncope; rare – paresthesia, tremor, seizures; very rare – hyposthesia, disturbances or loss of taste and smell, hallucinations, benign intracranial hypertension, sensory or sensorimotor peripheral neuropathy, myoclonus.

Visual system*: rare – visual disturbances, e.g., blurred vision; frequency not known – transient vision loss, uveitis.

Auditory system*: uncommon – vertigo; rare – tinnitus; frequency not known – hearing loss, hearing impairment.

Psychiatric system*: common – insomnia; rare – anxiety, confusion, nervousness; very rare – psychotic reactions (e.g., with hallucinations, paranoia), depression, agitation, sleep disturbances, nightmares; isolated cases – psychotic disorders with behavior dangerous to the patient, including suicidal thoughts or suicide attempts, mania.

Cardiovascular system: rare – tachycardia, arterial hypotension; isolated cases – ventricular tachycardia, which may lead to cardiac arrest, ventricular arrhythmia, and torsades de pointes (mainly observed in patients with risk factors for QT interval prolongation), QT interval prolongation as measured by ECG.

Musculoskeletal system*: rare – arthralgia, myalgia, tendon injury, including tendinitis (e.g., Achilles tendon); very rare – tendon rupture (e.g., shoulder, hand, Achilles tendon); this adverse effect may occur within 48 hours of starting treatment; the risk of such ruptures is higher in patients receiving concomitant corticosteroids, elderly patients, and those with high physical stress on tendons; bilateral muscle weakness, particularly dangerous in patients with pre-existing myasthenia gravis; in isolated cases – rhabdomyolysis.

Hepatic and renal system: common – elevated liver enzymes (e.g., ALT/AST); uncommon – increased bilirubin, elevated serum creatinine; very rare – hepatic reactions such as hepatitis; acute renal failure (e.g., due to interstitial nephritis).

Blood system: sometimes – eosinophilia, leukopenia; rare – neutropenia, thrombocytopenia; very rare – agranulocytosis; frequency not known – bone marrow failure, including aplastic anemia, pancytopenia, agranulocytosis, hemolytic anemia.

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

Skin and subcutaneous tissue: rare – drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), persistent drug-induced erythema, skin hyperpigmentation.

General disorders*: sometimes – asthenia, candidiasis, development of superinfection; very rare – allergic pneumonia, malaise, back pain, chest pain, limb pain.

Other adverse effects associated with fluoroquinolone administration may include extrapyramidal symptoms and other muscular disorders, allergic vasculitis, porphyria attacks in patients with porphyria, anxiety, suicidal thoughts, panic attacks, neuralgia, and attention disturbances as potential aspects of long-term, disabling, and potentially irreversible fluoroquinolone-associated adverse reactions, which may lead to loss of work capacity.

Reporting of adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the drug. Healthcare professionals, pharmacists, as well as patients or their legal representatives should report all suspected adverse reactions and lack of drug efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua

* Very rare cases of long-term (lasting several months or years), disabling, and potentially irreversible serious reactions to drugs affecting various organ systems and sensory organs (including such reactions as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbance, neuropathy accompanied by paresthesia, depression, fatigue, memory impairment, sleep disturbances, hearing impairment, visual disturbances, taste and smell disturbances) have been associated with the use of quinolones and fluoroquinolones, regardless of the presence of risk factors (see section "Special Warnings and Precautions for Use").

** Cases of aortic aneurysm and aortic dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any cardiac valve have been observed in patients receiving fluoroquinolones (see section "Special Warnings and Precautions for Use").

Shelf life. 2 years.

Storage conditions.

Store in the original packaging, out of reach of children, at a temperature not exceeding 30 °C.

Packaging.

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

Prescription status.

Prescription only.

Manufacturer.

Evertogen Life Sciences Limited.

Address.

Plot No: S-8, S-9, S-13/P & S-14/P TSIIC, Pharma SEZ, Green Industrial Park, Polepally (V), Jadcherla (M), Mahabubnagar, Telangana, IN-509 301, India.