Novox-500 film-coated tablets 500 mg blister No. 5

Instructions Novox-500 film-coated tablets 500 mg blister No. 5

Composition

active ingredient: levofloxacin;

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

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

Dosage form

Film-coated tablets.

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

Pharmacotherapeutic group

Antibacterials for systemic use. Fluoroquinolones.

ATX code J01M A12.

Pharmacological properties

Pharmacodynamics

Levofloxacin is a broad-spectrum antibiotic from the quinolone group. Levofloxacin, like other fluorinated quinolones, blocks bacterial DNA gyrase, thereby disrupting the function of bacterial DNA. Levofloxacin is active against gram-positive and gram-negative pathogenic microorganisms, including strains resistant to penicillins, cephalosporins and/or aminoglycosides. The development of resistance can significantly affect the sensitivity of local strains to the drug. Therefore, it is advisable to take this information into account when prescribing the drug, especially in the case of the treatment of severe infections. Levofloxacin has a wide 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 pneumopnia, 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. When administered orally, levofloxacin is rapidly and almost completely absorbed. Its peak concentration in blood plasma is observed 1 hour after administration. Absolute bioavailability is almost 100%. The pharmacokinetics of levofloxacin are linear in the dose range of 50-600 mg. Food intake slightly affects the absorption of the drug.

Distribution. Approximately 30-40% of levofloxacin is bound to serum proteins. The cumulative effect of levofloxacin at a dosage of 500 mg once daily is not clinically significant. There is a slight but predictable accumulation at 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. The maximum concentration of levofloxacin in bronchial mucosa and bronchial epithelial secretions at a dose above 500 mg per os was 8.3 and 10.8 mg/ml, respectively.

Distribution in lung tissue: The maximum concentration of levofloxacin in lung tissue at a dose of more than 500 mg per os was approximately 11.3 mg/ml and was reached within 4-6 hours after administration. The concentration in the lungs consistently exceeded that in plasma.

Distribution in blister fluid: The maximum concentration of levofloxacin in blister fluid after administration of 500 mg 1-2 times a day was 6.7 mg/ml.

Distribution in cerebrospinal fluid: Levofloxacin is excreted in small amounts into the 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: The mean concentration of levofloxacin within 8-12 hours after a single dose of 150 mg, 300 mg or 500 mg per os was 44 mg/ml, 91 mg/ml and 200 mg/ml, respectively.

Metabolism: Levofloxacin is metabolized to a very small extent, the metabolites being desmethyl-levofloxacin and levofloxacin N-oxide. These metabolites account for less than 5% of the drug excreted in the urine.

Elimination. After oral administration, levofloxacin is eliminated from the blood plasma relatively slowly (the half-life is 6-8 hours). Excretion is mainly renal (more than 85% of the administered dose). The pharmacokinetics of levofloxacin after intravenous and oral administration do not differ significantly.

Indication

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;

For the treatment of the above infections, levofloxacin should only be used when it is considered inappropriate to use antibacterial agents that are usually recommended for the initial treatment of these infections.

acute pyelonephritis and complicated urinary tract infections;

chronic bacterial prostatitis.

Contraindication

Hypersensitivity to levofloxacin, other fluoroquinolones or to any ingredient of the drug. Epilepsy. Tendon damage associated with taking fluoroquinolones. Children's age (up to 18 years). Pregnancy and breastfeeding.

Interaction with other medicinal products and other types of interactions

Effects of other drugs on levofloxacin.

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

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

Sucralfate.

The bioavailability of levofloxacin tablets is significantly reduced when the drug is administered concomitantly with sucralfate. If a patient needs to receive both sucralfate and levofloxacin, it is best to take sucralfate 2 hours after taking the drug.

Theophylline, fenbufen or similar nonsteroidal anti-inflammatory drugs.

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

Probenecid and cimetidine.

Probenecid and cimetidine have a statistically significant effect on the elimination of levofloxacin. The renal clearance of levofloxacin is reduced by 24% in the presence of cimetidine and by 34% in the presence of probenecid. This is because both drugs are capable of blocking the tubular secretion of levofloxacin. However, at the doses tested in the study, it is unlikely that the statistically significant kinetic differences are of clinical relevance. Caution should be exercised when levofloxacin is co-administered with drugs that affect tubular secretion, such as probenecid and cimetidine, especially in patients with renal impairment.

Other information.

The following drugs do not have any clinically significant effect on the pharmacokinetics of levofloxacin when used concomitantly: calcium carbonate, digoxin, glibenclamide, ranitidine.

The effect of levofloxacin on other drugs.

Cyclosporine.

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

Vitamin K antagonists.

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

Drugs that prolong the QT interval.

Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs known to prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, and antipsychotic drugs).

Other significant information.

There is no evidence of an effect of levofloxacin on the pharmacokinetics of theophylline (which is a substrate of the CYP1A2 enzyme), indicating that levofloxacin is not a CYP1A2 inhibitor.

Other forms of interaction.

Eating.

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

Application features

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

Prolonged, disabling and potentially irreversible serious adverse reactions.

In very rare cases, prolonged (months or years), disabling and potentially irreversible serious adverse reactions affecting different, and sometimes multiple, body systems (including musculoskeletal, nervous, mental and sensory) have been reported in patients treated with quinolones and fluoroquinolones, regardless of age and existing risk factors. The drug should be discontinued immediately at the first signs or symptoms of any serious adverse reaction and a doctor should be consulted.

Methicillin-resistant S. aureus (MRSA) has a very high probability of being co-resistant to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of infections known or suspected to be caused by MRSA, unless laboratory tests have confirmed that the pathogen is susceptible to levofloxacin.

Levofloxacin can be used to treat acute bacterial sinusitis and exacerbation of chronic bronchitis, if these infections have been appropriately diagnosed.

Fluoroquinolone resistance in E. coli (the most common cause of urinary tract infections) varies between countries. The local prevalence of fluoroquinolone resistance in E. coli should be taken into account 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 as early as 48 hours after initiation of treatment with quinolones and fluoroquinolones and have been reported to occur even up to several months after discontinuation of treatment 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, patients with solid organ transplants and patients receiving concomitant corticosteroids. Therefore, concomitant use of corticosteroids should be avoided.

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

Diseases caused by Clostridium difficile.

Diarrhea, particularly severe, persistent and/or bloody, occurring during or after treatment with levofloxacin (including within a few weeks after treatment), may be a symptom of Clostridium difficile disease. The most severe form of this disease is pseudomembranous colitis. Therefore, the physician should consider the possibility of Clostridium difficile disease if a patient develops severe diarrhea during or after treatment with levofloxacin. If Clostridium difficile disease is suspected, levofloxacin should be discontinued immediately and appropriate treatment should be initiated as soon as possible. Drugs that inhibit intestinal motility are contraindicated in this case.

Patients with a tendency to seizures.

Quinolones may lower the seizure threshold and precipitate seizures. Levofloxacin is contraindicated in patients with a history of epilepsy. As with other quinolones, it should be used with extreme caution in patients prone to seizures and in patients receiving concomitant treatment with agents that lower the seizure threshold, such as theophylline. Levofloxacin should be discontinued if a seizure occurs.

Patients with glucose-6-phosphate dehydrogenase deficiency.

Patients with latent or overt glucose-6-phosphate dehydrogenase deficiency may be predisposed to hemolytic reactions when treated with quinolone antibiotics. Therefore, if levofloxacin is used, these patients should be monitored for possible hemolysis.

Patients with renal failure.

Since levofloxacin is excreted mainly by the kidneys, dose adjustment is required for patients with impaired renal function (renal failure).

Hypersensitivity reactions.

Levofloxacin can cause serious, potentially fatal hypersensitivity reactions (e.g. angioedema to anaphylactic shock), in some cases after the first dose. If hypersensitivity reactions occur, levofloxacin should be discontinued, a doctor should be consulted and appropriate treatment should be initiated.

Severe skin adverse reactions.

Severe cutaneous 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), which can be fatal, have been reported with levofloxacin (see section 4.8).

When prescribing the drug, patients should be warned about the signs and symptoms of severe skin reactions and monitored closely. If signs and symptoms suggestive of these reactions appear, levofloxacin should be discontinued immediately and alternative treatment should be considered.

If a patient develops a serious reaction such as SJS, TEN or DRESS syndrome while taking levofloxacin, they should never be treated with levofloxacin again.

Change in blood glucose levels.

Prevention of photosensitization.

Photosensitivity has been reported with levofloxacin. To prevent photosensitivity, it is recommended that patients avoid unnecessary exposure to strong sunlight or artificial sources of UV light (e.g., sunlamps, tanning beds) during treatment and for 48 hours after stopping levofloxacin.

Patients receiving vitamin K antagonists.

Due to the possible increase in blood coagulation parameters (prothrombin time, international normalized ratio) and/or an increase in the frequency of hemorrhagic complications in patients receiving levofloxacin in combination with a vitamin K antagonist (e.g. warfarin), blood coagulation parameters should be monitored during concomitant use of these agents.

Psychotic reactions.

Psychotic reactions have been reported in patients taking quinolones, including levofloxacin. Very rarely, these have progressed to suicidal ideation and self-harm, sometimes after only a single dose of levofloxacin. If a patient develops these reactions, levofloxacin should be discontinued and appropriate measures should be taken. Levofloxacin should be used with caution in patients with psychotic disorders or a history of psychiatric illness.

QT prolongation.

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

congenital or acquired long QT syndrome;

simultaneous use of drugs that have the ability to prolong the QT interval (such as class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotic drugs);

electrolyte imbalance (e.g. hypokalemia, hypomagnesemia);

heart disease (e.g., heart failure, myocardial infarction, bradycardia).

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

Peripheral neuropathy.

Cases of sensory or sensorimotor polyneuropathy resulting in paresthesia, hypoesthesia, dysesthesia, or weakness have been reported in patients treated with quinolones and fluoroquinolones. Patients treated with the drug should inform their physician if they experience symptoms of neuropathy, such as pain, burning, tingling, numbness, or weakness, to prevent the development of a potentially irreversible condition.

Hepatobiliary disorders.

Cases of hepatic necrosis up to and including fatal hepatic failure have been reported with levofloxacin (predominantly in patients with severe underlying diseases such as sepsis). Patients should be advised to discontinue treatment and seek medical advice if signs and symptoms of liver disease such as anorexia, jaundice, dark urine, pruritus or abdominal pain occur.

Acute pancreatitis.

Acute pancreatitis may occur in patients taking levofloxacin. Patients should be informed of the characteristic symptoms of acute pancreatitis. Patients who experience nausea, malaise, abdominal discomfort, acute abdominal pain or vomiting should be examined immediately by a doctor. 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").

Exacerbation of myasthenia gravis.

Fluoroquinolones, including levofloxacin, have neuromuscular blocking effects and may exacerbate muscle weakness in patients with myasthenia gravis. In the post-marketing period, serious adverse reactions, including fatalities and conditions requiring respiratory support, have been associated with the use of fluoroquinolones in patients with myasthenia gravis. Levofloxacin is not recommended for use in patients with a history of myasthenia gravis.

Visual impairment.

If you experience any visual disturbances or adverse reactions from the organs of vision while taking levofloxacin, you should immediately consult an ophthalmologist.

Superinfection.

The use of levofloxacin, especially long-term, may lead to overgrowth of non-susceptible (resistant) microorganisms. If superinfection develops during therapy, appropriate measures should be taken.

Aortic aneurysm and dissection and regurgitation/insufficiency of the heart valve.

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

both aortic aneurysms and dissections and heart valve regurgitation/insufficiency: connective tissue diseases such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, hypertension, rheumatoid arthritis;

aortic aneurysms and dissections: vascular disorders such as Takayasu arteritis or giant cell arteritis, atherosclerosis, Sjögren's syndrome;

regurgitation/heart valve insufficiency: infective endocarditis.

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

Patients should seek immediate medical attention in the emergency department if they experience sudden abdominal, chest, or back pain.

Patients should be advised to seek immediate medical attention in the event of acute shortness of breath, new onset of palpitations, or development of abdominal or lower extremity edema.

Impact on laboratory test results.

In patients treated with levofloxacin, urine opiates may give false-positive results. Positive opiates from screening tests may need to be confirmed by more specific methods.

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

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

Sodium

This medicine 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, in the absence of human studies and based on experimental data indicating a risk of damage to the articular cartilage of the growing organism by fluoroquinolones, levofloxacin should not be administered to pregnant women.

If pregnancy is diagnosed during treatment with the drug, the doctor should be informed.

Breastfeeding period.

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

Fertility

Levofloxacin did not cause impaired fertility or reproductive function in animals.

The ability to influence the reaction speed when driving or working with other mechanisms

Levofloxacin has minor or moderate influence on the ability to drive and use machines. In some patients, the drug may cause headache, dizziness/vertigo, drowsiness, insomnia, visual disturbances, confusion, therefore, during its use, one should refrain from driving and working with complex mechanisms that require increased attention and speed of psychomotor reactions.

Method of administration and doses

The drug is taken 1-2 times a day. The dose depends on the type and severity of the infection. The duration of treatment depends on the course of the disease and is no more than 14 days. It is recommended to continue treatment for at least 48-72 hours after normalization of body temperature or confirmed destruction of pathogens by microbiological tests.

The tablets are swallowed without chewing, with sufficient liquid. They are used regardless of meals. The tablet is scored for ease of dividing into parts if necessary.

Dosage for patients with normal renal function who have a creatinine clearance greater than 50 mL/min:

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

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

** If it is necessary to prescribe a dose of 125 mg, levofloxacin preparations in the appropriate dosage are used.

Dosage for patients with hepatic impairment.

No dose adjustment is necessary, as levofloxacin is metabolized to a minor extent in the liver and excreted mainly by the kidneys.

Dosage for elderly patients.

If renal function is not impaired, there is no need for dose adjustment.

Children

Children (under 18 years of age) should not use the drug, as damage to the articular cartilage cannot be ruled out.

Overdose

Symptoms: confusion, dizziness, impaired consciousness and seizures, hallucinations, tremor, nausea, erosion of mucous membranes, prolongation of the QT interval.

Treatment: symptomatic therapy. Taking into account the possible prolongation of the QT interval, ECG monitoring is required. In case of apparent overdose, gastric lavage is prescribed. Antacids can be used to protect the gastric mucosa. Hemodialysis, including peritoneal dialysis and chronic ambulatory peritoneal dialysis, are ineffective in removing levofloxacin from the body. There is no specific antidote.

Side effects

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

The frequency of side effects was determined using the following criteria: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1000 to <1/100), rare (>1/10000 to <1/1000), very rare (>1/10000), frequency unknown (cannot be estimated from the available data).

Within each group, adverse reactions are presented in order of decreasing seriousness.

Infections and infestations:

uncommon: fungal infections, including Candida fungi, proliferation of other resistant microorganisms, disruption of the normal intestinal microflora and development of secondary infection.

Allergic reactions: sometimes - itching, rash, hyperhidrosis; rarely - urticaria, bronchospasm/dyspnea; very rarely - angioedema, hypotension, anaphylactic shock, photosensitivity; in isolated cases - severe bullous rashes, such as Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exudative erythema multiforme, leukocytic vasculitis, stomatitis.

Such reactions can sometimes be observed even after the first dose within a few minutes or hours after administration.

From the digestive tract, metabolism: often - nausea, diarrhea; sometimes - anorexia, vomiting, abdominal pain, dyspepsia, flatulence, constipation; rarely - diarrhea with blood impurities, which in isolated cases may indicate enterocolitis, including pseudomembranous colitis; very rarely - hyperglycemia, hypoglycemia (possibly hypoglycemic coma), especially in patients with diabetes mellitus, pancreatitis.

From the side of the central nervous system*: sometimes - headache, dizziness/vertigo, syncope; rarely - paresthesia, tremor, convulsions; very rarely - hypoesthesia, impaired or loss of taste and smell perception, hallucinations, benign intracranial hypertension, sensory or sensorimotor peripheral neuropathy.

On the part of the organs of vision*: rarely - visual disturbances, for example, blurred vision; frequency unknown - transient loss of vision, uveitis.

From the auditory system*: infrequently - vertigo; rarely - tinnitus; frequency unknown - hearing loss, hearing impairment.

Psychiatric disorders: often - insomnia; rarely - anxiety, confusion, nervousness; very rarely - psychotic reactions (e.g. with hallucinations, paranoia), depression, agitation, sleep disorders, nightmares; rarely - psychotic disorders with behavior threatening to the patient, including suicidal thoughts or suicide attempts.

From the cardiovascular system: rarely - tachycardia, arterial hypotension; isolated - ventricular tachycardia, which can lead to cardiac arrest, ventricular arrhythmia and ventricular tachycardia of the "pirouette" type (observed mainly in patients with risk factors for QT interval prolongation), prolongation of the QT interval recorded by ECG.

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

From the blood system: sometimes - eosinophilia, leukopenia; rarely - neutropenia, thrombocytopenia; very rarely - agranulocytosis; in isolated cases - hemolytic anemia, pancytopenia.

On the part of the endocrine system: rarely - syndrome of inappropriate antidiuretic hormone secretion (SNS ADH).

Skin and subcutaneous tissue disorders: rarely - drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), persistent drug erythema.

General disorders*: sometimes - asthenia, candidiasis, development of superinfection; very rarely - allergic pneumonitis, fever, pain in the back, chest, extremities.

Other undesirable effects that have been associated with the administration of fluoroquinolones may include extrapyramidal symptoms and other disorders of the muscular system, allergic vasculitis, and attacks of porphyria in patients with porphyria.

Reporting adverse reactions after registration of a medicinal product is of great importance. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the automated pharmacovigilance information system at the link: https://aisf.dec.gov.ua

* Very rare cases of prolonged (over several months or years), disabling and potentially irreversible serious drug reactions affecting various body systems and sensory organs (including reactions such as tendinitis, tendon rupture, arthralgia, pain in the extremities, gait disturbance, neuropathy accompanied by paresthesia, depression, fatigue, memory impairment, sleep disturbances, hearing, vision, 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 dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any of the heart valves have been observed in patients receiving fluoroquinolones (see section "Special warnings and precautions for use").

Expiration date

2 years.

Storage conditions

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

Packaging

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

Vacation category

According to the recipe.

Producer

Evertogen Life Sciences Limited.

Location

Plot No.: S-8, S-9, S-13/P and S-14/P T E C I A C, S I Z Pharma, Green Industrial Park, Polepally (V), Yedcherla (M), Mahabubnagar, Telangana, IH-509 301, India /

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.