Levofloxacin-Astrapharm film-coated tablets 500 mg blister No. 7

Instructions Levofloxacin-Astrapharm film-coated tablets 500 mg blister No. 7

Composition

active ingredient: levofloxacin;

1 tablet contains 250 mg or 500 mg of levofloxacin;

excipients: crospovidone, microcrystalline cellulose, sodium stearyl fumarate, “SeleCoatTM” coating (hypromellose, polyethylene glycol 6000, titanium dioxide (E 171)).

Dosage form

Film-coated tablets.

Main physicochemical properties: oval-shaped tablets with a biconvex surface, coated with a white shell.

Pharmacotherapeutic group

Antibacterials for systemic use. Fluoroquinolones.

ATX code J01M A12.

Pharmacological properties

Pharmacodynamics.

Levofloxacin-Astrafarm is a broad-spectrum antibiotic from the quinolone group, containing the active substance levofloxacin. 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, when prescribing the drug, it is advisable to take this information into account, especially in the case of the treatment of severe infections. Levofloxacin has a wide range of action against microorganisms both in vitro and in vivo: Enterococcus faecalis, methicillin-sensitive 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.

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%. Levofloxacin is subject to linear pharmacokinetics in the range of 50–600 mg. Food intake slightly affects the absorption of the drug.

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.

The maximum concentration of levofloxacin in bronchial mucosa and bronchial epithelial secretion at a dose above 500 mg per os was 8.3 and 10.8 mg/ml, respectively.

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 blood plasma.

The maximum concentration of levofloxacin in blister fluid after administration of 500 mg 1–2 times a day was 6.7 mg/ml, respectively.

Levofloxacin does not penetrate well into the cerebrospinal fluid.

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.

The mean concentration of levofloxacin within 8–12 hours after a single dose of 150 mg or 300 mg, or 500 mg per os was 44 mg/ml, 91 mg/ml and 200 mg/ml, respectively.

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

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

Indication

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

acute bacterial sinusitis;

exacerbation of chronic bronchitis;

community-acquired pneumonia;

complicated skin and soft tissue infections

(in the case of the treatment of the above infections, the drug is used only when the use of other antibacterial agents, which are usually prescribed for the initial treatment of these infections, is impossible);

complicated urinary tract infections (including acute pyelonephritis);

chronic bacterial prostatitis.

Official recommendations on the appropriate use of antibacterial agents should be considered.

Contraindication

Hypersensitivity to levofloxacin, other fluoroquinolones or to any component of the drug.

Epilepsy.

Tendon damage associated with the use of fluoroquinolones.

Childhood.

Pregnancy or breastfeeding.

Interaction with other medicinal products and other types of interactions

Effects of other medicinal products on levofloxacin

Iron salts, antacids containing magnesium and aluminum, didanosine.

The absorption of levofloxacin is significantly reduced when taken simultaneously with iron salts and antacids containing magnesium or aluminum. The tablets should be taken at least 2 hours after taking drugs containing divalent or trivalent cations, such as iron salts or antacids containing magnesium or aluminum. No interactions have been found with calcium carbonate.

It is recommended not to take drugs containing divalent or trivalent cations, such as iron salts, zinc salts, antacids containing magnesium or aluminum, or didanosine (this only applies to didanosine dosage forms containing aluminum or magnesium buffering agents), within 2 hours before or after taking levofloxacin tablets (see section "Method of administration and dosage").

Sucralfate

The bioavailability of levofloxacin is significantly reduced when the drug is used simultaneously with sucralfate. If the patient needs to receive both sucralfate and levofloxacin, it is better to take sucralfate 2 hours after taking Levofloxacin-Astrapharm tablets.

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, 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 probenecid. This is due to the fact that both drugs are able to block the tubular secretion of levofloxacin. However, in the study, statistically significant kinetic differences were not clinically relevant. Caution should be exercised when levofloxacin is used concomitantly with drugs that affect tubular secretion, such as probenecid and cimetidine, especially in patients with renal insufficiency.

Other drugs

Studies have shown that there was no clinically significant effect on the pharmacokinetics of levofloxacin when levofloxacin was used together with the following drugs: calcium carbonate, digoxin, glibenclamide, ranitidine.

Effect of levofloxacin on other drugs

Cyclosporine

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

Vitamin K antagonists

Coagulation monitoring is recommended in patients receiving concomitant vitamin K antagonists (e.g. warfarin) due to increased international normalized ratio (INR) and/or bleeding, which may be severe.

QT-prolonging drugs

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, and macrolides).

Eating

No clinically significant interaction with food has been observed. Levofloxacin-Astrapharm tablets can therefore be taken regardless of meals.

Application features

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

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

Methicillin-resistant S. aureus

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 where MRSA is known or suspected to be the causative agent, unless laboratory tests have confirmed susceptibility to levofloxacin (and when it is considered impractical to use commonly recommended antibacterial agents for the treatment of MRSA infections).

The most common causative agent of urinary tract infections is levofloxacin-resistant E. coli, which should be taken into account when prescribing levofloxacin to patients with urinary tract diseases.

Tendinitis and tendon rupture (particularly of 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 tendonitis and tendon rupture is increased in elderly patients (over 60 years of age), patients with impaired renal function, patients with solid organ transplants, patients receiving daily doses of 1000 mg levofloxacin and patients receiving concomitant corticosteroids. Therefore, concomitant use of corticosteroids should be avoided. The daily dose should be adjusted in elderly patients, taking into account creatinine clearance. Elderly patients should be monitored if levofloxacin is prescribed to them.

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 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 hemorrhagic, during or after treatment with the drug may be a symptom of Clostridium difficile disease, the most severe form of which is pseudomembranous colitis. If pseudomembranous colitis is suspected, the drug should be discontinued immediately and supportive therapy and, if necessary, specific therapy (e.g., oral vancomycin) should be initiated without delay. Agents that inhibit intestinal motility are contraindicated in this clinical situation.

Patients prone 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, levofloxacin should be used with extreme caution in patients prone to seizures, such as those with central nervous system lesions, in concomitant therapy with fenbufen and similar nonsteroidal anti-inflammatory drugs or drugs that increase seizure susceptibility (lower the seizure threshold), such as theophylline. If seizures occur, levofloxacin treatment should be discontinued.

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with glucose-6-phosphate dehydrogenase activity defects are prone to hemolytic reactions when treated with quinolone antibacterial agents, therefore, levofloxacin should be used with caution in them.

Patients with renal insufficiency

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

Hypersensitivity reactions

Levofloxacin may cause severe hypersensitivity reactions (e.g. angioedema up to and including anaphylactic shock). In such cases, patients should discontinue treatment immediately and consult a doctor.

Severe skin adverse reactions

Severe skin 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.

During use of the medicinal product, patients should be warned about the signs of severe skin reactions and their condition should be carefully monitored.

At the first sign of these reactions, levofloxacin should be discontinued immediately and alternative treatment should be considered. If a patient experiences a serious skin reaction such as toxic epidermal necrolysis (TEN: also known as Lyell's syndrome), Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS) while taking levofloxacin, this medicine should not be prescribed at any time in the future.

Dysglycemia

Fluctuations in blood glucose levels, including cases of hyperglycemia and hypoglycemia, have been reported with levofloxacin, as with other quinolones, especially 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 (see section 4.8).

Prevention of photosensitivity

Although photosensitivity occurs very rarely with levofloxacin, in order to avoid it, patients are advised not to expose themselves to strong sunlight or artificial UV radiation (e.g. artificial ultraviolet lamps, solariums) while taking levofloxacin and for 48 hours after stopping levofloxacin.

Patients receiving vitamin K antagonists

Due to the possible increase in MHC and/or bleeding in patients taking levofloxacin in combination with a vitamin K antagonist (e.g. warfarin), coagulation tests should be monitored in such cases.

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

QT prolongation

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

congenital long QT syndrome;

acquired QT prolongation syndrome;

concomitant use of drugs known to prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotic drugs);

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

Elderly patients and women are more sensitive to drugs that prolong the QT interval;

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

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 be advised to 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 necrotizing hepatitis, up to life-threatening hepatic failure, have been reported with levofloxacin, predominantly in patients with severe underlying diseases such as sepsis (see section 4.8). Patients should be advised to discontinue treatment and consult a doctor if signs of liver disease such as anorexia, jaundice, dark urine, pruritus or abdominal pain occur.

Laboratory studies

In patients treated with levofloxacin, urine tests for opiates may give false-positive results. It may be necessary to confirm positive results for opiates using specific methods.

Levofloxacin inhibits the growth of Mycobacterium tuberculosis, and therefore a false-negative result may be observed when conducting a bacteriological examination in patients with tuberculosis.

Aortic aneurysm or dissection and heart valve regurgitation/insufficiency

Epidemiological studies have reported an increased risk of aortic aneurysm and dissection, especially in elderly patients, and of aortic and mitral valve regurgitation after the use of fluoroquinolones. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and of regurgitation/insufficiency of any of the cardiac valves have been reported in patients receiving fluoroquinolones (see section 4.8).

Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with a positive family history of aneurysm or congenital heart valve disease, 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.

§ both for aortic aneurysm and dissection, and for regurgitation/valve insufficiency (e.g. connective tissue disorders such as Marfan syndrome, vascular type Ehlers-Danlos syndrome or Turner syndrome, Behçet's disease, hypertension, rheumatoid arthritis) or additionally

§ in case of 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

§ in case of regurgitation/valvular insufficiency (e.g. infective endocarditis). The risk of aortic aneurysm and dissection and their rupture may be 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.

Prolonged, disabling and potentially irreversible serious adverse reactions

In patients treated with quinolones and fluoroquinolones, regardless of their age and the presence of risk factors, very rare cases of prolonged (over several months or years), disabling and potentially irreversible serious adverse drug reactions affecting various body systems (musculoskeletal, nervous system, psyche, sensory organs) have been observed. Patients should be advised to immediately discontinue levofloxacin at the first symptoms of any serious adverse reaction and consult a doctor.

Fluoroquinolones, including levofloxacin, block neuromuscular transmission and may cause muscle weakness in patients with myasthenia gravis. Serious adverse reactions, including fatalities and the need for respiratory support, have been reported with fluoroquinolones in the post-marketing setting in patients with myasthenia gravis. Levofloxacin is not recommended for use in patients with a history of myasthenia gravis.

Vision disorders.

If visual impairment or other effects on the eyes are observed, an ophthalmologist should be consulted immediately (see sections “Adverse reactions”, “Ability to influence the reaction speed when driving vehicles or other mechanisms”).

Superinfection.

When using levofloxacin, especially long-term, the development of opportunistic infections and the growth of resistant microorganisms is possible. If a secondary infection develops, appropriate measures should be taken.

Excipients

This medicinal product contains sodium stearyl fumarate. Caution should be exercised when used in patients on a controlled sodium diet.

Use during pregnancy or breastfeeding

Due to the lack of human studies and the possibility of quinolone damage to articular cartilage in a growing body, the drug should not be prescribed during pregnancy or breastfeeding. If pregnancy occurs during treatment with the drug, the doctor should be informed.

Ability to influence reaction speed when driving vehicles or other mechanisms

In some patients, the drug may cause headache, dizziness/vertigo, drowsiness, insomnia, visual disturbances, and confusion, so during its use, one should refrain from driving or operating other mechanisms.

Method of administration and doses

The drug should be 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.

Swallow the tablets without chewing, with sufficient liquid. Use regardless of meals.

The drug should be administered at least 2 hours before or 2 hours after the use of iron salts, zinc salts, antacids containing magnesium or aluminum, didanosine (applies only to forms containing aluminum or magnesium in buffering agents) and sucralfate (see section "Interaction with other medicinal products and other types of interaction").

The following dosage recommendations should be followed for adult patients with normal renal function and creatinine clearance greater than 50 ml/min:

Dosage for patients with renal impairment whose creatinine clearance is less than 50 mL/min

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

The tablets are not intended to be divided. If a lower dosage is required, a different dosage form of levofloxacin should be used.

Dosage for patients with impaired liver function.

No dose adjustment is necessary since levofloxacin is only slightly metabolized in the liver.

Dosage for elderly patients.

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

Children.

The drug is not used in children, as damage to the articular cartilage cannot be ruled out.

Overdose

Treatment: symptomatic and supportive. ECG monitoring should be considered as QT prolongation may occur. Levofloxacin is not removed by either hemodialysis or peritoneal dialysis; there is no specific antidote.

Side effects

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

From the blood system: leukopenia, eosinophilia, thrombocytopenia, neutropenia, agranulocytosis, pancytopenia, hemolytic anemia.

Immune system disorders: hypersensitivity reactions, including anaphylactic/anaphylactoid shock, angioedema (see section "Special warnings and precautions for use"); anaphylactic and anaphylactoid reactions may sometimes occur even after the first dose.

Metabolic: anorexia, hypoglycemia, especially in patients with diabetes mellitus (see section "Special warnings and precautions for use"); hyperglycemia, hypoglycemic coma.

Psychiatric: insomnia, agitation, confusion, nervousness, states of fear, psychotic disorders (including hallucinations, paranoia), depression, anxiety, restlessness, abnormal dreams, nightmares; psychotic reactions with self-destructive behavior, including suicidal thoughts or actions (see section "Special warnings and precautions for use").

Nervous system*: dizziness, headache, drowsiness, convulsions, tremor, paresthesia, sensory or sensorimotor peripheral neuropathy, dysgeusia (subjective taste disorder), including ageusia (loss of taste); parosmia (smell disorder), including anosmia (absence of smell); dyskinesia, extrapyramidal disorders, other disorders of motor coordination, also during gait, fainting, benign intracranial hypertension, syncope.

On the part of the organs of vision*: visual disturbances such as blurred vision, blurred vision; temporary loss of vision.

From the auditory system*: vertigo, tinnitus, hearing impairment, hearing loss.

Cardiovascular system**: tachycardia, palpitations, ventricular tachycardia, which can lead to cardiac arrest; ventricular arrhythmias and torsade de pointes (predominantly in patients with risk factors for QT prolongation); prolongation of the QT interval on the electrocardiogram (see sections "Special warnings and precautions for use" ("QT prolongation") and "Overdose"), arterial hypotension, leukocytoclastic vasculitis.

Respiratory system: shortness of breath (dyspnea), bronchospasm, allergic pneumonitis.

Gastrointestinal: diarrhea; nausea; vomiting; abdominal pain; dyspepsia; flatulence/bloating; constipation; hemorrhagic diarrhea, which in rare cases may indicate enterocolitis, including pseudomembranous colitis, pancreatitis.

Hepatobiliary system: increased liver enzymes (ALT/AST, alkaline phosphatase, GGTP); increased blood bilirubin; hepatitis; jaundice and severe liver damage, including cases of acute liver failure (sometimes fatal), mainly in patients with severe underlying diseases (see section "Special warnings and precautions for use").

Skin and subcutaneous tissue disorders: rash, itching, urticaria, hypersensitivity to sunlight and ultraviolet radiation, toxic epidermal necrolysis (Lyell's syndrome), Stevens-Johnson syndrome, exudative erythema multiforme, hyperhidrosis, photosensitivity reactions, leukocytoclastic vasculitis, stomatitis, DRESS syndrome, localized skin rash caused by the drug and medications.

Sometimes mucocutaneous reactions may occur even after taking the first dose.

Musculoskeletal system*: tendon damage (see sections "Contraindications", "Features of use"), including their inflammation (tendinitis) (e.g., Achilles tendon), arthralgia, myalgia, tendon rupture (e.g., Achilles), ligament rupture, muscle rupture, arthritis. Muscle weakness is possible, which may be of particular importance for patients with myasthenia gravis, rhabdomyolysis.

On the part of the urinary system: increased serum creatinine levels, acute renal failure (for example, due to interstitial nephritis).

General disorders: asthenia, fever (pyrexia), pain (including back, chest and extremity pain), porphyria attacks in patients with porphyria.

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

* Very rare cases of prolonged (several months or years), disabling and potentially irreversible serious drug reactions, sometimes affecting multiple body systems and senses (including reactions such as tendinitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathy associated with paraesthesia, depression, fatigue, memory impairment, sleep disorders and disturbances of hearing, vision, taste and smell), have been reported with the use of quinolones and fluoroquinolones, in some cases in the absence of risk factors (see section "Special instructions").

** Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any of the heart valves have been reported in patients receiving fluoroquinolones (see section "Special warnings and precautions for use").

Expiration date

3 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging

7 tablets in a blister; 1 or 2 blisters in a box.

Vacation category

According to the recipe.

Producer

LLC "ASTRAFAM", Ukraine.

Address

08132, Kyiv region, Kyiv-Svyatoshynskyi district, Vyshneve town, Kyivska st., 6.