Tavanik film-coated tablets 250 mg 10 pcs. in Moscow

Tavanik film-coated tablets 250 mg 10 pcs. in Moscow

Hospital-acquired infections caused by Pseudomonas aeruginosa (Pseudomonas aeruginosa),

may require combination treatment.

Risk of developing resistance.

The prevalence of acquired resistance in cultured strains of microorganisms may vary by geographic region and over time. In this regard, information on drug resistance in a specific country is required. For the treatment of severe infections or if treatment is ineffective, a microbiological diagnosis must be established with the isolation of the pathogen and determination of its sensitivity to levofloxacin.

Methicillin-resistant streptococcus aureus.

There is a high likelihood that methicillin-resistant Staphylococcus aureus will be resistant to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of known or suspected infections caused by methicillin-resistant Staphylococcus aureus if laboratory tests have not confirmed the sensitivity of this microorganism to levofloxacin.

Disability and potential irreversible serious adverse reactions associated with fluoroquinolones.

The use of fluoroquinolones, incl. levofloxacin has been associated with disability and the development of irreversible serious adverse reactions from various body systems that can develop simultaneously in the same patient. Adverse reactions caused by fluoroquinolones include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and nervous system side effects (hallucinations, anxiety, depression, insomnia, headaches, and confusion). These reactions may develop from several hours to several weeks after starting levofloxacin therapy. The development of these adverse reactions was observed in patients of any age or without the presence of previous risk factors. If the first signs or symptoms of any serious adverse reactions occur, use of levofloxacin should be discontinued immediately. The use of fluoroquinolones should be avoided, incl. levofloxacin, in patients who have experienced any of these serious adverse reactions.

Patients predisposed to developing seizures.

Like other quinolones, levofloxacin should be used with great caution in patients with a predisposition to seizures. Such patients include patients with previous CNS lesions, such as stroke, severe TBI; patients concomitantly receiving drugs that lower the seizure threshold of the brain, such as fenbufen and other similar NSAIDs, or other drugs that lower the seizure threshold, such as theophylline (see “Interactions”). If seizures develop, treatment with levofloxacin should be discontinued.

Pseudomembranous colitis.

Diarrhea that develops during or after treatment with levofloxacin, especially severe, persistent and/or bloody, may be symptoms of pseudomembranous colitis caused by Clostridium difficile. If pseudomembranous colitis is suspected, treatment with levofloxacin should be stopped immediately and specific antibiotic therapy (vancomycin, teicoplanin or oral metronidazole) should be started immediately. Drugs that inhibit intestinal motility are contraindicated.

Tendinitis and tendon rupture.

Tendinitis has been reported rarely with quinolones, including levofloxacin, and can sometimes lead to rupture of tendons, including the Achilles tendon, and may be bilateral. This side effect may occur within 48 hours of starting treatment or several months after completion of fluoroquinolone therapy. Elderly patients are more prone to developing tendonitis; in patients taking fluoroquinolones, the risk of tendon rupture may increase with concomitant use of corticosteroids. In addition, post-transplant patients have an increased risk of developing tendonitis, so it is recommended to be careful when prescribing fluoroquinolones to this category of patients. In patients with impaired renal function, the daily dose should be adjusted based on creatinine clearance. Patients should be advised to remain calm at the first sign of tendonitis or tendon rupture and to contact their healthcare provider. If you suspect the development of tendonitis or tendon rupture, you should immediately stop treatment with Tavanic® and begin appropriate treatment of the affected tendon, for example, providing it with sufficient immobilization (see “Contraindications” and “Side effects”).

Hypersensitivity reactions.

Levofloxacin may cause serious, potentially fatal hypersensitivity reactions (angioedema, anaphylactic shock), even with initial doses (see "Side Effects"). Patients should immediately stop taking the drug and consult a doctor. If they develop, patients should immediately stop taking the drug and immediately consult a doctor.

Severe bullous reactions.

Cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been observed while taking levofloxacin (see "Side effects"). In case of development of any reactions from the skin or mucous membranes, the patient should immediately consult a doctor and not continue treatment until his consultation.

From the liver and bile ducts.

Cases of hepatic necrosis, including fatal liver failure, have been reported with the use of levofloxacin, mainly in patients with severe underlying diseases, such as sepsis (see "Side effects"). Patients should be warned to stop treatment and seek immediate medical attention if signs and symptoms of liver damage occur, such as anorexia, jaundice, dark urine, itching and abdominal pain.

Patients with impaired renal function.

Since levofloxacin is excreted mainly through the kidneys, patients with impaired renal function require mandatory monitoring of renal function, as well as adjustment of the dosage regimen (see “Dosage and Administration”). When treating elderly patients, it should be borne in mind that patients in this group often have impaired renal function (see “Dosage and Administration”).

Preventing the development of photosensitivity reactions.

Although photosensitivity occurs very rarely with the use of levofloxacin, to prevent its development, patients are not recommended to be unnecessarily exposed to strong solar or artificial UV irradiation (for example, visiting a solarium) during treatment and for 48 hours after treatment with levofloxacin.

Superinfection.

As with the use of other antibiotics, the use of levofloxacin, especially for a long time, can lead to increased proliferation of microorganisms that are insensitive to it (bacteria and fungi), which can cause changes in the microflora that is normally present in humans. As a result, superinfection may develop. Therefore, during treatment, it is imperative to re-evaluate the patient’s condition, and if superinfection develops during treatment, appropriate measures should be taken.

Prolongation of the QT interval.

Very rare cases of QT prolongation have been reported in patients taking fluoroquinolones, including levofloxacin.

When using fluoroquinolones, including levofloxacin, caution should be exercised in patients with known risk factors for prolongation of the QT interval: in patients with uncorrected electrolyte disturbances (with hypokalemia, hypomagnesemia); c congenital long QT syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); while taking drugs that can prolong the QT interval, such as class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics.

Elderly and female patients may be more sensitive to drugs that prolong the QT interval. Therefore, fluoroquinolones, including levofloxacin, should be used with caution (see Precautions, Dosage and Administration, Side Effects and Overdose, Interactions).

Patients with glucose-6-phosphate dehydrogenase deficiency.

Patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency are predisposed to hemolytic reactions when treated with quinolones, which should be taken into account when treated with levofloxacin.

Hypo- and hyperlycemia (dysglycemia).

As with the use of other quinolones, cases of hyperglycemia and hypoglycemia have been observed with the use of levofloxacin, usually in patients with diabetes mellitus receiving concomitant treatment with oral hypoglycemic drugs (for example, glibenclamide) or insulin preparations. Cases of hypoglycemic coma have been reported. In patients with diabetes mellitus, monitoring of blood glucose concentrations is required (see “Side Effects”).

Peripheral neuropathy

. Sensory and sensorimotor peripheral neuropathy, which may have a rapid onset, has been reported in patients taking fluoroquinolones, including levofloxacin. If the patient develops symptoms of neuropathy, levofloxacin should be discontinued. This minimizes the risk of developing irreversible changes. Patients should be informed to report any symptoms of neuropathy to their healthcare provider. Fluoroquinolones should not be prescribed to patients with a history of peripheral neuropathy.

Exacerbation of pseudoparalytic myasthenia gravis (myasthenia gravis).

Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may increase muscle weakness in patients with myasthenia gravis. Post-marketing adverse reactions, including pulmonary failure requiring mechanical ventilation and death, have been associated with the use of fluoroquinolones in patients with myasthenia gravis. The use of levofloxacin in a patient with an established diagnosis of pseudoparalytic myasthenia gravis is not recommended (see section "Side effects").

Application for airborne anthrax infection.

The use of levofloxacin in humans for this indication is based on susceptibility data from Bacillus anthracis obtained from in vitro and experimental animal studies, as well as limited data from the use of levofloxacin in humans. Treating physicians should refer to national and/or international documents that reflect the collectively developed point of view on the treatment of anthrax.

Psychotic reactions.

Psychotic reactions, including suicidal ideation/attempts, have been reported in patients taking fluoroquinolones, including levofloxacin, sometimes after a single dose. If such reactions develop, treatment with levofloxacin should be discontinued and appropriate therapy should be prescribed. The drug should be prescribed with caution to patients with psychosis or patients with a history of mental illness (see Precautions).

Visual impairment.

If any visual impairment develops, immediate consultation with an ophthalmologist is necessary (see “Side effects”).

Effect on laboratory tests.

In patients taking levofloxacin, the determination of opiates in urine may lead to false-positive results, which should be confirmed by more specific methods.

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis

and subsequently lead to false negative results of the bacteriological diagnosis of tuberculosis.

Impact on the ability to drive vehicles or engage in other potentially hazardous activities.

Side effects of Tavanic®, such as dizziness or vertigo, drowsiness and visual disturbances (see section “Side effects”), may reduce psychomotor reactions and the ability to concentrate. This may pose a risk in situations where these abilities are of particular importance (for example, when driving a car, when servicing machinery, when performing work in an unstable position).

Nosological classification (ICD-10)

• A16 Respiratory tuberculosis, not confirmed bacteriologically or histologically
• A22 Anthrax
• A41.9 Septicemia, unspecified
• J01 Acute sinusitis
• J18 Pneumonia without specifying the pathogen
• J42 Chronic bronchitis, unspecified
• L08.9 Local infection of skin and subcutaneous tissue, unspecified
• N12 Tubulointerstitial nephritis, not specified as acute or chronic
• N39.0 Urinary tract infection without established location
• T88.9 Complication of surgical and therapeutic intervention, unspecified

Pharmacokinetics

Absorption. Levofloxacin is rapidly and almost completely absorbed after oral administration; food intake has little effect on its absorption. Absolute bioavailability when taken orally is 99–100%. After a single dose of 500 mg of levofloxacin, Cmax in blood plasma is reached within 1–2 hours and is (5.2 ± 1.2) mcg/ml. The pharmacokinetics of levofloxacin is linear in the dose range from 50 to 1000 mg. Css of levofloxacin in blood plasma when taking 500 mg of levofloxacin 1 or 2 times a day is achieved within 48 hours.

On the 10th day of oral administration of Tavanic® 500 mg 1 time per day, the Cmax of levofloxacin in the blood plasma was (5.7 ± 1.4) mcg/ml, and the Cmin of levofloxacin (concentration before taking the next dose) in the blood plasma was ( 0.5±0.2) µg/ml.

On the 10th day of oral administration of Tavanic® 500 mg 2 times a day, Cmax of levofloxacin in plasma was (7.8 ± 1.1) μg/ml, and Cmin was (3 ± 0.9) μg/ml.

Distribution. The binding to serum proteins is 30–40%. After a single and repeated dose of 500 mg of levofloxacin, the Vd of levofloxacin is on average 100 l, which indicates good penetration of levofloxacin into organs and tissues of the human body.

Penetration into the bronchial mucosa, epithelial lining fluid, alveolar macrophages. After a single oral dose of 500 mg of levofloxacin, the Cmax of levofloxacin in the bronchial mucosa and epithelial lining fluid was reached within 1 hour or 4 hours and amounted to 8.3 mcg/g and 10.8 mcg/ml, respectively, with penetration coefficients into the bronchial mucosa and epithelial lining fluid compared to plasma concentrations of 1.1–1.8 and 0.8–3, respectively.

After 5 days of oral administration of 500 mg levofloxacin, the mean concentrations of levofloxacin 4 hours after the last dose in the epithelial lining fluid were 9.94 μg/ml and in alveolar macrophages - 97.9 μg/ml.

Penetration into lung tissue. Cmax in lung tissue after oral administration of 500 mg of levofloxacin was approximately 11.3 mcg/g and was achieved 4-6 hours after dosing with penetration coefficients of 2-5 compared to plasma concentrations.

Penetration into alveolar fluid. After 3 days of taking 500 mg of levofloxacin 1 time or 2 times a day, the Cmax of levofloxacin in the alveolar fluid was 4 and 6.7 μg/ml, respectively, and was achieved 2–4 hours after dosing with a penetration coefficient of 1 compared with plasma concentrations blood.

Penetration into bone tissue. Levofloxacin penetrates well into cortical and cancellous bone tissue, both in the proximal and distal parts of the femur with a penetration coefficient (bone tissue/blood plasma) of 0.1–3. Cmax of levofloxacin in the cancellous bone tissue of the proximal femur after taking 500 mg of the drug orally was approximately 15.1 mcg/g (2 hours after dosing).

Penetration into the cerebrospinal fluid. Levofloxacin penetrates poorly into the cerebrospinal fluid.

Penetration into prostate tissue. After oral administration of 500 mg levofloxacin once daily for 3 days, the average concentration of levofloxacin in prostate tissue was 8.7 mcg/g, the average prostate/blood plasma concentration ratio was 1.84.

Concentrations in urine. Mean urinary concentrations 8 to 12 hours after oral doses of 150, 300, and 600 mg of levofloxacin were 44, 91, and 162 mcg/mL, respectively.

Metabolism. Levofloxacin is metabolized to a small extent (5% of the dose taken). Its metabolites are demethyllevofloxacin and N-oxidelevofloxacin, which are excreted by the kidneys. Levofloxacin is stereochemically stable and does not undergo chiral transformations.

Excretion. After oral administration, levofloxacin is eliminated from the blood plasma relatively slowly (T1/2 - 6-8 hours). Excretion is primarily through the kidneys (more than 85% of the dose taken). The total clearance of levofloxacin after a single dose of 500 mg was (175±29.2) ml/min.

There are no significant differences in the pharmacokinetics of levofloxacin when administered intravenously and orally, which confirms that oral administration and intravenous administration are interchangeable.

Pharmacokinetics in certain groups of patients. The pharmacokinetics of levofloxacin do not differ between men and women.

Pharmacokinetics in elderly patients do not differ from those in younger patients, with the exception of differences in pharmacokinetics associated with differences in creatinine clearance.

In renal failure, the pharmacokinetics of levofloxacin changes. As renal function deteriorates, renal excretion and renal clearance are reduced and the half-life is prolonged.

Pharmacokinetic parameters for renal failure after a single oral dose of 500 mg of Tavanic® are presented in the table.

Indications for the drug Tavanic®

Bacterial infections sensitive to levofloxacin in adults.

acute sinusitis;

exacerbation of chronic bronchitis;

community-acquired pneumonia;

uncomplicated urinary tract infections;

complicated urinary tract infections (including pyelonephritis);

chronic bacterial prostatitis;

infections of the skin and soft tissues;

comprehensive treatment of drug-resistant forms of tuberculosis;

prevention and treatment of anthrax through airborne transmission.

When using Tavanic®, official national recommendations for the proper use of antibacterial drugs, as well as the sensitivity of pathogenic microorganisms in a particular country, should be taken into account (see “Special Instructions”).

Compound