Tavanik - instructions for use, dose, side effects, contraindications

Excipients: hypromellose - 5,400 mg, crospovidone - 7,000 mg, microcrystalline cellulose - 33,870 mg; sodium stearyl fumarate - 5,000 mg; film sheath: (E 171) -1,358 mg, talc 0.407 mg, ferric oxide red (E 172) 0.007 mg, and iron oxide yellow (E 172) 0.007 mg.

One Tavanic® 500 mg tablet contains:

Active substance: levofloxacin - 500,000 mg (corresponding to 512,460 mg levofloxacin hemihydrate);

Excipients: hypromellose - 10,800 mg, crospovidone - 14,000 mg, microcrystalline cellulose - 67,740 mg; sodium stearyl fumarate - 10,000 mg; film sheath: (E 171) -2.716 mg, talc 0.815 mg, iron oxide red (E 172) 0.014 mg, and iron oxide yellow (E 172) 0.014 mg.

Description:Oblong biconvex tablets with a separation groove on both sides, covered with a film coat of pale yellowish pink color.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A Fluoroquinolones

J.01.M.A.12 Levofloxacin

Pharmacodynamics:

Tavanik® - a synthetic antibacterial preparation of a wide spectrumactions from the group of fluoroquinolones, containing as an active substance levofloxacin - the left-handed isomer of ofloxacin.

Levofloxacin blocks DNA gyrase and topoisomerase IV, disrupts supercoiling and cross-linking of DNA gaps, inhibits DNA synthesis, causes profound morphological changes in the cytoplasm, cell wall and membranes of microbial cells. Levofloxacin active against most strains of microorganisms, as in conditions in vitro, and in vivo.

In vitro

Sensitive microorganisms (MPC ≤2 mg / L, inhibition zone ≥17 mm)

- Aerobic Gram-positive microorganisms: Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus faecalis, Enterococcus spp., Listeria monocytogenes, Staphylococcus coagulase-negative methi-S(I) [coagulase-negative methicillin-sensitive / -modern sensitive]] , Staphylococcus aureus methi-S (methicillin-sensitive), Staphylococcus epidermidis methi-S (methicillin-sensitive), Staphylococcus spp. CNS (coagulase-negative), Streptococci group C and G, Streptococcus agalactiae, Streptococcus pneumoniae peni I/S/R (penicillin-moderately sensitive / -sensitive / -resistant), Streptococcus pyogenes, Viridans streptococci peni-S/R (penicillin-sensitive /- resistant).

- Aerobic Gram-negative microorganisms: Acinetobacter baumannii, Acinetobacter spp., Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter cloacae, Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S/R (ampicillin-sensitive / -resistant), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella spp., Moraxella catarrhalis D + / D- (producing and non-producing beta-lactamases), Morganella morganii, Neisseria gonorrhoeae non PPNG/PPNG (non-producing and producing penicillinase), Neisseria meningitidis, Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida, Pasteurella spp., Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Providencia spp., Pseudomonas aeruginosa (hospital infections caused by Pseudomonas aeruginosa, may require combined treatment), Pseudomonas spp., Salmonella spp., Serratia marcescens, Serratia spp.

- Anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus, Propionibacterium spp., Veillonella spp.

- Other microorganisms: Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Legionella spp., Mycobacterium spp., Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

Moderately sensitive microorganisms (IPC = 4 mg / l; zone of inhibition 16-14 mm)

- Aerobic Gram-positive microorganisms: Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis methi-R (methicillin-resistant), Staphylococcus haemolyticus methi-R (methicillin-resistant).

- Aerobic Gram-negative microorganisms: Campylobacter jejuni/coli.

- Anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

Resistant to levofloxacin microorganisms (MIC of ≥8 mg / L, inhibition zone ≤13 mm)

- Aerobic Gram-positive microorganisms: Staphylococcus aureus methi-R (methicillin-resistant), Staphylococcus coagulase-negative methi-R (coagulase-negative methicillin-resistant).

- Aerobic Gram-negative microorganisms: Alcaligenes xylosoxidans.

- Anaerobic microorganisms: Bacteroides thetaiotaomicron.

- Other microorganisms: Mycobacterium avium.

Resistance

Resistance to levofloxacin develops as a result of a phased process of mutations of genes encoding both topoisomerases of type II: DNA-gyrase and topoisomerase IV. Other mechanisms of resistance, such as the mechanism of influence on the penetration barriers of a microbial cell (a mechanism characteristic of Pseudomonas aeruginosa) and the mechanism of efflux (active excretion of an antimicrobial agent from a microbial cell), can also reduce the sensitivity of microorganisms to levofloxacin.

Due to the peculiarities of the mechanism of action of levofloxacin, there is usually no cross-resistance between levofloxacin and other antimicrobial means.

Clinical efficacy (effectiveness in clinical trials in the treatment of infections caused by the microorganisms listed below)

Aerobic Gram-positive microorganisms: Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes.

Aerobic Gram-negative microorganisms: Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella (Branhamella) catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens.

Other: Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae.

Pharmacokinetics:

Absorption

Levofloxacin is quickly and almost completely absorbed after ingestion, eating has little effect on its absorption. Absolute bioavailability with oral administration is 99-100%. After a single dose of 500 mg of levofloxacin, the maximum concentration in the blood plasma (C_m_Oh) is achieved within 1-2 hours and is 5.2 + 1.2 μg / ml. The pharmacokinetics of levofloxacin is linear in the dosage range of 50 to 1000 mg. The equilibrium state of the concentration of levofloxacin in blood plasma with the intake of 500 mg of levofloxacin 1 or 2 times a day is reached within 48 hours.

On the 10th day of taking Tavanik® 500 mg once a day C_m_Oh levofloxacin was 5.7 + 1.4 μg / ml, and the minimum concentration of levofloxacin (concentration before taking the next dose) (C_m_Oh) in the blood plasma was 0.5 + 0.2 μg / ml.

On the 10th day of taking Tavanik® 500 mg twice a day C_m_Oh was 7.8 + 1.1 μg / ml, a C_min - 3.0 + 0.9 μg / ml.

Distribution

The connection with serum proteins is 30-40%. After a single and repeated administration of 500 mg of levofloxacin, the volume of distribution of levofloxacin is, on the average, 100 liters, which indicates a good penetration of levofloxacin into the organs and tissues of the human body.

Penetration into the bronchial mucosa, epithelial lining fluid, alveolar macrophages

After a single oral administration of 500 mg of levofloxacin, the maximum concentrations of levofloxacin in the bronchial mucosa and epithelial lining fluid were achieved within 1 hour or 4 hours and were 8.3 μg / g and 10.8 μg / ml, respectively, with penetration coefficients in the bronchial mucosa and epithelial lining fluid, compared to the concentration in the blood plasma of 1.1-1.8 and 0.8-3, respectively.

After 5 days of ingestion with 500 mg of levofloxacin, the average concentrations of levofloxacin 4 hours after the last administration of the drug in the epithelial lining fluid were 9.94 μg / ml and in alveolar macrophages 97.9 μg / ml.

Penetration into lung tissue

Maximum concentrations in the lung tissue after oral administration of 500 mg of levofloxacin were approximately 11.3 μg / g and were achieved 4-6 hours after the drug was administered with penetration factors of 2-5, compared with the concentration in the blood plasma.

Penetration into the alveolar fluid

After 3 days of taking 500 mg of levofloxacin 1 or 2 times a day, the maximumconcentrations of levofloxacin in the alveolar fluid were achieved 2-4 hours after the administration of the drug and were 4.0 and 6.7 μg / ml, respectively, with a penetration factor of 1, compared with the concentrations in the blood plasma.

Penetration into bone tissue

Levofloxacin well penetrates into the cortical and spongy bone tissue, both in the proximal and distal parts of the femur, with a coefficient of penetration (bone tissue / blood plasma) of 0.1-3. The maximum concentrations of levofloxacin in the spongy bone of the proximal femur after taking 500 mg of the oral preparation were approximately 15.1 μg / g (2 hours after the drug was administered).

Penetration into the cerebrospinal fluid

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Penetration into prostate tissue

After oral administration of 500 mg of levofloxacin 1 time per day for 3 days, the average concentration of levofloxacin in the prostate tissue was 8.7 μg / g, the average ratio of prostatic / plasma concentrations was 1.84.

Concentrations in the urine

Average concentrations in the urine 8-12 hours after ingestion of 150, 300 and 600 mg of levofloxacin were 44 μg / ml, 91 μg / ml and 162 μg / ml, respectively.

Metabolism

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

Excretion

After oral administration levofloxacin relatively slowly excreted from the blood plasma (half-life (T1 / 2) - 6-8 hours). Excretion, mainly through the kidneys (more than 85% of the dose). 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 with its intravenous administration and ingestion, which confirms that oral and intravenous administration are interchangeable.

Pharmacokinetics in selected patient groups

The pharmacokinetics of levofloxacin in men and women do not differ.

Pharmacokinetics in elderly patients does not differ from that in young patients, except for differences in pharmacokinetics associated with differences in creatinine clearance (CC).

With renal failure, the pharmacokinetics of levofloxacin varies.As the kidney function worsens, excretion through the kidneys and kidney clearance (C1R) decrease, and T1 / 2 increases.

Pharmacokinetics in renal failure after a single oral intake of 500 mg of Tavanic®.

CK (ml / min)	<20	20-49	50-80
C1R (ml / min)	13	26	57
T1 / 2 (h)	35	27	9

Indications:

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;

for the comprehensive treatment of drug-resistant forms of tuberculosis;

prevention and treatment of anthrax during airborne infection.

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

Contraindications:

Hypersensitivity to levofloxacin or other quinolones, as well as to any of the excipients of Tavanic®.

Epilepsy.

Pseudo-paralytic myasthenia gravis (myasthenia gravis) (see the sections "Side effect", "Special instructions").

Lesions of tendons with a history of fluoroquinolones.

Children and adolescents under 18 years of age (due to the incompleteness of skeletal growth, since the risk of losing cartilage growth points can not be completely ruled out).

Pregnancy (can not completely exclude the risk of cartilage growth points in the fetus).

The period of breastfeeding (you can not completely exclude the risk of damage to the cartilage points of bone growth in the child).

Carefully:

In patients who are predisposed to developing seizures [in patients with previous central nervous system (CNS) lesions, patients who receive concomitant drugs that lower the threshold for seizure preparedness of the brain, such as fenbufen, theophylline] (see "Interaction with other drugs" "),

In patients with latent or manifested deficiency of glucose-6-phosphate dehydrogenase (increased risk of hemolytic reactions in the treatment of quinolones).

In patients with impaired renal function (mandatory monitoring of kidney function, as well as correction of the dosing regimen,See section "Dosing and Administration").

In patients with known risk factors for lengthening the interval QT: in elderly patients; in female patients, in patients with uncorrected electrolyte disorders (hypokalemia, hypomagnesemia); with the syndrome of congenital lengthening of the interval QT; with diseases of the heart (heart failure, myocardial infarction, bradycardia); while taking medications that can lengthen the interval QT (antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, neuroleptics) (see sections "Overdose", "Interaction with other drugs", "Special instructions"),

In patients with diabetes mellitus receiving oral hypoglycemic drugs, for example, glibenclamide or insulin preparations (the risk of developing hypoglycemia increases).

In patients with severe adverse reactions to other fluoroquinolones, such as severe neurologic reactions (increased risk of similar undesirable reactions with levofloxacin).

In patients with psychoses or in patients with a history of mental illness (see p.section "Special instructions").

Pregnancy and lactation:

Levofloxacin is contraindicated in pregnant and lactating women.

Dosing and Administration:

Mode of application

Tablets Tavanic® 250 mg or 500 mg are taken orally once or twice a day. Tablets should be swallowed without chewing and drinking with a sufficient amount of liquid (0.5 to 1 cup). If necessary, the tablets can be broken on the separating groove.

The drug can be taken before meals or at any time between meals, as eating does not affect the absorption of the drug (see section "Pharmacokinetics").

The drug should be taken at least 2 hours before or 2 hours after taking drugs containing magnesium and / or aluminum, iron, zinc, or sucralfate (see section "Interaction with other drugs").

Given that the bioavailability of levofloxacin when taking Tavanic® in tablets is 99-100%, in the case of transfer of the patient from intravenous infusion of the drug Tavanik® on taking tablets should be continued treatment in the same dose that was used for intravenous infusion (see section "Pharmacokinetics").

Missing one or more doses of the drug

If you accidentally missed taking the drug, you should, as soon as possible, take another dose and continue to take Tavanic® according to the recommended its dosage regimen.

Doses and duration of treatment

Dosing regimen is determined by the nature and severity of the infection, as well as the suspected pathogen susceptibility. Duration of treatment varies depending on the course of the disease.

The recommended dosing regimen and duration of treatment in patients with normal renal function (CK> 50 mL / min)

- Acute sinusitis: 2 tablets Tavanik® 250 mg or 1 tablet Tavanik® 500 mg once a day (respectively 500 mg levofloxacin) - 10-14 days.

Exacerbation of chronic bronchitis: 2 tablets Tavanik® 250 mg or 1 tablet Tavanik® 500 mg once a day (respectively 500 mg levofloxacin) - 7-10 days.

Community-acquired pneumonia: 2 tablets Tavanik® 250 mg or 1 tablet Tavanik® 500 mg 1-2 times a day (respectively, 500-1000 mg levofloxacin) - 7-14 days.

- Uncomplicated urinary tract infections: 1 tablet Tavanik® 250 mg once a day (respectively 250 mg levofloxacin) - 3 days.

Complicated urinary tract infections: 2 tablets Tavanik® 250 mg once a day or 1 tablet Tavanik® 500 mg once a day (respectively 500 mg levofloxacin) - 7-14 days.

Pyelonephritis: 2 tablets Tavanik® 250 mg once a day or 1 tablet Tavanik® 500 mg once a day (respectively 500 mg levofloxacin) - 7-10 days.

Chronic bacterial prostatitis: 2 tablets Tavanik® 250 mg or 1 tablet Tavanik® 500 mg once a day (respectively 500 mg levofloxacin) - 28 days.

Infections of skin and soft tissues: 2 tablets Tavanik® 250 mg or 1 tablet Tavanik® 500 mg 1-2 times a day (respectively, 500-1000 mg levofloxacin) - 7-14 days.

Complex treatment of drug-resistant forms of tuberculosis: 1 tablet Tavanik® 500 mg 1-2 times a day (respectively, 500-1000 mg levofloxacin) - up to 3 months.

Prevention and treatment of anthrax during airborne infection: 2 tablets Tavanik® 250 mg or 1 tablet Tavanik® 500 mg (respectively 500 mg levofloxacin) once a day for up to 8 weeks.

Dosing regimen in patients with impaired renal function (CK <50 ml / min)

Levofloxacin is excreted mainly by the kidneys, therefore, in the treatment of patients with impaired renal function, a dose reduction is required (see table below).

QC	Dosing regimen Tavanic® tablets
QC	The recommended dose for CK> 50 ml / min for 250 mg / 24 h	Recommended dose for CK> 50 ml / min: 500 mg / 24 h	Recommended dose for CK> 50 ml / min: 500 mg / 12 h
50-20 ml / min	the first dose: 250 mg then 125 mg / 24 h	the first dose: 500 mg then 250 mg / 24 h	the first dose: 500 mg then 250 mg / 12 h
19-10 ml / min	the first dose: 250 mg then 125 mg / 48 h	the first dose: 500 mg then 125 mg / 24 h	the first dose: 500 mg then 125 mg / 12 h
<10 ml / min (including hemodialysis and CAPD¹	the first dose: 250 mg then 125 mg / 48 h	the first dose: 500 mg then 125 mg / 24 h	the first dose: 500 mg then 125 mg / 24 h

¹ after hemodialysis or permanent ambulatory peritoneal dialysis (CAPD) does not require the introduction of additional doses.

Dosing regimen in patients with impaired hepatic function

If the liver function is not corrected, correction of the dosing regimen is not required, since levofloxacin only slightly metabolized in the liver.

Dosage regimen in elderly patients

For elderly patients, correction of the dosing regimen is not required, except for cases when the CK is reduced to 50 ml / min and below.

Side effects:

The following side effects are presented in accordance with the following gradations of their incidence: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000) (including individual messages); the frequency is unknown (it is not possible to determine the frequency of occurrence according to the available data).

Data obtained in clinical trials and in post-marketing use of the drug

Heart Disease

Rarely: sinus tachycardia, palpitation.

Frequency unknown (post-marketing data): interval lengthening QT, ventricular arrhythmias, ventricular tachycardia, ventricular pirouette tachycardia, which can lead to cardiac arrest (see sections "Overdose", "Special instructions").

Violations of the blood and lymphatic system

Infrequently: leukopenia (a decrease in the number of leukocytes in the peripheral blood), eosinophilia (an increase in the number of eosinophils in peripheral blood).

Rarely: neutropenia (a decrease in the number of neutrophils in peripheral blood), thrombocytopenia (a decrease in the number of platelets in the peripheral blood).

Frequency unknown (postmarketing data): pancytopenia (decrease in the number of all formed elements in the peripheral blood),agranulocytosis (absence or sharp decrease in the amount of granulocytes in peripheral blood), hemolytic anemia.

Disturbances from the nervous system

Often: headache, dizziness.

Infrequently: drowsiness, tremor, dysgeusia (perversion of taste).

Rarely: paresthesia, convulsions (cf. section "Special instructions").

Frequency unknown (postmarketing data): peripheral sensory neuropathy, peripheral sensory-motor neuropathy (see section "Special instructions"), dyskinesia, extrapyramidal disorders, agevzia (loss of taste sensations), parosmia (frustration of smell, especially subjective sense of smell, objectively absent), including loss of smell; fainting, benign intracranial hypertension.

Disturbances on the part of the organ of sight

Rarely: visual impairments, such as the vagueness of the visible image.

Frequency unknown (postmarketing data): transient loss of vision, uveitis.

Hearing disorders and labyrinthine disorders

Infrequently: Vertigo (feeling of deflection or twisting or own body or surrounding objects).

Rarely: ringing in the ears.

Frequency unknown (postmarketing data): hearing loss, hearing loss.

Disturbances from the respiratory system, chest and mediastinal organs

Infrequently: dyspnea.

Frequency unknown (postmarketing data): bronchospasm, allergic pneumonitis.

Disorders from the gastrointestinal tract

Often: diarrhea, vomiting, nausea.

Infrequently: pain in the abdomen, indigestion, flatulence, constipation.

Frequency unknown (postmarketing data): hemorrhagic diarrhea, which in very rare cases can be a sign of enterocolitis, including pseudomembranous colitis (see section "Special instructions"), pancreatitis.

Disorders from the nochek and urinary tract

Infrequently: increased serum creatinine concentration.

Rarely: acute renal failure (eg, due to the development of interstitial nephritis).

Disturbances from the skin and subcutaneous tissues

Infrequently: rash, itching, hives, hyperhidrosis.

Frequency unknown (post-marketing data): toxic epidermal necrolysis, Stevens-Johnson syndrome, exudative erythema multiforme, photosensitivity reactions (hypersensitivity to solar and ultraviolet radiation) (see section "Special instructions"), leukocytoclastic vasculitis, stomatitis.

Reactions from the skin and mucous membranes can sometimes develop even after taking the first dose of the drug.

Disturbances from musculoskeletal system and connective tissue

Infrequently: arthralgia, myalgia.

Rarely: tendon damage, including tendonitis (eg Achilles tendon), muscle weakness, which can be especially dangerous in patients with pseudo-paralytic myasthenia (myasthenia gravis) (see section "Special instructions").

Frequency unknown (postmarketing data): rhabdomyolysis, tendon rupture (eg Achilles tendon This side effect can occur within 48 hours after the start of treatment and can be bilateral (see also section "Special instructions")) ligament rupture, muscle rupture, arthritis.

Disorders from the metabolism and nutrition

Infrequently: anorexia.

Rarely: hypoglycemia, especially in patients with diabetes mellitus (possible signs of hypoglycemia: "wolfish" appetite, nervousness, perspiration, trembling).

Frequency unknown: hyperglycemia, hypoglycemic coma (see section "Special instructions").

Infectious and parasitic diseases

Infrequently: fungal infections, the development of resistance of pathogenic microorganisms.

Vascular disorders

Rarely: lowering of blood pressure.

General disorders

Infrequently: asthenia.

Rarely: pyrexia (fever).

Frequency unknown: pain (including pain in the back, chest and extremities).

Immune system disorders

Rarely: angioedema.

Frequency unknown (postmarketing data): anaphylactic shock, anaphylactoid shock. Anaphylactic and anaphylactoid reactions can sometimes develop even after taking the first dose of the drug.

Disturbances from the liver and bile ducts

Often: an increase in the activity of "hepatic" enzymes in the blood (for example, alanine aminotransferase (ALT), aspartate aminotransferase (ACT)), increased activity of alkaline phosphatase (AP) and gamma-glutamyl transferase (GGT).

Infrequently: increasing the concentration of bilirubin in the blood.

Frequency unknown (post-marketing data): severe hepatic insufficiency,including cases of development of acute hepatic insufficiency, sometimes with fatal outcome, especially in patients with severe underlying disease (eg, in patients with sepsis) (see section "Special instructions"); hepatitis, jaundice.

Disorders of the psyche

Often: insomnia.

Infrequently: anxiety, confusion, confusion.

Rarely: mental disorders (eg, hallucinations, paranoia), depression, agitation (agitation), sleep disturbances, nightmares.

Frequency unknown (postmarketing data): mental disorders with behavioral disorders with self-harm, including suicidal thoughts and suicidal attempts.

Other possible unwanted effects, related to all fluoroquinolones

Rarely: Attacks of porphyria (a very rare metabolic disease) in patients with porphyria.

Overdose:

Overdose Symptoms

Based on the data obtained in toxicological studies conducted in animals, the most important expected symptoms of an acute overdose of Tavanic® are central nervous system (impaired consciousness, including confusion, dizziness and convulsions).

In the post-marketing use of the drug in overdose, there were effects from the central nervous system, including confusion, convulsions, hallucinations and tremors.

Perhaps the development of nausea and the occurrence of erosion of the mucous membrane of the gastrointestinal tract.

In clinico-pharmacological studies, conducted with doses of levofloxacin exceeding the therapeutic, there was an extension of the interval QT.

Treatment of overdose

In case of an overdose, careful monitoring of the patient, including monitoring the electrocardiogram, is required. Treatment is symptomatic. In the case of an acute overdose of Tavanic® tablets, gastric lavage and administration of antacids are indicated to protect the gastric mucosa. Levofloxacin is not excreted by dialysis (hemodialysis, peritoneal dialysis and continuous ambulatory peritoneal dialysis). There is no specific antidote.

Interaction:

Interactions requiring caution

With preparations containing magnesium, aluminum, iron and zinc, didanosine

Preparations containing divalent or trivalent cations,such as zinc or iron salts (medicines for the treatment of anemia), magnesium and / or aluminum-containing drugs (such as antacids), didanosine (only dosage forms containing aluminum or magnesium as a buffer), it is recommended to take at least 2 hours before or 2 hours after taking Tavanic® tablets.

Calcium salts have a minimal effect on the absorption of levofloxacin when ingested.

With sucralfate

The effect of Tavanic® is significantly weakened by the simultaneous use of sucralfate (a means to protect the gastric mucosa). Patients receiving levofloxacin and sucralfate, it is recommended to take sucralfate 2 hours after taking levofloxacin.

FROM theophylline, fenbufen, or similar drugs from a group of non-steroidal anti-inflammatory drugs that reduce the threshold of convulsive brain readiness

The pharmacokinetic interaction of levofloxacin with theophylline has not been revealed. However, with the simultaneous use of quinolones and theophylline, non-steroidal anti-inflammatory drugs and other drugs that reduce the threshold of convulsive brain readiness, there may be a marked decrease in the threshold of convulsive readiness of the brain.

The concentration of levofloxacin with simultaneous administration of fenbufen is only increased by 13%.

With indirect anticoagulants (antagonists of vitamin K)

In patients treated with levofloxacin in combination with indirect anticoagulants (eg, warfarin), prothrombin time / international normalized ratio and / or bleeding, including severe, increased. Therefore, with simultaneous use of indirect anticoagulants and levofloxacin, regular monitoring of blood clotting parameters is necessary.

With probenecid and cimetidine

With the simultaneous use of drugs that disrupt renal tubular secretion, such as probenecid and cimetidine, and levofloxacin, caution should be used, especially in patients with renal insufficiency. Removal (renal clearance) of levofloxacin is slowed by cimetidine by 24% and probenecid by 34%. It is unlikely that this can be of clinical significance in normal kidney function.

With cyclosporine

Levofloxacin increased T1 / 2 cyclosporine by 33%. Since this increase is clinically insignificant, correction of the dose of cyclosporine when it is used simultaneously with levofloxacin is not required.

With glucocorticosteroids

Simultaneous reception of glucocorticosteroids increases the risk of rupture of tendons.

FROM drugs that extend the interval QT

Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs that extend the range QT (for example, antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, neuroleptics).

Other

Conducted clinical and pharmacological studies to study the possible pharmacokinetic interactions of levofloxacin with digoxin, glibenclamide, ranitidine and warfarin showed that the pharmacokinetics of levofloxacin when used concomitantly with these drugs does not change sufficiently to make it clinically important.

Special instructions:

Hospital infections caused by Pseudomonas aeruginosa (Pseudomonas aeruginosa), may require combined treatment.

The prevalence of acquired resistance of the sown strains of microorganisms can vary depending on the geographic region and over time. In this regard, information about drug resistance in a particular country is required.For the treatment of severe infections or in the ineffectiveness of treatment, a microbiological diagnosis should be made, isolating the pathogen and determining its sensitivity to levofloxacin.

Methicillin-resistant golden streptococcus

There is a high probability that methicillin-resistant golden Staphylococcus will be resistant to fluoroquinolones, including levofloxacin. therefore levofloxacin It is not recommended for treatment of established or suspected infections caused by methicillin-resistant Staphylococcus aureus, in the case of if laboratory tests did not confirm the sensitivity of this microorganism to levofloxacin.

Patients who are predisposed to develop seizures

Like other quinolones, levofloxacin should be used with great care in patients with a predisposition to convulsions. Such patients include patients with previous lesions of the central nervous system, such as stroke, severe craniocerebral trauma; patients simultaneously receiving drugs that reduce the threshold of convulsive brain readiness, such as fenbufen and others similar non-steroidal anti-inflammatory drugs or other drugs that lower the threshold for convulsive alertness, such as theophylline (see section "Interaction with other drugs").

Pseudomembranous colitis

Developed during or after levofloxacin treatment, diarrhea, especially severe, persistent and / or with blood, may be a symptom of pseudomembranous colitis caused by Clostridium difficile. In case of suspected development of pseudomembranous colitis, treatment with levofloxacin should be stopped immediately and immediately begin specific antibiotic therapy (vancomycin, teicoplanin or metronidazole inside). Drugs that inhibit the intestinal peristalsis are contraindicated.

Tendonitis

Rarely observed tendonitis in the use of quinolones, including levofloxacin, can lead to the rupture of tendons, including the Achilles tendon. This side effect can develop within 48 hours after the start of treatment and can be bilateral. Older patients are more prone to tendonitis. The risk of rupture of tendons can increase with simultaneous administration of glucocorticosteroids.If suspected of tendonitis, Tavanic® should be discontinued immediately and appropriate treatment of the affected tendon should begin, for example, by ensuring sufficient immobilization (see the "Contraindications" and "Side effects" sections).

Hypersensitivity reactions

Levofloxacin can cause serious, potentially fatal, hypersensitivity reactions (angioedema, anaphylactic shock), even with the use of initial doses (see the "Side effect" section). Patients should immediately stop taking the drug and consult a doctor.

Severe bullous reactions

When taking levofloxacin, there were cases of severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (see section "Side effect"). In case of any reactions from the skin or mucous membranes, the patient should immediately consult a doctor and do not continue treatment until his consultation.

Disturbances from the liver and bile ducts

There have been reports of hepatic necrosis, including the development of fatal liver failure with levofloxacin, mainly in patients with severe underlying diseases, for example, with sepsis (see section "Side effect"). Patients should be warned about the need for discontinuation of treatment and urgent medical attention in case of signs and symptoms of liver damage such as anorexia, jaundice, darkening of urine, pruritus and abdominal pain.

Patients with renal insufficiency

As levofloxacin excreted mainly through the kidneys, in patients with impaired renal function, mandatory monitoring of kidney function is required, as well as correction of the dosing regimen (see section "Method of administration and dose"). In the treatment of elderly patients, it should be borne in mind that patients of this group often have impaired renal function (see section "Method of administration and dose").

Prevention of the development of photosensitization reactions

Although photosensitization is very rare in the use of levofloxacin, it is not recommended for patients to be prevented from developing during treatment and to undergo, without special need for strong sunlight or artificial ultraviolet irradiation (for example, to visit the solarium) for 48 hours after the end of treatment with levofloxacin.

Superinfection

As with the use of other antibiotics, the use of levofloxacin, especially for a long time, can lead to increased reproduction of insensitive microorganisms (bacteria and fungi), which can cause changes in microflora, which is normally present in humans. As a result, superinfection may develop. Therefore, during the treatment, it is mandatory to reevaluate the patient's condition, and, if developed during the treatment of superinfection, appropriate measures should be taken.

Interval lengthening QT

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

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

Elderly patients and female patients may be more sensitive to drugs that extend the interval QT. Therefore, care should be taken to use fluoroquinolones, including levofloxacin (see the sections "With caution", "Method of administration and dose", "Side effect" and "Overdose" "Interaction with other drugs").

Patients with deficiency of glucose-6-phosphate dehydrogenase

Patients with a latent or manifested deficiency of glucose-6-phosphate dehydrogenase have a predisposition to hemolytic reactions in the treatment with quinolones, which should be taken into account when treating levofloxacin.

Hypo-and hyperglycemia (dysglycemia)

As with the use of other quinolones, when levofloxacin was used, cases of hyperglycaemia and hypoglycemia were observed, usually in patients with diabetes mellitus, who received treatment with oral hypoglycemic drugs (eg, glibenclamide) or with insulin preparations. There have been reports of cases of hypoglycemic coma.Patients with diabetes are required to monitor the concentration of glucose in the blood (see section "Side effect").

Peripheral Neuropathy

In patients taking fluoroquinolones, including levofloxacin, sensory and sensory-motor peripheral neuropathy was noted, the onset of which can be rapid. If the patient has symptoms of neuropathy, the use of levofloxacin should be discontinued. This minimizes the possible risk of irreversible changes.

Exacerbation of pseudo-paralytic myasthenia gravis (myasthenia gravis)

Fluoroquinolones, including levofloxacin, are characterized by neuromuscular blocking of activity and may increase muscle weakness in patients with pseudo-paralytic myasthenia gravis. In the postmarketing period, adverse reactions were observed, including pulmonary insufficiency, requiring artificial ventilation, and fatal outcome, which were associated with the use of fluoroquinolones in patients with pseudo-paralytic myasthenia gravis. The use of levofloxacin in a patient with an established diagnosis of pseudo-paralytic myasthenia gravis is not recommended (see the "Side effect" section).

Application in the airborne route of infection with anthrax

The use of levofloxacin in humans according to this indication is based on data on sensitivity to it Bacillus anthracis, obtained in studies in vitro and in experimental studies conducted on animals, as well as on limited data on the use of levofloxacin in humans. The attending physicians should refer to national and / or international documents that reflect the common point of view on the treatment of anthrax.

Psychotic reactions

When using quinolones, including levofloxacin, reported on the development of psychotic reactions, which in very rare cases progressed to the development of suicidal thoughts and behavioral disorders with self-harm (sometimes after taking a single dose of levofloxacin (see the section "Side effect")). With the development of such reactions, treatment with levofloxacin should be discontinued and appropriate therapy prescribed. Caution should be used to prescribe the drug to patients with psychoses or patients who have a history of mental illness.

Visual disturbances

With the development of any visual impairment, an immediate consultation of the ophthalmologist is needed (see.section "Side effect").

Impact on laboratory tests

In patients receiving levofloxacin, the definition of opiates in urine can lead to false positive results, which should be confirmed by more specific methods.

Levofloxacin can inhibit growth Mycobacterium tuberculosis and lead in the future to false-negative results of a bacteriological diagnosis of tuberculosis.

Effect on the ability to drive transp. cf. and fur:

Such side effects of Tavanic® as dizziness or vertigo, drowsiness, and visual impairment (see the "Side effect" section) can reduce psychomotor reactions and the ability to concentrate. This can represent a certain risk in situations where these abilities are of particular importance (for example, when driving, servicing machines and mechanisms, performing work in an unstable position).

Form release / dosage:Tablets, film-coated, 250 mg, 500 mg.

Packaging:

Tablets, film-coated, 250 mg.

By 3, 5, 7 or 10 tablets in a blister of PVC / aluminum foil.

1 blister with instructions for use in a cardboard box.

Tablets, film-coated, 500 mg.

For 5, 7 or 10 tablets in a blister of PVC / aluminum foil.

1 blister with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

After the expiration date, the drug can not be used.

Terms of leave from pharmacies:On prescription

Registration number:П N012242 / 01

Date of registration:11.08.2011

The owner of the registration certificate:Sanofi-Aventis Deutschland GmbHSanofi-Aventis Deutschland GmbH Germany

Manufacturer: & nbsp

SANOFI WINTHROP INDUSTRIE France

Representation: & nbspSanofi Aventis GroupSanofi Aventis Group

Information update date: & nbsp04.10.2015

Illustrated instructions

Instructions

Tavanic® (Tavanic®)