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

Tavanik® is a synthetic broad-spectrum antibacterial agent 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 ≥7 7 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 β+/β- (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 removal of the antimicrobial from the 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 agents.

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:

After an intravenous 60-minute infusion of levofloxacin at a dose of 500 mg to healthy volunteers, the maximum plasma concentration (C_m_Oh) averaged 6.2 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 when 500 mg of levofloxacin is administered 1 or 2 times a day is reached within 48 hours.

On the 10th day of intravenous administration of the drug Tavanik® 500 mg once a day C_m_Ohlevofloxacin was 6.4 + 0.8 μg / ml, and the minimum concentration of levofloxacin (concentration before administration of the next dose) in blood plasma (C_m_Oh) was 0.6 + 0.2 μg / ml.

On the 10th day of intravenous administration of the drug Tavanik® 500 mg twice a day C_m_Ohlevofloxacin was 7.9 + 1.1 μg / ml, a C_min was 2.3 + 0.5 μg / ml.

Distribution

The connection with serum proteins is 30-40%. The volume of distribution of levofloxacin averages 100 l after single and repeated intravenous administration of 500 mg, 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

Levofloxacin penetrates well into the bronchial mucosa, epithelial lining fluid, alveolar macrophages with penetration coefficients in the bronchial mucosa and epithelial lining fluid, compared with the concentration in the blood plasma of 1.1-1.8 and 0.8-3, respectively .

Penetration into lung tissue

Levofloxacin well penetrates into the lung tissue with penetration factors of 2-5, compared with the concentration in the blood plasma.

Penetration into the alveolar fluid

Levofloxacin well penetrates into the alveolar fluid with a coefficient of penetration of 1, compared with the concentrations in the blood plasma. When levofloxacin was administered 500 mg 1 or 2 times a day for 3 days, the maximum concentrations of levofloxacin in the alveolar fluid were achieved 2-4 hours after administration and were 4.0 and 6.7 μg / ml, respectively.

Penetration into bone tissue

Levofloxacin well penetrates into the cortical and spongy bone tissue, both in the proximal and distal femur with a coefficient of penetration (bone tissue / blood plasma) of 0.1-3.

Penetration into the cerebrospinal fluid

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Penetration into prostate tissue

Levofloxacin well penetrates into the prostate tissue (the average ratio of prostatic / plasma concentrations was 1.84).

Concentrations in the urine

In the urine, high concentrations of levofloxacin are created, several times higher than the concentration of levofloxacin in the blood plasma.

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 intravenous 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 administration 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 routes of 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.

Indications:

Bacterial infections sensitive to levofloxacin in adults:

community acquired pneumonia;

complicated urinary tract infections (including pyelonephritis); uncomplicated urinary tract infections;

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 Tawanic®, official national recommendations for the proper use of antibacterial drugs, and the sensitivity of pathogens 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.

Lesions tendons when using fluoroquinolones history. Pseudo-paralytic myasthenia gravis (myasthenia gravis) (see the sections "Side effect", "Special instructions").

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 convulsions [in patients with previous central nervous system (CNS) lesions, patients taking concomitant medications that lower the threshold for convulsive brain readiness, 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 mandatory control of kidney function, as well as correction of the dosing regimen, see section "Method of administration and dose").

In patients with known risk factors for lengthening the interval QT: in patients the elderly; in female patients, in patients with uncorrected electrolyte disorders (with hypokalemia, hypomagnesemia); with the syndrome congenital lengthening interval QT; with heart disease (cardiac insufficiency, myocardial infarction, bradycardia); with simultaneous admission medicines capable of lengthening the interval QT (antiarrhythmic class facilities IA and III, tricyclic antidepressants, macrolides, neuroleptics) (see sections "Overdose", "Interaction with other drugs", "Special instructions"),

- In patients with diabetes mellitus receiving treatment with 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 section "Special instructions").

Pregnancy and lactation:Tavanic® is contraindicated for use in pregnant and lactating women.

Dosing and Administration:

Dosing regimen 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. As with other antibiotics,treatment with Tavanic® is recommended to continue for at least 48-78 hours after the normalization of body temperature or reliable eradication of the pathogen.

Treatment with Tavanic® should not be interrupted or terminated prematurely without a doctor's instructions.

Depending on the patient's condition, after a few days of treatment, you can switch from intravenous infusion to taking the same dose of the drug in tablets (because the bioavailability of levofloxacin when taking Tavanic® tablets is 99-100%) (see "Pharmacokinetics ").

If the medication is accidentally missed, the missed dose should be introduced as soon as possible and then continue to inject Tavanic® according to the recommended dosing regimen.

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

- Community-acquired pneumonia: 500 mg of levofloxacin 1-2 times a day

(respectively a daily dose of 500-1000 mg levofloxacin) - 7-14 days.

Complicated urinary tract infections: 500 mg of levofloxacin once a day (respectively, the daily dose of 500 mg of levofloxacin) - 7-14 days.

Pyelonephritis: 500 mg of levofloxacin once a day (respectively, the daily dose of 500 mg of levofloxacin) is 7-10 days.

Uncomplicated urinary tract infections: 250 mg of levofloxacin once a day (respectively a daily dose of 250 mg of levofloxacin) - 3 days.

- Chronic bacterial prostatitis: 500 mg of levofloxacin once a day (corresponding to a daily dose of 500 mg of levofloxacin) is 28 days;

Infections of skin and soft tissues: 500 mg of levofloxacin 1-2 times a day (respectively, the daily dose of 500-1000 mg of levofloxacin) - 7-14 days. Complex treatment of drug-resistant forms of tuberculosis: 500 mg of levofloxacin 1-2 times a day (respectively, the daily dose of 500-1000 mg of levofloxacin) - up to 3 months.

Prevention and treatment of anthrax during airborne infection: 500 mg of levofloxacin once a day (respectively, the daily dose of 500 mg of levofloxacin) - for up to 8 weeks.

Dosing regimen in patients with impaired renal function (CK <50 ml / min) Levofloxacin is excreted mainly through the kidneys, so when treating patients with impaired renal function, it is required to reduce the dose of the drug (see table below).

QC	Dosage regimen of Tavanic®
QC	Recommended dose for CK> 50 ml / min: 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	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	first dose: 500 mg then 125/12 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 125/24 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.

Mode of application

The infusion solution of Tavanic® is administered once or twice a day. Infusion solution of Tavanic®500 mg is injected SLOWLY intravenously drip.Duration of infusion of 1 vial of Tawanik drug solution^® 500 mg (100 ml with 500 mg levofloxacin) should be at least 60 minutes, in the case of half-bottle administration (50 ml with 250 mg levofloxacin), the infusion should last at least 30 minutes (see section "Special instructions"),

Tavanik^®, infusion solution, 500 mg is compatible with the following infusion solutions: 0.9% sodium chloride solution, 5% dextrose solution, 2.5% Ringer's dextrose solution, combined solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).

Drug solution Tavanik^® 500 mg should not be mixed with heparin or solutions that have an alkaline reaction (eg sodium bicarbonate solution).

After removing the vial from the cardboard bundle, the infusion solution can be stored without light protection for more than 3 days under room lighting!

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 elements in the peripheral blood), agranulocytosis (absence or sharp decrease in the number of granulocytes in the 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 developeven 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 data from toxicological studies on animals, the most important expected symptoms of an acute overdose of Tavanic® are central nervous system symptoms (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 erosion of the mucous membrane of the gastrointestinal tract.In clinico-pharmacological studies, carried out with doses of levofloxacin exceeding the therapeutic ones, the elongation of the interval QT.

Treatment of overdose

In case of an overdose, careful monitoring of the patient, including ECG monitoring, is required. Treatment is symptomatic. Levofloxacin is not excreted by dialysis (hemodialysis, peritoneal dialysis and continuous ambulatory peritoneal dialysis). There is no specific antidote.

Interaction:

Interactions requiring caution

With 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 vitamins K)

In patients who took levofloxacin in combination with indirect anticoagulants (for example, 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.

FROM probenecid and cimetidine

With the simultaneous use of drugs that disrupt renal tubular secretion, such as probenecid and cimetidine, and levofloxacin should be used with caution, 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 the half-life of 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.

With medications that extend the interval QT

Levofloxacin, like other fluoroquinolones, should be used with caution in patients taking drugs that extend the interval 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 calcium carbonate, 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.

Duration of infusion

It should be strictly adhered to the recommended duration of administration, which should be at least 60 min (for 100 ml infusion solution) or 30 min (for 50 ml solution). The experience with levofloxacin shows that during the infusion, there can be increased heart rate and transient decrease in blood pressure. In rare cases, there may be vascular collapse.If there is a marked decrease in blood pressure during the infusion of levofloxacin, the infusion is immediately stopped.

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 concurrently taking medications that lower the threshold for convulsive brain readiness, such as fenbufen and other non-steroidal anti-inflammatory drugs similar to it, or other drugs that lower the threshold of convulsive readiness, 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, for example, providing him with sufficient immobilization (see the sections "Contraindications" and "Side effect").

Hypersensitivity reactions

Levofloxacin can cause serious, potentially fatal hypersensitivity reactions (angioedema, anaphylactic shock) (see "Side effect" section). Patients should immediately stop the injection and consult a doctor.

Severe bullous reactions

When taking levofloxacin, cases of severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (see Fig.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 required mandatory monitoring of kidney function, 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 p.See section "Dosing and Administration").

Prevention of the development of photosensitization reactions

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

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 elderly 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 concomitantly 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", "Overdose" and "Interaction with other medicinal products").

Patients with deficiency of glucose-6-phosphate dehydrogenase

In patients with latent or manifested deficiency glucose-6-phosphate dehydrogenase has 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, with the use of levofloxacin, cases of hyperglycaemia and hypoglycemia have been observed, especially in patients with diabetes mellitus, receiving concurrent treatment with oral hypoglycemic drugs (eg, glibenclamide) or 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 a neuromuscular blocking 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).

Prevention and treatment of anthrax in case of airborne infection

The use of levofloxacin in humans according to this indication is based on data on sensitivity to it Bacillus anthracis, received in in vitro studies and 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 rare cases progressed to the development of suicidal thoughts and behavioral disorders with self-harm (sometimes after the introduction of a single dose of levofloxacin).With the development of such reactions, treatment with levofloxacin should be discontinued and appropriate treatment should be 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 required (see the "Side effect" section).

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,when performing work in an unstable situation).

Form release / dosage:

Solution for infusions 5 mg / ml.

Packaging:

For 100 ml of the drug in a colorless glass bottle (type I).

The bottle is sealed with a rubber stopper, crimped with an aluminum cap and covered with a protective plastic lid.

1 bottle with instructions for use in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:П N012242 / 02

Date of registration:03.08.2011

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

Manufacturer: & nbsp

SANOFI-AVENTIS Deutschland, GmbH Germany

Representation: & nbspSanofi Aventis GroupSanofi Aventis Group

Information update date: & nbsp04.10.2015

Illustrated instructions

Instructions

Tavanic® (Tavanic®)