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

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

Compound

Film-coated tablets	1 table
active substance:
levofloxacin	250 mg
(corresponds to 256.23 mg levofloxacin hemihydrate)
500 mg
(corresponds to 512.46 mg levofloxacin hemihydrate)
excipients: crospovidone - 7 mg/14 mg; hypromellose - 5.4 mg/10.8 mg; MCC - 33.87 mg/67.74 mg; sodium stearyl fumarate - 5 mg/10 mg
film shell: hypromellose - 5.433 mg/10.866 mg; macrogol 8000 - 0.288 mg/0.575 mg; talc - 0.407 mg/0.815 mg; titanium dioxide (E171) - 1.358 mg/2.716 mg; iron oxide red (E172) - 0.007 mg/0.014 mg; iron oxide yellow (E172) - 0.007 mg/0.014 mg

Pharmacodynamics

Tavanic® is a synthetic broad-spectrum antibacterial drug from the group of fluoroquinolones, containing levofloxacin, a levorotatory isomer of ofloxacin, as an active substance.

Levofloxacin blocks DNA gyrase and topoisomerase IV, disrupts supercoiling and cross-linking of DNA breaks, inhibits DNA synthesis, and causes profound morphological changes in the cytoplasm, cell wall and membranes of microbial cells.

Levofloxacin is active against most strains of microorganisms both in vitro and in vivo.

In vitro:

Sensitive microorganisms (MIC≤2 mg/ml; 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/moderately sensitive), Staphylococcus aureus methi-S, Staphylococcus epi dermidis methi -S, Staphylococcus spp (CNS), Streptococci groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae peni-S/I/R (penicillin-sensitive/moderately 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 (ampicil lean-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, Neisseria meningitidis, Pasteurella canis , Pasteurella dagmatis, Pasteuralla multocida, Pasteurella spp, Proteus mirabilis, Proteus vulgaris, Providencia Rettteri, Providencia Stuartii, Providencia spp, Pseuudomonas aerugin OSA (Hospital infections caused by Pseudomonas Aeruginosa may require combined treatment), Pseudomonas spp, Salmonella spp, serratia marceescens, 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, Ricketsia spp., Ureaplasma urealyticum.

Moderately sensitive microorganisms (MIC = 4 mg/l; inhibition zone - 16–14 mm):

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

Aerobic gram-negative microorganisms: Campylobacter jejuni/coli.

Anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

Levofloxacin-resistant microorganisms (MIC≥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 stepwise process of mutations in the genes encoding both type II topoisomerases: DNA gyrase and topoisomerase IV. Other resistance mechanisms, such as the mechanism of influencing the penetration barriers of the microbial cell (a mechanism characteristic of Pseudomonas aeruginosa) and the mechanism of efflux (active removal of the antimicrobial agent from the microbial cell), may also reduce the sensitivity of microorganisms to levofloxacin.

Due to the peculiarities of the mechanism of action of levofloxacin, cross-resistance between levofloxacin and other antimicrobial agents is not usually observed.

Clinical efficacy (effectiveness in clinical studies in the treatment of infections caused by the following microorganisms):

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.

Others: Chlamydia pneumoniae; Legionella pneumophila, Mycoplasma pneumoniae.

Tavanik tab.p.p.o.500mg No. 10

Indications

Treatment of infectious and inflammatory diseases caused by microorganisms sensitive to levofloxacin:

community-acquired pneumonia;
complicated urinary tract infections and pyelonephritis;
chronic bacterial prostatitis;
infections of the skin and soft tissues;
for complex treatment of drug-resistant forms of tuberculosis;
prevention and treatment of anthrax through airborne transmission.

For the treatment of the following infectious and inflammatory diseases, levofloxacin can be used as an alternative to other antimicrobial drugs:

acute sinusitis;
exacerbation of chronic bronchitis;
uncomplicated cystitis.

When using Tavanic®, official national recommendations for the proper use of antibacterial drugs, as well as the sensitivity of microorganisms in a particular country, should be taken into account.

pharmachologic effect

A synthetic broad-spectrum antibacterial drug from the group of fluoroquinolones, containing levofloxacin, a levorotatory isomer of ofloxacin, as an active substance. Levofloxacin blocks DNA gyrase and topoisomerase IV, disrupts supercoiling and cross-linking of DNA breaks, inhibits DNA synthesis, and causes profound morphological changes in the cytoplasm, cell wall and membranes of microbial cells.

Levofloxacin is active against most strains of microorganisms, both in vitro and in vivo.

In vitro sensitive (MIC ≤ 2 mg/ml; zone of inhibition ≥17 mm) aerobic gram-positive microorganisms:

Bacillus anthratis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus spp.
(including Enterococcus faecalis), Listeria monocytogenes, Staphylococcus spp. (coagulase-negative, methicillin-sensitive/methicillin-moderately sensitive strains), Staphylococcus aureus methi-S (methicillin-sensitive strains), Staphylococcus epidermidis methi-S (methicillin-sensitive strains), Staphylococcus spp. CNS (coagulase negative), Streptococcus spp. groups C and G (including Streptococcus agalactiae, Streptococcus pneumoniae peni I/S/R (penicillin-sensitive/moderately sensitive/resistant strains), Streptococcus pyogenes, Streptococcus viridans (penicillin-sensitive/resistant strains); aerobic gram-negative microorganisms :
Acinetobacter baumannii, Acinetobacter spp., Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter spp. (including Enterobacter cloacae, Enterobacter aerogenes), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S/R ( ampicillin-sensitive/resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (including Klebsiella oxytoca, Klebsiella pneumoniae), Moraxella catarrhalis β+/β- (strains producing and not producing β-lactamase), Morganella morganii , Neisseria gonnorrhoeae non PPNG/PPNG (penicillinase-producing and non-penicillinase-producing strains), Neisseria meningitidis, Pasteurella spp. (incl.
Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas spp. (hospital infections caused by Pseudomonas aeruginosa may require combination treatment), Salmonella spp., Serratia spp. (including Serratia marcescens); anaerobic microorganisms:
Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterum spp., Veilonella spp.;
other microorganisms:
Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Legionella spp., Mycobacterium spp. (including Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

Levofloxacin is moderately active (MIC = 4 mg/l; inhibition zone 16-14 mm) against aerobic gram-positive microorganisms:

Corynebacterium urealiticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis methi-R (methicillin-resistant strains), Staphylococcus haemolyticus methi-R (methicillin-resistant strains);
aerobic gram-negative microorganisms:
Campilobacter jejuni, Campilobacter coli;
anaerobic microorganisms:
Prevotella spp., Porphyromonas spp.

to levofoloxacin (MIC ≥ 8 mg/l; inhibition zone ≤ 13 mm):

Staphylococcus aureus methi-R (methicillin-resistant strains), Staphylococcus coagulase-negative methi-R (coagulase-negative methicillin-resistant strains);
aerobic gram-negative microorganisms:
Alcaligenes xylosoxidans;
anaerobic microorganisms:
Bacteroides thetaiotaomicron;
other microorganisms:
Mycobacterium avium.

Clinical effectiveness

In clinical studies, the drug was effective in treating infections caused by the following microorganisms.

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, Moraxela (Branhamella) catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens.

Other:

Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae.

Resistance

Due to the peculiarities of the mechanism of action of levofloxacin, cross-resistance between levofloxacin and other antimicrobial agents is not usually observed.

Drug interactions

Combinations requiring caution

It is recommended to take at least than 2 hours before or 2 hours after taking Tavanic® tablets.

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

The effect of Tavanic® is significantly weakened by simultaneous use of sucralfate. For patients receiving levofloxacin and sucralfate, it is recommended that sucralfate be taken 2 hours after taking levofloxacin.

No pharmacokinetic interaction of levofloxacin with theophylline was detected. The concentration of levofloxacin with simultaneous use of fenbufen increases only by 13%. However, with the simultaneous administration of quinolones and theophylline, NSAIDs and other drugs that reduce the threshold of convulsive readiness of the brain, a pronounced decrease in the threshold of convulsive readiness of the brain is possible.

In patients receiving levofloxacin in combination with indirect anticoagulants (for example, warfarin), an increase in prothrombin time/INR and/or bleeding was observed, incl. and heavy. Therefore, with the simultaneous use of indirect anticoagulants and levofloxacin, regular monitoring of blood coagulation parameters is necessary.

When simultaneous use of levofloxacin and drugs that interfere with the renal tubular secretion of levofloxacin, such as probenecid and cimetidine, caution should be exercised, especially in patients with renal failure. The elimination (renal clearance) of levofloxacin is slowed down by cimetidine by 24% and probenecid by 34%. This is unlikely to be of clinical significance if renal function is normal.

Levofloxacin increased T1/2 of cyclosporine by 33%. Because this increase is clinically insignificant; no dose adjustment of cyclosporine is required when used concomitantly with levofloxacin.

Concomitant use of corticosteroids increases the risk of tendon rupture.

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

Other combinations

Clinical and pharmacological studies conducted to study the possible pharmacokinetic interaction of levofloxacin with digoxin, glibenclamide, ranitidine and warfarin showed that the pharmacokinetics of levofloxacin when used simultaneously with these drugs does not change sufficiently to be of clinical significance.

Dosage regimen

The drug is taken orally at 250 or 500 mg 1 or 2 times a day. The tablets should be swallowed without chewing and washed down with a sufficient amount of liquid (0.5 to 1 glass). If necessary, tablets can be broken along the dividing groove.

The drug can be taken before meals or at any time between meals, because. food intake does not affect the absorption of the drug.

The drug should be taken at least 2 hours before or 2 hours after taking antacids containing magnesium and/or aluminum, zinc, iron salts or taking sucralfate.

Considering that the bioavailability of levofloxacin when using the drug Tavanik® in tablets is 99-100%, if the patient is transferred from IV administration of the drug to taking tablets, treatment should be continued at the same dose that was used with IV infusion.

The dosage regimen is determined by the nature and severity of the infection, as well as the sensitivity of the suspected pathogen. The duration of treatment varies depending on the course of the disease.

Patients with normal renal function (creatinine clearance >50 ml/min)

The following dosage regimen and duration of treatment are recommended.

Acute sinusitis:

2 tablets each 250 mg or 1 tablet. 500 mg 1 time/day (respectively 500 mg of levofloxacin) - 10-14 days.

Exacerbation of chronic bronchitis:

2 tablets each 250 mg or 1 tablet. 500 mg 1 time/day (respectively 500 mg of levofloxacin) - 7-10 days.

Community-acquired pneumonia:

2 tablets each 250 mg or 1 tablet. 500 mg 1-2 times/day (respectively 500-1000 mg of levofloxacin) - 7-14 days.

Complicated urinary tract infections:

2 tablets each 250 mg 1 time/day (corresponding to 250 mg levofloxacin) or 1 tablet. 500 mg 1 time / day (respectively 500 mg of levofloxacin) - 7-14 days.

Uncomplicated cystitis:

1 tab. 250 mg 1 time / day (respectively 250 mg of levofloxacin) - 3 days.

Pyelonephritis:

2 tablets each 250 mg 1 time/day or 1 tablet. 500 mg 1 time / day (respectively 500 mg of levofloxacin) - 7-10 days.

Chronic bacterial prostatitis:

2 tablets each 250 mg or 1 tablet. 500 mg 1 time / day (respectively 500 mg of levofloxacin) - 28 days.

Skin and soft tissue infections:

2 tablets each 250 mg or 1 tablet. 500 mg 1-2 times/day (respectively 500-1000 mg of levofloxacin) - 7-14 days.

As part of complex therapy for drug-resistant forms of tuberculosis:

1 tab. 500 mg 1-2 times/day (respectively 500-1000 mg of levofloxacin) - up to 3 months.

Prevention and treatment of anthrax through airborne transmission:

2 tablets each 250 mg or 1 tablet. 500 mg (respectively 500 mg of levofloxacin) 1 time / day - up to 8 weeks.

Patients with impaired renal function (creatinine clearance ≤50 ml/min)

correction of the dosage regimen is required depending on the CC value, because Levofloxacin is primarily excreted by the kidneys.

QC	Recommended dose
>50 ml/min	250 mg/24 h	500 mg/24 h	500 mg/12 h
50-20 ml/min	first dose 250 mg then 125 mg/24 h	first dose 500 mg then 250 mg/24 h	first dose 500 mg then 250 mg/12 h
19-10 ml/min	first dose 250 mg then 125 mg/48 h	first dose 500 mg then 125 mg/24 h	first dose 500 mg then 125 mg/12 h
*)	first dose 250 mg then 125 mg/48 h	first dose 500 mg then 125 mg/24 h	first dose 500 mg then 125 mg/24 h

* No additional doses are required after hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

In case of liver dysfunction

no dosage adjustment is required since levofloxacin is only slightly metabolized in the liver.

For elderly patients

no adjustment of the dosage regimen is required, except in cases where the CC is reduced to 50 ml/min or lower.

Skipping a drug dose

If you accidentally miss taking the drug, you must take the tablet as soon as possible and then continue taking Tavanic® according to the recommended dosage regimen.

Overdose

Symptoms:

Based on data obtained from toxicological studies conducted in animals, the most important expected symptoms of an acute overdose of Tavanic® are central nervous system symptoms (impaired consciousness, including confusion, dizziness and convulsions). During post-marketing use of the drug in overdose, CNS effects have been observed, including confusion, convulsions, hallucinations and tremor. Nausea and erosion of the gastrointestinal mucosa are possible. In clinical and pharmacological studies conducted with doses of levofloxacin exceeding therapeutic levels, prolongation of the QT interval was shown.

Treatment:

carrying out symptomatic therapy, careful monitoring of the patient, including ECG monitoring. In case of acute overdose of Tavanic® tablets, gastric lavage and administration of antacids are indicated to protect the gastric mucosa. Levofloxacin is not eliminated by dialysis (hemodialysis, peritoneal dialysis and continuous peritoneal dialysis). There is no specific antidote.

Contraindications for use

epilepsy;
pseudoparalytic myasthenia gravis (myasthenia gravis);
tendon lesions associated with a history of fluoroquinolones;
childhood and adolescence up to 18 years of age (due to incomplete skeletal growth, since the risk of damage to cartilaginous growth zones cannot be completely excluded);
pregnancy (the risk of damage to the cartilaginous growth zones of the fetus cannot be completely excluded);
period of breastfeeding (the risk of damage to the cartilaginous growth zones of bones in a child cannot be completely eliminated);
hypersensitivity to levofloxacin or other quinolones, as well as to any of the excipients of the drug.

Carefully:

in patients predisposed to the development of seizures (in patients with previous lesions of the central nervous system, in patients simultaneously receiving drugs that lower the threshold of convulsive activity of the brain, such as fenbufen, theophylline);
in patients with latent or manifest deficiency of glucose-6-phosphate dehydrogenase (increased risk of hemolytic reactions when treated with quinolones);
in patients with impaired renal function (mandatory monitoring of renal function is required, as well as correction of the dosage regimen);
in patients with known risk factors for QT interval prolongation: in elderly patients; in female patients; in patients with uncorrected electrolyte disturbances (with hypokalemia, hypomagnesemia); with congenital long QT syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); while taking medications that can prolong the QT interval (class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics);
in patients with diabetes mellitus receiving oral hypoglycemic drugs (for example, glibenclamide) or insulin (the risk of hypoglycemia increases);
in patients with severe adverse reactions to other fluoroquinolones, such as severe neurological reactions (increased risk of developing similar adverse reactions when using levofloxacin);
in patients with psychosis or in patients with a history of mental illness;
in elderly patients, in patients after transplantation, as well as with concomitant use of GCS (increased risk of developing tendinitis and tendon rupture).

Use in children

Contraindicated in childhood and adolescence under 18 years of age (due to incomplete skeletal growth, since the risk of damage to cartilaginous growth plates cannot be completely excluded).

Restrictions for children

Contraindicated

Use in elderly patients

For elderly patients

no adjustment of the dosage regimen is required, except in cases where the CC is reduced to 50 ml/min or lower.

Restrictions for elderly patients

Use with caution

Use for liver dysfunction

In case of liver dysfunction, no special dose selection is required, since Tavanic® is metabolized in the liver to an extremely small extent.

Restrictions for liver dysfunction

Possible use

Use during pregnancy and breastfeeding

The drug is contraindicated for use during pregnancy and in breastfeeding women.

Restrictions when breastfeeding

Contraindicated

Restrictions during pregnancy

Contraindicated

Use for renal impairment

Carefully

the drug should be prescribed to patients with impaired renal function (mandatory monitoring of renal function is required, as well as correction of the dosage regimen).

Restrictions for impaired renal function

Use with caution

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C.

Terms of sale

The drug is available with a prescription.

special instructions

Hospital-acquired infections caused by Pseudomonas aeruginosa may require combination treatment.

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.

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

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 tendonitis, 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.

Like other quinolones, levofloxacin should be used with great caution in patients with a predisposition to seizures: in patients with previous lesions of the central nervous system, such as stroke, severe traumatic brain injury; in patients simultaneously receiving drugs that lower the seizure threshold of the brain, such as fenbufen and other similar NSAIDs, as well as other drugs that lower the seizure threshold, such as theophylline. If seizures develop, treatment with levofloxacin should be discontinued.

Diarrhea that develops during or after treatment with levofloxacin, especially severe, persistent and/or bloody, may be a symptom 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.

Tendonitis has been reported rarely with quinolones, including levofloxacin, and can sometimes lead to rupture of tendons, including the Achilles tendon. This side effect may occur within 48 hours of starting treatment or several months after completion of fluoroquinolone therapy and may be bilateral. 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.

Patients should be advised to remain calm at the first sign of tendonitis or tendon rupture and to contact their healthcare provider. If tendinitis is suspected, treatment with Tavanic® should be stopped immediately and appropriate treatment of the affected tendon should be initiated, for example by providing sufficient immobilization.

Levofloxacin may cause serious, potentially fatal hypersensitivity reactions (angioedema, anaphylactic shock), even when used in initial doses. Patients should immediately stop taking the drug and consult a doctor.

Cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been observed with the use of levofloxacin. If any reactions develop from the skin or mucous membranes, the patient should immediately consult a doctor and not continue treatment until consultation with a specialist.

Cases of liver necrosis, including fatal liver failure, have been reported with the use of levofloxacin, mainly in patients with severe underlying diseases (for example, sepsis). The patient should be warned about the need to stop treatment and urgently consult a doctor if signs and symptoms of liver damage appear, such as anorexia, jaundice, dark urine, itching, abdominal pain.

Because Levofloxacin is excreted mainly by the kidneys; in patients with impaired renal function, mandatory monitoring of renal function is required, as well as adjustment of the dosage regimen. When treating elderly patients, it should be taken into account that patients in this group often have impaired renal function.

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

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

Very rare cases of QT prolongation have been reported in patients receiving 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); with congenital long QT syndrome, with heart disease (heart failure, myocardial infarction, bradycardia), while taking medications that can prolong the QT interval, such as class IA and III antiarrhythmics, 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 in them.

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

As with 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. Cases of hypoglycemic coma have been reported. In patients with diabetes mellitus, monitoring of blood glucose concentrations is required.

Cases of sensory and sensorimotor peripheral neuropathy, which may have a rapid onset, have been reported in patients receiving fluoroquinolones, including levofloxacin. If the patient develops symptoms of neuropathy, levofloxacin should be discontinued. This minimizes the possible 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.

Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. In the post-marketing period, adverse reactions, including pulmonary failure requiring mechanical ventilation and death, have been observed with the use of fluoroquinolones in patients with pseudoparalytic myasthenia gravis. The use of levofloxacin in patients with an established diagnosis of pseudoparalytic myasthenia gravis is not recommended.

The use of levofloxacin for the prevention and treatment of airborne anthrax is based on data on the sensitivity of Bacillus anthracis to it from in vitro and experimental studies in animals, as well as on limited data from the use of levofloxacin in humans. The attending physician should refer to national and/or international documents that reflect the collectively developed point of view on the treatment of anthrax.

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.

If any visual impairment develops, immediate consultation with an ophthalmologist is necessary.

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 and machinery

Side effects of Tavanic®, such as dizziness or vertigo, drowsiness and visual disturbances, 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).

Side effect

Determination of the frequency of side effects: very often (≥1/10), often (≥1/100,

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

From the cardiovascular system:

rarely - sinus tachycardia, palpitations, decreased blood pressure; frequency unknown (post-marketing data) - prolongation of the QT interval, ventricular arrhythmias, ventricular tachycardia, ventricular tachycardia of the “pirouette” type, which can lead to cardiac arrest.

From the hematopoietic system:

uncommon - leukopenia, eosinophilia; rarely - neutropenia, thrombocytopenia; frequency unknown (post-marketing data) - pancytopenia, agranulocytosis, hemolytic anemia.

From the nervous system:

often - headache, dizziness; infrequently - drowsiness, tremor, dysgeusia (taste perversion); rarely - paresthesia, convulsions; frequency unknown (post-marketing data) - peripheral sensory neuropathy, peripheral sensorimotor neuropathy, dyskinesia, extrapyramidal disorders, ageusia (loss of taste), parosmia (disorder of the sense of smell, especially the subjective sensation of an objectively absent smell), including loss of smell, syncope, benign intracranial hypertension.

Mental disorders:

often - insomnia; infrequently - feeling of anxiety, confusion; rarely - mental disorders (hallucinations, paranoia), depression, agitation (excitement), sleep disturbances, nightmares; frequency unknown (post-marketing data) - mental disorders with behavioral disorders with self-harm, including suicidal thoughts and suicide attempts.

From the side of the organ of vision:

rarely - visual disturbances, such as blurred visible images; frequency unknown (post-marketing data) - transient vision loss, uveitis.

Hearing and labyrinth disorders:

infrequently - vertigo (a feeling of deviation or spinning of one’s own body or surrounding objects); rarely - ringing in the ears; frequency unknown (post-marketing data) - hearing loss, hearing loss.

From the respiratory system:

infrequently - shortness of breath; frequency unknown (post-marketing data) - bronchospasm, allergic pneumonitis.

From the digestive system:

often - diarrhea, vomiting, nausea; infrequently - abdominal pain, dyspepsia, flatulence, constipation; frequency unknown (post-marketing data) - hemorrhagic diarrhea, which in very rare cases may be a sign of enterocolitis, including pseudomembranous colitis, pancreatitis.

From the liver and biliary tract:

often - increased activity of ALT, AST, alkaline phosphatase, GGT; infrequently - increased concentration of bilirubin in the blood; frequency unknown (post-marketing data) - severe liver failure, including cases of acute liver failure (sometimes fatal), especially in patients with severe underlying disease (for example, sepsis); hepatitis, jaundice.

From the urinary tract:

uncommon - increased serum creatinine concentration; rarely - acute renal failure (for example, due to the development of interstitial nephritis).

For the skin and subcutaneous tissues:

uncommon - rash, itching, urticaria, hyperhidrosis; frequency unknown (post-marketing data) - toxic epidermal necrolysis, Stevens-Johnson syndrome, exudative erythema multiforme, photosensitivity reactions (increased sensitivity to solar and UV radiation), leukocytoclastic vasculitis, stomatitis. Reactions from the skin and mucous membranes can sometimes develop even after the first dose of the drug.

From the immune system:

rarely - angioedema; frequency unknown (post-marketing data) - anaphylactic shock, anaphylactoid shock. Anaphylactic and anaphylactoid reactions can sometimes develop even after taking the first dose of the drug.

From the musculoskeletal system:

infrequently - arthralgia, myalgia; rarely - tendon damage, including tendonitis (for example, Achilles tendon), muscle weakness, which can be especially dangerous in patients with pseudoparalytic myasthenia gravis; frequency unknown (post-marketing data) - rhabdomyolysis, tendon rupture (for example, Achilles tendon; this side effect can be observed within 48 hours after the start of treatment and can be bilateral), ligament rupture, muscle rupture, arthritis.

From the side of metabolism:

infrequently - anorexia; rarely - hypoglycemia, especially in patients with diabetes mellitus (possible symptoms of hypoglycemia: voracious appetite, nervousness, perspiration, trembling); frequency unknown - hyperglycemia, hypoglycemic coma.

Infectious and parasitic diseases:

infrequently - fungal infections, development of resistance of pathogenic microorganisms.

General reactions:

infrequently - asthenia; rarely - pyrexia (fever); frequency unknown - pain (including pain in the back, chest, limbs).

Other possible adverse effects that apply to all fluoroquinolones

Very rarely - attacks of porphyria in patients already suffering from this disease.

Possible product names

Tavanik tablet 500 mg No. 10
TAVANIK 500 MG TAB. P/OB. No. 10
TAVANIK 0.5 N10 TABLE PLEN/O
TAVANIK TABLE. P/O PLEN 500 MG X10
TAVANIK TAB. P/O PLEEN. 500 MG No. 10
TAVANIK 500MG TAB. P/PL/OB. X10 (R)
(Tavanic) Tavanic tablet 500 mg No. 10

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.

Creatinine Cl, ml/min	<20	20–49	50–80
Renal clearance, ml/min	13	26	57
T1/2, h	35	27	9

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”).

Contraindications

hypersensitivity to levofloxacin or other quinolones, as well as to any of the excipients of the drug Tavanic®;

epilepsy;

pseudoparalytic myasthenia gravis (myasthenia gravis) (see “Side effects”, “Special instructions”);

history of tendon damage when taking fluoroquinolones;

childhood and adolescence up to 18 years of age (due to incomplete growth of the skeleton, since the risk of damage to cartilaginous growth points cannot be completely excluded);

pregnancy (the risk of damage to cartilaginous growth points in the fetus cannot be completely eliminated);

period of breastfeeding (the risk of damage to the cartilaginous growth points of bones in a child cannot be completely eliminated).

With caution: patients predisposed to the development of seizures (patients with previous lesions of the central nervous system; patients simultaneously receiving drugs that lower the threshold of convulsive readiness of the brain, such as fenbufen, theophylline) (see “Interaction”); patients with latent or manifest deficiency of glucose-6-phosphate dehydrogenase (increased risk of hemolytic reactions when treated with quinolones); patients with impaired renal function (mandatory monitoring of renal function is required, as well as correction of the dosage regimen, see “Dosage and Administration”); patients with known risk factors for prolongation of the QT interval: elderly; females, patients with uncorrected electrolyte disturbances (hypokalemia, hypomagnesemia); with congenital long QT syndrome; heart diseases (heart failure, myocardial infarction, bradycardia); while taking medications that can prolong the QT interval (antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, antipsychotics) (see “Overdose”, “Interaction”, “Special instructions”); patients with diabetes mellitus receiving oral hypoglycemic drugs, such as glibenclamide or insulin drugs (the risk of hypoglycemia increases); patients with severe adverse reactions to other fluoroquinolones, such as severe neurological reactions (increased risk of similar adverse reactions when using levofloxacin); patients with psychosis or a history of mental illness (see “Special Instructions”).

Tavanic, 5 pcs., 500 mg, film-coated tablets

Hospital-acquired infections caused by Pseudomonas aeruginosa

, may require combination treatment.

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 unless laboratory tests have confirmed the sensitivity of this organism to levofloxacin.

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”).

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.

Rarely observed, tendonitis with quinolones, including levofloxacin, can lead to rupture of tendons, including the Achilles tendon. This side effect can develop within 48 hours after starting treatment and can be bilateral. Elderly patients are more prone to developing tendinitis. The risk of tendon rupture may increase when taking corticosteroids simultaneously. If tendonitis is suspected, treatment with Tavanic® should be stopped immediately and appropriate treatment of the affected tendon should be initiated, for example by providing 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 the development of 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 renal failure.

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).

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 in them (see Caution).

, “Method of administration and dosage”, “Side effects” and “Overdose” “Interaction”).

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 possible risk of developing irreversible changes.

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.

With the use of quinolones, including levofloxacin, the development of psychotic reactions has been reported, which in very rare cases progressed to the development of suicidal ideation and behavior disorders with self-harm (sometimes after taking a single dose of levofloxacin (see "Side effects"). When such reactions develop Treatment with levofloxacin should be discontinued and appropriate therapy should be prescribed.The drug should be used with caution in patients with psychosis or patients with a history of mental illness.

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 certain risk in situations where these abilities are of particular importance (for example, when driving a car, when servicing machines and mechanisms, when performing work in an unstable position).

Side effects

The side effects listed below are presented in accordance with the following gradations of the frequency of their occurrence: very common (≥1/10), frequent (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000) (including isolated reports), unknown frequency (it is not possible to determine the frequency of occurrence based on available data).

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

From the heart: rarely - sinus tachycardia, palpitations; unknown frequency (post-marketing data) - prolongation of the QT interval, ventricular arrhythmias, ventricular tachycardia, ventricular tachycardia of the “pirouette” type, which can lead to cardiac arrest (see “Overdose”, “Special instructions”).

From the blood and lymphatic system: infrequently - leukopenia (decreased number of leukocytes in peripheral blood), eosinophilia (increased number of eosinophils in peripheral blood); rarely - neutropenia (decreased number of neutrophils in peripheral blood), thrombocytopenia (decreased number of platelets in peripheral blood); unknown frequency (post-marketing data) - pancytopenia (decrease in the number of all formed elements in the peripheral blood), agranulocytosis (absence or sharp decrease in the number of granulocytes in the peripheral blood), hemolytic anemia.

From the nervous system: often - headache, dizziness; infrequently - drowsiness, tremor, dysgeusia (taste perversion); rarely - paresthesia, convulsions (see "Special Instructions"); unknown frequency (post-marketing data) - peripheral sensory neuropathy, peripheral sensorimotor neuropathy (see "Special Instructions"), dyskinesia, extrapyramidal disorders, ageusia (loss of taste), parosmia (disorder of the sense of smell, especially the subjective sensation of an objectively absent odor ), including loss of smell, syncope, benign intracranial hypertension.

From the side of the organ of vision: rarely - visual disturbances, such as blurriness of the visible image; unknown frequency - transient loss of vision, uveitis.

From the organ of hearing and labyrinthine disorders: infrequently - vertigo (a feeling of deviation or spinning of one’s own body or surrounding objects); rarely - ringing in the ears; unknown frequency (post-marketing data) - hearing loss, hearing loss.

From the respiratory system, chest and mediastinal organs: infrequently - shortness of breath; unknown frequency (post-marketing data) - bronchospasm, allergic pneumonitis.

From the gastrointestinal tract: often - diarrhea, vomiting, nausea; infrequently - abdominal pain, dyspepsia, flatulence, constipation; unknown frequency (post-marketing data) - hemorrhagic diarrhea, which in very rare cases may be a sign of enterocolitis, including pseudomembranous colitis (see "Special Instructions"), pancreatitis.

From the kidneys and urinary tract: infrequently - increased concentration of creatinine in the blood serum; rarely - acute renal failure (for example, due to the development of interstitial nephritis).

From the skin and subcutaneous tissues: infrequently - rash, itching, urticaria, hyperhidrosis; unknown frequency (post-marketing data) - toxic epidermal necrolysis, Stevens-Johnson syndrome, exudative erythema multiforme, photosensitivity reactions (increased sensitivity to solar and UV radiation) (see "Special Instructions"), leukocytoclastic vasculitis, stomatitis. Reactions from the skin and mucous membranes can sometimes develop even after taking the first dose of the drug.

From the musculoskeletal system and connective tissue: infrequently - arthralgia, myalgia; rarely - tendon damage, including tendonitis (for example, Achilles tendon), muscle weakness, which can be especially dangerous in patients with pseudoparalytic myasthenia gravis (see "Special Instructions"); unknown frequency (post-marketing data): rhabdomyolysis, tendon rupture (eg Achilles tendon). This side effect can be observed within 48 hours after the start of treatment and can be bilateral in nature (see also section “Special Instructions”), ligament rupture, muscle rupture, arthritis.

From the side of metabolism and nutrition: infrequently - anorexia; rarely - hypoglycemia, especially in patients with diabetes mellitus (possible signs of hypoglycemia: voracious appetite, nervousness, perspiration, trembling); unknown frequency - hyperglycemia, hypoglycemic coma (see "Special Instructions").

Infectious and parasitic diseases: infrequently - fungal infections, development of resistance of pathogenic microorganisms.

From the side of blood vessels: rarely - decreased blood pressure.

General disorders: infrequently - asthenia; rarely - pyrexia (fever); unknown frequency - pain (including pain in the back, chest and limbs).

From the immune system: rarely - angioedema; unknown frequency (post-marketing data) - anaphylactic shock, anaphylactoid shock.

Anaphylactic and anaphylactoid reactions can sometimes develop even after taking the first dose of the drug.

From the liver and biliary tract: often - increased activity of liver enzymes in the blood (for example ALT, AST), increased activity of alkaline phosphatase and GGT; infrequently - increased concentration of bilirubin in the blood; unknown frequency (post-marketing data) - severe liver failure, including cases of acute liver failure, sometimes fatal, especially in patients with a severe underlying disease (for example, in patients with sepsis) (see "Special Instructions"), hepatitis, jaundice.

From the mental side: often - insomnia; infrequently - feeling of restlessness, anxiety, confusion; rarely - mental disorders (for example, hallucinations, paranoia), depression, agitation (excitement), sleep disturbances, nightmares; unknown frequency (post-marketing data) - mental disorders with behavioral disorders with self-harm, including suicidal thoughts and suicide attempts.

Other possible undesirable effects that apply to all fluoroquinolones: very rarely - attacks of porphyria (a very rare metabolic disease) in patients already suffering from this disease.

TAVANIK

special instructions

Hospital-acquired infections caused by Pseudomonas aeruginosa ( Pseudomonas aeruginosa )
may require combination treatment.

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.

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 lesions of the central nervous system, such as stroke, severe traumatic brain injury; patients simultaneously receiving drugs that lower the seizure threshold of the brain, such as fenbufen and other similar non-steroidal anti-inflammatory drugs or other drugs that lower the seizure threshold, such as theophylline (see section "Interaction with other drugs").

Pseudomembranous colitis

Diarrhea that develops during or after treatment with levofloxacin, especially severe, persistent and/or bloody, may be a symptom 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

Rarely observed, tendonitis with quinolones, including levofloxacin, can lead to rupture of tendons, including the Achilles tendon. This side effect can develop within 48 hours after starting treatment and can be bilateral. Elderly patients are more prone to developing tendinitis. The risk of tendon rupture may be increased when taking corticosteroids concomitantly. If tendonitis is suspected, treatment with Tavanic® should be stopped immediately and appropriate treatment of the affected tendon should be initiated, for example by providing sufficient immobilization (see sections “Contraindications” and “Side Effects”).

Hypersensitivity reactions

Levofloxacin may cause serious, potentially fatal, hypersensitivity reactions (angioedema, anaphylactic shock), even with initial doses (see section "Side effects"). Patients should immediately stop taking the drug and 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 section "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.

Disorders of the liver and biliary tract

Cases of hepatic necrosis, including the development of fatal liver failure, have been reported with the use of levofloxacin, mainly in patients with severe underlying diseases, such as sepsis (see section "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 kidney failure

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 section "Dosage and Administration"). When treating elderly patients, it should be borne in mind that patients in this group often have impaired renal function (see section “Dosage and Administration”).

Preventing the development of photosensitivity reactions

Superinfection

As with the use of other antibiotics, the use of levofloxacin, especially for a long time, can lead to increased proliferation of microorganisms (bacteria and fungi) that are insensitive to it, 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.

QT
interval prolongation 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); with congenital long QT syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); while taking medications 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 sections “With caution”, “Dosage and administration”, “Side effects” and “Overdose”, “Interaction with other drugs”).

Patients with glucose-6-phosphate dehydrogenase deficiency

Hypo- and hyperglycemia (dysglycemia)

Peripheral neuropathy

Exacerbation of
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

With the use of quinolones, including levofloxacin, the development of psychotic reactions has been reported, which in very rare cases progressed to the development of suicidal thoughts and behavior disorders with self-harm (sometimes after taking a single dose of levofloxacin (see section "Side effects")). 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.

Visual impairment

If any visual impairment develops, immediate consultation with an ophthalmologist is necessary (see section “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.

Interaction

Interactions requiring caution

With preparations containing magnesium, aluminum, iron and zinc, didanosine. Medicines 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 taken orally

With sucralfate. The effect of Tavanic® is significantly weakened by the simultaneous use of sucralfate (a drug for protecting the gastric mucosa).

For patients receiving levofloxacin and sucralfate, it is recommended that sucralfate be taken 2 hours after taking levofloxacin.

With theophylline, fenbufen or similar drugs from the NSAID group that reduce the threshold of convulsive readiness of the brain. No pharmacokinetic interaction of levofloxacin with theophylline was detected.

However, with the simultaneous use of quinolones and theophylline, NSAIDs and other drugs that reduce the threshold of convulsive readiness of the brain, a pronounced decrease in the threshold of convulsive readiness of the brain is possible.

The concentration of levofloxacin while taking fenbufen increases only by 13%.

With indirect anticoagulants (vitamin K antagonists) In patients treated with levofloxacin in combination with indirect anticoagulants (for example, warfarin), an increase in PT/INR and/or the development of bleeding was observed, incl. and heavy. Therefore, with the simultaneous use of indirect anticoagulants and levofloxacin, regular monitoring of blood coagulation parameters is necessary.

With probenecid and cimetidine. With the simultaneous use of drugs that interfere with renal tubular secretion, such as probenecid and cimetidine, and levofloxacin, caution should be exercised, especially in patients with renal failure.

The elimination (renal clearance) of levofloxacin is slowed down by cimetidine by 24% and probenecid by 34%. This is unlikely to be of clinical significance if renal function is normal.

With cyclosporine. Levofloxacin increased the half-life of cyclosporine by 33%. Since this increase is clinically insignificant, no dose adjustment of cyclosporine is required when used concomitantly with levofloxacin.

With GCS. Concomitant use of corticosteroids increases the risk of tendon rupture.

With drugs that prolong the QT interval. Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs that prolong the QT interval (for example, class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics).

Other. Clinical and pharmacological studies conducted to study the possible pharmacokinetic interactions of levofloxacin with digoxin, glibenclamide, ranitidine and warfarin showed that the pharmacokinetics of levofloxacin when used simultaneously with these drugs does not change sufficiently to be of clinical significance.

Instructions for use TAVANIC

When prescribing the drug to elderly patients, it should be borne in mind that patients in this group often have impaired renal function.

In patients with previous brain damage (including stroke or severe brain injury), the use of Tavanic may provoke seizures.

In severe pneumonia caused by pneumococcus, the use of Tavanic may not be effective enough.

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

Severe allergic reactions may sometimes be preceded by milder skin manifestations. However, these reactions can develop after the first dose - a few minutes or hours after using the drug.

To avoid the development of photosensitivity, patients should avoid exposure to the sun or UV exposure (for example, exposure to the sun at high altitudes or visiting a solarium).

If pseudomembranous colitis is suspected, Tavanik should be discontinued immediately and appropriate treatment should be initiated. In such cases, drugs that inhibit intestinal motility should not be used.

In elderly patients, when using the drug Tavanic, the likelihood of developing tendinitis increases. The use of corticosteroids appears to increase the risk of tendon rupture. If tendonitis is suspected, Tavanik should be immediately discontinued and appropriate treatment should be initiated, ensuring a state of rest in the affected area.

Tavanic should be taken at least 2 hours before or 2 hours after taking sucralfate, magnesium- or aluminum-containing antacids, as well as iron salts.

With the simultaneous use of vitamin K antagonists, control of the blood coagulation system is necessary.

Tavanic should be prescribed with caution simultaneously with probenecid and cimetidine, which block tubular secretion. This applies primarily to patients with impaired renal function.

During treatment you should avoid drinking alcohol.

Experience with other quinolones suggests that they can cause exacerbation of porphyria. A similar effect cannot be excluded when using the drug Tavanic.

When using fluoroquinolones in patients with glucose-6-phosphate dehydrogenase deficiency, hemolysis of erythrocytes is possible. Considering this, treatment with Tavanik in this category of patients should be carried out with extreme caution.

The recommended duration of administration should be strictly adhered to, which should be at least 60 minutes for 100 ml of infusion solution. Experience with the use of levofloxacin shows that increased heart rate and a transient drop in blood pressure may occur during infusion. In rare cases, vascular collapse may occur. If a significant drop in blood pressure is observed during the infusion, the administration is stopped immediately.

Elderly patients with normal renal function do not require dosage adjustment.

Use in pediatrics

Tavanic is contraindicated for the treatment of children and adolescents due to the likelihood of damage to articular cartilage.

Impact on the ability to drive vehicles and operate machinery

Tavanic can cause dizziness or stiffness, drowsiness, visual disturbances, and also reduce the ability to concentrate and the speed of psychomotor reactions. This should be taken into account if it is necessary to use the drug in persons whose activities involve driving a car, servicing machines and mechanisms, or performing work in an unstable position.

Directions for use and doses

Pills

Orally, 1 or 2 times a day, without chewing and with a sufficient amount of liquid (0.5 to 1 glass), before meals or at any time between meals, because food intake does not affect the absorption of the drug (see “Pharmacokinetics”). If necessary, tablets can be broken along the dividing groove.

The drug should be taken at least 2 hours before or 2 hours after taking antacids containing magnesium and/or aluminum, iron salts or sucralfate (see “Interactions”).

Considering that the bioavailability of levofloxacin when taking Tavanic® tablets is 99–100%, if a patient is transferred from an IV infusion of Tavanik® to taking tablets, treatment should be continued at the same dose that was used with IV infusion ( see "Pharmacokinetics").

Skipping one or more doses of the drug

If you accidentally miss a dose of the drug, you should take the next dose as soon as possible and then continue to take Tavanic® according to the recommended dosage regimen.

Doses and duration of treatment

Recommended dosage regimen and duration of treatment in patients with normal or moderately reduced renal function (Cl creatinine >50 ml/min.):

Acute sinusitis - 2 tablets. Tavanic® 250 mg or 1 tablet. Tavanic® 500 mg 1 time per day (corresponding to 500 mg levofloxacin) - 10–14 days.

Exacerbation of chronic bronchitis - 2 tables. Tavanic® 250 mg or 1 tablet. Tavanic® 500 mg 1 time per day (respectively 500 mg of levofloxacin) - 7-10 days.

Community-acquired pneumonia - 2 tables. Tavanic® 250 mg or 1 tablet. Tavanic® 500 mg 1-2 times a day (respectively 500-1000 mg of levofloxacin) - 7-14 days.

Uncomplicated urinary tract infections - 1 table. Tavanic® 250 mg 1 time per day (respectively 250 mg of levofloxacin) - 3 days.

Complicated urinary tract infections - 2 tables. Tavanik® 250 mg 1 time per day or 1 tablet. Tavanic® 500 mg 1 time per day (respectively 500 mg of levofloxacin) - 7-14 days.

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

Chronic bacterial prostatitis - 2 tables. Tavanik ® 250 mg or 1 tablet. Tavanic® 500 mg 1 time per day (respectively 500 mg of levofloxacin) - 28 days.

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

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

Prevention and treatment of anthrax through airborne transmission - 2 tables. Tavanic® 250 mg or 1 tablet. Tavanic® 500 mg (respectively 500 mg of levofloxacin) 1 time per day for up to 8 weeks.

Dosage regimen in patients with impaired renal function (Cl creatinine ≤50 ml/min)

Levofloxacin is excreted primarily through the kidneys, therefore, when treating patients with impaired renal function, it is necessary to reduce the dose of the drug. Relevant information on this matter is contained in the table.

Dosage regimen

Creatinine Cl, ml/min	Doses
Recommended dose for creatinine Cl more than 50 ml/min	250 mg/24 h	500 mg/24 h	500 mg/12 h
50–20	first - 250 mg	first - 500 mg	first - 500 mg
50–20	then - 125 mg/24 hours	then - 250 mg/24 hours	then - 250 mg/12 hours
19–10	first - 250 mg	first - 500 mg	first - 500 mg
19–10	then - 125 mg/48 hours	then - 125 mg/24 hours	then - 125 mg/12 hours
<10 (including hemodialysis and CAPD*)	first - 250 mg	first - 500 mg	first - 500 mg
<10 (including hemodialysis and CAPD*)	then - 125 mg/48 hours	then - 125 mg/24 hours	then - 125 mg/24 hours

* No additional doses are required after hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

Dosage regimen in patients with impaired liver function. If liver function is impaired, no dosage adjustment is required, since levofloxacin is only slightly metabolized in the liver.

Dosage regimen in elderly patients. For elderly patients, no dosage adjustment is required, except in cases where creatinine Cl decreases to 50 ml/min or lower.

Tavanic, 500 mg, film-coated tablets, 10 pcs.

Hospital-acquired infections caused by Pseudomonas aeruginosa

, may require combination treatment.

Methicillin-resistant streptococcus aureus.

Patients predisposed to developing seizures.

Pseudomembranous colitis.

Tendinitis.

Hypersensitivity reactions.

Severe bullous reactions.

From the liver and bile ducts.

Patients with renal failure.

Preventing the development of photosensitivity reactions.

Superinfection.

Prolongation of the QT interval.

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

Elderly and female patients may be more sensitive to drugs that prolong the QT interval. Therefore, fluoroquinolones, including levofloxacin, should be used with caution in them (see Caution).

, “Method of administration and dosage”, “Side effects” and “Overdose” “Interaction”).

Patients with glucose-6-phosphate dehydrogenase deficiency.

Hypo- and hyperlycemia (dysglycemia).

Peripheral neuropathy.

Exacerbation of pseudoparalytic myasthenia gravis (myasthenia gravis).

Application for airborne anthrax infection.

Psychotic reactions.

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.

Overdose

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

During post-marketing use of the drug in overdose, CNS effects have been observed, including confusion, convulsions, hallucinations and tremor.

Nausea and erosions of the gastrointestinal mucosa may develop.

In clinical and pharmacological studies conducted with doses of levofloxacin exceeding therapeutic levels, prolongation of the QT interval was shown.

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

special instructions

Hospital-acquired infections caused by Pseudomonas aeruginosa may require combination treatment.

Methicillin-resistant streptococcus aureus.

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.

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.

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.

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.

Preventing the development of photosensitivity reactions.

Superinfection.

Prolongation of the QT interval.

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

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.

Hypo- and hyperlycemia (dysglycemia).

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).

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.

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).