Levofloxacin-Teva, 500 mg, film-coated tablets, 14 pcs.

Levofloxacin-teva 500 mg 14 pcs. film-coated tablets

pharmachologic effect

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

Levofloxacin has a bactericidal effect and is active against a large number of pathogens of bacterial infections both in vitro and in vivo.

Sensitive microorganisms (minimum inhibitory concentration (MIC &ge2 mg/l):

Aerobic gram-positive microorganisms: Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus spp. (including Enterococcus faecalis), Listeria monocytogenes, Staphylococcus spp. (coagulase-negative, methicillin-sensitive/leukotoxin-containing/moderately sensitive strains), incl. Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), Streptococcus spp. groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-sensitive/moderately sensitive/resistant strains), Streptococcus pyogenes, Streptococcus spp. viridans group (penicillin-sensitive/resistant strains).

Aerobic gram-negative microorganisms: Acinetobacter spp., incl. Acinetobacter baumannii, Acinetobacillus actinomycetecomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter spp., incl. Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (ampicillin-sensitive/resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp., incl. Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis (beta-lactamase producing and non-producing strains), Morganella morganii, Neisseria gonorrhoeae (penicillinase producing and non-producing strains), Neisseria meningitidis, Pasteurella spp., incl. Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida, Proteus mirabilis, Proteus vulgaris, Providencia spp., incl. Providencia rettgeri, Providencia stuartii, Pseudomonas spp., incl. Pseudomonas aeruginosa (hospital infections caused by Pseudomonas aeruginosa may require combination treatment), Serratia spp., incl. Serratia marcescens, Salmonella spp.

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

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

Moderately sensitive microorganisms (MIC = 4 mg/l):

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

Aerobic gram-negative microorganisms: Campylobacter jejuni, Campylobacter coli.

Anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

Resistant microorganisms (MIC more than 8 mg/l):

Aerobic gram-positive microorganisms: Staphylococcus aureus (methicillin-resistant strains), other Staphylococcus spp. (coagulase-negative methicillin-resistant strains).

Aerobic gram-negative microorganisms: Alcaligenes xylosoxidans.

Anaerobic microorganisms: Bacteroides thetaiotaomicron.

Other microorganisms: Mycobacterium avium.

Clinical efficacy (effectiveness in clinical studies against 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 catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens.

Other microorganisms: Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae.

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.

Composition and release form Levofloxacin-teva 500 mg 14 pcs. film-coated tablets

Tablet - 1 tablet:

• Active substance: levofloxacin (in the form of hemihydrate) - 500 mg;
• Excipients: colloidal silicon dioxide 12 mg, hyprolose 28 mg, sodium carboxymethyl starch (type A) 55 mg, talc 55.2 mg, croscarmellose sodium 20.6 mg, magnesium stearate 6.74 mg.
• Shell composition: opadry 15B26688 brown (hypromellose 2910 3 CP 4.76 mg, hypromellose 2910 6 CP 4.76 mg, titanium dioxide (E171) 3.044 mg, macrogol 400 1.12 mg, polysorbate 80 140 mcg, iron dye yellow oxide (E172) 120 mcg, dye iron oxide red (E172) 43 mcg, iron dye black oxide (E172) 13 mcg).

14 pieces per package, cardboard packs.

Description of the dosage form

Film-coated tablets of pale pink color with a yellowish tint, capsule-shaped, with a score line on one side, engraved “LX” on one side of the score line and “500” on the other.

Directions for use and doses

Acute sinusitis: 500 mg 1 time/day for 10-14 days.

Community-acquired pneumonia: 500 mg 1-2 times a day, 7-14 days.

Exacerbation of chronic bronchitis: 250-500 mg 1 time / day for 7-10 days.

Uncomplicated urinary tract infections: 250 mg 1 time / day for 3 days.

Complicated urinary tract infections: 500 mg 1 time / day for 7-14 days.

Pyelonephritis: 500 mg 1 time / day for 7-10 days.

Chronic bacterial prostatitis: 500 mg 1 time / day, course of treatment - 28 days.

Skin and soft tissue infections: 500 mg 1-2 times a day for 7-14 days.

Complex therapy of drug-resistant forms of tuberculosis: 500 mg 1-2 times a day, course of treatment - up to 3 months.

The duration of treatment depends on the type and severity of the disease. If necessary, it is possible to switch from one dosage form of levofloxacin to another.

After relief of symptoms of acute inflammation and normalization of temperature, it is recommended to continue therapy with levofloxacin for 48-72 hours.

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.

No dose adjustment is required in patients with impaired liver function.

Pharmacokinetics

Suction:

After oral administration, levofloxacin is rapidly and almost completely absorbed from the small intestine. Food intake has little effect on the speed and completeness of absorption. The bioavailability of levofloxacin in a dose of 500 mg after oral administration is almost 100%. After taking a single dose of 500 mg, the Cmax of levofloxacin is 5.2±1.2 mcg/ml, the time to reach Cmax is 1.3 hours.

Distribution:

Plasma protein binding is 30-40%. Penetrates well into organs and tissues: lungs, bronchial mucosa, genitourinary system, bone tissue, cerebrospinal fluid, prostate gland, polymorphonuclear leukocytes and alveolar macrophages.

Metabolism and excretion:

In the liver, a small portion is oxidized and/or deacetylated.

It is excreted from the body primarily by the kidneys by glomerular filtration and tubular secretion. T1/2 - 6-8 hours. After oral administration, approximately 87% of the dose is excreted unchanged by the kidneys within 48 hours, less than 4% within 72 hours through the intestines.

Pharmacokinetics in special groups of patients:

In renal failure, a decrease in the clearance of levofloxacin and its excretion by the kidneys depends on the degree of decrease in creatinine clearance (CC). With CC 50-80 ml/min T1/2 is 9 hours, renal clearance is 57 ml/min; with CC 20-49 ml/min T1/2 is 27 hours, renal clearance is 26 ml/min; with CC less than 20 ml/min T1/2 is 35 hours, renal clearance is 13 ml/min.

Indications for use Levofloxacin-teva 500 mg 14 pcs. film-coated tablets

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:

• Lower respiratory tract (exacerbation of chronic bronchitis, community-acquired pneumonia);
• ENT organs (including acute sinusitis);
• urinary tract and kidneys (including acute pyelonephritis);
• skin and soft tissues (abscesses, furunculosis);
• chronic bacterial prostatitis;
• intra-abdominal infections;
• drug-resistant forms of tuberculosis - as part of complex therapy.

When using the drug, 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.

Contraindications

• Hypersensitivity to levofloxacin, other fluoroquinolones or components of the drug;
• epilepsy;
• tendon damage due to previous treatment with quinolones;
• pregnancy;
• lactation period;
• children and adolescents up to 18 years of age;
• lactose intolerance or lactase deficiency, as well as glucose-galactose malabsorption.

Due to the inability to split the tablet in two, the use of the drug is contraindicated in patients with impaired renal function:

• In patients with CC less than 50 ml/min, it is impossible to use a dosage regimen with an initial dose of 250 mg/24 hours;
• in patients with CC less than 20 ml/min, it is impossible to use a dosage regimen with an initial dose of 500 mg/24 hours and 500 mg/12 hours;
• with CC less than 10 ml/min (including during hemodialysis and continuous ambulatory peritoneal dialysis), it is impossible to use it for all dosage regimens.

Carefully:

• With deficiency of glucose-6-phosphate dehydrogenase;
• in patients with psychosis or in patients with a history of mental illness;
• in patients predisposed to the development of seizures (in patients with previous lesions of the central nervous system and patients simultaneously receiving drugs that reduce the threshold of convulsive readiness of the brain, such as fenbufen, theophylline);
• in patients with impaired renal function with CC 50-20 ml/min;
• in patients with known risk factors for prolongation of the QT interval on the ECG: 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 , capable of prolonging the QT interval, such as class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics, in elderly patients and women;
• in patients with diabetes mellitus receiving oral hypoglycemic agents, such as glibenclamide, or insulin;
• in patients with severe adverse reactions to other fluoroquinolones, such as severe neurological reactions.

Application of Levofloxacin-teva 500 mg 14 pcs. film-coated tablets during pregnancy and breastfeeding

Contraindicated during pregnancy and lactation.

Contraindication: children and adolescents under 18 years of age.

special instructions

The prevalence of acquired resistance of microorganisms may vary depending on the geographical region and over time, and therefore it is necessary to determine the sensitivity of the pathogen to levofloxacin.

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

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 tendonitis. The risk of tendon development may increase with concomitant use of corticosteroids. If tendinitis is suspected, treatment with the drug should be stopped immediately and appropriate therapy should be started for the affected tendon, for example by providing sufficient immobilization.

Levofloxacin may cause serious, potentially fatal hypersensitivity reactions (angioedema, anaphylactic shock), even after the first dose of the drug. If they develop, patients should immediately stop taking the drug and immediately consult a doctor.

Severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with levofloxacin. 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.

Cases of liver 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. 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.

Because Levofloxacin is excreted mainly through 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 borne in mind that patients in this group often have impaired renal function.

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.

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); congenital long QT syndrome; heart diseases (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 in them.

Despite the fact that photosensitivity during treatment with levofloxacin is quite rare, patients are not recommended to be exposed to strong solar or artificial ultraviolet radiation during treatment and for 48 hours after the end of treatment.

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, levofloxacin should be immediately discontinued and appropriate treatment (vancomycin, teicoplanin, or oral metronidazole) should be initiated. The use of drugs that suppress intestinal motility is contraindicated.

Like other fluoroquinolones, levofloxacin should be used with caution in patients with a predisposition to the development of seizures: in patients with previous lesions of the central nervous system (stroke, severe traumatic brain injury), in patients simultaneously receiving drugs that reduce the threshold of convulsive activity of the brain, such as fenbufen and other NSAIDs, or other drugs such as theophylline. If seizures occur, use of the drug should be discontinued.

Patients with glucose-6-phosphate dehydrogenase deficiency (an inherited metabolic disorder) may respond to fluoroquinolones by destroying red blood cells (hemolysis). In this regard, treatment with levofloxacin should be carried out with caution.

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.

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.

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). 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.

With the simultaneous use of indirect anticoagulants and levofloxacin, regular monitoring of blood coagulation parameters 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.

Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may increase muscle weakness in patients with myasthenia gravis. 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 patients with an established diagnosis of pseudoparalytic myasthenia gravis is not recommended.

Impact on the ability to drive vehicles and operate machinery:

During treatment, you should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms of an overdose of levofloxacin appear at the level of the central nervous system (confusion, dizziness, impaired consciousness and convulsions). In addition, gastrointestinal disorders (for example, nausea, vomiting) and erosive lesions of the mucous membranes of the gastrointestinal tract may occur. Studies conducted using ultra-high doses of levofloxacin have shown prolongation of the QT interval.

Treatment: gastric lavage and symptomatic therapy. Levofloxacin is not eliminated by hemodialysis or peritoneal dialysis. There is no specific antidote.

Side effects Levofloxacin-teva 500 mg 14 pcs. film-coated tablets

The incidence of adverse reactions is classified according to WHO recommendations: very often (&le1/10), often (from &le1/100 to <1/10), infrequently (from >1/1000 to <1/100), rarely (from >1/100). 10,000 to <1/1000), very rare (from <1/10,000, including isolated cases), frequency unknown (it was not possible to determine the frequency of occurrence based on available data).

From the cardiovascular system: rarely - sinus tachycardia, palpitations, decreased blood pressure; frequency unknown - 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 (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); frequency unknown - pancytopenia (decrease in the number of all formed elements in the peripheral blood), agranulocytosis (absence and/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; frequency unknown - 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.

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; frequency unknown - mental disorders with behavioral disorders with self-harm, including suicidal thoughts and suicide attempts.

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

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; frequency unknown - hearing loss, hearing loss.

From the respiratory system: infrequently: shortness of breath; frequency unknown - bronchospasm, allergic pneumonitis.

From the gastrointestinal tract: often - diarrhea, nausea, vomiting; infrequently - abdominal pain, flatulence, constipation, dyspepsia; frequency unknown - stomatitis, 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 liver enzymes in the blood (for example, ALT, AST, increased activity of alkaline phosphatase and GGT; infrequently - increased concentration of bilirubin in the blood; frequency unknown - severe liver failure, including cases of acute liver failure, sometimes fatal, especially in patients with severe underlying disease (eg, patients with sepsis); hepatitis, jaundice.

From the urinary system: infrequently - hypercreatininemia (increased creatinine concentration 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; frequency unknown - Stevens-Johnson syndrome, toxic epidermal necrolysis, exudative erythema multiforme, photosensitivity reactions (increased sensitivity to solar and ultraviolet radiation), leukocytoclastic vasculitis. Reactions from the skin and mucous membranes can sometimes develop even after taking the first dose of the drug.

From the musculoskeletal system: infrequently - arthralgia, myalgia; rarely - tendon lesions, including tendonitis (for example, Achilles tendon), muscle weakness, which can be especially dangerous in patients with pseudoparalytic myasthenia gravis; frequency unknown - 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 and nutrition: infrequently - anorexia; rarely - hypoglycemia, especially in patients with diabetes mellitus (possible signs 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 disorders: infrequently - asthenia; rarely - pyrexia (fever); frequency unknown - pain (including pain in the back, chest and limbs).

From the immune system: rarely - angioedema; frequency unknown - anaphylactic shock, anaphylactoid shock. Anaphylactic and anaphylactoid reactions can sometimes develop even after taking the first dose of the drug.

Other possible undesirable effects that apply to all fluoroquinolones:

Very rare: attacks of porphyria (a very rare metabolic disease) in patients with porphyria.

Drug interactions

There are reports of a marked decrease in the seizure threshold with the simultaneous use of quinolones and substances that reduce the cerebral seizure threshold. This also applies to the simultaneous use of quinolones and theophylline, as well as NSAIDs - derivatives of propionic acid.

No pharmacokinetic interaction of levofloxacin with theophylline was detected.

Oral administration with drugs containing divalent and 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 as aluminum or magnesium buffer), leads to decreased absorption and weakening of the effect of levofloxacin, so it should be prescribed 2 hours before or 2 hours after taking the above medications.

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

The effect of levofloxacin 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.

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

With the simultaneous use of vitamin K antagonists, monitoring of blood coagulation parameters is necessary.

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

When 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.

Levofloxacin, when used simultaneously with class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, and antipsychotics, may cause a prolongation of the QT interval. Levofloxacin increases T1/2 of cyclosporine by 33%. Because this increase is clinically insignificant; no dose adjustment of cyclosporine is required when used concomitantly with levofloxacin.

Taking GCS increases the risk of tendon rupture.

The pharmacokinetics of levofloxacin when used simultaneously with digoxin, glibenclamide, ranitidine, warfarin does not change sufficiently to be of clinical significance.

Release form and composition

Dosage forms:

• solution for infusion: transparent greenish-yellow liquid (100 ml in transparent glass bottles without color, 1 bottle in a cardboard box);
• film-coated tablets: capsule-shaped, pale pink with a yellow tint, with “LX” and “500” engraved on one side, with a separating line on each side (7 pcs. in blisters, in a cardboard pack of 1 or 2 blister).

Each pack also contains instructions for using Levofloxacin-Teva.

1 ml of solution contains:

• active ingredient: levofloxacin hemihydrate – 5.125 mg (equivalent to the content of 5 mg of levofloxacin);
• auxiliary components: sodium chloride, hydrochloric acid, water for injection.

1 tablet contains:

• active ingredient: levofloxacin hemihydrate – 512.46 mg (equivalent to the content of 500 mg of levofloxacin);
• auxiliary components: hyprolose, colloidal silicon dioxide, croscarmellose sodium, sodium carboxymethyl starch (type A), magnesium stearate, talc;
• film shell: Opadry 15B26688 brown – macrogol-400, hypromellose 2910 6cP, hypromellose 2910 3cP, polysorbate-80, titanium dioxide (E171), iron oxide dye red (E172), iron oxide dye yellow (E172), iron oxide dye black ( E172).

Contraindications

Absolute:

• epilepsy (including medical history);
• indication in the anamnesis of tendon lesions caused by taking fluoroquinolones;
• pregnancy period;
• breast-feeding;
• age under 18 years;
• individual intolerance to drugs of the quinolone group;
• hypersensitivity to the components of Levofloxacin-Teva.

In addition, additional contraindications for each of the dosage forms:

• solution: peripheral neuropathy, decreased threshold for convulsive activity (including acute cerebrovascular accident, inflammatory diseases of the central nervous system, traumatic brain injury), glucose-6-phosphate dehydrogenase deficiency;
• tablets: pseudoparalytic myasthenia gravis (myasthenia gravis).

Levofloxacin-Teva should be prescribed with caution in case of impaired renal function (creatinine clearance less than 50 ml/min), impaired liver function, diabetes mellitus, congenital long QT syndrome, concomitant use of drugs that can cause prolongation of the QT interval (including antiarrhythmic drugs IA and III classes, macrolides, tricyclic antidepressants, antipsychotics, antifungal drugs), electrolyte imbalance (including hypokalemia, hypomagnesemia), cardiovascular diseases (including chronic heart failure, myocardial infarction, bradycardia), mental illness (including medical history), concomitant therapy with drugs that reduce threshold of convulsive readiness of the brain (theophylline, fenbufen), in elderly patients, female patients.

In addition, when prescribing individual dosage forms of Levofloxacin-Teva, caution should be exercised if the patient has the following diseases/conditions:

• solution: pseudoparalytic myasthenia gravis, hepatic porphyria, use of hemodialysis and peritoneal dialysis;
• tablets: the patient’s predisposition to the development of seizures (including previous lesions of the central nervous system), latent or manifest deficiency of glucose-6-phosphate dehydrogenase.

Overdose

Symptoms: central nervous system disorders, including confusion, hallucinations, convulsions, tremors. Nausea, erosive lesions of the mucous membranes may occur, and if average therapeutic doses are exceeded, QT interval prolongation may occur.

Treatment: prescription of symptomatic therapy. There is no specific antidote, so in case of overdose, careful monitoring of the patient's condition (including electrocardiogram monitoring) is required. If an acute overdose occurs while taking tablets, then immediate gastric lavage and the use of antacids to protect the gastric mucosa are indicated. The use of dialysis (hemodialysis, peritoneal dialysis, continuous ambulatory peritoneal dialysis) is ineffective.

Indications for use

The use of Levofloxacin-Teva is indicated for the following infectious and inflammatory diseases caused by microorganisms sensitive to levofloxacin:

• community-acquired pneumonia;
• exacerbation of chronic bronchitis;
• acute bacterial sinusitis;
• uncomplicated and complicated urinary tract infections, including pyelonephritis;
• chronic form of bacterial prostatitis;
• skin and soft tissue infections;
• drug-resistant forms of tuberculosis - as part of complex therapy;
• anthrax - prevention and treatment of airborne infection.

Drug interactions

No pharmacokinetic interaction of levofloxacin with theophylline was detected. However, when treating Levofloxacin-Teva, it should be taken into account that quinolones may enhance the ability of fenbufen, theophylline and similar non-steroidal anti-inflammatory drugs (NSAIDs) to lower the threshold of convulsive readiness of the brain.

Combination with fenbufen increases the concentration of levofloxacin by 13%.

With concomitant therapy with probenecid, cimetidine and other drugs that interfere with renal tubular secretion, there is a slight slowdown in the elimination of levofloxacin. This combination may have clinically significant effects in patients with impaired renal function and caution is advised.

The combination of levofloxacin with warfarin and other indirect anticoagulants, coumarin derivatives, increases the risk of bleeding and/or hypercoagulation. Therefore, if it is necessary to use these drugs simultaneously, regular monitoring of blood clotting indicators (prothrombin time, international normalized ratio) is required.

The risk of developing hyperglycemia or hypoglycemia increases when Levofloxacin-Teva is combined with oral hypoglycemic agents (including glibenclamide) or insulin, therefore, more careful monitoring of blood glucose levels in patients with diabetes is required during the treatment period.

Combination therapy with glucocorticosteroids increases the risk of tendon rupture.

T1/2 of cyclosporine increases by 33%, however, dose adjustment is not required when used simultaneously with levofloxacin.

With simultaneous use of Levofloxacin-Teva with class IA and III antiarrhythmic drugs, tetracyclic and tricyclic antidepressants, neuroleptics, macrolides, some antihistamines (including astemizole, ebastine, terfenadine), antifungal drugs, imidazole derivatives, the QT interval may be prolonged.

The solution for infusion is not compatible with alkaline solutions and heparin. It can be mixed with combined solutions for parenteral nutrition (electrolytes, amino acids, carbohydrates).

If it is necessary to simultaneously use the tablet form of Levofloxacin-Teva with dosage forms of didanosine containing aluminum or magnesium as a buffer, or other magnesium-, aluminum-, zinc or iron-containing agents, it is recommended to take a break of at least 2 hours between oral administration of levofloxacin and these drugs.

When levofloxacin is taken orally, calcium salts have a minimal effect on its absorption.

When concomitantly treated with sucralfate, it should be taken only 2 hours after oral administration of Levofloxacin-Teva, so as not to weaken the effect of levofloxacin.

The results of clinical and pharmacological studies indicate the absence of clinically significant pharmacokinetic interaction of levofloxacin with ranitidine, warfarin, digoxin, glibenclamide.

special instructions

The therapeutic effect of levofloxacin in severe pneumonia caused by Streptococcus pneumoniae may be ineffective.

Combination therapy may be required to treat hospital-acquired infections caused by Pseudomonas aeruginosa.

For the treatment of severe infections or in the absence of sufficient effect from therapy, it is necessary to confirm the diagnosis with the results of a microbiological study, including determining the sensitivity of the isolated pathogen to levofloxacin.

It is not recommended to prescribe Levofloxacin-Teva for the treatment of infections caused by methicillin-resistant Staphylococcus aureus, due to the established resistance of the latter to all fluoroquinolones.

It should be taken into account that with intravenous administration of the drug, a transient decrease in blood pressure, increased heart rate, and vascular collapse may occur. In this regard, it is necessary to monitor blood pressure during the infusion and, in case of a pronounced decrease in blood pressure, immediately stop the procedure for administering Levofloxacin-Teva.

Rupture of tendons, including the Achilles tendon, may develop within 48 hours after taking the first dose of the drug and be bilateral. With simultaneous treatment with glucocorticosteroids, the risk of tendon rupture increases. Elderly patients are more prone to developing tendinitis. Suspicion of tendinitis is grounds for immediate discontinuation of levofloxacin.

If the development of pseudomembranous colitis is suspected (the symptom is severe, persistent and/or bloody diarrhea), the use of levofloxacin should be discontinued immediately. In such cases, the use of drugs that inhibit intestinal motility is contraindicated.

In order to reduce the risk of developing photosensitivity reactions during therapy and for 48 hours after its completion, patients should avoid exposure to direct sunlight or artificial ultraviolet irradiation.

Due to the fact that the use of levofloxacin can promote increased proliferation of microorganisms that are insensitive to it (bacteria and fungi), causing a change in the normal composition of the microflora in the body and the development of superinfection, a mandatory re-evaluation of the patient’s condition is required during treatment.

With the use of levofloxacin, the rapid development of sensory and sensorimotor peripheral neuropathy is possible. To prevent or minimize the risk of irreversible changes, when the first symptoms of neuropathy appear, it is necessary to stop treatment with the drug.

The existing risk of developing psychotic reactions, which may occur after the use of a single dose of levofloxacin and progress until the patient develops suicidal thoughts or actions, should be taken into account. Particular attention should be paid to patients with a history of psychosis or mental illness. When the first signs of mental disorders appear, treatment with Levofloxacin-Teva should be discontinued.

In patients with sepsis or other severe underlying disease, the use of levofloxacin increases the risk of developing hepatic necrosis (including cases of fatal liver failure). It is recommended to carefully monitor such patients and if signs or symptoms appear that indicate liver damage (including dark urine, abdominal pain, itching, anorexia, jaundice), stop drug therapy and immediately consult a doctor.

During treatment with levofloxacin, the results of laboratory tests to determine opiates in the urine may be false positive. In addition, due to the inhibition of Mycobacterium tuberculosis growth by levofloxacin, further bacteriological diagnosis of tuberculosis may give a false negative result.

Impact on the ability to drive vehicles and complex mechanisms

During treatment with Levofloxacin-Teva, patients are advised to refrain from potentially hazardous activities that require increased attention and high speed of psychomotor reactions, including driving.