Levofloxacin solution for infusion 5mg/ml 100ml vials, 50pcs

Composition

Per 100 ml:

Active ingredient:  levofloxacin hemihydrate 512.5 mg (in terms of levofloxacin) 500.0 mg;

Auxiliary substances:  sodium chloride 900 mg; sodium edetate 5 mg; sodium hydroxide or hydrochloric acid concentrated to pH 4.3-5.3; water for injection up to 100 ml.

Theoretical osmolarity 320 mOsm / l

Pharmacological action

Pharmacotherapy group

Antimicrobial agent-fluoroquinolone.

ATX code:

J01MA12

Pharmacological properties

Pharmacodynamic Aleflox-Alium is a synthetic broad-spectrum antibacterial drug from the group of fluoroquinolones. Levofloxacin, the Active ingredient of the drug, is an optically active levorotatory isomer of ofloxacin. Levofloxacin blocks DNA hydraase and topoisomerase IV, disrupts supercoiling and crosslinking of DNA breaks, inhibits DNA synthesis, and causes deep morphological changes in the cytoplasm, cell wall, and membranes of microbial cells.

Summary data on levofloxacin activity based on in vitro studies and clinical trials are presented below.

Sensitive microorganisms (MPC < 2 mg / l; inhibition zone > 17 mm)Aerobic gram-positive microorganisms: Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus faecalis, Enterococcus spp., Listeria monocytogenes, Staphylococcus coagulase-negative methi-S(I) (coagulase-negative methicillin-sensitive/-moderately sensitive), Staphylococcus aureus methi-S (methicillin-sensitive), Staphylococcus epidermidis methi-S (methicillin-sensitive), Staphylococcus spp. CNS (coagulase-negative), Streptococci of groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae peni-I/S/R (penicillin-moderately sensitive/ – sensitive/ – resistant), Streptococcus pyogenes, Streptococcus viridans peni-S/R (penicillin-sensitive/ – resistant).

Aerobic gram-negative microorganisms: Acinetobacter baumannii, Acinetobacter spp., Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter cloacae, Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S/R (ampicillin-sensitive/resistant), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella spp, Moraxela catarrhalis p+/p-(producing and not producing beta-lactamases), Morganella morganii, Neisseria gonorrhoeae non-PPNG/PPNG (reproducirse and producing penicillinase), Neisseria meningitidis, Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida, Pasteurella spp., Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Providencia spp, Pseudomonas aeruginosa (hospital infections caused by Pseudomonas aeruginosa may require combined treatment), Pseudomonas spp, Salmonella spp, Serratia marcescens, Serratia spp.

anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp, Clostridium perfringens, Fusobacterium spp, Peptostreptococcus, Propionibacterum spp, Veillonella spp..

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

Moderately sensitive microorganisms (MPC = 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 (methicillin-resistant).

Aerobic gram-negative microorganisms: CamPylobacter jejuni / coli.

Anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

Levofloxacin-resistant microorganisms (MPC > 8 mg / l; inhibition zone >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: Micobacterium avium.

Resistance to levofloxacin develops as a result of a step-by-step process of mutation of genes encoding both type II topoisomerases: DNA gyrase and topoisomerase IV (modification of the target of action). Other mechanisms of resistance, such as the effect on microbial cell penetration barriers (a mechanism characteristic of Pseudomonas aeruginosa) and the efflux mechanism (active removal of an antimicrobial agent from a microbial cell), may also reduce the sensitivity of microorganisms to levofloxacin.

There is cross-resistance between levofloxacin and other fluoroquinolones. Due to the mechanism of action, there is usually no cross-resistance between levofloxacin and other groups of antibacterial drugs.

Clinical efficacy(efficacy in clinical trials 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, Moraxela (Branhamella) catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens.

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

Pharmacokinetics After intravenous 60-minute infusion of levofloxacin at a dose of 500 mg to healthy volunteers, the maximum plasma concentration (Cmax) averaged 6.2 mcg / ml.

The pharmacokinetics of levofloxacin are linear in the dose range from 50 to 1000 mg. The equilibrium state of levofloxacin concentration in blood plasma with the introduction of 500 mg of levofloxacin 1 or 2 times a day is reached within 48 hours.

On day 10 of intravenous use of levofloxacin 500 mg once a day, the cmax was 6.4±0.8 mcg / ml, and the minimum concentration of levofloxacin (concentration before the next dose) in blood plasma (Cmin) was 0.6±0.2 mcg/ml.

On day 10 of intravenous use of levofloxacin 500 mg twice daily, Cmax was 7.9±1.1 mcg / ml, and Cmin was 2.3±0.5 mcg / ml.

Distribution of binding to plasma proteins is 30-40%. The volume of distribution of levofloxacin is approximately 100 liters after a single and multiple intravenous use of 500 mg, which indicates good penetration of the drug into human organs and tissues. The equilibrium concentration is reached within 48 hours after taking levofloxacin at a dose of 500 mg 1 or 2 times a day.

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

Penetration into the lung tissue Levofloxacin penetrates well into the lung tissue, the penetration coefficient is 2-5 compared to the concentration in blood plasma.

Penetration into the alveolar uid Penetrates well into the alveolar uid with a penetration coefficient of 1, compared to the concentration in the blood plasma. When levofloxacin 500 mg was administered 1 or 2 times a day for 3 days, the maximum concentrations of levofloxacin in the alveolar fluid were reached 2-4 hours after use and amounted to 4.0 and 6.7 mcg / ml, respectively.

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

Penetration into the cerebrospinal fluid Levofloxacin does not penetrate well into the cerebrospinal fluid.

Penetration into the prostate tissue Levofloxacin penetrates well into the prostate tissue, the average concentration ratio of the prostate gland/blood plasma is 1.84.

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

Metabolism Levofloxacin is extensively metabolized to form dimethyl-levofloxacin and levofloxacin-N-oxide. These metabolites account for less than 5% of the dose excreted through the kidneys. Levofloxacin is stereochemically stable and does not undergo chiral transformations.

Elimination The half-life of levofloxacin (T%^%1/2) is 6-8 hours. Excretion of the drug is mainly carried out by the kidneys (more than 85% of the administered dose). The total clearance of levofloxacin after a single 500 mg dose is 175±29.2 ml/min. There are no significant differences in the pharmacokinetics of levofloxacin when administered intravenously and when taken orally, which confirms that oral use and the intravenous route of use are interchangeable.

Pharmacokinetics in selected groups of patients. In patients with renal insufficiency, the pharmacokinetics of levofloxacin are altered. As renal function worsens, renal excretion and renal clearance (C1R) decrease, and T%^%1/2 increases.

The value of pharmacokinetic parameters in renal insufficiency.

In elderly patients (older than 65 years), the kinetics of levofloxacin does not differ from those in patients of other age groups, with the exception of pharmacokinetic differences associated with changes in creatinine clearance (CC).

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

Indications

Bacterial infections sensitive to levofloxacin in adults:

• community-acquired pneumonia;
• complicated urinary tract infections (including pyelonephritis);
• uncomplicated urinary tract infections;
• chronic bacterial prostatitis;
• skin and soft tissue infections;
• for the complex treatment of drug-resistant forms of tuberculosis;
• prevention and treatment of anthrax in the airborne route of infection.

When using Leflox-Alium, you should take into account the official national recommendations for the proper use of antibacterial drugs, as well as the sensitivity of pathogens in a particular country (see the section “Special instructions”).

Use during pregnancy and lactation

Levofloxacin is contraindicated during pregnancy and lactation.

Contraindications

• hypersensitivity to levofloxacin or other hinolona and/or other components of the drug;
• epilepsy;
• lesions of the tendons that occurred during previous treatment with fluoroquinolones;
• childhood and adolescence to 18 years (due to the incomplete growth of the skeleton, as it is impossible to completely eliminate the lesion of cartilage growth points);
• pregnancy and breastfeeding (it is impossible to completely eliminate the risk of destruction of the cartilage growth points in the fetus and child);
• psevdoparalitichesky myasthenia gravis (myasthenia gravis).

With caution

In patients predisposed to the development of seizures [in patients with previous lesions of the central nervous system (CNS), in patients simultaneously taking drugs that reduce the threshold of convulsive readiness of the brain, such as fenbufen, theophylline] (see the section “Interaction with other drugs”).

In patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency (increased risk of hemolytic reactions during quinolone treatment).

In patients with impaired renal function (mandatory monitoring of renal function is required, as well as correction of the dosage regimen, see the section “Dosage and use”). In patients with known risk factors for prolongation of the QT interval: in elderly patients; in female patients, in patients with uncorrected electrolyte disorders (hypokalemia, hypomagnesemia); with congenital prolongation of the QT interval syndrome; with heart diseases (heart failure, myocardial infarction, bradycardia); while taking medications that can prolong the QT interval (class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, neuroleptics) (see sections “Overdose”, “Interaction with other drugs”, “Special instructions”).

Patients with diabetes mellitus who are treated with oral hypoglycemic drugs, such as glibenclamide or insulin preparations (the risk of hypoglycemia increases).

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

In patients with psychosis or in patients with a history of mental illness (see section “Special instructions”).

Side effects

The following side effects are presented according to the following frequency gradations: very frequent (>1/10); frequent (>>1/100, >><1/10); infrequent (>1/1000, <1/10); infrequent (><1/100); rare (>1/10000, <1/100); rare (><1/1000); very rare (

Data obtained in clinical trials and post-marketing use of the drug Disorders of the heart are rare: sinus tachycardia, palpitation sensation. 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 the sections “Overdose”, “Special instructions”).

Disorders of the blood and lymphatic system are common: leukopenia (a decrease in the number of white blood cells in the peripheral blood), eosinophilia (an increase in the number of eosinophils in the peripheral blood). Rare: neutropenia (a decrease in the number of neutrophils in the peripheral blood), thrombocytopenia (a decrease in the number of platelets in the 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.

Nervous system disorders are frequent: headache, dizziness. Infrequent: drowsiness, tremor, dysgeusia (perversion of taste). Rare: paresthesia, convulsions (see section “Special instructions”). Unknown frequency (post-marketing data): peripheral sensory neuropathy, peripheral sensory-motor neuropathy (see section “Special instructions”), dyskinesia, extrapyramidal disorders, loss of taste sensations, parosmia (a disorder of the sense of smell, especially a subjective sense of smell that is objectively absent), including loss of smell, syncope, benign intracranial hypertension.

Visual disturbances are very rare: visual disturbances, such as blurring of the visible image. Unknown frequency: transient vision loss.

Hearing disorders and labyrinthine disorders are common: vertigo (a feeling of deflection or whirling of one’s own body or surrounding objects). Rare: tinnitus. Unknown frequency (post-marketing data): hearing loss.

Respiratory, thoracic, and mediastinal disorders are common: shortness of breath. Unknown frequency (post-marketing data): bronchospasm, allergic pneumonitis.

Gastrointestinal disorders Common: diarrhea, vomiting, nausea. Infrequent: abdominal pain, dyspepsia, flatulence, constipation. Unknown frequency (post-marketing data): hemorrhagic diarrhea, which in very rare cases can be a sign of enterocolitis, including pseudomembranous colitis (see section “Special instructions”), pancreatitis.

Renal and urinary tract disorders: Frequent: increased serum creatinine. Rare: acute renal failure (for example, due to the development of interstitial nephritis).

Skin and subcutaneous tissue disorders are common: rash, pruritus, urticaria, hyperhidrosis. Unknown frequency (post-marketing data): toxic epidermal necrolysis, Stevens-Johnson syndrome, exudative erythema multiforme, photosensitization reactions (hypersensitivity to sunlight and ultraviolet radiation) (see the section “Special instructions”), leukocytoclastic vasculitis, stomatitis. Reactions from the skin and mucous membranes can sometimes develop even after the first dose of the drug is administered.

Musculoskeletal system and connective tissue disorders: arthralgia, myalgia. Rare: tendon involvement, including tendinitis (such as Achilles tendon), muscle weakness that can be particularly dangerous in patients with pseudoparalytic myasthenia gravis (see section “Special instructions”). Unknown frequency (post-marketing data): rhabdomyolysis, tendon rupture (for example, Achilles tendon. This side effect may occur within 48 hours after starting treatment and may be bilateral in nature( see also the section “Special instructions”)), ligament rupture, muscle rupture, arthritis.

Metabolic and nutritional disorders are common: anorexia. Rare: hypoglycemia, especially in patients with diabetes mellitus (possible signs of hypoglycemia: “wolfish” appetite, nervousness, perspiration, trembling). Unknown frequency: hyperglycemia, hypoglycemic coma (see section “Special instructions”).

Infectious and parasitic diseases are common: fungal infections, development of resistance of pathogenic microorganisms.

Vascular disorders are frequent: phlebitis. Rare: low blood pressure.

General disorders and disorders at the injection site Frequent: reaction at the injection site (soreness, hyperemia of the skin). Infrequent: asthenia. Rare: pyrexia (increased body temperature). Unknown frequency: pain (including pain in the back, chest, and extremities).

Immune system disorders Rare: angioedema. Unknown frequency (post-marketing data): anaphylactic shock, anaphylactoid shock. Anaphylactic and anaphylactoid reactions can sometimes develop even after the first dose of the drug is administered.

Liver and biliary tract disorders are frequent: increased activity of” liver ” enzymes in the blood (for example, alanine aminotransferase (AlAT), aspartate aminotransferase (AsAT)), increased activity of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT). Infrequent: increased bilirubin concentration in the blood. Unknown frequency (post-marketing data): severe hepatic insufficiency, including cases of acute hepatic insufficiency, sometimes fatal, especially in patients with a severe underlying disease (for example, in patients with sepsis), hepatitis, jaundice.

Mental disorders are frequent: insomnia. Infrequent: feelings of restlessness, anxiety, confusion. Rare: mental disorders (such as hallucinations, paranoia), depression, agitation (agitation), sleep disorders, nightmares. Unknown frequency (post-marketing data): mental disorders with self-harm behavioral disorders, including suicidal thoughts and suicide attempts.

Other possible adverse effects related to all fluoroquinolones are very rare: attacks of porphyria (a very rare metabolic disease) in patients with porphyria.

Interaction

Interactions that require caution with theophylline, fenbufen, or similar drugs from the group of nonsteroidal anti-inflammatory drugs that reduce the threshold of convulsive readiness of the brain. There was no pharmacokinetic interaction between levofloxacin and theophylline. However, with the simultaneous use of quinolones with theophylline, with nonsteroidal anti-inflammatory drugs 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 the presence of fenbufen, the levofloxacin concentration increases by approximately 13%.

With indirect anticoagulants (vitamin K antagonists)Patients treated with levofloxacin in combination with indirect anticoagulants (for example, warfarin) experienced an increase in prothrombin time/international normalized ratio and/or the development of bleeding, including severe bleeding. Therefore, with the simultaneous use of indirect anticoagulants and levofloxacin, regular monitoring of blood clotting parameters is necessary.

Caution should be exercised with probenecid and cimetidine when concomitant use of drugs that interfere with renal tubular secretion, such as probenecid and cimetidine, and levofloxacin, especially in patients with renal insufficiency. Elimination (renal clearance)of levofloxacin is slowed by cimetidine by 24% and probenecid by 34%.

With cyclosporin, the T 1/2 of cyclosporin increases by 33% when levofloxacin is co-administered.

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

Other clinical and pharmacological studies have shown that the combined use of calcium carbonate, glibenclamide, ranitidine, digoxin did not have a clinically significant effect on the pharmacokinetics of levofloxacin.

Other relevant informationsimple use of glucocorticosteroids increases the risk of tendon rupture.

No changes in the pharmacokinetics of theophylline (a marker substrate for CYP1A2) were observed in levofloxacin interaction studies, which indicates that levofloxacin is not an inhibitor of the CYP1A2 isoenzyme.

How to take, course of use and dosage

Dosage regimen and duration of treatment 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. As with other antibiotics, treatment with Leflox-Alium is recommended to continue for at least 48-78 hours after normalization of body temperature or reliable eradication of the pathogen.

Treatment with Leflox-Alium should not be interrupted or terminated prematurely without a doctor’s instruction.

Depending on the patient’s condition, after a few days of treatment, you can switch from intravenous infusion to taking the same dose of the drug in tablets (due to the fact that the bioavailability of levofloxacin when taking levofloxacin tablets is 99-100%) (see the section “Pharmacokinetics”).

If the drug is accidentally missed, then the missed dose should be administered as soon as possible and then continue to administer Leflox-Alium according to the recommended dosage regimen.

Recommended dosage regimen and duration of treatment in patients with normal renal function (creatinine clearance> 50 ml / min)- Community-acquired pneumonia: 500 mg of levofloxacin 1-2 times a day (respectively, the daily dose of 500-1000 mg of levofloxacin) – 7-14 days. – Complicated urinary tract infections: 500 mg of levofloxacin once a day (respectively, the daily dose of 500 mg of levofloxacin) – 7-14 days. – Pyelonephritis: 500 mg of levofloxacin once a day (respectively, the daily dose of 500 mg of levofloxacin) – 7-10 days. – Uncomplicated urinary tract infections: 250 mg of levofloxacin once a day (respectively, the daily dose of 250 mg of levofloxacin) – 3 days. – Chronic bacterial prostatitis: 500 mg of levofloxacin once a day (respectively, the daily dose of 500 mg of levofloxacin) – 28 days. – Infections of the skin and soft tissues: 500 mg of levofloxacin 1-2 times a day (respectively, the daily dose of 500-1000 mg of levofloxacin) – 7-14 days. – Complex treatment of drug-resistant forms of tuberculosis: 500 mg of levofloxacin 1-2 times a day (respectively, a daily dose of 500-1000 mg of levofloxacin) – up to 3 months. – Prevention and treatment of anthrax with airborne infection: 500 mg of levofloxacin 1 time a day (respectively, a daily dose of 500 mg of levofloxacin) – for up to 8 weeks.

Dosage regimen in patients with impaired renal function (CCLevofloxacin is mainly excreted through the kidneys, so when treating patients with impaired renal function, it is necessary to reduce the dose of the drug (see the table below).

1 = No additional doses are required after hemodialysis or continuous outpatient peritoneal dialysis (PAPD).

Dosage regimen in patients with impaired hepatic function, no dosage adjustment is required in patients with impaired liver function, 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 of a decrease in creatinine clearance to 50 ml / min or lower.

Method of applicationinfusion solution of the drug Leflox-Alium is administered once or twice a day. Infusion solution of the drug Leflox-Alium 500 mg is administered SLOWLY intravenously by drip. The duration of infusion of 1 vial of Leflox-Alium 500 mg solution (100 ml with 500 mg of levofloxacin) should be at least 60 minutes, in the case of use of half a vial (50 ml with 250 mg of levofloxacin), the duration of infusion should be at least 30 minutes (see the section “Special instructions”).

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

A solution of Leflox-Alium 500 mg should not be mixed with heparin or solutions that have an alkaline reaction (for example, with a solution of sodium bicarbonate).

After removing the bottle from the cardboard pack, the infusion solution can be stored in room light without light protection for no more than 3 days!

Overdose

Based on data obtained in animal studies, the most important expected symptoms of levofloxacin overdose are central nervous system symptoms (impaired consciousness, including confusion, dizziness, and seizures), as well as prolongation of the QT interval.

Central nervous system effects, including confusion, convulsions, hallucinations, and tremors, have been observed in post-marketing use of the drug in overdose.

Nausea and erosion of the gastrointestinal mucosa may occur.

In clinical and pharmacological studies conducted with doses of levofloxacin exceeding therapeutic ones, 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. Levofloxacin is not eliminated by dialysis (hemodialysis, peritoneal dialysis, and permanent outpatient peritoneal dialysis).

There is no specific antidote.

Special instructions

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

The prevalence of acquired resistance of the seeded strains of microorganisms may vary depending on the geographical region and over time. In this regard, information on drug resistance in a particular country is required; for the treatment of severe infections or if treatment is ineffective, a microbiological diagnosis should be established with the isolation of the pathogen and determination of its sensitivity to levofloxacin.

Methicillin-resistant Staphylococcus aureus There is a high probability that methicillin-resistant 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 Staphylococcus aureus, if laboratory tests have not confirmed the sensitivity of this microorganism to levofloxacin.

Duration of infusions It is necessary to strictly adhere to the recommended duration of use, which should be at least 60 minutes (for 100 ml of infusion solution) or 30 minutes (for 50 ml of solution). Experience with the use of levofloxacin shows that during the infusion there may be an increased heartbeat and a transient decrease in blood pressure. In rare cases, there may be a vascular collapse. If there is a marked decrease in blood pressure during the infusion of levofloxacin, the infusion is stopped immediately.

Patients predisposed to seizures Like other quinolones, levofloxacin should be used with great caution in patients with a predisposition to seizures. These patients include patients with previous central nervous system disorders, such as stroke, severe traumatic brain injury; patients who are taking concomitant medications that lower the threshold for convulsive readiness of the brain, such as fenbufen and other similar nonsteroidal anti-inflammatory drugs or other drugs that lower the threshold for convulsive readiness, such as theophylline (see the 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 metronidazole orally) should be initiated immediately. Drugs that inhibit intestinal motility are contraindicated.

Tendinitis Rarely observed tendinitis with quinolones, including levofloxacin, can lead to tendon rupture, including the Achilles tendon. This side effect may develop within 48 hours of starting treatment and may be bilateral. Elderly patients are more likely to develop tendinitis. The risk of tendon rupture may increase with concomitant use of corticosteroids. If tendinitis is suspected, you should immediately stop treatment with Leflox-Alium and start appropriate treatment of the affected tendon, for example, by ensuring that it is sufficiently immobilized (see the sections “Contraindications” and “Side effects”).

Hypersensitivity Reactionsilevofloxacin can cause serious, potentially fatal hypersensitivity reactions (angioedema, anaphylactic shock) (see section “Side effects”). Patients should immediately stop the drug use and consult a doctor.

Severe bullous reactionswhen taking levofloxacin, there have been cases of severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (see the section “Side effects”). In case of any skin or mucosal reactions, the patient should immediately consult a doctor and not continue treatment until after consultation.

Liver and biliary tract disorders Cases of hepatic necrosis, including fatal liver failure, have been reported with levofloxacin, mainly in patients with severe underlying medical conditions, such as sepsis (see section “Adverse effects”). Patients should be warned to stop treatment and seek immediate medical attention if signs and symptoms of liver damage appear, such as anorexia, jaundice, dark urine, itching, and abdominal pain.

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

Prevention of photosensitization reactions Although photosensitization is very rare when levofloxacin is used, to prevent its development, patients are not recommended to be exposed to strong solar or artificial ultraviolet radiation (for example, to visit a tanning salon) during treatment and within 48 hours after the end of treatment with levofloxacin.

Superinfectio Nas with other antibiotics, the use of levofloxacin, especially for a long time, can lead to increased reproduction 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 necessary to re-evaluate the patient’s condition and, if superinfection develops during treatment, appropriate measures should be taken.

QT prolongation Very rare cases of QT prolongation have been reported in patients taking fluoroquinolones, including levofloxacin. Caution should be exercised when using fluoroquinolones, including levofloxacin, in patients with known risk factors for QT prolongation: in elderly patients; in patients with uncorrected electrolyte disturbances (hypokalemia, hypomagnesemia); with congenital QT prolongation syndrome; with heart diseases (heart failure, myocardial infarction, bradycardia); while taking medications that can prolong the QT interval, such as antiarrhythmics class IA and III, 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 use”, “Side effects”, “Overdose” and “Interaction with other drugs”).

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

Hypo and hyperglycemia (dysglycemia)As with other quinolones, hyperglycaemia and hypoglycaemia have been reported with levofloxacin, especially in diabetic patients receiving concomitant treatment with oral hypoglycaemic drugs (e. g., glibenclamide) or insulin preparations. Cases of hypoglycemic coma have been reported. Blood glucose monitoring is required in patients with diabetes mellitus (see section “Side effects”).

Peripheral neuropathyin patients taking fluoroquinolones, including levofloxacin, sensory and sensorimotor peripheral neuropathy has been reported, the onset of which may be rapid. If the patient develops symptoms of neuropathy, levofloxacin should be discontinued. This minimizes the possible risk of irreversible changes.

Exacerbation of pseudoparalytic myasthenia gravis Fluoroquinolones, including levofloxacin, are characterized by neuromuscular blocking activity and may increase muscle weakness in patients with pseudoparalytic myasthenia gravis. In the post-marketing period, adverse reactions were observed, including pulmonary insufficiency that required mechanical ventilation, and death, which were associated with the use of fluoroquinolones in patients with pseudoparalytic myasthenia gravis. The use of levofloxacin in a patient with an established diagnosis of pseudoparalytic myasthenia gravis is contraindicated (see the section “Contraindications”).

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

Psychotic reactionswhen using quinolones, including levofloxacin, psychotic reactions have been reported, which in rare cases progressed to the development of suicidal thoughts and behavioral disorders with self-harm (sometimes after a single dose of levofloxacin). If such reactions occur, treatment with levofloxacin should be discontinued and appropriate treatment should be prescribed. Caution should be exercised when prescribing the drug to patients with psychosis or a history of mental illness.

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

Effects on laboratory tests in patients taking levofloxacin, the determination of opiates in the urine may lead to false positive results, which should be confirmed by more specific methods. Levofloxacin can inhibit the growth of Mycobacterium tuberculosis and subsequently lead to false negative results of the bacteriological diagnosis of tuberculosis.

Influence on the ability to drive vehicles and mechanisms

Side effects of levofloxacin such as dizziness or vertigo, drowsiness, and visual disturbances (seesection “Side effects”), may reduce psychomotor reactions and the ability to concentrate. This can pose a certain risk in situations where these abilities are particularly important (for example, when driving a car, when servicing machines and mechanisms, when performing work in an unstable position).

Storage conditions

Store in a dark place at a temperature not exceeding 25°C. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date indicated on the package.

Active ingredient

Levofloxacin

Conditions of release from pharmacies

By prescription

Dosage form

infusion solution