Levofloxacin STADA - instructions for use, dose, side effects, contraindications

Excipients: giprolose 10.00 mg, cellulose microcrystalline 114.20 mg, carboxymethyl starch sodium 7.00 mg, crospovidone 13.00 mg, croscarmellose sodium 17.00 mg, silicon dioxide colloid 6.00 mg, magnesium stearate 10.00 mg;

shell: hypromellose 10.11 mg, talc 1.12 mg, titanium dioxide 1.77 mg, triacetate 0.80 mg.

Description:

Double-convex capsule capsules coated with a white or almost white film membrane, with a risk on one side.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A Fluoroquinolones

J.01.M.A.12 Levofloxacin

Pharmacodynamics:

Levofloxacin is a synthetic broad-spectrum antibacterial agent from the group of fluoroquinolones, contains as an active substance levofloxacin (levorotatory isofloxacin isomer).

Has a bactericidal effect by blocking the DNA-gyre (topoisomerase II) and topoisomerase IV. violates the supercoiling and cross-linking of DNA gaps, inhibits DNA synthesis, causes profound morphological changes in the cytoplasm, cell The wall and membrane of the microbial cell. Levofloxacin active against most strains of microorganisms both in conditions in vitro, and in vivo.

Sensitive microorganisms

(IPC ≤ 2 mg / ml, inhibition zone ≥ 17 mm)

Aerobic Gram-positive microorganisms: Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus spp. (at t.h. Enterococcus faecalis), Listeria monocytogenes, Staphylococcus spp. (coagulase-negative methicillin- sensitive/ moderately sensitive strains), including Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin- Sensitive strains), Staphylococcus spp. (leukotoxin-containing); Streptococci trousers FROM and G, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin- sensitive/ moderately sensitive/ resistant strains), Streptococcus pyogenes, Streptococcus groups viridans (penicillin-sensitive/ resistant strains).

Aerobic Gram-negative microorganisms: Acinetobacter spp. (at t.h. Acinetobacter baumannii), Actinobacillus actinomycetemcomitans, Citrobacter Freundii, Eikenella corrodens, Enterobacter spp. (at t.h. Enterobacter aerogenes, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (ampicillin- sensitive/ resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (at t.h. Klebsiella oxytoca, Klebsiella pneumoniae), Moraxella catarrhalis (producing and not producing beta-lactamase strains), Morganella morganii, Neisseria gonorrhoeae (producing and ns producing penicillinase strains), Neisseria meningitidis, Pasteurella spp. (at t.h. Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida), Proteus mirabilis, Proteus vulgaris, Providencia spp. (at t.h. Providencia rettgeri, Providencia stuartii), Pseudomonas spp. (at t.h. Pseudomonas aeruginosa; ghospitalized infection, caused by Pseudomonas aeruginosa, may demand combined treatment), Salmonella spp., Serratia spp. (at t.h. Serratia marcescens),

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 spp. (at t.h. Legionella pneumophila), Mycobacterium spp. (at t.h. Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

Moderately sensitive microorganisms

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

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

Aerobic Gram-negative microorganisms: Campilobacter jejuni, Campilobacter coli.

Anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

Resistant to levofloxacin microorganisms

(IPC ≥ 8 mg / L, inhibition zone ≤ 13 mm)

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

Aerobic Gram-negative microorganisms: Alcaligenes xylosoxidans.

Anaerobic microorganisms: Bacteroides thetaiotaomicron.

Other microorganisms: Mycobacterium avium.

Resistance

Resistance to levofloxacin develops as a result of a step-by-step process of mutations of genes that call both topoisomerases of the type II: DNA-gyrase and topoisomerase IV. Other mechanisms of resistance are the mechanism of influence on the penetration barriers of a microbial cell (characteristic for Pseudomonas aeruginosa) and the mechanism of efflux (active removal of the antimicrobial from the microbial cell), can also reduce the sensitivity of microorganisms to levofloxacin.

Due to the peculiarities of the mechanism of action, usually there is a cross-resistance between levofloxacin and other classes of antibacterial agents. Despite the presence of cross-resistance between levofloxacin and other fluoroquinolones, the high activity of levofloxacin is possible with the stability of the microorganism to other fluoroquinolones, in particular to ofloxacin (see section "Specific guidance").

Pharmacokinetics:

Absorption

After ingestion levofloxacin quickly and almost completely absorbed; food intake has little effect on the speed and completeness of absorption. Bioavailability with ingestion is 99-100%. After a single dose of 500 mg of levofloxacin, the maximum concentration in the blood plasma is reached within 1-2 hours and is 5.2 μg / ml. The state of the equilibrium concentration when taking 500 mg of levofloxacin once or twice a day is reached within 48 hours.

Distribution

Binding to blood plasma proteins - 30-40%.The volume of distribution after a single and repeated administration of levofloxacin in a dose of 500 mg averages 100 l, which recovers on a wide distribution in the organs and tissues of the body.

Levofloxacin penetrates well into the organs and tissues: lungs, bronchial mucosa, ENT organs, urogenital system organs, liver, gall bladder tissues, skin, bone and cartilaginous tissue, polymorphonuclear leukocytes, alveolar macrophages. It is found in sputum, tear fluid, prostatic fluid, bile. Poor penetrates into the cerebrospinal fluid.

Penetration of the bronchial mucosa, epithelial lining fluid, alveolar macrophages.

After a single oral intake of 500 mg of levofloxacin mThe maximum concentrations in bronchial mucosa and epithelial lining fluid for 1 and 4 hours are 8.3 μg / g and 10.8 μg / ml, respectively. After 5 days of use, 4 hours after the last ingestion, the average concentrations of levofloxacin in the fluid of the epithelial lining are about 9.94 μg / ml, in the alveolar macrophages - 97.9 μg / ml.

Penetration into the lung tissue.

Maximum concentrations in the pulmonary tissue after PThe inside of 500 mg of levofloxacin is reached after 4-6 hours and is about 11.3 μg / g with a penetration factor of 2-5 compared to the concentration in the blood plasma.

Penetration into the alveolar tissue.

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

Penetration into bone tissue.

Levofloxacin penetrates well into the cortical and spongy layers of the bone tissue of the proximal and distal parts of the femur, with a coefficient of penetration (bone tissue / blood plasma) of 0.1-3. After 2 hours after taking a 15 dose of 500 mg, the maximum concentration of levofloxacin in the spongy tissue of the proximal femur is about 15.1 μg / g.

Penetration into the cerebrospinal fluid in small quantities.

Penetration into the tissue of the prostate gland.

After taking 500 mg of levofloxacin once a day for 3 days, the concentration of levofloxacin in the prostate tissue averages 8.7 μg / g (1.84 times higher than the concentration in the blood plasma).

Concentrations in the urine.

The average concentrations of levofloxacin in the urine after 8-12 hours after ingestion at a dose of 150, 300 and 600 mg are 44, 91 and 162 μg / ml, respectively.

Metabolism

Levofloxacin is slightly metabolized in the liver to form metabolites of desmethyllevofloxacin and N-hydroxyl-floxacin, which are then excreted by the kidneys. Levofloxacin is stereochemically stable and does not undergo chiral transformations.

Excretion

After ingestion, it is relatively slowly excreted from the blood plasma (the average half-life is 6-8 hours). It is excreted from the body in an unchanged form mainly by the kidneys (more than 85% of the dose taken internally) by glomerular filtration and tubular secretion. Less than 4% of the dose is excreted by the intestine within 72 hour, less than 5% - with urine in the form of metabolites. The total clearance of levofloxacin after a single dose of 500 mg is 175 ± 29.2 ml / min.

Linearity

The pharmacokinetics of levofloxacin in the dose range from 50 to 1000 mg is linear. There are no significant differences in the pharmacokinetics of levofloxacin when taken orally and intravenously in equal doses, so both modes of administration are interchangeable.

Pharmacokinetics the patients of special groups

Patients with impaired renal function. As the kidney function decreases, the pharmacokinetics of levofloxacin changes: the excretion through the kidneys and renal clearance of levofloxacin decrease, the elimination half-life increases.

Pharmacokinetic parameters in patients with renal insufficiency after a single oral intake of 500 mg of levofloxacin:

Creatinine clearance (ml / min)	<20	20 - 49	50 -80
The clearance of levofloxacin (ml / min)	13	26	57
Half-life (hour)	35	27	9

Patients with impaired liver function. Liver failure does not affect the pharmacokinetics of levofloxacin.

Patients of advanced age. There are no significant differences in the pharmacokinetics of levofloxacin in patients older than 65 years and younger individuals, except for differences related to creatinine clearance.

In men and women pharmacokinetics of levofloxacin does not differ significantly.

Indications:

Bacterial infections caused by susceptible to levofloxacin microorganisms 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
Drug-resistant forms of tuberculosis (as part of complex therapy).

When using the drug Levofloxacin should be guided by the current national recommendations on the proper use of antibacterial drugs, taking into account the sensitivity of pathogenic microorganisms in a particular country / region.

Contraindications:

- Hypersensitivity to levofloxacin, other quinolones or any of the excipients of the drug Levofloxacin.

- Epilepsy.

- Myasthenia gravis gravis (pseudo-paralytic myasthenia gravis).

- The defeat of the tendons during the previous treatment with quinolones.

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

- Pregnancy (you can not completely exclude the risk of damage to the cartilage points of bone growth in the fetus).

- The period of breastfeeding (due to the risk of destruction of cartilage points of bone growth in a child).

Carefully:

- Patients predisposed to the development of seizures (cerebral atherosclerosis, cerebrovascular disease (including history), organic lesions of the central nervous system), or in patients receiving both drugs that reduce the seizure threshold of the brain preparedness (theophylline, fenbufen, other non-steroidal anti-inflammatory drugs; see section "Interaction with other drugs").

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

- In patients with impaired renal function (monitoring of renal function and correction of dosing regimen are required, see section "Dosing and Administration"),

- In patients with risk factors for lengthening the interval QT: Elderly (over 65 years), female with uncorrected electrolyte disorders (hypokalemia, hypomagnesemia), syndrome of congenital prolongation of the interval QT, with diseases of the heart (heart failure, myocardial infarction, bradycardia); in patients concurrently taking medications that are able to lengthen the interval QT (antiarrhythmic drugs of classes IA and III, tricyclic and tetracyclic antidepressants, macrolides, antipsychotics, antifungal agents / imidazole derivatives; some antihistamines, including. astemizole, terfenadine, ebastine; see the sections "Interaction with other medicines", "Special instructions").

- In patients with diabetes mellitus, receiving hypoglycemic agents for ingestion, for example, glibenclamide or insulin preparations (increased risk of hypoglycemia, see "Interaction with other drugs", "Special instructions").

- In patients with severe adverse reactions against other fluoroquinolones, such as severe neurologic reactions (the risk of developing similar reactions with levofloxacin).

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

- Joint application with glucocorticosteroids (increased risk of rupture of tendons), indirect anticoagulants (increased risk of bleeding), drugs that block tubular secretion (in patients with impaired renal function) (see.section "Interaction with other drugs").

Pregnancy and lactation:

A drug Levofloxacin is contraindicated for use during pregnancy and during breastfeeding (see section "Contraindications").

Dosing and Administration:

Inside, 1 or 2 times a day (every 24 hours or 12 hours).

Tablets should be swallowed whole, not chewing, and washed down with a sufficient amount of liquid (from ½ up to 1 cup); take before meals or between meals.

Doses and duration of therapy are determined by the nature and severity of the infection, as well as the susceptibility of the suspected microorganism.

Patients with a normal or moderately reduced function kidneys (creatinine clearance more than 50 ml / min) the following dosing regimen and the duration of therapy with Levofloxacin are recommended:

- Acute Sinusitis: 500 mg once a day for 10-14 days.

- Exacerbation of chronic bronchitis: 500 mg once a day - 7-10 days.

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

- Uncomplicated urinary tract infections: 250 mg once a day for 3 days.

- Complicated urinary tract infections: 500 mg once a day - 7-14 days.

- Pyelonephritis: 500 mg once a day - 7-10 days.

- Chronic bacterial prostatitis: 500 mg once a day - 28 days.

- Infections of the skin and soft tissues: 500 mg 1 -2 times a day - 7-14 days.

- Drug-resistant forms of tuberculosis (as part of complex therapy): 500 mg 1-2 times a day - up to 3 months.

Given that the bioavailability of levofloxacin for oral administration and intravenous administration is practically the same, the drug Levofloxacin can be used to continue the course of therapy initiated with intravenous infusion of levofloxacin in the same dose (see section "Pharmacokinetics").

Treatment with drug Levofloxacin it is recommended to continue after normalization of body temperature or reliable destruction of the pathogen within 48-72 hours.

If the reception is missed preparation Levofloxacin, it is necessary to take the next dose as soon as possible and then observe equal time intervals between receptions - 24 hours (with the mode of reception 1 time per day) or 12 hours (with the mode of reception 2 times a day).

Special patient groups

Patients with impaired renal function (creatinine clearance <50 mL / min)

Because the levofloxacin is excreted mainly by the kidneys, in patients with renal insufficiency, a dose reduction and / or an increase in the dosage interval of the drug Levofloxacin, depending on the creatinine clearance:

Clearance creatinine (ml / min)	The recommended dose of the drug for clearance of creatinine more than 50 ml / min
Clearance creatinine (ml / min)	250 mg once a day	500 mg once a day	500 mg twice a day
50-20	the first dose of 250 mg, then 125 mg / 24 hour	the first dose of 500 mg, followed by 250 mg / 24 hour	the first dose of 500 mg, then 250 mg / 12 hour
19-10	the first dose of 250 mg, then 125 mg / 48 hour	the first dose of 500 mg, followed by 125 mg / 24 hour	the first dose of 500 mg, then 125 mg / 12 hour
<10 ml / min (including hemodialysis and CAPD)¹	the first dose of 250 mg, then 125 mg / 48 hour	the first dose of 500 mg, followed by 125 mg / 24 hours	the first dose of 500 mg, then 125 mg / 24 hour

¹ after hemodialysis or permanent ambulatory peritoneal dialysis (CAPD) introduction of additional doses of the drug Levofloxacin not required.

Elderly patients

Correction of the dose ns is required, except for cases when the creatinine clearance is reduced to 50 ml / min and below.

Patients with impaired hepatic function

Dose correction is not required, since levofloxacin is slightly metabolized in the liver.

Side effects:

The frequency of the following possible side effects of levofloxacin is indicated in accordance with the classification of the World Health Organization: Often - more than 10%; often - more than 1% and less than 10%; infrequently - more than 0.1% and less than%; rarely - more than 0,01% and less than 0,1%; rarely - less than 0.01%, including individual cases; frequency unknown - can not be determined on the basis of available data.

Disorders from the heart: rarely - Sinus tachycardia, palpitation; frequency unknown - lengthening of the interval QT, ventricular arrhythmias, ventricular tachycardia of the "pirouette" type, which can lead to cardiac arrest, see "Special instructions").

Vascular disorders: rarely - lowering blood pressure.

Disorders from the blood and lymphatic system: infrequently - Lakopenia, eosinophilia; rarely - neutropenia, thrombocytopenia; frequency unknown pancytopenia, agranulocytosis, hemolytic anemia.

Disorders from the nervous system: often - headache, dizziness; infrequently - drowsiness, tremor, perversion of taste; rarely - paresthesia, convulsions (see p. sections "Interaction with other medicines", "Special instructions"); frequency unknown - peripheral sensory neuropathy, peripheral sensory-motor neuropathy (see section "Special instructions"), dyskinesia, extrapyramidal disorders,loss of taste sensations, parosmia (odor disorder, especially subjective sense of smell, objectively absent), loss of smell, fainting, benign intracranial hypertension.

Mental disorders: often - insomnia; infrequently - anxiety, anxiety, confusion; rarely - mental disorders (eg, hallucinations, paranoia), depression, agitation, sleep disorders, nightmares; frequency unknown - a violation of the psyche with a violation of behavior with self-harm, including suicidal thoughts and suicidal attempts.

Disorders from the side of the organ of vision: very rarely - visual impairment, for example, the vagueness of the visible image; frequency unknown - transient loss of vision.

Hearing disorders and labyrinthine disturbances: infrequently - Vertigo; rarely - ringing in the ears; frequency unknown - decrease / loss of hearing.

Disturbances from the respiratory system, chest and mediastinal organs: infrequently - Shortness of breath; frequency unknown - bronchospasm, allergic pneumonitis.

Disturbances from the gastrointestinal tract: often - diarrhea, vomiting, nausea; infrequently - abdominal pain, indigestion, flatulence, constipation; frequency unknown - hemorrhagic diarrhea, which in very rare cases can be a sign of enterocolitis, including pseudomembranous colitis (see section "Special instructions"), pancreatitis.

Disorders from the liver and biliary tract: often - an increase in the activity of "hepatic" transaminases (alanine aminotransferase, aspartate aminotransferase), alkaline phosphatase and gamma-glutamyltransferase; infrequently - increasing the concentration of bilirubin in the blood; frequency unknown - severe hepatic insufficiency, including cases of development of acute hepatic insufficiency, sometimes with fatal outcome, especially in patients with severe underlying disease (for example, in patients with sepsis (see section "Special instructions"), hepatitis, jaundice.

Disorders from the kidneys and urinary tract: infrequently - increased serum creatinine concentration; rarely - Acute renal failure (eg, due to the development of interstitial nephritis).

Disturbances from the skin and subcutaneous tissues: infrequently - rash, itching, hives, hyperhidrosis; frequency unknown - toxic epidermal necrolysis, syndrome Stevens-Johnson, exudative erythema multiforme, reactions photosensitivity (see. section "Special instructions"), leukocytoclastic vasculitis, stomatitis. Reactions from the skin and mucous membranes can sometimes develop even after taking the first dose of levofloxacin.

Disturbances from musculoskeletal and connective tissue: infrequent - Arthralgia, myalgia; rarely - the defeat tendons, including tendinitis (eg Achilles tendon), muscular weakness, which can be especially dangerous in patients with gravis (myasthenia gravis gravis; see "Special thekazaniya "); frequency unknown - rhabdomyolysis, tendon rupture (eg Achilles tendon; this adverse reaction can occur within 48 hours after the start of treatment and be two-way (see "Cautions"), rupture of ligaments, muscle tear, arthritis..

Disorders from the metabolism and nutrition: infrequently - anorexia; rarely - hypoglycemia, especially in patients with diabetes (signs: excessive appetite, nervousness, sweating, tremor); frequency unknown - hyperglycemia, hypoglycemic coma (see section "Special instructions").

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

Immune system disorders: rarely - angioedema; frequency unknown - anaphylactic / anaphylactoid shock. Anaphylactic and anaphylactoid reactions can develop sometimes after taking the first dose of levofloxacin.

General disorders and disorders at the site of administration: infrequently - asthenia; rarely increased body temperature; frequency unknown - pain (including pain in the back, chest, extremities).

Other possible unwanted reactions, related to all fluoroquinolones: rarely - Attacks of porphyria in patients with porphyria.

Overdose:

Symptoms: impairment of consciousness, including confusion, dizziness, convulsions, hallucinations, tremors; interval lengthening QT on an electrocardiogram (ECG); nausea, erosion of the mucous membrane of the gastrointestinal tract.

Treatment. Careful monitoring of the patient, including ECG monitoring, is necessary.It shows gastric lavage and antacid administration for the protection of the gastric mucosa. Treatment is symptomatic. Levofloxacin is not excreted by dialysis (hemodialysis, peritoneal dialysis, permanent ambulatory peritoneal dialysis). There is no specific antidote.

Interaction:

Preparations containing magnesium, aluminum, iron, zinc, didanosine

Magnesium and / or aluminum-containing antacids, preparations containing bivalent or trivalent cations of zinc or iron (for example, multivitamins, medicines for the treatment of anemia), didanosine (only dosage forms containing magnesium or aluminum as a buffer), form chelate complexes with levofloxacin. When combined with these agents, the absorption of levofloxacin in the gastrointestinal tract slows down, which leads to a decrease in its concentration in the blood plasma and a weakened effect. These drugs should be taken at least 2 hours before or 2 hours after taking the drug Levofloxacin.

Salts of calcium have a minimal effect on the absorption of levofloxacin when combined.

Sucralfate

The effect of levofloxacin is significantly weakened by simultaneous application of sucralfate. Patients receiving levofloxacin and sucralfate, it is recommended to take sucralfate 2 hours after taking levofloxacin.

Theophylline, fenbufen and similar drugs from the group of non-steroidal anti-inflammatory drugs (NSAIDs), lowering the threshold of convulsive readiness of the brain

Pharmacokinetic interaction of levofloxacin with theophylline ns was revealed. The concentration of levofloxacin when administered together with fenbufen is only increased by 13%. However, with the simultaneous use of other quinolones with theophylline, NSAIDs and other drugs that reduce the threshold of seizure readiness of the brain, there is an increased risk of seizures (see the section "With caution", "Special instructions").

Glucocorticosteroids

Joint use with levofloxacin increases the risk of rupture of tendons (see sections "With caution", "Special instructions").

Indirect anticoagulants (antagonists of vitamin K)

When combined with levofloxacin with indirect anticoagulants (for example, warfarin) in patients there was an increase in prothrombin time / international normalized relationship and / or development of bleeding, incl. heavy. Therefore, when they are used simultaneously, regular monitoring of blood clotting indices is required (see "With caution").

Probenecid, cimetidine

Drugs that block tubular secretion, slow the withdrawal of levofloxacin (cimetidine by 24%, probenecid by 34%); caution should be exercised when combined use, especially in patients with renal insufficiency (see "With caution"). Clinical significance for patients with normal function of noctuidus is unlikely.

Cyclosporin

Levofloxacin increases the half-life of cyclosporine by 33% (clinically insignificant); correction of the dose of cyclosporine is not required.

Drugs that extend the interval QT

Like other fluoroquinolones, the drug Levofloxacin should be used with caution in patients taking drugs that can lengthen the interval QT (for example, antiarrhythmic drugs of classes IA and III, Tricyclic and tetracyclic antidepressants, macrolides, antipsychotics, antifungals / imidazole derivatives; some antihistamines, 15 t. h. astemizole, terfenadine, ebastine) (see the sections "With caution", "Special instructions").

There was no clinically significant change in pharmacokinetics levofloxacin for application with digoxin, glibenclamide, ranitidine, warfarin.

Special instructions:

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

The prevalence of acquired resistance sown strains of microorganisms can vary depending on the geographical region and over time. In this regard, with the appointment of the drug Levofloxacin information on the resistance to levofloxacin in a particular country / region should be used. In the treatment of severe infections or in the ineffectiveness of treatment, a microbiological diagnosis should be made, isolating the pathogen and determining sensitivity to levofloxacin.

Methicillin-resistant Staphylococcus aureus

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

Predisposition to development of seizures

Like other quinolones, the drug Levofloxacin should be used with extreme caution in patients with a predisposition to seizures. These are patients with atherosclerosis of the cerebral vessels, with previous lesions of the central nervous system (for example, stroke, severe craniocerebral trauma in the anamnesis) or patients simultaneously receiving drugs that lower the threshold of convulsive brain readiness (fenbufen, others similar to it, theophylline; see the sections "With caution", "Interaction with other medicinal products").

Pseudomembranous colitis

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

Tendonitis

Rarely observed with the use of quinolones, including levofloxacin, tendonitis, can lead to the rupture of tendons, incl. Achilles tendon. This undesirable reaction can develop within 48 hours after the start of treatment and can be bilateral. Older patients are more prone to tendonitis. Risk of rupture of tendons may increase with simultaneous reception of glucocorticosteroids. If suspected of tendonitis, it is necessary to immediately stop taking the drug Levofloxacin and begin appropriate treatment of the affected tendon, for example, by providing him with sufficient immobilization (see the sections "Contraindications", "With caution", "Side effect", " (Interaction with other drugs ").

Hypersensitivity reactions

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

Heavy bullous reactions

When levofloxacin was taken, there were cases of severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (see "Side effect" section). In case of any reactions from the skin or mucous membranes, the patient should immediately consult a doctor and before taking the medicine not take the drug Levofloxacin.

Disturbances from the liver and bile ducts

There were reports of cases of liver necrosis, incl. with the development of fatal liver failure, with the use of levofloxacin in patients, mainly with a severe underlying disease, for example, sepsis (see section "Side effect"). The patient should be warned about the need to stop treatment and urgent medical attention in case of signs and symptoms of liver damage, such as anorexia, jaundice, darkening of the urine, skin itching, abdominal pain.

Renal insufficiency

Because the levofloxacin excreted mainly by the kidneys, in patients with Mr.The destruction of the kidney function requires mandatory monitoring of kidney function and correction of the dosing regimen in accordance with the creatinine clearance (see section "Method of administration and dose").In the treatment of elderly patients, one should keep in mind the possible decrease in kidney function (see section "Dosing and Administration").

The photosensitization reaction

Although photosensitization with levofloxacin is very rare, to prevent its development, patients are not recommended during treatment and within 48 hours after the end of therapy with the drug Levofloxacin without special need to be exposed to strong natural or artificial ultraviolet radiation (for example, to sunbathe, visit the solarium).

Superinfection

The use of levofloxacin, as well as other antibacterial drugs, especially for a long time, can lead to increased reproduction of insensitive microorganisms (bacteria and fungi) and changes in microflora, which is normally present in humans. As a result, the development of superinfection is possible. Against the background of taking the drug Levofloxacin it is necessary to reevaluate the patient's condition and, in case of development of superinfection during treatment, take appropriate measures.

Interval lengthening QT

Very rare cases of lengthening of the interval have been reported QT on ECG in patients taking fluoroquinolones, including levofloxacin. Therefore, fluoroquinolones, including levofloxacin, used with caution in patients with known risk factors for lengthening the interval QT: uncorrected electrolyte disturbances (hypokalemia, hypomagnesemia), congenital interval elongation syndrome QT, heart disease (heart failure, myocardial infarction, bradycardia) or in patients taking medications that can lengthen the interval QT (for example, antiarrhythmic drugs of classes IA and III, tricyclic and tetracyclic antidepressants, macrolides, antipsychotics, antifungal agents / imidazole derivatives; some antihistamines (astemizole, terfenadine, ebastine). Elderly patients and female patients may be more sensitive to drugs that extend the interval QT. Therefore, they have fluoroquinolones, including the drug Levofloxacin, should be used with caution (see the sections "With caution", "Method of administration and dose", "Side effect", "Interaction with other drugs").

Deficiency of glucose-6-phosphate dehydrogenase

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

Hypo-and hyperglycemia

When using levofloxacin, as well as other fluoroquinolones, there have been cases of development of hypoglycemia and hyperglycemia, usually in patients with diabetes mellitus receiving treatment with hypoglycemic agents for ingestion (for example, glibenclamide) or insulin preparations. There have been reports of cases of hypoglycemic coma. In patients with diabetes mellitus, when using 1Svofloxacin, monitoring of blood glucose concentration is required (see the "Side effect" section).

Pperipheral neuropathy

In patients taking fluoroquinolones, including levofloxacin, sensory or sensory-motor peripheral neuropathy was noted, the onset of which can be rapid. When a patient develops symptoms of peripheral neuropathy, taking the drug Levofloxacin should be terminated (this minimizes the risk of irreversible changes).

Exacerbation of pseudo-paralytic myasthenia gravis (myasthenia gravis)

Fluoroquinolones, including levofloxacin, are characterized by neuromuscular blocking of activity and may increase muscle weakness in patients with pseudo-paralytic myasthenia gravis. There were adverse reactions, including pulmonary insufficiency, requiring artificial ventilation, and death associated with the use of fluoroquinolones in patients with pseudo-paralytic myasthenia gravis. Application of the drug Levofloxacin in patients with established diagnosis of pseudo-paralytic myasthenia gravis is not recommended (see the sections "Contraindications", "Side effect").

Psychotic reactions

When using fluoroquinolones, including levofloxacin, reported the development of psychotic reactions, which in very rare cases progressed to the development of suicidal thoughts and behavioral disorders with self-harm (sometimes after taking a single dose of levofloxacin, see the section "Side effect"). With the development of such reactions, the drug intake Levofloxacin it is necessary to stop and carry out appropriate therapy. Caution is necessary to prescribe the drug Levofloxacin patients with psychosis or with a history of mental illness (see section "With caution").

Visual impairment

Three development of any visual impairment against the background of taking the drug Levofloxacin an immediate consultation of the ophthalmologist is needed (see the "Side effect" section).

Impact on laboratory test results

Definition of opiates in urine in patients taking the drug Levofloxacin, can lead to false positive results, which should be confirmed by more specific methods.

Levofloxacin, inhibiting growth Mycobacterium tuberculosis, can lead subsequently to false-negative results of a bacteriological diagnosis of tuberculosis.

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

Such possible side effects on the background of drug treatment Levofloxacin, like dizziness, vertigo, drowsiness, visual impairment (see "Side effect"), can reduce the speed of psychomotor reactions and the ability to concentrate attention. This can present a certain risk in situations in which these abilities are of particular importance (for example, when driving vehicles, working with mechanisms,work in an unstable position).

Form release / dosage:

The tablets covered with a film membrane, 500 mg.

Packaging:

5 or 10 tablets in a contoured cell pack from a polyvinyl chloride film and aluminum foil. 1 contour cell pack of 5 or 10 tablets or 2 contour packs of 5 tablets together with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001340

Date of registration:26.07.2011 / 22.09.2015

Expiration Date:Unlimited

The owner of the registration certificate:NIZHFARM, JSC NIZHFARM, JSC Russia

Manufacturer: & nbsp

HETERO LABS, Limited India

Information update date: & nbsp06.03.2018

Illustrated instructions

Instructions

Levofloxacin STADA (Levofloxacin Stada)