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

Name	Amount (mg)
Core
Active substance:
Levofloxacin hemihydrate (in terms of levofloxacin)	256,230 (250)	512,460 (500)
Excipients:
Microcrystalline cellulose	27,77	55,54
Crospovidone	26,0	52,0
Hypromellose	8,0	16,0
Talc	3,5	7,0
Magnesium stearate	3,5	7,0
Shell (Opadrai the pink 03B84851)
Hypromellose	6,250	12,500
Titanium dioxide	2,587	5,174
Macrogol-400	0,625	1,250
Talc	0,500	1,000
Iron Oxide Red Dye Oxide	0,020	0,040
Dye iron oxide yellow	0,018	0,036

Description:

250 mg tablets: Tablets are capsular-shaped, biconvex, covered with a film membrane, light pink in color, with a dividing risk on both sides. On one side of the tablet - engraving "J" and "250".

Tablets 500 mg: Tablets are capsular-shaped, biconvex, covered with a film membrane, light pink in color, with a dividing risk on both sides. On one side of the tablet - engraving "J" and "500".

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, containing as an active substance levofloxacin - the left-handed isomer of ofloxacin. Levofloxacin blocks the DNA-gyrase (topoisomerase II) and topoisomerase IV, disrupts supercoiling and cross-linking of DNA gaps, inhibits DNA synthesis, causes profound morphological changes in the cytoplasm, cell wall and membranes of microbial cells.

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

Sensitive microorganisms (minimum suppressive concentration (MIC) ≤2 mg / l)

Aerobic Gram-positive microorganisms: Bacillus anthracis, Corynebacterium diphtheria, Corynebacterium jeikeium, Enterococcus spp. (incl. 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), Streptococcus spp. group C and G, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin sensitive / moderately sensitive / resistant strains), Streptococcus pyogenes, Streptococcus spp. groups viridans (penicillin is moderately sensitive / resistant strains).

Aerobic Gram-negative microorganisms: Acinetobacter spp., (incl. Acinetobacter baumannii), Actinobacillus actinomycetemcomitans, 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 β-lactamase-producing and β-lactamase-induced), Morganella morganii, Neisseria gonorrhoeae (penicillinase-producing and non-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 (hospital infection, caused by Pseudomonas aeruginosa, may demand combined treatment)), Salmonella spp., Serratia spp. (at Tom number of Serratia marcescens).

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

Moderately sensitive microorganisms (IPC = 4 mg / L)

Aerobic Gram-positive microorganisms: Corynebacterium urealylicum, 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 to levofloxacin microorganisms (IPC≥8 mg / l)

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

Aerobic Gram-negative microorganisms: Alcaligenes xylosoxidans.

Anaerobic microorganisms: Bacteroides thetaiotaomicron.

Other microorganisms: Mycobacterium avium.

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

Due to the peculiarities of the mechanism of action of levofloxacin, there is usually no cross-resistance between levofloxacin and other antimicrobial agents.

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

- aerobic Gram-positive microorganisms: Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes;

- aerobic gram-negative microorganisms. Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens;

- other microorganisms: Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae.

Pharmacokinetics:

Absorption

Levofloxacin is quickly and almost completely absorbed after ingestion.Food intake has little effect on the speed and completeness of absorption. Absolute bioavailability with oral administration is 99-100%. After a single dose of 500 mg of levofloxacin, the maximum plasma concentration is reached within 1-2 hours and is 5.2 ± 1.2 μg / ml. The pharmacokinetics of levofloxacin is linear in the dosage range of 50 to 1000 mg. The equilibrium state of the concentration of levofloxacin in plasma with the administration of 500 mg of levofloxacin 1 or 2 times a day is reached within 48 hours.

On the 10th day of taking levofloxacin 500 mg once a day, the maximum concentration of levofloxacin in plasma was 5.7 ± 1.4 μg / ml, and the minimum concentration of levofloxacin (concentration before taking the next dose) in plasma was 0.5 ± 0 , 2 μg / ml.

On the 10th day of taking levofloxacin 500 mg twice a day, the maximum concentration of levofloxacin in plasma was 7.8 ± 1.1 μg / ml, and the minimum concentration of levofloxacin (concentration before taking the next dose) in plasma was 3.0 ± 0 , 9 μg / ml.

Distribution

The connection with plasma proteins is 30-40%. After a single administration of 500 mg of levofloxacin, the volume of distribution of levofloxacin is approximately 100 liters, which indicates a good penetration of levofloxacin into the organs and tissues of the human body.

Penetration into the bronchial mucosa, epithelial lining fluid, alveolar macrophages

After a single oral intake of 500 mg of levofloxacin, the maximum concentrations of levofloxacin in the bronchial mucosa and epithelial lining fluid were achieved within 1-4 hours and were 8.3 μg / g and 10.8 μg / ml, respectively, with coefficients of penetration into the bronchial mucosa and the fluid of the epithelial lining as compared to the concentration in the blood plasma of 1.1-1.8 and 0.8-3, respectively.

After 5 days of oral administration of 500 mg of levofloxacin, the average concentrations of levofloxacin 4 hours after the last administration of the drug in the epithelial lining fluid were 9.94 μg / ml and in alveolar macrophages 97.9 μg / ml.

Penetration into lung tissue

Maximum concentrations in the lung tissue after oral administration of 500 mg of levofloxacin were approximately 11.3 μg / g and were achieved 4-6 hours after taking the drug with penetration factors of 2-5 compared to the concentration in the blood plasma.

Penetration into the alveolar fluid

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

Penetration into bone tissue

Levofloxacin well penetrates into the cortical and spongy bone tissue, both in the proximal and distal femur with a coefficient of penetration (bone tissue / blood plasma) of 0.1-3. The maximum concentrations of levofloxacin in the spongy bone of the proximal femur after taking 500 mg of the drug inside were approximately 15.1 μg / g (2 hours after taking the drug).

Penetration into the cerebrospinal fluid

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Penetration into prostate tissue

After oral administration of 500 mg levofloxacin 1 time per day for 3 days, the average concentration of levofloxacin in the prostate tissue was 8.7 μg / g, the average ratio of prostatic / plasma concentrations was 1.84.

Concentrations in the urine

Average concentrations in the urine 8-12 hours after ingestion of doses of 150, 300 and 600 mg of levofloxacin were 44 μg / ml, 91 μg / ml and 162 μg / ml, respectively.

Metabolism

Levofloxacin is metabolized to a small extent (5% of the dose taken). Its metabolites are desmethyllevofloxacin and Nlevofloxacin, which are excreted by the kidneys. Levofloxacin is stereochemically stable and does not undergo chiral transformations.

Excretion

After oral administration levofloxacin relatively slowly excreted from the blood plasma (half-life (T1 / 2) - 6-8 hours). It is excreted from the body mainly by the kidneys through glomerular filtration and tubular secretion. After oral administration, approximately 87% of the dose received is excreted by the kidneys unchanged for 48 hours, less than 4% through the intestine within 72 hours. The total clearance of levofloxacin after a single dose of 500 mg was 175 ± 29.2 ml / min.

There are no significant differences in the pharmacokinetics of levofloxacin with its intravenous administration and ingestion, which confirms that oral and intravenous administration are interchangeable.

Pharmacokinetics in selected patient groups

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

With renal failure, the pharmacokinetics of levofloxacin varies. As the kidney function decreases, excretion through the kidneys and kidney clearance decreases, and T1 / 2 increases, as shown in the table below:

Creatinine clearance (CC) [ml / min]	less than 20	20-49	50-80
Kidney clearance [ml / min]	13	26	57
T1/ 2 [h]	35	27	9

Pharmacokinetics in elderly patients does not differ from that in young patients, except for differences in pharmacokinetics associated with differences in QC.

Indications:

Infectious-inflammatory diseases caused by susceptible to levofloxacin microorganisms:

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;
complex treatment of drug-resistant forms of tuberculosis.

Contraindications:

- Hypersensitivity to levofloxacin, the components of the drug or to other quinolones;

- epilepsy;

- lesions of tendons with the administration of fluoroquinolones in the anamnesis;

- children and adolescents under 18 years of age (due to incomplete growth of the skeleton, since the risk of damage to the cartilaginous growth points can not be completely excluded);

- pregnancy (the risk of destruction of the cartilage growth points in the fetus can not be completely ruled out);

- the period of breastfeeding (you can not completely exclude the risk of damage to the cartilage points of bone growth in the child);

- pseudo-paralytic myasthenia gravis (myasthenia gravis).

Carefully:

In patients who are predisposed to developing seizures (in patients with previous lesions of the central nervous system (CNS) simultaneously receiving drugs that reduce the threshold of convulsive brain readiness, such as fenbufen, theophylline).

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

In patients with impaired renal function.

In patients with known risk factors for lengthening the interval QT on an electrocardiogram (ECG): in patients with uncorrected electrolyte disorders (hypokalemia, hypomagnesemia); with the syndrome of congenital lengthening interval QT; with diseases of the heart (heart failure, myocardial infarction, bradycardia); while concomitantly taking medications that can lengthen the interval QT, such as antiarrhythmics IA and class III, tricyclic antidepressants, macrolides, neuroleptics, in elderly patients and women.

In patients with diabetes mellitus receiving oral hypoglycemic agents, for example, glibenclamide or insulin.

In patients with severe adverse reactions to other fluoroquinolones, such as severe neurologic reactions.

In patients with psychoses and psychiatric illnesses in the anamnesis.

Pregnancy and lactation:

Levofloxacin is contraindicated for use in pregnancy and during breastfeeding.

Dosing and Administration:

Dosing regimen and duration of treatment

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

Tablets should be swallowed without chewing and drinking with a sufficient amount of liquid (0.5 to 1 cup). If necessary, the tablets can be broken down by dividing risk.

The drug can be taken before meals or at any time between meals, as eating does not affect the absorption of the drug.The drug should be taken at least 2 hours before or 2 hours after taking antacid preparations containing magnesium and / or aluminum, salts of iron, zinc or sucralfate. If you missed taking the drug, you should take the pill as soon as possible, without waiting for the next time. Further, to observe equal intervals of time between doses - 24 h (with the mode of reception 1 time in knocking) or 12 h (with the mode of reception 2 times a day).

The dosage regimen is determined by the nature and severity of the infection, but by the sensitivity of the suspected pathogen. Duration of treatment varies depending on the course of the disease. In all cases, treatment should continue at least 48-72 hours after the disappearance of the symptoms of the disease.

Recommended dosage regimen and duration of treatment in patients with normal or moderately reduced renal function (CK> 50 mL / min):

- acute sinusitis: 500 mg once a day - 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 - 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 for 28 days.

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

- complex treatment of drug-resistant forms of tuberculosis: 500 mg 1-2 times a day for up to 3 months;

Dosing regimen in patients with impaired renal function Levofloxacin is excreted mainly by the kidneys, therefore, in the treatment of patients with impaired renal function, a dose reduction is required (see table below).

Creatinine clearance	Dosing regimen
	Recommended dose for CK> 50 ml / min: 250 mg / 24 hour	Recommended dose for CK> 50 ml / min: 500 mg / 24 hour	The recommended dose for CK> 50 ml / min: 500 mg / 12 h
50-20 ml / min	first dose: 250 mg then: 125 mg / 24 hour	first dose: 500 mg then: 250 mg / 24 hour	first dose: 500 mg then: 250 mg / 12 hour
19-10 ml / min	first dose: 250 mg then: 125 mg / 48 hour	first dose: 500 mg then: 125 mg / 24 hour	first dose: 500 mg then: 125 mg / 12 hour
<10 ml / min (including hemodialysis and CAPD¹ )	first dose: 250 mg then: but 125 mg / 48 hour	first dose: 500 mg then: 125 mg / 24 hour	first dose: 500 mg then: 125 mg / 24 hour

1 after hemodialysis or continuous outpatient peritoneal dialysis (CAPD) no additional doses are required.

Dosing regimen in patients with impaired hepatic function

If the liver function is not corrected, correction of the dosing regimen is not required, since levofloxacin only slightly metabolized in the liver.

Dosage regimen in elderly patients

For elderly patients, correction of the dosing regimen is not required, except for cases when the CK is reduced to 50 ml / min and below.

Children

Levofloxacin is contraindicated in children and adolescents (see "Contraindications").

Side effects:

The following side effects are presented in accordance with the following grades of their frequency: very frequent (≥1 / 10), frequent (≥1 / 100, <1/10); infrequent (≥1 / 1000, <1/100); Rare (≥1 / 10000, <1/1000); very rare (<1/10000) (including individual messages), unknown frequency (it is not possible to determine the frequency of occurrence according to available data).

Violations from the side of the cardio - cardiovascular system

Rare: sinus tachycardia, palpitation, lowering blood pressure.

Unknown frequency: interval elongation QT on the ECG, ventricular arrhythmias, ventricular tachycardia, ventricular pirouette tachycardia, which can lead to cardiac arrest.

Violations of the blood and lymphatic system

Infrequent: leukopenia (a decrease in the number of leukocytes in the peripheral blood), eosinophilia (an increase in the number of eosinophils in peripheral blood).

Rare: neutropenia (a decrease in the number of neutrophils in peripheral blood), thrombocytopenia (a decrease in the number of platelets in the peripheral blood).

Unknown frequency: pancytopenia (decrease in the number of all elements in the peripheral blood), agranulocytosis (absence or sharp decrease in the number of granulocytes in the peripheral blood), hemolytic anemia.

Disturbances from the nervous system

Frequent: headache, dizziness.

Infrequent: drowsiness, tremor, dysgeusia (perversion of taste).

Rare: paresthesia, convulsions.

Unknown frequency: peripheral sensory neuropathy, peripheral sensory-motor neuropathy, dyskinesia, extrapyramidal disorders, agevia (loss of taste sensations), parosmia (odor disorder, especially subjective sense of smell, objectively absent), including loss of smell, fainting, benign intracranial hypertension.

Disturbances on the part of the organ of sight

Rare: visual impairments, such as the vagueness of the visible image.

Unknown frequency: temporary loss of vision.

Hearing disorders and labyrinthine disorders

Infrequent: vertigo (feeling of deflection or twisting, or of one's own body, or surrounding objects).

Rare: ringing in the ears.

Unknown frequency: hearing loss, hearing loss.

Disturbances from the respiratory system, chest and mediastinal organs

Infrequent: shortness of breath.

Unknown frequency: bronchospasm, allergic pneumonitis.

Immune system disorders

Rare: angioedema, hypersensitivity.

Unknown frequency: anaphylactic shock, anaphylactoid shock.

Disorders from the gastrointestinal tract and metabolism

Frequent: nausea, diarrhea, vomiting.

Infrequent: loss of appetite (anorexia), abdominal pain, indigestion (dyspepsia), flatulence, constipation.

Rare: decreased blood sugar (hypoglycemia), which is of particular importance for patients with diabetes mellitus (possible signs of hypoglycemia: "wolfish" appetite, anxiety, sweat, trembling).

Unknown frequency: hemorrhagic diarrhea (bloody diarrhea), which in very rare cases can be a sign of enterocolitis, including pseudomembranous colitis; pancreatitis, hyperglycemia, hypoglycemic coma.

Disorders from the kidneys and urinary tract

Infrequent: increased serum creatinine concentration.

Rare: acute renal failure (eg, due to the development of interstitial nephritis).

Disturbances from the skin and subcutaneous tissues

Infrequent: rash, itching, hives, hyperhidrosis.

Unknown frequency: Lyell's syndrome (toxic epidermal necrolysis), Stevens-Johnson syndrome (severe skin rashes with the formation of blisters), exudative erythema multiforme, photosensitivity reactions (hypersensitivity to sun and ultraviolet radiation), leukocytoclastic vasculitis, stomatitis.

Reactions from the skin and mucous membranes can sometimes develop even after taking the first dose of the drug.

Disturbances from musculoskeletal system and connective tissue

Infrequent: arthralgia, myalgia

Rare: tendon lesions, including tendonitis (eg Achilles tendon),joint and muscle pain, muscle weakness, which can be especially dangerous in patients with pseudo-paralytic myasthenia gravis (myasthenia gravis).

Unknown frequency: acute necrosis of skeletal muscles (rhabdomyolysis), tendon rupture (eg Achilles tendon). This side effect can be observed within 48 hours after the start of treatment and can be bilateral, a rupture of ligaments and muscles, and arthritis.

Disturbances from the liver and bile ducts

Frequent: increased activity of "hepatic" enzymes in the blood (for example, alanine aminotransferase (ALT), aspartate aminotransferase (ASAT), alkaline phosphatase, gamma glutamyl transferase (GGT)).

Infrequent: increased serum bilirubin concentration.

Unknown frequency: severe hepatic insufficiency, including cases of development of acute hepatic insufficiency, sometimes fatal, especially in patients with severe underlying disease, hepatitis, jaundice.

Disorders of the psyche

Frequent: insomnia.

Infrequent: a sense of anxiety, confusion, nervousness.

Rare: mental disorders (eg, hallucinations, paranoia), depression, agitation (agitation), sleep disturbances, nightmares.

Unknown frequency: mental disorders with behavioral disorders with self-harm, including suicidal thoughts and suicidal attempts.

Infectious and parasitic

Infrequent: fungal infections, the development of resistance of pathogenic microorganisms.

Other side effects

Infrequent: general weakness (asthenia).

Rare: pyrexia (fever).

Unknown frequency: pain, including in the back, chest and extremities.

Possible adverse effects associated with all fluoroquinolones

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

Overdose:

Overdose Symptoms

Based on the data obtained in animal studies, the most important expected symptoms of drug overdose are symptoms from the central nervous system (impaired consciousness, including confusion, dizziness and convulsions).

Can be noted: nausea, erosion of the mucous membrane of the gastrointestinal tract, lengthening the interval QT, hallucinations and tremors.

Treatment

In case of an overdose, careful monitoring of the patient, including ECG monitoring, is required.Treatment is symptomatic. It shows gastric lavage and antacid administration for the protection of the gastric mucosa. Levofloxacin is not excreted by dialysis (hemodialysis, peritoneal dialysis and permanent peritoneal dialysis). The specific antidote is not known.

Interaction:

With iron salts, zinc salts, antacid agents containing magnesium and / or aluminum

It is recommended that preparations containing divalent or trivalent cations such as iron salts (anemia treatment agents), zinc salts, didanosine (only dosage forms containing aluminum or magnesium as the buffer) and antacid agents containing magnesium and / or aluminum should be taken at least 2 hours before or 2 hours after taking levofloxacin. As with simultaneous use, the absorption of levofloxacin will decrease and its effect will be weakened.

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

FROM sucralfate

The effect of levofloxacin is significantly weakened by the simultaneous use of sucralfate (a means for protecting the gastric mucosa). Patients using levofloxacin and sucralfate, it is recommended to take sucralfate 2 hours after taking levofloxacin.

With theophylline, fenbufen or similar drugs from a group of non-steroidal anti-inflammatory drugs that reduce the threshold of convulsive brain readiness

The pharmacokinetic interaction of levofloxacin with theophylline has not been revealed. The concentration of levofloxacin with simultaneous administration of fenbufen is only increased by 13%.

However, with the simultaneous use of quinolones and theophylline, non-steroidal anti-inflammatory drugs and other drugs that reduce the threshold of convulsive brain readiness, there may be a marked decrease in the threshold of convulsive readiness of the brain.

With indirect anticoagulants

In patients treated with levofloxacin in combination with indirect anticoagulants (eg, warfarin), there was an increase in prothrombin time / normalized international relations and / or development of bleeding, including severe bleeding. Therefore, with simultaneous use of indirect anticoagulants and levofloxacin, regular monitoring of blood clotting parameters is necessary.

With probenecid and cimetidine

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

Removal (renal clearance) of levofloxacin is slowed by cimetidine by 24% and probenecid by 34%. It is unlikely that this can be of clinical significance in normal kidney function.

With cyclosporine

Levofloxacin increased T1 / 2 cyclosporine by 33%. Since this increase is clinically insignificant, correction of the dose of cyclosporine when it is used simultaneously with levofloxacin is not required.

With glucocorticosteroids

Simultaneous reception of glucocorticosteroids increases the risk of rupture of tendons.

With medications that extend the RT interval.

Levofloxacin, like other fluoroquinolones, should be used with caution in patients who use drugs that extend the range QT (for example, antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, neuroleptics).

Other

Conducted clinical and pharmacological studies to study the possible pharmacokinetic interactions of levofloxacin with digoxin, glibenclamide, ranitidine showed that the pharmacokinetics of levofloxacin when used concomitantly with these drugs does not change sufficiently, that it would be of clinical importance.

Special instructions:

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

The prevalence of acquired resistance of strains of microorganisms can vary depending on the geographic region and over time. In this regard, information about the resistance to levofloxacin in a particular country is required. It is required to establish a microbiological diagnosis with the isolation of the pathogen and determine its sensitivity to levofloxacin.

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

Patients who are predisposed to develop seizures

Like other fluoroquinolones, levofloxacin should be used with caution in patients with predisposition to developing seizures: in patients with previous CNS lesions (stroke, severe craniocerebral trauma), in patients simultaneously receiving drugs lowering the threshold of convulsive brain readiness, such as fenbufen and other non-steroidal anti-inflammatory drugs , or other drugs, such as theophylline.

Pseudomembrane colitis

Developed during or after treatment with levofloxacin, diarrhea, especially severe, persistent and / or with blood, may be a symptom of pseudomembrane colitis caused by Clostridium difficile. In case of suspicion of the development of pseudomembranous colitis, treatment with levofloxacin should be stopped immediately and immediately begin specific antibiotic therapy (vancomycin, teicoplanin or metronidazole inside).

Drugs that inhibit the intestinal peristalsis are contraindicated.

Tendonitis

Rarely observed tendonitis in the use of quinolones, including levofloxacin, can lead to the rupture of tendons, including the Achilles tendon. This side effect can develop within 48 hours after the start of treatment and can be bilateral. Older patients are more prone to tendonitis. The risk of rupture of tendons can increase with simultaneous administration of glucocorticosteroids. If suspicion of tendonitis should immediately stop treatment with the drug and begin appropriate treatment of the affected tendon, for example, providing him with sufficient immobilization (see "Contraindications" and "Side effect").

Hypersensitivity reactions

Levofloxacin can cause serious, potentially fatal, hypersensitivity reactions (including angioedema, anaphylactic shock), even after taking the first dose of the drug. In these cases, treatment with levofloxacin should be discontinued, the physician should be immediately informed and the necessary medical measures (including anti-shock) initiated.

Severe bullous reactions

When levofloxacin was used, cases of severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, were observed.In the case of any reactions from the skin or mucous membranes, the patient should immediately consult a doctor and do not continue treatment until he consults.

Disturbances from the liver and bile ducts

There have been reports of cases of liver necrosis, including the development of fatal liver failure, with the use of levofloxacin, mainly in patients with severe underlying diseases (eg sepsis). The patient should be informed that if symptoms of hepatic insufficiency (anorexia, jaundice, darkening of the urine, itching, abdominal pain) appear, discontinue treatment and consult a doctor.

Patients with renal insufficiency

As levofloxacin excreted mainly by the kidneys, in patients with impaired renal function required mandatory monitoring of kidney function, as well as correction of the dosing regimen. In the treatment of elderly patients, it should be borne in mind that patients of this group often have impaired renal function.

Prevention of the development of photosensitization reactions

When levofloxacin is used, cases of photosensitization are noted.To prevent its development, patients are advised not to be subjected to extreme sunlight or artificial ultraviolet irradiation (for example, to visit a solarium) without special need during treatment and 48 hours after discontinuation of therapy.

Superinfection

As with the use of other antibiotics, the use of levofloxacin, especially for a long time, can lead to increased reproduction of insensitive microorganisms (bacteria and fungi), which can cause changes in microflora, which is normally present in humans, which can lead to the development of superinfection . Therefore, during the treatment, it is mandatory to reevaluate the patient's condition and, if it develops during the treatment of superinfection, appropriate measures should be taken.

The elongation of the OT interval

Lengthening of the interval has been reported QT when using levofloxacin in some patients.

When using levofloxacin, care should be taken in patients with predisposing to lengthen the interval QT factors: uncorrected electrolyte disturbances (hypokalemia, hypomagnesemia); congenital lengthening syndrome QT; heart disease (heart failure, myocardial infarction, bradycardia); use with other drugs that extend the interval QT (antiarrhythmic agents IA and class III, tricyclic antidepressants, macrolides, neuroleptics). Elderly patients and women may be more sensitive to drugs that extend the interval QT. Therefore, it should be used with caution in them levofloxacin.

Patients with deficiency of glucose-6-phosphate dehydrogenase

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

Hypoglycemia and hyperglycaemia

As with the use of other quinolones, when levofloxacin was used, cases of hypoglycemia and hyperglycemia were observed, especially in patients with diabetes mellitus, who received simultaneous treatment with oral hypoglycemic drugs (eg, glibenclamide) or with insulin preparations. There have been reports of cases of hypoglycemic coma. Patients with diabetes are required to monitor the concentration of glucose in the blood.

Peripheral Neuropathy

In patients receiving fluoroquinolones, including levofloxacin, sensory and sensory-motor peripheral neuropathy was noted, the onset of which can be rapid. If the patient has symptoms of neuropathy, the use of levofloxacin should be discontinued. This minimizes the possible risk of irreversible changes.

Exacerbation of pseudo-paralytic myasthenia gravis (myasthenia gravis gravis)

Fluoroquinolones, including levofloxacin, can block neuromuscular activity and enhance the muscle weakness of patients with pseudo-paralytic myasthenia gravis. In the postmarketing period, adverse reactions were observed, including pulmonary insufficiency, requiring artificial ventilation, and fatal outcome, which were associated with the use of fluoroquinolones in patients with pseudo-paralytic myasthenia gravis. The use of levofloxacin in patients with established diagnosis of myasthenia gravis gravis Not recommended.

Psychotic reactions

Reactions from the psyche may occur even after the first use of fluoroquinolones, including levofloxacin. In very rare cases, depression or psychotic reactions progress to the occurrence of suicidal thoughts and behavior with a tendency to self-harm, including suicidal attempts. If patients develop such reactions, levofloxacin should be withdrawn and appropriate measures taken. Caution should be exercised when using levofloxacin in patients with psychoses and patients with psychiatric illnesses in an anamnesis.

Disturbances on the part of the organ of sight

If there is a disturbance on the part of the eye, consultation of the ophthalmologist is necessary.

With the simultaneous use of indirect anticoagulants and levofloxacin, regular monitoring of blood clotting indices is necessary.

The ability of levofloxacin to suppress growth Mycobacterium spp. can lead to false-negative results in microbiological diagnosis of tuberculosis.

In patients receiving levofloxacin, false-positive results can be obtained when determining opioids in urine.

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

Fluoroquinolones, including levofloxacin, may impair the ability of patients to drive and engage in other potentially dangerous speciesactivities that require increased attention and speed of psychomotor reactions, due to influence on the nervous system and visual impairment.

Form release / dosage:

Pills, film-coated 250 mg 500 mg.

Packaging:

For 5 or 10 tablets per blister of Al / PVC.

For 1 or 2 blisters in a cardboard box with instructions for use.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002937

Date of registration:01.04.2015 / 08.12.2015

Expiration Date:01.04.2020

The owner of the registration certificate:PROTEK-SVM, LLC PROTEK-SVM, LLC Russia

Manufacturer: & nbsp

JUBILANT LIFE SCIENCES Ltd. India

Information update date: & nbsp06.03.2018

Illustrated instructions

Instructions

Levofloxacin-LEXM (Levofloxacin-LEKSVM)