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

Excipients: microcrystalline cellulose - 30.83 mg; hypromellose - 8.99 mg; croscarmellose sodium - 9.30 mg; polysorbate 80 - 1.55 mg; calcium stearate - 3.10 mg.

Shell composition: [hypromellose 7.50 mg, giprolose (hydroxypropyl cellulose) 2.91 mg, talc 2.89 mg, titanium dioxide 1.63 mg, iron oxide yellow (iron oxide) 0.07 mg] or [dry mixture for film coating, containing hypromellose - 50.0%, giprolose (hydroxypropyl cellulose) - 19.4%, talc - 19.26%, titanium dioxide - 1 OC87%, iron oxide yellow (iron oxide) - 0.47%] - 15.0 mg.

Dosage 500 mg

active substance: levofloxacin 500 mg (in terms of levofloxacin hemihydrate - 512.46 mg);

Excipients: microcrystalline cellulose - 61.66 mg; hypromellose - 17.98 mg; croscarmellose sodium - 18.60 mg; polysorbate 80 - 3.10 mg; calcium stearate - 6.20 mg.

Shell composition: [hypromellose - 15.00 mg, giprolose (hydroxypropylcellulose) - 5.82 mg, talc - 5.78 mg, titanium dioxide - 3.26 mg,iron oxide yellow (iron oxide) 0.14 mg] or [dry film coating mixture containing hypromellose 50.0%, giprolose (hydroxypropylcellulose) 19.4%, talc 19.26%, titanium dioxide 10 , 87%, iron oxide yellow (iron oxide) - 0.47%] - 30.0 mg.

Description:

Round biconvex tablets, covered with a film coating of yellow color. On the cross-section, two layers are visible: the core is from white to light yellow and the shell is yellow.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A Fluoroquinolones

J.01.M.A.12 Levofloxacin

Pharmacodynamics:

Levofloxacin is a synthetic antibacterial agent with a broad spectrum of action andz a group of fluoroquinolones, a left-handed isomer of ofloxacin. Levofloxacin blocks DNA gyrase and topoisomerase IV, disrupts supercoiling and cross-linking of DNA gaps, inhibits DNA synthesis, causes profound morphological changes in the cytoplasm, cell wall and bacterial membranes.

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

In vitro:

Sensitive microorganisms (minimum suppressive concentration (MIC) ≤ 2 mg / l; zone of inhibition ≥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 strains), Staphylococcus aureus methi-S (methicillin-sensitive strains), Staphylococcus epidermidis methi-S (methicillin-sensitive strains), Staphylococcus spp. CNS (coagulase-negative); Streptococcus spp. groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae peni I/S/R (penicillin-sensitive / moderately sensitive / resistant strains), Streptococcus pyogenes, Viridans streptococci peni-S/R (penicillin-sensitive / resistant strains).

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 strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella spp., Moraxella catarrhalis P+/(3- (producing and non-producing beta-lactamase strains), Morganella morganii, Neisseria gonorrhoeae non PPNG/PPNG (non-producing and penicillinase-producing strains), 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., Serratia spp., Serratia marcescens, Salmonella spp.

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 pneumophila, Legionella spp., Mycobacterium spp., 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 faecium, Staphylococcus epidermidis methi-R (Methicillin-resistant strains), Staphylococcus haemolyticus methi-R (methicillin-resistant strains).

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

Anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

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

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

Aerobic Gram-negative microorganisms: Alcaligenes xylosoxidans.

Other microorganisms: Mycobacterium avium.

Resistance

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 (effectiveness in clinical trials in the treatment of infections caused by the microorganisms listed below)

Aerobic Gram-positive microorganisms: Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes.

Aerobic Gram-negative microorganisms: Citrobacter Freundii, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella (Branhamella) catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens.

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. Bioavailability of levofloxacin after oral administration is 99-100%. After taking a single dose of 500 mg of levofloxacin, the maximum concentration in the blood plasma is 5,2 ± 1.2 μg / ml, the time to reach a maximum concentration of 1.3 hours. The pharmacokinetics of levofloxacin is linear in the dose range of 50 to 1000 mg. The equilibrium state of the concentration of levofloxacin in blood plasma when taken 500 mg 1 or 2 times a day is reached within 48 hours.

Distribution

Connection with blood plasma proteins - 30-40%. It penetrates well into organs and tissues: lungs, bronchial mucosa, sputum, organs of the genitourinary system, bone tissue, cerebrospinal fluid, prostate gland, polymorphonuclear leukocytes, alveolar macrophages. After a single and repeated administration of 500 mg of levofloxacin, the volume of distribution is, on average, 100 liters.

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 hour or 4 hours, and were 8.3 μg / g and 10.8 μg / ml, respectively, with penetration coefficients in 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 dose in the epithelial lining fluid were 9.94 μg / ml and in the alveolar macrophages 97.9 μg / ml.

Penetration and pulmonary tissue

The maximum concentration in lung tissue after oral administration of 500 mg of levofloxacin was approximately 11.3 mg / g and was reached after 4-6 hours after dosing with coefficients penetration 2-5, as compared with the concentration in the blood plasma.

Penetration into the alveolar fluid

After 3 days of 500 mg of levofloxacin 1 or 2 times per day maximum levofloxacin concentration in the alveolar fluid are achieved within 2-4 hours after dosing and were 4.0 and 6.7 ug / ml, respectively, with a penetration coefficient 1 by compared with the concentration in the blood plasma.

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 concentration of levofloxacin in the spongy bone of the proximal femur after receiving 500 mg of the drug inside was about 15.1 g / g (at 2 hours after drug administration).

Penetration into the cerebrospinal fluid

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Penetration into prostate tissue

After oral administration of 500 mg of 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 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 demethyllevofloxacin and Nlevofloxacin oxide, which are excreted by the kidneys. Levofloxacin is stereochemically stable and does not undergo chiral transformations.

Excretion

It is excreted from the body mainly by the kidneys through glomerular filtration and tubular secretion. Half-life (T_1/2) - 6-8 hours After oral intake, approximately 85% of the dose is given by the kidneys within 48 hours. A small part is excreted by the intestine (less than 4% of the accepted dose is excreted within 72 hours). The total clearance of levofloxacin after a single dose of 500 mg is 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.

Pharmacokinetics in elderly patients does not differ from that in young patients, except for differences in pharmacokinetics associated with differences in creatinine clearance (CC).

With renal failure, the pharmacokinetics of levofloxacin varies. As the kidney function decreases, excretion through the kidneys and kidney clearance (CIR) decrease, and T_1/2increases.

Pharmacokinetic parameters in renal failure after a single oral intake of 500 mg of levofloxacin are given in Table 1.

Table 1

CK (ml / min)	<20	20-49	50-80
CIR (ml / min)	13	26	57
T_1/2 (H)	35	27	9

Indications:

Infectious-inflammatory diseases caused by susceptible to levofloxacin microorganisms:

- acute sinusitis;

- exacerbation of chronic bronchitis;

- community acquired pneumonia;

- complicated urinary tract infections (including pyelonephritis);

- uncomplicated urinary tract infections;

- chronic bacterial prostatitis;

- infections of the skin and soft tissues;

- anthrax with an airborne infection route (prevention and treatment);

- tuberculosis (complex treatment of drug-resistant forms).

When using the drug Levofloxacin should take into account the official national recommendations for the proper use of antibacterial drugs, as well as the sensitivity of pathogenic microorganisms (see section "Special instructions").

Contraindications:

- Dand susceptibility to levofloxacin or other quinolones, as well as to any of the components of the drug;

- epilepsy;

- lesions of tendons during the previous treatment with quinolones;

- pseudo-paralytic myasthenia gravis (myasthenia gravis);

- 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 destruction of cartilage points of bone growth in the child).

Carefully:

- Predisposition to convulsive reactions (atherosclerosis of cerebral vessels, cerebral circulatory disorders (in the anamnesis), organic diseases of the central nervous system, simultaneous reception of drugs lowering the threshold of convulsive readiness of the brain, for example, fenbufen, theophylline);

- deficiency of glucose-6-phosphate dehydrogenase (increased risk of hemolytic reactions in the treatment of quinolones);

- renal dysfunction (mandatory mandatory control of kidney function, as well as correction of dosing regimens, see section "Method of administration and dose");

- known risk factors for lengthening the interval QT: elderly patients, female patients, uncorrected electrolyte disorders (eg, hypokalemia, hypomagnesemia), congenital lengthening interval syndrome QT, heart disease (heart failure, myocardial infarction, bradycardia), simultaneous use of drugs that extend the interval QT (antiarrhythmic drugs of class IA and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal, imidazole derivatives, some antihistamines, including astemizole, terfenadine, ebastine);

- in patients with diabetes mellitus, receiving oral hypoglycemic drugs, for example, glibenclamide or insulin preparations (the risk of developing hypoglycemia increases);

- severe adverse reactions to other fluoroquinolones, such as severe neurologic reactions (increased risk of similar undesirable reactions with levofloxacin);

- psychoses and other psychiatric disorders in the anamnesis;

- hepatic porphyria.

Pregnancy and lactation:

A drug Levofloxacin contraindicated in pregnancy and during breastfeeding.

Dosing and Administration:

The drug is taken orally once or twice a day. Tablets can not be chewed and sewed up with enough liquid (0.5 to 1 cup), you can take before meals or between meals. Doses are determined by the nature and severity of the infection, as well as the suspected pathogen susceptibility. Given that the bioavailability of levofloxacin in tablets is 99-100%, in the case of transfer of the patient from intravenous infusion to the taking of tablets, the treatment should be continued at the same dose that was used for intravenous infusion (see section "Pharmacological properties").

Patients with a normal or moderately reduced function of the night (QC more than 50 ml / min) the following dosing regimen is recommended:

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

Complicated urinary tract infections: 500 mg once a day - 7-14 days. Pyelonephritis: 500 mg once a day - 7-10 days.

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

Tuberculosis (complex treatment of drug-resistant forms): 500 mg 1-2 times a day - up to 3 months.

Prevention and treatment of anthrax in case of airborne infection: 500 mg once a day - up to 8 weeks.

Patients with impaired renal function (at a QC less than 50 ml / min) correction of the dosing regimen is required (see Table 2).

The day of providing the drug dosage regimen at a dose of 125 mg is recommended to use levofloxacin preparations in another dosage form: 250 mg tablets with a risk.

table 2

QC	Dosing regimen
QC	The recommended dose for CK> 50 ml / min for 250 mg / 24 h	The recommended dose for CK> 50 ml / min at 500 mg / 24 h	The recommended dose for CK> 50 ml / min at 500 mg / 12 h
50-20 ml / min	the first dose is 250 mg, then 125 mg / 24 h	the first dose is 500 mg, then 250 mg / 24 h	the first dose is 500 mg, then 250 mg / 12 h
19-10 ml / min	the first dose is 250 mg, then 125 mg / 48 h	the first dose is 500 mg, then 125 mg / 24 h	the first dose is 500 mg, then 125 mg / 12 h
<10 ml / min (including hemodialysis and CAPD *)	the first dose is 250 mg, then 125 mg / 48 h	the first dose is 500 mg, then 125 mg / 24 h	the first dose is 500 mg, then 125 mg / 24 h

* after hemodialysis or permanent ambulatory peritoneal dialysis (CAPD), no additional doses are required

Patients with impaired hepatic function

If the liver function is not required, a special dose selection is required, since levofloxacin is metabolized in the liver only to a very small extent.

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.

As with other antimicrobial agents, treatment with the drug Levofloxacin it is recommended to continue at least 48-78 hours after the normalization of body temperature or after a laboratory-confirmed recovery.

Side effects:

Classification of the incidence of adverse events according to recommendations World Health Organization (WHO):

very often> 1/10;

often from> 1/100 to <1/10;

infrequently from> 1/1000 to <1/100;

rarely from> 1/10000 to <1/1000;

very rarely <1/10000, including individual messages;

frequency is unknown - according to available data, establish the incidence does not seem possible.

Heart Disease:

rarely - sinus tachycardia, palpitation;

frequency unknown - interval elongation QT, ventricular arrhythmias, ventricular pirouette tachycardia, which can lead to cardiac arrest (See sections "Overdose", "Special instructions").

Violations from the blood and lymphatic system:

infrequently - leukopenia, eosinophilia; rarely - neutropenia, thrombocytopenia;

frequency unknown - pancytopenia, agranulocytosis, hemolytic anemia.

Impaired nervous system:

often - headache, dizziness;

infrequently - drowsiness, tremor, dysgeusia (perversion of taste);

rarely - paresthesia, convulsions (see section "Special instructions");

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

Disorders from the side of the organ of vision:

very rarely - visual impairment, such as the vagueness of the visible image;

frequency unknown - transient loss of vision.

Hearing disorders and labyrinthine disturbances:

infrequently - vertigo (feeling of deflection or twisting or of one's own body or surrounding objects);

rarely - ringing in the ears;

frequency unknown - hearing loss, hearing loss.

Disturbances from the respiratory system, chest and mediastinal organs:

infrequently - shortness of breath;

frequency unknown - bronchospasm, allergic pneumonitis.

Disorders from the gastrointestinal tract:

often - diarrhea, vomiting, nausea;

infrequently - abdominal pain, indigestion, flatulence, constipation;

frequency is 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 kidneys and urinary tract:

infrequently - an increase in the concentration of creatinine in the blood plasma;

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

Disturbances from the skin and subcutaneous tissues:

infrequently - a rash, itching, hives, hyperhidrosis;

frequency unknown - toxic epidermal necrolysis, Stevens-Johnson syndrome, exudative erythema multiforme, photosensitivity reactions (see section "Special instructions"), leukocytoclastic vasculitis, stomatitis.

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

Disturbances from the musculoskeletal system and connective tissue:

infrequently - arthralgia, myalgia;

rarely - the defeat of tendons, including tendonitis, muscle weakness, which can be especially dangerous in patients with pseudo-paralytic myasthenia gravis (myasthenia gravis) (see section "Special instructions");

frequency is unknown - rhabdomyolysis, tendon rupture (this side effect can be observed within 48 hours after the beginning of treatment and can be bilateral), ligament ruptures, muscle ruptures, arthritis.

Disorders from the side of metabolism and nutrition:

infrequently - anorexia;

rarely - hypoglycemia, especially in patients with diabetes mellitus (possible signs of hypoglycemia: "wolfish" appetite, nervousness, perspiration, trembling);

frequency unknown - hyperglycemia, hypoglycemic coma (see section "Special instructions").

Infectious and parasitic diseases:

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

Vascular disorders:

rarely - lowering blood pressure;

General disorders:

infrequently - asthenia; rarely pyrexia;

frequency unknown - pain (including pain in the back, chest and extremities).

Immune system disorders:

rarely - angioedema;

frequency unknown - anaphylactic shock, anaphylactoid shock.

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

Disturbances from the liver and bile ducts:

often - increased activity of "liver" enzymes, increased activity

alkaline phosphatase and gamma-glutamyl transferase;

infrequently - an increase in the concentration of bilirubin in the blood plasma;

frequency unknown - severe hepatic impairment,including cases of development of acute hepatic insufficiency, sometimes with a fatal outcome, especially in patients with severe underlying disease (eg, in patients with sepsis), hepatitis, jaundice.

Disorders of the psyche:

often - insomnia;

infrequently - a feeling of anxiety, anxiety, confusion;

rarely - mental disorders (eg, hallucinations, paranoia), depression, agitation (agitation), sleep disturbances, nightmares;

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

Other possible side effects related to all fluoroquinolones are:

very rarely - exacerbation of porphyria.

Overdose:

Symptoms

Symptoms of an overdose of levofloxacin appear at the level of the central nervous system (confusion, dizziness, impaired consciousness and seizures like epipriplets). In addition, there may be gastrointestinal disorders (eg, nausea) and erosive lesions of the mucosa, lengthening of the interval QT.

Treatment

In case of an overdose, careful monitoring of the patient, including monitoring the electrocardiogram, is required.

Treatment should be symptomatic.In case of acute overdosage, gastric lavage and administration of antacids are indicated to protect the gastric mucosa. Levofloxacin is not excreted by dialysis (hemodialysis, peritoneal dialysis and permanent peritoneal dialysis). There is no specific antidote.

Interaction:

Preparations containing magnesium, aluminum, iron and zinc, didanosine

Preparations containing divalent or trivalent cations, such as zinc or iron salts (drugs for the treatment of anemia), magnesium and / or aluminum-containing drugs (such as antacids), didanosine (only dosage forms containing aluminum or magnesium as a buffer), it is recommended to take at least 2 hours before or 2 hours after taking the drug Levofloxacin.

Salts of calcium

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

Sucralfate

The effect of levofloxacin is significantly weakened by the simultaneous use of sucralfate (a means for protecting the gastric mucosa). It is recommended that sucralfate 2 hours after taking the drug Levofloxacin.

Theophylline, fenbufen, or similar drugs from the group of non-steroidal anti-inflammatory drugs (NSAIDs) that lower the threshold of convulsive brain readiness.

The pharmacokinetic interaction of levofloxacin with theophylline has not been revealed. However, with the simultaneous use of quinolones and theophylline, NSAIDs and other drugs that reduce the threshold of convulsive readiness of the brain, there may be a marked decrease in the threshold of convulsive readiness of the brain.

The concentration of levofloxacin with simultaneous administration of fenbufen is only increased by 13%.

Indirect anticoagulants (antagonists of vitamin K)

In patients treated with levofloxacin in combination with indirect anticoagulants (eg, warfarin), there was an increase in prothrombin time / international normalized ratio 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.

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.

Cyclosporin

Levofloxacin increased T_1/2 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.

Glucocorticosteroids

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

Medications that extend the range of OT

Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs that extend the range QT (antiarrhythmic drugs of class IA and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal, imidazole derivatives, some antihistamines, including astemizole, terfenadine, ebastine).

Other

Conducted clinical and pharmacological studies to study possiblepharmacokinetic interactions of levofloxacin with digoxin, glibenclamide, ranitidine, and warfarin have shown that the pharmacokinetics of levofloxacin when used concomitantly with these drugs does not change sufficiently to make it clinically important.

Special instructions:

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

The prevalence of acquired resistance of the sown 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. For the treatment of severe infections or in the ineffectiveness of treatment, a microbiological diagnosis should be made, isolating the pathogen and determining its sensitivity to levofloxacin. Staphylococcus aureus (methicillin-resistant strains). There is a high likelihood that Methicillin-Resistant Staphylococcus aureus will be resistant to fluoroquinolones, including levofloxacin. therefore levofloxacin not is recommended for the treatment of established or suspected infections caused by methicillin-resistant Staphylococcus aureus, if laboratory tests did not confirm the susceptibility of this microorganism to levofloxacin.

Patients who are predisposed to developing seizures. Like other quinolones, levofloxacin should be used with great care in patients with a predisposition to convulsions. Such patients include patients with previous lesions of the central nervous system, such as stroke, severe craniocerebral trauma; patients simultaneously receiving drugs that reduce the threshold of convulsive brain readiness, such as fenbufen and other similar NSAIDs or other drugs that lower the threshold of convulsive readiness, such as theophylline (see "Interaction with other drugs").

Pseudomembranous colitis. Developed during or after levofloxacin treatment, diarrhea, especially severe, persistent and / or with blood, may be a symptom of pseudomembranous colitis caused by Clostridium difficile. In case of suspected development of 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 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 suspected of tendonitis should immediately stop treatment with the drug Levofloxacin and begin appropriate treatment of the affected tendon, for example, by providing him with sufficient immobilization (see the sections "Contraindications" and "Side effects").

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

Severe bullous reactions. When taking levofloxacin, there were cases of severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (see section "Side effect"). 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.

Disorders from the liver and biliary tract. There have been reports of hepatic necrosis, including the development of fatal liver failure with levofloxacin, mainly in patients with severe underlying diseases, for example, with sepsis (see section "Side effect"). Patients should be warned about the need for discontinuation of treatment and urgent medical attention in case of signs and symptoms of liver damage such as anorexia, jaundice, darkening of urine, pruritus and abdominal pain.

Patients with renal insufficiency. As levofloxacin excreted mainly through the kidneys,in patients with impaired renal function, mandatory monitoring of kidney function is required, as well as correction of the dosing regimen (see section "Method of administration and dose"). In the treatment of elderly patients, it should be borne in mind that patients of this group often have violations of the function of the nights (see section "Method of administration and dose").

Prevention of the development of photosensitization reactions. Although photosensitization with the use of levofloxacin develops very rarely, to prevent its development, patients are not recommended during treatment and subjected to intensive sunlight or artificial ultraviolet irradiation (for example, to visit the solarium) for 48 hours after the end of treatment with levofloxacin.

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. As a result, superinfection may develop.Therefore, during treatment, it is necessary to re-evaluate the patient's condition and, if developed during the treatment of superinfection, take appropriate measures.

Interval lengthening QT. Very rare cases of lengthening of the interval have been reported QT in patients taking fluoroquinolones, including levofloxacin. When using fluoroquinolones, including levofloxacin, caution should be exercised in patients with known risk factors for lengthening the interval QT: in patients with uncorrected electrolyte disturbances (with 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 antiarrhythmic drugs of classes IA and III, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal, imidazole derivatives, some antihistamines, including astemizole, terfenadine, ebastine. Elderly patients and female patients may be more sensitive to drugs,extending the interval QT. Therefore, care should be taken to use fluoroquinolones, including levofloxacin (see the sections "With caution", "Side effect", "Interaction with other medicinal products").

Patients with deficiency of glucose-6-phosphate dehydrohease. 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.

Hypo-and hyperglycemia (dysglycemia). As with the use of other quinolones, when levofloxacin was used, cases of hyperglycaemia and hypoglycemia were observed, usually in patients with diabetes mellitus, who received 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 (dm. "Side effect").

Peripheral neuropathy. In patients taking fluoroquinolones, including levofloxacin. marked sensory and sensory-motor peripheral neuropathy, the beginning of which can be rapid. If a patient develops symptoms of neuropathy, the use of the drug Levofloxacin must be terminated. This minimizes the possible risk of irreversible changes.

Exacerbation of pseudo-paralytic myasthenia gravis (myasthenia gravis). Fluoroquinolones, including levofloxacinCharacterized by blocking neuromuscular activity holding and may enhance muscle weakness in patients with gravis. There were adverse reactions, including pulmonary insufficiency, requiring artificial ventilation, and death, which were associated with the use of fluoroquinolones in patients with pseudo-paralytic myasthenia gravis. The use of levofloxacin in patients with an established diagnosis of gravis is not recommended (0m. Section "Side effects").

Application in the airborne route of infection with anthrax. The use of levofloxacin in humans according to this indication is based on data on sensitivity to it Bacillus anthracis, obtained in studies in vitro and in experimental studies conducted on animals, as well as on limited data on the use of levofloxacin in humans. The attending physicians should refer to national and / or international documents that reflect the common point of view on the treatment of anthrax.

Psychotic reactions. When using quinolones, 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 section "Side effect"). With the development of such reactions, drug treatment Levofloxacin should stop and prescribe appropriate therapy. Caution should be used to prescribe the drug to patients with psychoses or patients who have a history of mental illness.

Vision disorders. With the development of any visual impairment, an immediate consultation of the ophthalmologist is required (see the "Side effect" section).

Effect on laboratory tests. In patients receiving levofloxacin, the definition of opiates in urine can lead to false positive results, which should be confirmed by more specific methods. Levofloxacin can inhibit growth Mycobacterium tuberculosis and lead in the future to false-negative results of a bacteriological diagnosis of tuberculosis.

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

During therapy with levofloxacin, you should refrain from driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, as dizziness, drowsiness and visual impairment are possible (see section "Side effect").

Form release / dosage:

Film coated tablets, 250 mg and 500 mg.

Packaging:

5 or 10 tablets in a planar cell packaging made of a polyvinylchloride film and aluminum foil or a high-density polyethylene can.

1 or 2 contiguous cell packs but 5 tablets, 1 circuit cell pack of 10 tablets or 1 can, together with instructions for use in a pack of cardboard.

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 expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001519/08

Date of registration:14.03.2008 / 07.08.2015

Expiration Date:Unlimited

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Information update date: & nbsp06.03.2018

Illustrated instructions

Instructions

Levofloxacin (Levofloxacin)