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

Excipients (core): microcrystalline cellulose - 30.00 mg, sodium carboxymethyl starch - 17.50 mg, povidone (polyvinylpyrrolidone) - 15.00 mg, magnesium stearate - 5.00 mg, croscarmellose sodium - 8.27 mg, silicon dioxide colloid - 3.00 mg .

Auxiliary substances (shell): Foam White - 15.00 mg, incl. polyvinyl alcohol - 7,035 mg, macrogol 3350 - 3,540 mg, talc - 2,610 mg, titanium dioxide - 1,815 mg.

1 tablet, film-coated, contains

Active substance: Levofloxacin hemihydrate in terms of levofloxacin - 500.00 mg

Excipients (core): microcrystalline cellulose - 60.00 mg, sodium carboxymethyl starch 35.00 mg, povidone (polyvinylpyrrolidone) 30.00 mg, magnesium stearate 10.00 mg, croscarmellose sodium 16.54 mg, silicon dioxide colloid 6.00 mg .

Auxiliary substances (shell): Defect White - 30,00 mg, incl. polyvinyl alcohol - 14,070 mg, macrogol 3350 - 7,080 mg, talc - 5,220 mg, titanium dioxide - 3,630 mg.

Description:

Dosage 250 mg: cylindrical, biconvex tablets, covered with a film shell of white or almost white color, with a risk, on the fracture are visible two layers - a core of light yellow color and a film membrane.

Dosage 500 mg: cylindrical, biconvex tablets, covered with a film shell of white or almost white color, on the fracture are visible two layers - a core of light yellow color and a film membrane.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A Fluoroquinolones

J.01.M.A.12 Levofloxacin

Pharmacodynamics:

Antimicrobial drug from the group of fluoroquinolones, the left-handed isomer of ofloxacin. Has a wide spectrum of antimicrobial action.

Levofloxacin blocks 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 bacterial membranes. Effective against most strains of microorganisms in vitro and in vivo. The action of the drug is sensitive:

in vitro sensitive (minimum suppressive concentration (MIC) ≤2 mg / ml)

aerobic Gram-positive microorganisms: Corynebacterium diphtheriae, 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); Streptococcus spp. groups FROM and G, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-sensitive/moderately sensitive/resistant strains), Streptococcus pyogenes, Streptococcus spp. groups viridans (penicillin-sensitive/resistant strains);

aerobic Gram-negative microorganisms: Acinetobacter spp. (at t.h. Acinetobacter baumannii), Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter spp. (at t.h. 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 non-reducing beta-lactamase strains), Morganella morganii, Neisseria gonorrhoeae (producing and non-reducing 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), Serratia spp. (at t.h. Serratia marcescens), Salmonella spp .;

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

others 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: Burkholderia cepacia, Campilobacter jejuni, Campilobacter coli;

anaerobic microorganisms: Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp., Porphyromonas spp.

Stable microorganisms (IPC ≥8 mg / l):

aerobic Gram-positive microorganisms: Corynebacterium jeikeium, Staphylococcus aureus (methicillin-resistant strains), others Staphylococcus spp. (coagulase-negative methicillin-resistant strains);

aerobic gram-negative microorganisms: Alcaligenes xylosoxidans;

other microorganisms: Mycobacterium avium.

Pharmacokinetics:

Ingestion levofloxacin quickly and almost completely absorbed (food intake has little effect on the speed and completeness of absorption). Bioavailability is 99%. Time to reach the maximum concentration (TC_m_Oh) in plasma - 1-2 hours. At reception 500 polymorphonuclear leukocytes, alveolar macrophages. The maximum concentration in the bronchial mucosa and fluid of the epithelial lining after oral administration of 500 mg of the drug is 8.3 μg / g and 10.8 μg / ml, respectively, the maximum concentration (C_m_Oh) in the plasma is 5.2 μg / ml. The connection with plasma proteins is about 30-40%.

Moderate cumulation of levofloxacin is observed already on the third day of taking the drug at a dose of 500 mg 2 times a day.Well penetrates into organs and tissues: lungs, mucous membranes bronchial membrane, sputum, organs of the genitourinary system; the maximum concentration of levofloxacin in the blister fluid is 4.0-6.7 μg / ml, the time to reach the maximum concentration in this case is 2-4 hours. The maximum concentration in the lung tissues after oral administration of 500 mg of the drug is 11.3 μg / and the time to reach the maximum concentration is 4-6 hours. Levofloxacin penetrates into the cerebrospinal fluid in small amounts. At oral intake of 500 mg / day of levofloxacin on the third day of treatment, the maximum concentration in the tissues of the prostate at 2, 6 and 24 hours after taking the drug was 8.7 μg / g, 8.2 μg / g and 2.0 μg / g, respectively . The ratio of prostatic / plasma concentrations averaged 1.84. The average value of the maximum concentration in the urine after taking 500 mg of the drug after 8-12 hours is 200 mg / l. In the liver, a small part of the preparation is oxidized and / or deacetylated. The half-life (T1 / 2) is 6-8 hours. It is excreted mainly by the kidneys (about 85% of the dose) by glomerular filtration and tubular secretion. 4% of the ingested dose of levofloxacin is excreted by the intestine within 72 hours. With violations of kidney function and a decrease in renal clearance, the half-life increases.

Indications:

Infectious-inflammatory diseases caused by susceptible to levofloxacin microorganisms:

- infections of the lower respiratory tract (exacerbation of chronic bronchitis, community-acquired pneumonia);

acute acute maxillary sinusitis;

uncomplicated urinary tract infections;

- Complicated urinary tract infections (including acute pyelonephritis);

- skin and soft tissue infections (festering atheromas, abscess, boils);

- chronic bacterial prostatitis;

- intra-abdominal infection;

- complex therapy of drug-resistant forms of tuberculosis.

Contraindications:

Hypersensitivity to levofloxacin or other fluoroquinolones, as well as to the adjuvant substances of the drug, epilepsy, and tendon damage in the past treatment with quinolones, pregnancy, lactation, children and adolescence (up to 18 years).

Carefully:

Elderly age (high probability of concomitant decrease in kidney function), deficiency of glucose-6-phosphate dehydrogenase, predisposition to convulsive reactions (cerebrovascular atherosclerosis, cerebral circulation disorders (in anamnesis),organic diseases of the central nervous system), renal failure, congenital lengthening syndrome Q-T, heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (eg, hypokalemia, hypomagnesemia), diabetes mellitus, myasthenia gravis gravis, psychosis and other psychiatric disorders in the anamnesis, hepatic porphyria. Simultaneous reception of drugs that extend the interval Q-T (antiarrhythmic IA and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal, imidazole derivatives, some antihistamines, including antihistamines. astemizole, terfenadine, ebastine) and lowering the threshold of convulsive readiness of the brain (fenbufen, theophylline).

Pregnancy and lactation:

Safety of use during pregnancy and lactation is not known. The drug is contraindicated during pregnancy. If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

The drug should be taken orally during meals or during a break between meals, without chewing,with enough liquid.

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

The recommended dose of the drug for adults with normal renal function (creatinine clearance (CK)> 50 ml / min):

In acute bacterial sinusitis - 500 mg once a day for 10-14 days;

With an exacerbation of chronic bronchitis - 250-500 mg once a day for 7-10 days;

With community-acquired pneumonia - 500 mg 1 or 2 times a day for 7-14 days;

In uncomplicated infections of the urinary tract and kidneys - 250 mg once a day for 3 days;

With complicated infections of the urinary tract - 250 mg once a day for 7-10 days;

With chronic bacterial prostatitis - 500 mg once a day for 28 days;

With infections of the skin and soft tissues - 250-500 mg 1-2 times a day for 7-14 days;

Intra-abdominal infections - 500 mg once a day - 7-14 days (in combination with antibacterial drugs acting on anaerobic flora);

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

For patients with impaired renal function (QC≤50 ml / min):

Dosing regimen with normal kidney function, every 24 hours	Creatinine clearance, ml / min
	50-20	19-10	<10 (including hemodialysis and CAPD *)
500 mg	first dose: 500 mg, then: 250 mg every 24 hours	first dose: 500 mg, then: 250 mg every 48 hours	first dose: 500 mg, then: 250 mg every 48 hours
250 mg	no dose adjustments required	250 mg every 48 hours, in the treatment of uncomplicated urinary tract infections dose adjustment is not required	There is no data on the possibility of dose adjustment

* Permanent outpatient peritoneal dialysis.

After hemodialysis or permanent ambulatory peritoneal dialysis (CAPD), no additional doses are required.

If the liver function is not required, a special dose selection is required, since levofloxacin It is only slightly metabolized in the liver and excreted mainly by the kidneys.

If you missed taking the drug you need to take a pill as soon as possible until the time of the next appointment is near. Continue to take levofloxacin according to the scheme.

The duration of therapy depends on the type of disease (see above). In all cases, treatment should continue from 48 to 72 hours after the disappearance of the symptoms of the disease.

Side effects:

From the digestive system: nausea, vomiting, diarrhea (including with blood), digestive disorders, decreased appetite, abdominal pain, pseudomembranous colitis, increased activity of "hepatic" transaminases, hyperbilirubinemia, hepatitis, dysbacteriosis.

From the cardiovascular system: lowering blood pressure, cardiovascular collapse, tachycardia, increased interval Q-T on cardiogram, atrial fibrillation.

From the side of metabolism: hypoglycemia (increased appetite, increased sweating, trembling, nervousness), hyperglycemia (dry mouth, thirst, increased urination, fatigue, blurred vision, dry or itchy skin, arrhythmia).

From the nervous system: headache, dizziness, weakness, drowsiness, insomnia, anxiety, paresthesia in the hands, fear, hallucinations, confusion, depression, movement disorders, seizures, peripheral sensory neuropathy, peripheral sensory-motor neuropathy, mental disorders with behavioral disorders harm, including suicidal thoughts and suicidal attempts, extrapyramidal disorders, agitation (agitation), nightmares.

From the sense organs: visual impairment, hearing, smell, taste and tactile sensitivity, ringing in the ears.

From the musculoskeletal system: arthralgia, muscle weakness, myalgia, tendon rupture, tendonitis, rhabdomyolysis.

From the urinary system: hypercreatininemia, interstitial nephritis, acute renal failure.

From the hematopoiesis: eosinophilia, hemolytic anemia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, pancytopenia, hemorrhages.

Allergic reactions: itching and hyperemia of the skin, swelling of the skin and mucous membranes, urticaria, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), bronchospasm, anaphylactic shock, allergic pneumonitis, vasculitis.

Other: asthenia, exacerbation of porphyria, photosensitivity, persistent fever, leukocytoclastic vasculitis, the development of superinfection.

Overdose:

Symptoms: confusion, dizziness, impaired consciousness, convulsions, nausea, vomiting and erosive lesions of the mucous membranes are possible. In carrying out studies have shown that when levofloxacin is used in doses exceeding the average therapeutic levels, an interval may be longer Q-T.

Treatment: if necessary, conduct symptomatic therapy. Levofloxacin is not excreted in hemodialysis, peritoneal dialysis and peritoneal dialysis. There is no specific antidote.

Interaction:

Quinolones can enhance the ability of drugs, including theophylline, non-steroidal anti-inflammatory drugs lower the threshold of convulsive readiness. With simultaneous reception with fenbufen higher concentrations of levofloxacin are observed than with monotherapy.

The effect of levofloxacin reduces drugs, oppressive bowel motility, sucralfate, magnesium- or aluminum-containing antacid agents, salts of iron and zinc.

Reception glucocorticosteroids increases the risk of rupture of tendons.

Levofloxacin increases anticoagulant activity warfarin.

The clearance (renal clearance) of levofloxacin slightly slows down under the action of cimetidine and probenecid in view of the possible blocking of the tubular secretion of levofloxacin in the kidneys.It should be noted that this interaction is of clinical importance, primarily for patients with impaired renal function.

Levofloxacin increases half-life cyclosporine.

Simultaneous use of levofloxacin and hypoglycemic agents leads to a change in the concentration of glucose in the blood plasma (hypoglycemia and hyperglycemia).

With simultaneous application with drugs that extend the interval Q-T (antiarrhythmic IA and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal, imidazole derivatives, some antihistamines, including antihistamines. astemizole, terfenadine, ebastine) it is possible to extend the interval Q-T.

Special instructions:

The drug should be used at least 2 hours before or 2 hours after taking iron, zinc, antacid and sucralfate salts.

During treatment with the drug it is necessary to avoid sunlight and artificial UV irradiation to avoid damage to the skin (photosensitivity).

When there are signs of tendenitis, pseudomembrane colitis, allergic reactions, the drug is immediately canceled.

It should be borne in mind that the development of seizures is possible in patients with a history of brain damage (stroke, severe trauma), and the risk of hemolysis is a deficiency in glucose-6-phosphate dehydrogenase.

With the simultaneous use of levofloxacin and warfarin, careful monitoring of prothrombin time and other coagulation parameters is necessary.

It is recommended to carefully monitor the concentration of glucose in the blood plasma while using the drug with hypoglycemic drugs.

As levofloxacin is excreted mainly by the kidneys, in patients with impaired renal function, mandatory monitoring of kidney function is required, as well as adjustment of the dosing regimen. Lengthening of the interval has been reported Q- T in patients who received fluoroquinolones, including levofloxacin. When using fluoroquinolones, including levofloxacin, caution should be exercised in patients with known risk factors for lengthening the interval Q-T: elderly age; violation of electrolyte balance (hypokalemia, hypomagnesemia); congenital lengthening syndrome Q-T; heart disease (heart failure, myocardial infarction, bradycardia); simultaneous reception of drugs that can lengthen the interval Q-T.

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.

Effect on the ability to drive transp. cf. and fur:During the period of drug treatment, care should be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated 250 mg, 500 mg.

Packaging:

For 5, 7, 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

By 5, 10, 20, 30, 40, 50 or 100 tablets in cans of polymeric for medicines.

One bank or 1, 2, 3, 4, 5, or 10 contour mesh packages together with the instruction for use are placed in a cardboard boxpacking (bundle).

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-002296

Date of registration:05.11.2013

Expiration Date:05.11.2018

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp06.03.2018

Illustrated instructions

Instructions

Levofloxacin (Levofloxacin)