Composition, form of production and packaging
Tablets covered with a film coat of white or almost white color, capsular, with a dividing risk on one side; On the cross-section, two layers are visible, on the break - the core of yellow color.
1 tab.
levofloxacin (in the form of hemihydrate) 500 mg
Excipients: crospovidone - 22 mg, hypromellose - 8 mg, microcrystalline cellulose - 65 mg, silicon colloidal dioxide - 5 mg, talc - 3 mg, magnesium stearate - 7 mg, water *.
The composition of the coating: hypromellose - 10.3 mg, macrogol - 1.2 mg, titanium dioxide - 6 mg, talc - 1.2 mg, methylparahydroxybenzoate - 0.12 mg, propylparahydroxybenzoate - 0.06 mg, water *.
* Removed during production.
5 pieces. - blisters (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
A broad-spectrum antimicrobial agent from the group of fluoroquinolones, containing as an active substance the levorotatory isofloxacin isomer. It blocks DNA-gyrase (topoisomerase II) and topoisomerase IV, disrupts supercoiling and cross-linking of DNA gaps, suppresses DNA synthesis, causes profound morphological changes in the cytoplasm, cell wall and membranes. Effective against most strains of microorganisms in vitro and in vivo.
To the drug are sensitive:
- aerobic Gram-positive microorganisms: Corynebactcrium diphtheriae, Enterococcus spp. (including Enterococcus faecalis), Listeria monocytogenes, Staphylococcus spp. (coagulase-negative methicillin susceptible / moderately sensitive strains), including Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-susceptible strains), Staphylococcus spp. (leukotoxin-containing); Streptococcus spp. Groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-sensitive / moderately sensitive / resistant strains), Streptococcus pyogenes, Streptococcus group of viridans (penicillin-sensitive / resistant strains);
- aerobic gram-negative microorganisms: Acinctobacter spp. (including Acinetobacter baumannii), Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter spp. (including Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (ampicillin-sensitive / resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (including Klebsiella oxytoca, Klebsiella pneumoniae), Moraxella catarrhalis (producing and non-producing beta-lactamase strains). Morganella morganii, Neisseria gonorrhoeae (producing and non-producing penicillinase strains), Neisseria meningitidis, Pasteurella spp. (including Pasteurella canis, Pasteurella dagmalis, Pasteurella multocida), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas spp. (including Pseudomonas aeruginosa), Serratia spp. (including Serratia marcescens), Salmonella spp .;
anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Reptostreptococcus spp., Propionibacterium spp., Veilonella spp .;
- Other microorganisms: Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella spp. (including Legionella pneumophila), Mycobacterium spp. (including Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.
Moderately sensitive microorganisms (MIC> 4 mg / l):
- aerobic Gram-positive microorganisms : Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis (methicillin-resistant strains), Staphylococcus haemolyticus (methicillin-resistant strains);
- aerobic gram-negative microorganisms: Burkholderia cepacia, Campylobacter jejuni, Campylobacter coli;
- anaerobic microorganisms: Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp., Porphyromonas spp.
Stable microorganisms (MIC> 8 mg / l):
- aerobic gram-positive microorganisms: Corynebacterium jeikeium, Staphylococcus aureus (methicillin-resistant strains), other Staphylococcus spp. (coagulase-negative methicillin-resistant strains);
- aerobic gram-negative microorganisms: Alcaligenes xylosoxidans;
- other microorganisms: Mycobacterium avium.
PHARMACOKINETICS
When ingestion, levofloxacin is rapidly and almost completely absorbed (food intake has little effect on the speed and completeness of absorption). Bioavailability is 99%. Т mах in plasma - 1-2 hours. At reception of 500 mg С max in a plasma makes 5,2 mkg / 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. It penetrates well into organs and tissues: lungs, bronchial mucosa, sputum, organs of the genitourinary system, polymorphonuclear leukocytes, alveolar macrophages. With max in the bronchial mucosa and the fluid of the epithelial lining after oral administration, 500 mg of the drug are 8.3 Ојg / g and 10.8 Ојg / ml, respectively; With MAX, levofloxacin in the blister fluid is 4.0-6.7 Ојg / ml, T max in this case is 2-4 hours. With max in the lung tissues after oral administration, 500 mg of the drug is 11.3 Ојg / g, and T max - 4-6 hours. Levofloxacin penetrates into the cerebrospinal fluid in small amounts. After oral administration of 500 mg / day of levofloxacin on the third day of treatment with Cmax in the tissues of the prostate at 2, 6 and 24 hours after the administration of the drug, 8.7 Ојg / g, 8.2 Ојg / g and 2.0 Ојg / g, respectively . The ratio of prostatic / plasma concentrations averaged 1.84. The average C max value 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. T 1/2 - 6-8 hours. 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. In cases of violations of kidney function and a decrease in renal clearance, T 1/2 is increased.
During clinical trials, there was no difference in the pharmacokinetics of the drug in men and women.
INDICATIONS
Infectious-inflammatory diseases caused by susceptible to levofloxacin microorganisms:
- lower respiratory tract (exacerbation of chronic bronchitis, community-acquired pneumonia);
- urinary tract and kidneys (including acute pyelonephritis);
- chronic bacterial prostatitis;
- skin and soft tissues (festering atheromas, abscess, boils);
- intra-abdominal infections;
acute bacterial sinusitis;
- tuberculosis (complex therapy of drug-resistant forms).
DOSING MODE
OD Levoks should be administered orally during meals or during a break between meals, without chewing, squeezed with enough liquid.
Doses of OD-Levox preparation are determined by the nature and severity of the infection, as well as by the suspected pathogen susceptibility.
The recommended dose for adults with normal renal function (CK)> 50 ml / min)
In acute bacterial sinusitis - 500 mg 1 time / day for 10-14 days.
With exacerbation of chronic bronchitis - 250-500 mg 1 time / day for 7-10 days.
In case of community-acquired pneumonia, 500 mg 1 or 2 times / day for 7-14 days.
In uncomplicated urinary tract infections and kidneys - 250 mg (1/2 tablet) 1 time / day for 3 days.
With complicated infections of the urinary tract - 250 mg (1/2 tablet) 1 time / day for 7-10 days.
With chronic bacterial prostatitis - 500 mg 1 time / day for 28 days.
With infections of the skin and soft tissues - 250-500 mg 1-2 times / day for 7-14 days.
Intra-abdominal infections - 500 mg 1 time / 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 / day, treatment course up to 3 months.
For patients with impaired renal function (CK <50 mL / min)
Dosing regimen with normal renal 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 dose adjustment is not required 250 mg every 48 hours in the treatment of uncomplicated urinary tract infections dose adjustment is not required No data on the possibility of dose adjustment
* permanent ambulatory peritoneal dialysis
Patients after hemodialysis or permanent ambulatory peritoneal dialysis (CAPD) do not require the administration of additional doses.
Patients with a dysfunction of the liver do not require a special choice of doses, since levofloxacin 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 admission is near. Then continue taking levofloxacin according to the scheme.
The duration of therapy depends on the type of disease. In all cases, treatment is recommended to continue for 48 to 72 hours after the disappearance of the symptoms of the disease.
SIDE EFFECT
On the part of the digestive system: nausea, vomiting, diarrhea (including with blood), digestive disorders, decreased appetite, abdominal pain, pseudomembranous colitis, increased activity of hepatic transaminases, hyperbilirubinemia, hepatitis, dysbiosis.
From the cardiovascular system: a decrease in blood pressure, vascular collapse, tachycardia, lengthening of the QT interval, atrial fibrillation.
On the part 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 side of the nervous system: headache, dizziness, weakness, drowsiness, insomnia, tremor, anxiety, paresthesia, fear, hallucinations, confusion, depression, movement disorders, convulsions, peripheral sensory neuropathy, peripheral sensory-motor neuropathy, extrapyramidal disorders, agitation (agitation), nightmares, mental disorders with behavioral disorders with self-harm, including suicidal thoughts and suicidal attempts.
Co side of the senses: impaired vision, hearing, smell, taste and tactile sensitivity, ringing in the ears.
From the musculoskeletal system: arthralgia, muscle weakness, myalgia, tendon rupture, tendonitis, rhabdomyolysis.
From the side of the urinary system: hypercreatenemia, interstitial nephritis, acute renal failure.
On the part of the organs of hematopoiesis: eosinophilia, hemolytic anemia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, pancytopenia, hemorrhages.
Allergic reactions: itching and flushing of the skin; edema of the skin, and mucous membranes, urticaria, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), bronchospasm, suffocation, anaphylactic shock, allergic pneumonitis, vasculitis.
Other: photosensitization, asthenia, exacerbation of porphyria, persistent fever, development of superinfection.
CONTRAINDICATIONS
- epilepsy;
- damage to the tendons during the previous treatment with quinolones;
- Pregnancy;
- lactation period;
- children and adolescence under 18;
- hypersensitivity to the components of the drug;
- hypersensitivity to other fluoroquinolones.
Precautions: elderly age (due to high probability of concomitant decrease in kidney function), deficiency of glucose-6-phosphate dehydrogenase, predisposition to convulsive reactions (atherosclerosis of cerebral vessels, cerebral circulatory disorders (in history), organic diseases of the central nervous system), renal failure , congenital QT interval prolongation syndrome, heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (eg, hypokalemia, hypomagnesemia), diabetes mellitus t, myasthenia gravis, psychosis and other psychiatric disorders in history, hepatic porphyria, simultaneous administration of drugs that extend the QT interval (antiarrhythmics of Class I and III, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal - imidazole derivatives, some antihistamines, in including astemizole, terfenadine, ebastin) and lowering the threshold of convulsive brain readiness (fenbufen, theophylline).
PREGNANCY AND LACTATION
Contraindicated in pregnancy and lactation (breastfeeding).
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution: kidney failure.
APPLICATION FOR CHILDREN
Contraindicated in childhood and adolescence (under 18 years).
APPLICATION IN ELDERLY PATIENTS
With caution: the elderly (due to the high likelihood of concomitant decline in kidney function).
SPECIAL INSTRUCTIONS
OD-Levox should be used at least 2 hours before or 2 hours after taking iron, zinc, antacid and sucralfate salts.
During treatment with OD-Levox, sun and artificial UV-irradiation should be avoided to avoid damage to the skin (photosensitivity).
When there are signs of tendinitis, pseudomembranous colitis, allergic reactions, OD-Levox immediately abolished.
It should be noted that in patients with a history of brain damage (stroke, severe trauma), convulsions may develop, with insufficiency of glucose-6-phosphate dehydrogenase - the risk of hemolysis.
With the simultaneous use of OD-Levox and warfarin, careful monitoring of prothrombin time and other coagulation indices is necessary.
It is recommended to carefully monitor the concentration of glucose in blood plasma with the simultaneous use of OD Levoksa with hypoglycemic drugs.
Because levofloxacin is excreted mainly by the kidneys, in patients with impaired renal function, mandatory monitoring of kidney function is required, as well as correction of the dosing regimen. Very rare cases of prolongation of the QT interval in patients receiving fluoroquinolones, including levofloxacin, have been reported.When using fluoroquinolones, including levofloxacin, caution should be exercised in patients with known risk factors for prolonging the QT interval: elderly age, electrolyte imbalance (hypokalemia, hypomagnesemia), congenital QT interval prolongation, heart disease (heart failure, myocardial infarction, bradycardia), simultaneous administration of drugs that can extend the QT interval.
In patients receiving fluoroquinolones, including levofloxacin, sensory and sensory-motor peripheral neuropathy was noted, the onset of which can be rapid. If the patient develops symptoms of neuropathy, the use of levofloxacin should be discontinued. This minimizes the possible risk of irreversible changes.
Impact on the ability to drive vehicles and manage mechanisms
During the treatment with OD-Levox, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: confusion, dizziness, impaired consciousness, convulsions, nausea, vomiting and erosive lesions of the mucous membranes are possible. During the research it was shown that when levofloxacin is used in doses exceeding the average therapeutic levels, the QT interval may be prolonged.
Treatment: if necessary, conduct symptomatic therapy. Levofloxacin is not excreted in hemodialysis, peritoneal dialysis and permanent peritoneal dialysis. There is no specific antidote.
DRUG INTERACTION
Quinolones can enhance the ability of drugs, including theophylline, NSAIDs, lower the threshold of convulsive readiness. With simultaneous administration with fenbufen, higher concentrations of levofloxacin are observed than with monotherapy.
The effect of levofloxacin reduces drugs that depress intestinal motility, sucralfate, magnesium or aluminum-containing antacids, iron and zinc salts.
Acceptance of GCS increases the risk of rupture of tendons.
Levofloxacin increases the anticoagulant activity of warfarin.
Elimination (renal clearance) of levofloxacin is slightly slowed by cimetidine and probenecid in view of the possible blocking of tubular secretion of levofloxacin in the kidneys. It should be noted that this interaction is of clinical importance, especially for patients with impaired renal function.
Levofloxacin increases T1 / 2 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 use with drugs that extend the QT interval (antiarrhythmic IA and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal, imidazole derivatives, some antihistamines, including astemizole, terfenadine, ebastin), QT interval prolongation is possible.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children, dry, protected from light at a temperature of no higher than 25 В° C. Shelf life - 2 years.
