Zolev is indicated for the treatment in adults of such infections caused by microorganisms sensitive to levofloxacin: acute bacterial sinusitis; exacerbation of chronic bronchitis; non-hospital pneumonia; complicated infections of the skin and soft tissues (in the case of the treatment of the above infections the drug is used only when the use of other antibacterial agents, usually intended for the initial treatment of these infections is impossible); complicated infections of the urinary tract (including pyelonephritis); chronic bacterial prostatitis; uncomplicated cystitis; pulmonary anthrax: post-contact prophylaxis and treatment. Levofloxacin in this dosage form (tablets) can be used to complete the course of therapy for patients who have shown improvement during their initial treatment with levofloxacin, a solution for infusion.
active substance: levofloxacin; 1 tablet contains levofloxacin hemihydrate equivalent to levofloxacin 250 mg or 500 mg or 750 mg;
Excipients: microcrystalline cellulose, corn starch, sodium starch (type A), hypromellose, colloidal silicon dioxide, povidone, magnesium stearate, titanium dioxide (E 171), talc, polyethylene glycol 6000, iron oxide red (E172).
Levofloxacin is a broad-spectrum antibiotic of the quinolone group, containing the active substance – levofloxacin. Levofloxacin, like other fluorinated quinolones, blocks bacterial DNA gyrase, as a result of which the function of bacterial DNA is disrupted. Levofloxacin is active against gram-positive and gram-negative pathogenic microorganisms, including strains resistant to penicillins, cephalosporins and / or aminoglycosides. The development of resistance can significantly affect the sensitivity of local strains to the drug, therefore, when prescribing the drug, it is advisable to take this information into account, especially in the case of treatment of severe infections. Levofloxacin has a wide spectrum of action against microorganisms both in vitro and in vivo: Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus aerlogenes, Enterococcus aerlogenes, Enterococcus agalacterrans, Enterobacteracterrans, Enterobacterobactero, Enterobacterobacterobacter sakazakii, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Klebsiella oxytoca, Legionella pneumopnia, Moraxella catarrhalis, Proteus mirabilis, Pseudomonas aeruginosa, Pseudomonas fluorescens, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Acinetobacter anitratus, Acinetobacter baumannii, Acinetobacter calcoaceticus, Bordetella pertussis, Citrobacter diversus, Citrobacter freundii, Morganella morganii, Proteus vulgaris, Providencia rettgeri et stuartii, Serratia marcescens, Clostridium perfringens.
Like other fluoroquinolones, levofloxacin is inactive against spirochetes
When administered orally, levofloxacin is rapidly and almost completely absorbed. Cmax in blood plasma is noted 1 hour after administration. Absolute bioavailability is almost 100%. Pharmacokinetics of levofloxacin is linear in the range of 50–600 mg. Food intake somewhat affects the absorption of the drug.
About 30-40% of levofloxacin binds to blood plasma proteins. The cumulative effect of levofloxacin at a dose of 500 mg once a day has no clinical significance. There is an insignificant, but foreseen, its cumulation when dosing 500 mg 2 times a day. Stable distribution rates are achieved within 3 days.
Distribution into tissues and body fluids. Distribution in the mucous membrane of the bronchi and the secretion of the bronchial epithelium
Cmax of levofloxacin in the bronchial mucosa and secretions of the bronchial epithelium at a dose of> 500 mg when taken orally was 8.3 and 10.8 mg / ml, respectively.
Distribution in lung tissues
Cmax of levofloxacin in the lung tissues at a dose of> 500 mg when taken orally was about 11.3 mg / ml and was reached within 4-6 hours after administration. The concentration in the lungs constantly exceeded that in the blood plasma.
Distribution of bubbles in the liquid
Cmax of levofloxacin in the bladder fluid after taking 500 mg 1-2 times a day was 6.7 mg / ml.
Distribution to CSF. Levofloxacin poorly penetrates the CSF
Distribution in the tissues of the prostate gland. After oral administration of 500 mg of levofloxacin 1 time per day for 3 days, the average concentrations in the tissues of the prostate gland were 8.7; 8.2 and 2 mg / g, respectively, after 2; 6 and 24 hours; the average concentration ratio in the prostate gland / blood plasma is 1.84.
Concentration in urine. Average concentration of levofloxacin for 8-12 hours after oral administration of a single dose 150; 300 or 500 mg was 44; 91 and 200 mg / ml, respectively.
Levofloxacin is metabolized to an insignificant extent, metabolites are dismethyl-levofloxacin and levofloxacin N-oxide. These metabolites make up <5% of the amount of drug excreted in the urine.
After oral administration, levofloxacin is removed from blood plasma relatively slowly (T1 / 2 – 6-8 hours). Excretion is carried out mainly by the kidneys (> 85% of the administered dose). There are no significant differences in the pharmacokinetics of levofloxacin after parenteral and oral administration.
Infections caused by microorganisms sensitive to the drug:
- acute sinusitis;
- exacerbation of chronic bronchitis;
- community-acquired pneumonia;
- complicated and uncomplicated urinary tract infections (including pyelonephritis);
- infections of the skin and soft tissues;
- chronic bacterial prostatitis;
- septicemia / bacteremia;
- intra-abdominal infections.
Take 1-2 times a day. The dose depends on the type and severity of the infection. The duration of treatment depends on the course of the disease and is no more than 14 days. It is recommended to continue treatment for another 48–72 hours after normalization of body temperature or elimination of pathogens confirmed by microbiological tests.
The tablets are swallowed without chewing, with a sufficient amount of liquid. Apply regardless of food intake. For convenience of dosing, the tablet can be divided (there is a dividing line on the tablet).
* No additional doses are required after hemodialysis or chronic ambulatory peritoneal dialysis (CAPD).
Dosing for patients with impaired liver function. No dose adjustment is required, since levofloxacin is metabolized to a small extent in the liver.
Dosing for elderly patients. If renal function is not impaired, there is no need for dose adjustment.
Hypersensitivity to levofloxacin, other fluoroquinolones or any ingredient of the drug; epilepsy; tendon injury associated with fluoroquinolone intake; During pregnancy and breastfeeding; age up to 18 years.
Allergic reactions: sometimes – itching, skin rash; rarely – urticaria, bronchospasm / shortness of breath; very rarely – angioedema, arterial hypotension, anaphylactic shock, photosensitivity; in some cases – a bullous rash, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), exudative erythema multiforme.
Such reactions can sometimes be noted even after the first dose for several minutes or hours after application.
From the gastrointestinal tract, metabolism: often – nausea, diarrhea; sometimes – anorexia, vomiting, abdominal pain, dyspepsia; rarely – diarrhea mixed with blood, which in some cases may indicate the development of enterocolitis, including pseudomembranous colitis; very rarely – hypoglycemia, especially in patients with diabetes mellitus.
From the side of the central nervous system: sometimes – headache, dizziness / vertigo, drowsiness, insomnia; rarely – paresthesia, tremor, confusion, convulsions, anxiety, depression, psychotic reactions, agitation; very rarely – hyposthesia, visual and auditory disorders, impaired taste and perception of smells, hallucinations, suicidal tendencies.
From the side of the cardiovascular system: rarely – tachycardia, arterial hypotension; very rarely – anaphylactic shock; in some cases – lengthening of the Q – T interval.
From the musculoskeletal system: rarely – arthralgia, myalgia, tendon damage, including tendonitis (eg Achilles tendon); very rarely – tendon rupture (for example Achilles), this side effect can be detected within 48 hours from the start of treatment; muscle weakness, which is especially dangerous for patients with myasthenia gravis; in some cases, rhabdomyolysis.
From the liver, kidneys: often – an increase in the level of liver enzymes (for example, ALT / ASAT); infrequently – an increase in bilirubin, plasma creatinine levels; very rarely – liver reactions such as hepatitis; ARF (eg due to interstitial nephritis).
From the side of the blood system: sometimes – eosinophilia, leukopenia; rarely – neutropenia, thrombocytopenia; very rarely – agranulocytosis; in some cases – hemolytic anemia, pancytopenia.
Others: sometimes – asthenia, candidiasis, development of superinfection; very rarely – allergic pneumonitis, fever.
Other side effects associated with the administration of fluoroquinolones may include extrapyramidal symptoms and other muscular disorders, allergic vasculitis, and porphyria attacks in patients with porphyria.
In nosocomial infections caused by Ps. aeruginosa, and severe pneumococcal pneumonia may require combination therapy.
In some cases, patients may experience tendonitis. Most often, tendonitis affects the Achilles tendon and can rupture. The risk of tendonitis and tendon rupture is increased in the elderly and in patients taking GCS. Therefore, careful monitoring of patients using levofloxacin is required. Patients with symptoms of tendonitis should consult a physician before starting treatment. If tendonitis is suspected, treatment with the drug should be stopped immediately and appropriate treatment for the affected tendon (eg immobilization) initiated.
Diarrhea, especially severe, persistent and / or bloody during or after drug treatment, may indicate the development of Clostridium difficile-associated colitis, the most severe form of which is pseudomembranous colitis. If there is a suspicion of pseudomembranous colitis, drug therapy should be discontinued immediately and symptomatic and specific treatment (for example vancomycin) should be started without delay. In this clinical situation, drugs that inhibit peristalsis are contraindicated.
Levofloxacin is contraindicated in patients with a history of epilepsy and, like other quinolones, should be used with caution in patients prone to seizures, such as those with pre-existing CNS disease.
Concomitant treatment with fenbufen and similar NSAIDs or drugs that lower the cerebral seizure threshold, such as theophylline, also requires caution.
Patients with latent or overt deficiency in glucose-6-phosphate dehydrogenase activity may tend to hemolytic reactions when using quinolone antibacterial drugs. Therefore, levofloxacin should be used with caution in such patients.
Although photosensitization with levofloxacin is very rare, patients are advised to avoid ultraviolet irradiation in order to prevent photosensitization. If psychotic reactions develop while taking quinolones, including levofloxacin, the drug should be discontinued and symptomatic therapy should be carried out. Zolev is prescribed with caution to patients with mental disorders or mental illness in history.
DURING PREGNANCY AND BREASTFEEDING
Due to the lack of studies with human participation and the possibility of damage to the articular cartilage by quinolones during the growth of the body, the drug cannot be prescribed during pregnancy and lactation. If pregnancy occurs during treatment with the drug, it is necessary to inform the doctor about this.
Children under the age of 18 should not be prescribed the drug, since damage to the articular cartilage cannot be ruled out.
ABILITY TO INFLUENCE THE RATE OF RESPONSE WHEN DRIVING VEHICLES OR WORKING WITH OTHER MECHANISMS
In some patients, the drug may cause headache, dizziness / vertigo, drowsiness, insomnia, visual impairment, confusion, therefore, during its use, you should refrain from driving vehicles and working with complex mechanisms that require increased attention and speed of psychomotor reactions.
Theophylline, fenbufen, or similar NSAIDs: Levofloxacin did not show any pharmacokinetic interaction with theophylline in one clinical study. A noticeable decrease in the cerebral convulsive threshold can be noted when quinolones are used simultaneously with theophylline, NSAIDs, or other drugs that lower the seizure threshold.
Probenecid and cimetidine: show a statistically significant effect on the elimination of levofloxacin; renal clearance of levofloxacin decreased with the combined use of cimetidine (24%) and probenecid (34%). Levofloxacin should be used with caution in conjunction with drugs that affect tubular secretion (probenecid and cimetidine), especially in patients with impaired renal function.
Cyclosporin: T1 / 2 of cyclosporin increases by 33% when administered concurrently with levofloxacin.
Vitamin K antagonists: due to the possible occurrence of bleeding in patients taking levofloxacin in combination with any vitamin K antagonist (for example, warfarin), the indicators of coagulation tests should be monitored if these drugs are used simultaneously.
The pharmacokinetics of levofloxacin did not change when administered in combination with the following drugs: calcium carbonate, digoxin, glibenclamide, ranitidine, warfarin.
dizziness, impaired consciousness, seizures, nausea, erosion of the mucous membranes. According to the results of studies, when using the drug in doses exceeding therapeutic doses, an extension of the Q – T interval was revealed.
Treatment is symptomatic and supportive. ECG monitoring should be provided, since prolongation of the Q – T interval may occur. Levofloxacin is not excreted either by hemodialysis or by peritoneal dialysis; there is no specific antidote.
At a temperature not higher than 30 ° C.