Levofloxacin tablets 500mg, No. 10

• Infectious and inflammatory diseases caused by sensitive microorganisms: acute sinusitis;

• exacerbation of chronic bronchitis;

• community-acquired pneumonia;

• complicated urinary tract infections (including pyelonephritis);

• uncomplicated urinary tract infections;

• prostatitis;

• infections of the skin and soft tissues;

• septicemia / bacteremia associated with the above indications;

• intra-abdominal infection.

For oral administration, a single dose is 250-500 mg.

The frequency of admission is 1-2 times / day.

The treatment regimen and the duration of use are set individually, depending on the indications.

Patients with impaired renal function require correction of the dosage regimen, depending on the CC value.

With a positive dynamics of the patient's clinical condition, after a few days of treatment, it is possible to switch from intravenous drip to oral administration of the drug in the same dose.

The duration of treatment, depending on the course of the disease, is no more than 14 days (with the exception of bacterial prostatitis).

It is recommended to continue treatment with levofloxacin for at least 48-72 hours after normalization of body temperature or after reliable eradication of the pathogen.

Film-coated tablets, yellow, round, biconvex; the cross section shows two layers; almost white to light yellow core without shell.

1 tab.

levofloxacin hemihydrate 512.46 mg,?

which corresponds to the content of levofloxacin 500 mg

Excipients: povidone - 25.8 mg, microcrystalline cellulose - 182.54 mg, magnesium stearate - 8 mg, crospovidone - 35.2 mg, sodium lauryl sulfate - 16 mg.

• Hypersensitivity to levofloxacin or other quinolones;

• epilepsy;

• tendon lesions during previous treatment with quinolones;

• children and adolescents up to 18 years old;

• pregnancy, breastfeeding period.

• It should be used with caution in patients with renal insufficiency, in elderly patients due to the high likelihood of a concomitant decrease in renal function, as well as with a deficiency of glucose-6-phosphate dehydrogenase.

pharmachologic effect

A synthetic antibacterial agent of a broad spectrum of action from the group, the levorotatory isomer of ofloxacin. Levofloxacin blocks DNA gyrase, disrupts supercoiling and stitching of DNA breaks, inhibits DNA synthesis, and causes deep morphological changes in the cytoplasm, cell wall and membranes.

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

Aerobic gram-positive microorganisms: Corynebacterium diphtheriae, Enterococcus faecalis, Enterococcus spp, Listeria monocytogenes, Staphylococcus coagulase-negative methi-S (I), Staphylococcus aureus methi-S. (CNS), Streptococci groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae peni I / S / R, Streptococcus pyogenes, Viridans streptococci peni-S / R.

Aerobic gram-negative microorganisms: Acinetobacter baumannil, Acinetobacter spp, Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Enterobacter cloacae, Enterobacter cloacae, Enterobacter cloacae, Enterobacter cloacae, Enterobacter coli, Enterobacter cloacae, Spp. Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella spp, Moraxela catarrhalis (3 + / p-, Morganella morganii, Neisseria gonorrhoeae non PPNG / PPNG, Neisseria meningis mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Providencia spp, Pseudomonas aeruginosa, Pseudomonas spp, Salmonella spp, Serratia marcescens, Serratia spp.

Anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp, Clostridium perfringens, Fusobacterium spp, Peptostreptococcus, Propionibacterum spp, Veilonella spp.

Other microorganisms: Bartonella spp, Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Legionella spp, Mycobacterium spp, Mycobacterium leprae, Micobacterium tuberculosis, Mycoplasma hominis.

Pharmacokinetics

The pharmacokinetics of levofloxacin with single and multiple administration of the drug is linear. Plasma profile of levofloxacin concentrations after intravenous administration is similar to that when taking tablets. Therefore, oral and / in the route of administration can be considered interchangeable.

Levofloxacin is rapidly and almost completely absorbed after oral administration. Food intake has little effect on the rate and completeness of absorption. The bioavailability of 500 mg of levofloxacin after oral administration is almost 100%. After taking a single dose of 500 mg of levofloxacin, Cmax is 5.2-6.9 ?g / ml, the time to reach Cmax is 1.3 hours, T1 / 2 is 6-8 hours.

After i.v. infusion of levofloxacin at a dose of 500 mg for 1 h, the mean value of Cmax in plasma was 6.2 ± 1.0 ?g / ml, Tmax - 1.0 ± 0.1 h to healthy volunteers.

Plasma protein binding - 30-40%. It penetrates well into organs and tissues: lungs, bronchial mucosa, phlegm, organs of the genitourinary system, bone tissue, cerebrospinal fluid, prostate gland, polymorphonuclear leukocytes, alveolar macrophages.

In the liver, a small portion is oxidized and / or deacetylated.

When taken orally, T1 / 2 is 6-8 hours. After a single intravenous injection at a dose of 500 mg, T1 / 2 is 6.4 ± 0.7 hours. It is excreted mainly by the kidneys by glomerular filtration and tubular secretion. Renal clearance is 70% of the total clearance. Less than 5% of levofloxacin is excreted as metabolites. In the urine, over a period of 24 hours, 70% is found unchanged, and for 48 hours - 87% of the dose taken orally or administered intravenously. In feces for a period of 72 hours, 4% of the dose taken orally or administered intravenously is detected.

Side effect

From the hematopoietic system: sometimes - eosinophilia, leukopenia; rarely - neutropenia, thrombocytopenia; very rarely - pronounced agranulocytosis; in some cases - hemolytic anemia, pancytopenia.

From the digestive system: often - nausea, diarrhea, increased ALT, ACT, dysbiosis; sometimes - loss of appetite, vomiting, abdominal pain, indigestion, hyperbilirubinemia; rarely - diarrhea with blood (in very rare cases, this can be a sign of intestinal inflammation or pseudomembranous colitis); very rarely - hepatitis.

From the side of the cardiovascular system: rarely - tachycardia, decreased blood pressure; very rarely - vascular collapse; in some cases - lengthening of the QT interval.

From the nervous system: sometimes - headache, dizziness, drowsiness, sleep disturbances; rarely - paresthesia in the hands, trembling, anxiety, states of fear, seizures and confusion; very rarely - psychotic reactions such as hallucinations and depression, movement disorders.

From the senses: very rarely - impairment of vision and hearing, smell, taste and tactile sensitivity.

From the side of metabolism: very rarely - hypoglycemia (manifested by a sharp increase in appetite, nervousness, perspiration, tremors); in some cases - exacerbation of the existing porphyria.

From the urinary system: rarely - hypercreatininemia; very rarely - deterioration of renal function up to acute renal failure (for example, due to allergic reactions - interstitial nephritis).

From the musculoskeletal system: rarely - tendon lesions (including tendonitis), joint and muscle pain; very rarely - tendon rupture (including rupture of the Achilles tendon, which can be bilateral in nature and appear within 48 hours after the start of treatment), muscle weakness (of particular importance for patients with myasthenia gravis); in some cases - rhabdomyolysis.

Allergic reactions: sometimes - itching and redness of the skin; rarely - anaphylactic and anaphylactoid reactions (manifested by symptoms such as urticaria, bronchospasm and possible severe suffocation, as well as - in rare cases - swelling of the face, larynx); very rarely - a sharp decrease in blood pressure, anaphylactic shock; in some cases - Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome) and exudative erythema multiforme, allergic pneumonitis, vasculitis.

Dermatological reactions: very rarely - photosensitization.

Others: sometimes - asthenia; very rarely - persistent fever, development of superinfection.

Local reactions: often with intravenous injection - pain, redness, phlebitis.

Application during pregnancy and lactation

Contraindicated during pregnancy and breastfeeding.

Application for violations of liver function

Patients with impaired liver function do not require a special selection of doses, since levofloxacin is metabolized in the liver only to an extremely insignificant extent.

Application for impaired renal function

Patients with impaired renal function require correction of the dosage regimen, depending on the CC value.

Patients after hemodialysis do not require additional doses.

Application in children

Levofloxacin cannot be used to treat children and adolescents (under 18 years of age) due to the likelihood of damage to the articular cartilage.

Use in elderly patients

When treating elderly patients, it should be borne in mind that patients in this group often suffer from impaired renal function.

special instructions

Hospital infections caused by Pseudomonas aeruginosa may require combination treatment.

The prevalence of acquired resistance in plated strains of microorganisms can vary depending on the geographic region and over time. Therefore, country-specific information on levofloxacin resistance is required. For the treatment of severe infections or in case of ineffectiveness of treatment, a microbiological diagnosis should be established with the isolation of the pathogen and determination of its sensitivity to levofloxacin.

There is a high likelihood that methicillin-resistant Staphylococcus aureus will be resistant to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of established or suspected infections caused by methicillin-resistant Staphylococcus aureus, if laboratory tests have not confirmed the susceptibility of this microorganism to levofloxacin.

Like other quinolones, levofloxacin should be used with great caution in patients with a predisposition to seizures. Such patients include patients with previous lesions of the central nervous system, such as stroke, severe traumatic brain injury; patients concurrently taking drugs that lower the seizure threshold of the brain, such as fenbufen and other similar NSAIDs or other drugs that lower the seizure threshold, such as theophylline

Diarrhea that develops during or after treatment with levofloxacin, especially severe, persistent and / or bloody, may be a symptom of pseudomembranous colitis caused by Clostridium difficile. In case of suspicion of the development of pseudomembranous colitis, treatment with levofloxacin should be stopped immediately and specific antibiotic therapy (vancomycin, teicoplanin or oral metronidazole) should be started immediately. Drugs that inhibit intestinal motility are contraindicated.

With quinolones, including levofloxacin, tendonitis is rare and can sometimes rupture tendons, including the Achilles tendon. This side effect can develop within 48 hours after starting treatment and can be bilateral. Elderly patients are more likely to develop tendonitis; in patients taking fluoroquinolones, the risk of tendon rupture may increase with the simultaneous use of corticosteroids. In addition, patients after transplantation have an increased risk of tendinitis, so it is recommended to be careful when prescribing fluoroquinolones in this category of patients. If you suspect the development of tendonitis, you should immediately stop treatment with levofloxacin and begin appropriate treatment of the affected tendon, for example, ensuring it is sufficiently immobilized.

Levofloxacin can cause serious, potentially fatal, hypersensitivity reactions (angioedema, anaphylactic shock), even with initial doses. In such cases, you should immediately stop using levofloxacin and consult a doctor.

With the use of levofloxacin, cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been observed. In case of development of any reactions from the skin or mucous membranes, the patient should immediately consult a doctor and not continue treatment until his consultation.

Cases of liver necrosis, including the development of fatal liver failure, have been reported with the use of levofloxacin, mainly in patients with severe underlying diseases, such as sepsis. Patients should be warned about the need to discontinue treatment and seek urgent medical attention if signs and symptoms of liver damage appear, such as anorexia, jaundice, dark urine, pruritus and abdominal pain.

Since levofloxacin is excreted mainly through the kidneys, in patients with impaired renal function, mandatory monitoring of renal function is required, as well as correction of the dosage regimen. When treating elderly patients, it should be borne in mind that renal dysfunction is often observed in patients of this group.

Although photosensitization with the use of levofloxacin develops very rarely, to prevent its development, patients are not recommended during treatment and within 48 hours after the end of treatment with levofloxacin to be exposed to strong solar or artificial ultraviolet radiation (for example, to visit a solarium).

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

Very rare cases of prolongation of the QT interval have been reported in patients taking fluoroquinolones, including levofloxacin.

When using fluoroquinolones, including levofloxacin, caution should be exercised in patients with known risk factors for prolongation of the QT interval: in patients with uncorrected electrolyte disturbances (with hypokalemia, hypomagnesemia); with congenital lengthening of the QT interval; with heart disease (heart failure, myocardial infarction, bradycardia); with the simultaneous use of drugs that can lengthen the QT interval, such as class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics.

Elderly and female patients may be more sensitive to drugs that prolong the QT interval. Therefore, fluoroquinolones, including levofloxacin, should be used with caution in this category of patients.

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

As with the use of other quinolones, cases of hyperglycemia and hypoglycemia have been observed with the use of levofloxacin. Against the background of therapy with levofloxacin, dysglycemia more often occurred in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, glibenclomide) or insulin. When using levofloxacin in such patients, the risk of developing hypoglycemia, up to hypoglycemic coma, increases. It is necessary to inform patients about the symptoms of hypoglycemia (confusion, dizziness, ravenous appetite, headache, nervousness, palpitations or increased heart rate, pallor of the skin, perspiration, trembling, weakness). If the patient develops hypoglycemia,it is necessary to immediately stop treatment with levofloxacin and start appropriate therapy. In these cases, it is recommended to switch to therapy with an antibiotic other than fluoroquinolones, if possible. When treating with levofloxacin in elderly patients, in patients with diabetes mellitus, careful monitoring of the blood glucose concentration is recommended.

In patients taking fluoroquinolones, including levofloxacin, cases of sensory and sensory-motor peripheral neuropathy have been reported, 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 developing irreversible changes.

Fluoroquinolones, including levofloxacin, are characterized by neuromuscular conduction blocking activity and may increase muscle weakness in patients with pseudoparalytic myasthenia gravis. Adverse reactions, including pulmonary insufficiency requiring mechanical ventilation, and death were observed, which were associated with the use of fluoroquinolones in patients with pseudoparalytic myasthenia gravis. The use of levofloxacin in a patient with an established diagnosis of pseudoparalytic myasthenia gravis is not recommended.

Application for airborne anthrax infection is based on data on the sensitivity of Bacillus anthracis to it, obtained in in vitro studies and in experimental studies conducted on animals, as well as on limited data on the use of levofloxacin in humans. Treating physicians should refer to national and / or international documents that reflect a common consensus on anthrax management.

Psychotic reactions, including suicidal thoughts / attempts, have been reported in patients taking fluoroquinolones, including levofloxacin, sometimes after taking a single dose. If any side effects from the central nervous system develop, including mental disorders, treatment with levofloxacin should be stopped immediately and appropriate therapy should be prescribed. In these cases, it is recommended to switch to therapy with an antibiotic other than fluoroquinolones, if possible. Care should be taken to prescribe the drug to patients with psychosis or patients with a history of mental illness.

In patients taking levofloxacin, the determination of opiates in urine can lead to false positive results, which should be confirmed by more specific methods.

Levofloxacin can inhibit the growth of Mycobacterium tuberculosis, which can lead to further false negative results of the bacteriological diagnosis of tuberculosis.

When carrying out intravenous infusion, the recommended duration of administration should be strictly adhered to. Experience with levofloxacin shows that an increased heart rate and a transient decrease in blood pressure can be observed during infusion. In rare cases, vascular collapse may develop. If during the intravenous infusion of levofloxacin a pronounced decrease in blood pressure is observed, then its administration is immediately stopped.

Influence on the ability to drive vehicles and mechanisms

During the period of treatment, it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Drug interactions

There are reports of a pronounced decrease in the threshold of convulsive readiness with the simultaneous use of quinolones and substances that can, in turn, lower the cerebral threshold of convulsive readiness. This also applies equally to the simultaneous use of quinolones and theophylline.

The effect of levofloxacin is significantly weakened when used simultaneously with sucralfate. The same thing happens with the simultaneous use of magnesium- or aluminum-containing antacids, as well as iron salts. Levofloxacin should be taken at least 2 hours before or 2 hours after taking these drugs.

With the simultaneous use of vitamin K antagonists, it is necessary to control the blood coagulation system.

Excretion (renal clearance) of levofloxacin is slightly slowed down by cimetidine and probenecid. It should be noted that this interaction has practically no clinical significance. However, with the simultaneous use of drugs such as probenecid and cimetidine, which block a certain route of excretion (tubular secretion), treatment with levofloxacin should be carried out with caution. This applies primarily to patients with limited renal function.

Levofloxacin slightly increases the T1 / 2 of cyclosporin.

Taking GCS increases the risk of tendon rupture.