Levolet R tablets 500mg, No. 10

Infectious and inflammatory diseases of mild and moderate severity caused by pathogens sensitive to the drug:

• community-acquired pneumonia;

• drug-resistant forms of tuberculosis (as part of complex therapy);

• complicated infections of the kidneys and urinary tract, including pyelonephritis;

• uncomplicated urinary tract infections;

• prostatitis, incl. bacterial;

• septicemia / bacteremia associated with the above indications;

• intra-abdominal infection.

Inside, IV.

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

For both dosage forms

Community-acquired pneumonia: 500 mg 1-2 times a day. The course of treatment is 7-14 days.

Uncomplicated urinary tract infections: 250 mg once a day. The course of treatment is 3 days.

Complicated urinary tract infections (including pyelonephritis): 250 mg once a day. The course of treatment is 7-10 days.

Prostatitis, incl. bacterial: 500 mg once a day. The course of treatment is 28 days.

Septicemia / bacteremia: 500 mg 1-2 times a day. The course of treatment is 10-14 days.

Intra-abdominal infection: 500 mg once a day. The course of treatment is 7-14 days, in combination with antibacterial drugs acting on the anaerobic flora.

As part of the complex therapy of drug-resistant forms of tuberculosis: 500 mg 1-2 times a day (500-1000 mg of levofloxacin per day), depending on the severity of the course of the disease and the applied therapy regimen. The course of treatment is up to 3 months.

Patients with normal or slightly impaired renal function (Cl creatinine> 50 ml / min) do not require dosage adjustment.

Additionally for film-coated tablets

Inside, before meals or between meals, without chewing, drinking plenty of fluids.

Sinusitis: 500 mg once a day. The course of treatment is 10-14 days.

Exacerbation of chronic bronchitis: 250-500 mg 1 time per day. The course of treatment is 10-14 days.

Skin and soft tissue infections: 250 mg 1-2 times a day or 500 mg once a day. The course of treatment is 7-14 days.

Application for impaired renal function

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

Table

Dosing regimen, depending on the value of Cl creatinine

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

No additional doses are required after hemodialysis or continuous ambulatory peritoneal dialysis.

Application for violations of liver function. In case of impaired liver function, a special selection of doses is not required, since levofloxacin is slightly metabolized in the liver.

The drug LevoletЃR in the form of a solution for infusion is administered intravenously drip, slowly. The duration of administration of the drug at a dose of 500 mg (100 ml of infusion solution / 500 mg of levofloxacin) should be at least 60 minutes. LevoletЃR solution is compatible with the following infusion solutions: 0.9% sodium chloride solution, 5% dextrose solution, 2.5% Ringer's solution with dextrose, combined solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes). The solution of the drug should not be mixed with heparin or solutions with an alkaline reaction (for example, with a solution of sodium bicarbonate).

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). As with the use of other antibiotics, it is recommended to continue treatment with LevoletЃR for at least 48Ц72 hours after normalization of body temperature or after reliable eradication of the pathogen.

Film-coated tablets, white or off-white, capsule-shaped, biconvex, embossed with 'RDY' on one side and '280' on the other.

1 tab.

levofloxacin hemihydrate 512.466 mg,?

which corresponds to the content of levofloxacin 500 mg

Excipients: microcrystalline cellulose (Avicel PH 101), corn starch, colloidal silicon dioxide, crospovidone, hypromellose (15 cps), microcrystalline cellulose (Avicel PH 102), magnesium stearate.

• Hypersensitivity to levofloxacin or other quinolones;

• hypersensitivity to auxiliary components of the drug;

• epilepsy;

• a history of tendon lesions associated with the intake of quinolones;

• children and adolescents up to 18 years old;

• pregnancy;

• lactation period (breastfeeding).

With care: old age (high probability of a concomitant decrease in renal function); 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.

—ообщалось об очень редких случа¤х удлинени¤ интервала QTу пациентов, принимающих фторхинолоны, включа¤ левофлоксацин.

ѕри применении фторхинолонов, включа¤ левофлоксацин, следует соблюдать осторожность у пациентов с известными факторами риска удлинени¤ интервала QT: у пациентов с нескорректированными электролитными нарушени¤ми (с гипокалиемией, гипомагниемией); с синдромом врождЄнного удлинени¤ интервала QT; с заболевани¤ми сердца (сердечна¤ недостаточность, инфаркт миокарда, брадикарди¤); при одновременном применении лекарственных препаратов, способных удлин¤ть интервал QT, таких как антиаритмические средства класса IAи III, трициклические антидепрессанты, макролиды, нейролептики.

ѕациенты пожилого возраста и пациенты женского пола могут быть более чувствительными к препаратам, удлин¤ющим интервал QT. ѕоэтому следует с осторожностью примен¤ть у этой категории больных фторхинолоны, включа¤ левофлоксацин.

” пациентов с латентным или манифестированным дефицитом глюкозо-6-фосфатдегидрогеназы имеетс¤ предрасположенность к развитию гемолитических реакций при лечении хинолонами, что следует принимать во внимание при лечении левофлоксацином.

 ак и при применении других хинолонов, при применении левофлоксацина наблюдались случаи развити¤ гипергликемии и гипогликемии. Ќа фоне терапии левофлоксацином дисгликеми¤ чаще возникала у пациентов пожилого возраста и пациентов с сахарным диабетом, получающих сопутствующую терапию пероральными гипогликемическими препаратами (например, глибенкломидом) или инсулином. ѕри применении левофлоксацина у таких пациентов возрастает риск развити¤ гипогликемии, вплоть до гипогликемической комы. Ќеобходимо информировать пациентов о симптомах гипогликемии (спутанность сознани¤, головокружение, 'волчий' аппетит, головна¤ боль, нервозность, ощущение сердцебиени¤ или учащение пульса, бледность кожных покровов, испарина, дрожь, слабость). ?сли у пациента развиваетс¤ гипогликеми¤, необходимо немедленно прекратить лечение левофлоксацином и начать соответствующую терапию. ¬ этих случа¤х рекомендуетс¤ перейти на терапию другим антибиотиком, отличным от фторхинолонов, если это возможно. ѕри проведении лечени¤ левофлоксацином у пациентов пожилого возраста, у пациентов с сахарным диабетом рекомендуетс¤ тщательный мониторинг концентрации глюкозы в крови.

” пациентов, принимающих фторхинолоны, включа¤ левофлоксацин, сообщалось о случа¤х развити¤ сенсорной и сенсорно-моторной периферической невропатии, начало которой может быть быстрым. ?сли у пациента развиваютс¤ симптомы нейропатии, применение левофлоксацина следует прекратить. Ёто минимизирует возможный риск развити¤ необратимых изменений.

‘торхинолоны, включа¤ левофлоксацин, характеризуютс¤ блокирующей нервно-мышечное проведение активностью и могут усиливать мышечную слабость у пациентов с псевдопаралитической миастенией. Ќаблюдались неблагопри¤тные реакции, включа¤ легочную недостаточность, потребовавшую проведение »¬Ћ, и летальный исход, которые ассоциировались с применением фторхинолонов у пациентов с псевдопаралитической миастенией. ѕрименение левофлоксацина у пациента с установленным диагнозом псевдопаралитической миастении не рекомендуетс¤.

ѕрименение при воздушно-капельном пути заражени¤ сибирской ¤звой основано на данных по чувствительности к нему Bacillus anthrасis,полученных в исследовани¤х in vitro и в экспериментальных исследовани¤х, проведенных на животных, а также на ограниченных данных применени¤ левофлоксацина у человека. Ћечащие врачи должны обращатьс¤ к национальным и/или международным документам, которые отражают выработанную общими усили¤ми точку зрени¤ по лечению сибирской ¤звы.

ѕсихотические реакции, включа¤ суицидальные мысли/попытки, отмечались у пациентов, принимающих фторхинолоны, включа¤ левофлоксацин, иногда после приема разовой дозы. ¬ случае развити¤ любых побочных эффектов со стороны ?Ќ—, включа¤ нарушени¤ психики, лечение левофлоксацином следует немедленно прекратить и назначить соответствующую терапию. ¬ этих случа¤х рекомендуетс¤ перейти на терапию другим антибиотиком, отличным от фторхинолонов, если это возможно. —ледует с осторожностью назначать препарат пациентам с психозами или пациентам, имеющим в анамнезе психические заболевани¤.

” пациентов, принимающих левофлоксацин, определение опиатов в моче может приводить к ложноположительным результатам, которые следует подтверждать более специфическими методами.

Ћевофлоксацин может ингибировать рост Mycobacterium tuberculosis, что может приводить в дальнейшем к ложноотрицательным результатам бактериологического диагноза туберкулеза.

ѕри проведении в/в инфузии следует строго придерживатьс¤ рекомендуемой продолжительности введени¤. ќпыт применени¤ левофлоксацина показывает, что во врем¤ инфузии может наблюдатьс¤ усиленное сердцебиение и транзиторное снижение ј?. ¬ редких случа¤х может развитьс¤ сосудистый коллапс. ?сли во врем¤ в/в инфузионного введени¤ левофлоксацина наблюдаетс¤ выраженное снижение ј?, то его введение немедленно прекращают.

¬ли¤ние на способность к управлению транспортными средствами и механизмами

¬ период лечени¤ необходимо воздерживатьс¤ от зан¤тий потенциально опасными видами де¤тельности, требующими повышенной концентрации внимани¤ и быстроты психомоторных реакций.

Ћекарственное взаимодействие

»меютс¤ сообщени¤ о выраженном снижении порога судорожной готовности при одновременном применении хинолонов и веществ, способных, в свою очередь, снижать церебральный порог судорожной готовности. ¬ равной мере это касаетс¤ также одновременного применени¤ хинолонов и теофиллина.

?ействие левофлоксацина значительно ослабл¤етс¤ при одновременном применении с сукральфатом. “о же самое происходит и при одновременном применении магний- или алюминийсодержащих антацидных средств, а также солей железа. Ћевофлоксацин следует принимать не менее, чем за 2 ч до или через 2 ч после приема этих средств.

ѕри одновременном использовании антагонистов витамина   необходим контроль за свертывающей системой крови.

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.