Expiration date: 01/202

The composition and form of issue:

Tablets, film-coated. 1 tablet contains:

the levofloxacin hemihydrate 256, 233, 512, 466 mg

(equivalent to levofloxacin 250 and 500 mg, respectively) 

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

shell: dye Opadry white OY 58900 (hypromellose 5 CP, titanium dioxide, macrogol 400) 

blistere in 10 PCs. in cardboard pack 1 blister.

Solution for infusion 5 mg/ml

levofloxacin hemihydrate, the 512 mg

(equivalent to 500 mg levofloxacin) 

excipients: dextrose hydrochloric acid sodium hydroxide water for injections 

vial PE 100 ml in a cardboard pack 1 bottle.

Description pharmaceutical form:

Tablets 250 mg: white or almost white capsuleline biconvex, film-coated, embossed "RDY" on one side, on the other hand, "279".

Tablets 500 mg: white or almost white capsuleline biconvex, film-coated, embossed "RDY" on one side, on the other — "280".

Infusion solution: transparent or slightly opalescent pale yellow.

Feature:

Fluoroquinolone, antimicrobial germicide of wide spectrum of action.

Pharmacokinetics:

Pharmacokinetics of levofloxacin after a single and repeated administration of the drug is linear. Plasma concentration profile of levofloxacin after I/V administration similar to that in the pill. Therefore, oral and intravenous routes of administration can be considered interchangeable.

The average volume of distribution (Vd) of levofloxacin ranges from 89 to 112 l (after single and multiple in/in the dose 500 mg). After the on/in infusion time levofloxacin dose 500 mg healthy volunteers, the average value of C Max in plasma was (6, 2±1, 0) µg/ml, Tmax— (1, 0±0, 1) h If ingestion is rapidly and almost completely absorbed (food intake has little effect on the speed and completeness of absorption). Bioavailability of 99%. Tmax is 1-2 h while receiving 250 and 500 mg, average value of C Max is 2, 8, 5, 2 µg/ml, respectively.

The plasma protein binding is 30-40%. Well into the organs and tissues: lungs, mucous membranes, bronchi, sputum, urogenital organs, polymorphonuclear leukocytes, alveolar macrophages. In the liver, a small part is oxidized and/or deacetylated.

Excreted mainly by the kidneys by glomerular filtration and tubular secretion. T1/2 when the pill 6-8 hours After a single on/in the dose 500 mg T1/2 is (6, 4±0, 7) h. Renal clearance is 70% of total clearance. Less than 5% of levofloxacin is excreted as metabolites. In the urine over a period of 24 hours is found unchanged to 70% of the administered dose, and 48 hours — 87%. In Calais over a period of 72 h revealed 4% of the administered dose. In renal failure reduce clearance of the drug and its excretion by the kidneys depends on the degree of reduction in creatinine Cl.

Description pharmacological action:

Does DNK-girazu (topoisomerase II) and topoisomerase IV, violates supercoiling and cross-linking of DNA breaks, inhibits DNA synthesis, causes profound morphological changes in cytoplasm, cell wall and membranes.

Levofloxacin is active against the following microorganisms, both in vitro and in vivo.

Sensitive microorganisms (minimum overwhelming concentration of the IPC, &le2 mg/ml)

Aerobic gram-positive microorganisms: Corynebacterium diphtheriae, Enterococcus faecalis, Enterococcus spp., Listeria monocytogenes, Staphylococcus coagulase-negative methi-S(I) (methicillin-sensitive/moderately sensitive strains), Staphylococcus aureus methi-S (methicillin-susceptible strains), Staphylococcus epidermidis methi-S (methicillin-susceptible strains), Staphylococcus spp. (CNS — lactosylceramide), Streptococcus spp. group C and G (including Streptococcus agalactiae, Streptococcus pneumoniae penis/I/R (penicillin-sensitive/moderately sensitive/resistant strains), Streptococcus pyogenes, Streptococcus viridans penis/R (penicillin-sensitive/resistant strains).

Aerobic gram-negative microorganisms: Acinetobacter baumannil, Acinetobacter spp., Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter spp. (including Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S/R (ampicillin-sensitive/resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (incl. Klebsiella oxytoca, Klebsiella pneumoniae), Moraxela catarrhalis &beta+/&beta- (producing and reproducirse &beta-lactamase strains), Morganella morganii, Neisseria gonorrhoeae non-PPNG/PPNG (and reproducirse producing penicillinase strains), Neisseria meningitidis, Pasteurella spp. (including conis Pasteurella, Pasteurella dagmatis, Pasteurella multocida) Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas spp. (including Pseudomonas aeruginosa), Serratia spp. (including Salmonella spp., Serratia marcescens).

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

Other microorganisms: Bartonella spp. Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Legionella spp., Mycobacterium spp. (including Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma hominis, Mycoplasma pneumoniae), Ricketsia spp., Ureaplasma urealyticum.

Moderately susceptible organisms (IPC&ge4 mg/l)

Aerobic gram-positive microorganisms: Corynebacterium urealiticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis methi-R (methicillin-resistant strains), Staphylococcus haemolyticus methi-R (methicillin-resistant strains).

Aerobic gram-negative organisms: Burkholderia cepacia, Campilobacter jejuni, Campilobacter coli.

Anaerobic microorganisms: Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides oralis, Prevotella spp., Porphyromonas spp.

Resistant organisms (IPC&ge8 mg/l)

Aerobic gram-positive microorganisms: Corynebacterium jeikeium, Staphylococcus aureus methi-R (methicillin-resistant strains), Staphylococcus coagulase-negative methi-R (coagulasenegative methicillin-resistant strains).

Aerobic gram-negative microorganisms: Alcaligenes xylosoxidans.

Other microorganisms: Mycobacterium avium.

Indications:

For both dosage forms

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

• community-acquired pneumonia
  
• drug-resistant forms of tuberculosis (complex therapy)
  
• complicated infections of kidneys and urinary tract, including pyelonephritis
  
• uncomplicated urinary tract infection
  
• prostatitis, including bacterial
  
• septicemia/bacteremia associated with the above indications
  
• intra-abdominal infection.
  

For tablets, film-coated (optional)

• infections of ENT-organs (acute sinusitis)
  
• infections of the lower respiratory tract (acute exacerbation of chronic bronchitis)
  
• infections of skin and soft tissues.
  

Contraindications:

• hypersensitivity to levofloxacin or other hinolonam
  
• hypersensitivity to support components of the drug
  
• epilepsy
  
• lesions of the tendons associated with the use of quinolones in history
  
• childhood and adolescence to 18 years
  
• pregnancy
  
• lactation (breastfeeding).
  

With caution:

• old age (high likelihood of having a concomitant loss of kidney function)
  
• the deficit glukozo-6-fosfatdegidrogenaza.
  

Side effects:

The incidence of side effects is classified depending on the frequency of occurrence: often (1-10%) sometimes (less than 0, 1-1%), rarely (0, 01-0, 1%), very rare (less than 0, 01%), including individual messages.

From the blood and organs of hematopoiesis: rarely — eosinophilia, leukopenia, rarely — neutropenia, thrombocytopenia very rare agranulocytosis pronounced in isolated cases — haemolytic anaemia, pancytopenia.

From the digestive system: often — nausea, diarrhea, increased ALT activity, ACT, goiter and sometimes loss of appetite, vomiting, abdominal pain, dyspepsia, hyperbilirubinemia rare — diarrhea with blood (in very rare cases, it may be a symptom of inflammatory bowel or pseudomembranous colitis) very rare — hepatitis.

Of the cardiovascular system: rarely- tachycardia, decrease in blood pressure very rarely circulatory collapse in some cases — prolonged QT interval.

In the Central and peripheral nervous system: sometimes — headache, dizziness, clumsiness, drowsiness, sleep disturbances, rarely — paresthesia in hands, tremors, restlessness, anxiety, seizures, convulsions, confusion very rare — psychotic reaction-type hallucinations and depression, movement disorders.

From the sensory organs: very rarely — visual disturbances and hearing, olfactory, gustatory and tactile sensitivity.

From the metabolic: very rarely — hypoglycemia (manifested by a sharp increase in appetite, nervousness, sweating, trembling) in some cases — worsening of porphyria.

From the urinary system: rarely — gipercreatininemia very rarely — kidney function impairment up to acute renal failure (for example due to allergic reactions — interstitial nephritis).

From the side of musculoskeletal system: rare — lesions tendonitis (including tendonitis), joint and muscle pain is very rare — tendon tears (including the Achilles, which may be bilateral in nature and occur within 48 h after the start of treatment), muscle weakness (is of particular importance for patients with myasthenia gravis) in some cases, rhabdomyolysis.

Allergic reactions: sometimes — itching and redness of the skin rare — anaphylactic and anaphylactoid reactions (manifested by symptoms such as urticaria, bronchospasm and possible severe dyspnea, and in rare cases, swelling of the face, throat) is very rare — 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.

Other: sometimes — fatigue, very rarely — persistent fever, development of superinfection.

Local reactions (for solution for infusion optional): often — pain, redness, phlebitis.

Drug interactions:

For both dosage forms

Increases T1/2 of cyclosporine.

NSAIDs, theophylline increases convulsive, corticosteroids increase the risk of tendon rupture.

Cimetidine and drugs that block tubular secretion, and slow excretion.

For tablets, film-coated (optional)

The completeness of absorption reduce drugs that suppress intestinal motility, sucralfate, antacid drugs containing aluminum salts and magnesium and preparations containing iron salts (needed to break between the reception of at least 2 hours).

For solution for infusion (optional)

While the use of indirect anticoagulants (including warfarin), it is necessary to control blood clotting.

Method of application and dose:

Inside, in/V.

Doses are determined by the nature and severity of the infection, and the alleged sensitivity of the pathogen.

For tablets, film-coated

Inside, before meals or in between meals, not liquid, squeezed enough liquid.

Sinusitis: 500 mg 1 time per 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.

Infections of skin and soft tissues: 250 mg 1-2 times a day or 500 mg 1 time per day. The course of treatment — 7-14 days.

For both dosage forms

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

Uncomplicated urinary tract infections: 250 mg 1 time per day. The course of treatment — 3 days.

Complicated urinary tract infections (including pyelonephritis): 250 mg 1 time per day. The course of treatment — 7-10 days.

Prostatitis, including bacterial (solution for infusion): 500 mg 1 time per 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 1 time per day. The course of treatment — 7-14 days in combination with antibacterial drugs acting on the anaerobic flora.

In the complex treatment of drug-resistant tuberculosis: 500 mg 1-2 times per day (500-1000 mg of levofloxacin per day), depending on the severity of the disease and the applied regimens. The course of treatment — up to 3 months.

Patients with normal or slightly impaired renal function (creatinine Cl >50 ml/min) correction mode is not required.

Application for violations of renal function. Patients with impaired renal function requires correction dosing regimen, depending on the values Cl creatinine.

Table. The dosage, depending on the values Cl creatinine

Creatinine Cl, ml/min	Dose for oral administration* and/in the introduction
	250 mg/24 h	500 mg/24 h	500 mg/12 h
	first dose of 250 mg	first dose of 500 mg	first dose of 500 mg
50–20	then 125 ??/24 h	then 250 ??/24 h	then 250 ??/12 h
19–10	then 125 ??/48 h	then 125 ??/24 h	then 125 ??/12 h
<10 (including hemodialysis and continuous ambulatory peritoneal dialysis)	then 125 ??/48 h	then 125 ??/24 h	then 125 ??/24 h

*Dose determined by the nature and severity of the infection, and the alleged sensitivity of the pathogen.

After hemodialysis or continuous ambulatory peritoneal dialysis does not require the introduction of additional doses.

Application for violations of liver function. When the liver does not require special selection of doses, as levofloxacin is metabolized in the liver slightly.

The drug Leveler in the form of a solution for infusion is injected in/in drip slowly. The duration of administration of the drug at the dose of 500 mg (100 ml of infusion solution of 500 mg of levofloxacin) should be at least 60 min. a Solution of the drug Leveler compatible with the following infusion fluids: 0 9% sodium chloride solution, 5% dextrose solution, 2, 5% ringer solution with dextrose, combination solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes). The drug solution should not be mixed with heparin or solutions with an alkaline reaction (e.g. with sodium bicarbonate).

In case of positive dynamics of the clinical condition of the patient after a few days of treatment it is possible to switch from intravenous injection to oral administration of the drug in the same dose.

The duration of treatment, depending on the course of the disease, is not more than 14 days (except bacterial prostatitis). As with other antibiotics, treatment with Leveler is recommended to continue for at least 48-72 hours after normalization of body temperature or after reliable eradication of the pathogen.

Overdose:

Symptoms: nausea, erosive lesions of the mucous membranes of the gastrointestinal tract, prolonged QT interval, mental confusion, dizziness, seizures.

Treatment: symptomatic, dialysis is ineffective.

Special instructions:

Treatment with levofloxacin, it is recommended to continue for at least 48-72 hours after normalization of body temperature or after reliable eradication of the pathogen. During treatment you must avoid sunlight and artificial UV radiation to avoid damage to the skin (photosensitization). When signs of tendinitis, pseudomembranous colitis levofloxacin immediately cancelled.

It should be borne in mind that patients with brain damage in medical history (stroke, severe head injury), may develop seizures, in case of insufficiency of glucose-6-phosphate dehydrogenase — the risk of hemolysis.

During the period of treatment must be careful when driving and occupation of other potentially hazardous activities, require high concentration and psychomotor speed reactions.

In case of severe pneumonia caused by Streptococcus pneumoniae, levofloxacin may not be effective.

In/in the introduction should be done for at least 60 min, during the introduction may be a heart rate and a transient decrease in blood pressure, rarely, can develop collapse. In marked decrease in blood pressure introduction of levofloxacin stopped. If you suspect the development of pseudomembranous colitis caused by Clostridium difficile, treatment levofloxacin cancel and appoint the corresponding therapy.