Levot P - instructions for use, dose, side effects, contraindications

Fluoroquinolone, a broad-spectrum antimicrobial bactericide. 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.

Levofloxacin is active against the following strains of microorganisms, as in conditions in vitro, and in vivo.

Sensitive microorganisms (minimum inhibitory concentration (MIC) less than 2 mg / ml).

Aerobic Gram-positive microorganisms: Corynebacterium diphtheriae, Enterococcus spp. (incl. Enterococcus faecalis), Listeria monocytogenes, Staphylococcus spp. (coagulase-negative methicillin-sensitive / moderately sensitive strains, leukotoxin-containing), including Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains); Streptococcus spp. groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-sensitive / moderately sensitive / resistant strains), Streptococcus pyogenes, Streptococcus groups viridans (penicillin-sensitive / resistant strains).

Aerobic Gram-negative microorganisms: Acinetobacter spp., in t.ch. 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 (penicillinase-producing and non-producing penicillinase strains), Neisseria meningitidis, Pasteurella spp. (at Tom number of, Pasteurella conis, Pasteurella dagmatis, Pasteurella multocida), Proteus mirabilis, Proteus vulgaris, Providencia spp. (at Tom number of, Providencia rettgeri, Providencia stuartii), Pseudomonas spp. (at Tom number of, Pseudomonas aeruginosa), Serratia spp. (at Tom number of Serratia marcescens), Salmonella spp.

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

Other microorganisms: Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Legionella spp., Mycobacterium spp. (at Tom number of, Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma hominis), Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

Moderately sensitive microorganisms (MIC of more than 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, Campilobacter jejuni, Campilobacter coli.

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

Stable microorganisms (MIC of more than 8 mg / l):

Aerobic Gram-positive microorganisms: Corynebacterium jeikeium, Staphylococcus aureus (methicillin-resistant strains), others Staphylococcus spp. (coagulase-negative methicillin-resistant strains).

Aerobic Gram-negative microorganisms: Alcaligenes xylosoxidans.

Other microorganisms: Mycobacterium avium.

Pharmacokinetics:

The pharmacokinetics of levofloxacin with a single and repeated administration of the drug is linear. The plasma profile of the concentrations of levofloxacin after intravenous administration is similar to that of tablets. Therefore, oral and intravenous routes of administration may be considered interchangeable. Average volume of distribution (Vd) Levofloxacin is from 89 to 112 liters (after a single and repeated intravenous administration at a dose of 500 mg). The connection with plasma proteins is 30-40%. After intravenous hourly infusion of levofloxacin at a dose of 500 mg to healthy volunteers, the mean peak concentration (Cmax) in the plasma was 6.2 ± 1.0 μg / ml, the time to reach the peak concentration (Tmax) - 1.0 ± 0.1 h. It penetrates well into organs and tissues: lungs, bronchial mucosa, sputum, organs of the genitourinary system,polymorphonuclear leukocytes, alveolar macrophages.

In the liver, a small portion is oxidized and / or deacetylated. After a single intravenous dose of 500 mg, the half-life (T1/2) is 6.4 ± 0.7 h. It is mainly excreted by the kidneys through glomerular filtration and tubular secretion. Kidney clearance is 70% of the total clearance. Less 5% Levofloxacin is excreted in the form of metabolites. In urine, for a period of 24 hours, unchanged form of 70% is detected, and in 48 hours 87% of the administered dose. In feces, for a period of 72 hours, 4% of the administered dose is detected.

In renal failure, the decrease in clearance of the drug and its excretion by the kidneys depends on the degree of decrease in the clearance of creatinine (CC).

Indications:

Infectious-inflammatory diseases of mild and moderate severity caused by drug-susceptible pathogens:

- community acquired pneumonia;

- complicated kidney and urinary tract infections, including pyelonephritis;

- uncomplicated urinary tract infections;

- bacterial prostatitis;

- septicemia / bacteremia associated with the above indications;

- intra-abdominal infection;

- in the complex therapy of drug-resistant forms of tuberculosis

Contraindications:

- epilepsy;

- affections of tendons associated with taking quinolones in anamnesis;

- children and adolescents under 18;

- pregnancy;

- lactation period (breastfeeding);

- hypersensitivity to levofloxacin or other quinolones;

- Hypersensitivity to auxiliary components of the drug.

Carefully:

Elderly age (high probability of concomitant decrease in kidney function), deficiency of glucose-6-phosphate dehydrogenase.

Dosing and Administration:

The drug is administered intravenously. The dose is determined by the nature and severity of the infection, as well as the suspected pathogen susceptibility.

Community-acquired pneumonia: 500 mg 1-2 times / 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. In severe infections, the dose may be increased. The course of treatment is 7-10 days. Bacterial prostatitis: 500 mg once a day. The course of treatment is 28 days.

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

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

In the composition complex therapy of drug-resistant forms of tuberculosis 500 mg 1- 2 times / day (500-1000 mg levofloxacin / day), depending on the severity of the course of the disease and the regimen used. The course of treatment is up to 3 months.

Application for violations of kidney function

Patients with slightly impaired renal function (CK> 50 ml / min) do not need dose adjustment.

Patients with impaired renal function require a correction of the dosing regimen, depending on the amount of creatinine clearance.

Creatinine clearance	Dosages for intravenous administration
	250 mg / 24 h	500 mg / 24 h	500 mg / 12 h
	the first dose of 250 mg	the first dose of 500 mg	the first dose of 500 mg
50-20 ml / min	then 125 mg / 24 h	then 250 mg / 24 h	then 250 mg / 12 h
19-10 ml / min	then 125 mg / 48 h	then 125 mg / 24 h	then 125 mg / 12 h
<10 ml / min (including hemodialysis and continuous ambulatory peritoneal dialysis)	then 125 mg / 48 h	then 125 mg / 24 h	then 125 mg / 24 h

After hemodialysis or permanent ambulatory peritoneal dialysis, no additional doses are required.

Application for violations of liver function

If the liver function is not required, a special dose selection is required, since levofloxacin metabolized in the liver in an extremely small measure.

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

With a positive dynamics of the clinical state of the patient after a few days of treatment, it is possible to switch from intravenous drip to oral administration of the drug at 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, treatment with Levoleth® R is recommended to continue for at least 48-72 hours after the normalization of body temperature or after a reliable eradication of the pathogen.

Side effects:

The frequency of side effects is classified according to the incidence of the event: often (1-10%), sometimes (0.1-1%), rarely (0.01-0.1%), very rarely (less than 0.01%), including individual messages.

On the part of the hematopoiesis 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 activity of alanine aminotransferase (ALT), aspartate aminotransferase (ACT), dysbiosis; sometimes, loss of appetite, vomiting, abdominal pain, digestive disorders, hyperbilirubinemia; rarely - diarrhea with blood (in very rare cases it can be a sign of inflammation of the intestine or pseudomembranous colitis); very rarely - hepatitis.

From the cardiovascular system: rarely - tachycardia, lowering blood pressure (BP); very rarely - vascular collapse; in some cases - lengthening the interval QT.

From the central and peripheral 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 depressions, movement disorders.

From the sense organs: very rarely - impaired 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, tremor); in some cases - exacerbation of existing porphyria.

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

From the musculoskeletal system: rarely - tendon damage (including tendonitis), joint and muscle pain; very rarely - tendon rupture (including Achilles, which may 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 asphyxiation, and also - in rare cases - swelling of the face, larynx); very rarely - a sharp decrease in blood pressure, anaphylactic shock; in selected cases - Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome) and exudative erythema multiforme, allergic pneumonitis, vasculitis.

Dermatological reactions: very rarely photosensitization.

Other: sometimes - asthenia; very rarely - persistent fever, development of superinfection. Local reactions: often - pain, redness, phlebitis.

Overdose:

Symptoms: nausea, erosive lesions of the mucous membranes of the gastrointestinal tract, lengthening of the interval QT, confusion, dizziness, convulsions. Treatment: symptomatic, dialysis is ineffective.

Interaction:

Increases the half-life of cyclosporine.

Non-steroidal anti-inflammatory drugs, theophylline increase convulsive readiness, glucocorticosteroids increase the risk of rupture of tendons.

Cimetidine and drugs that block tubular secretion slow down excretion.

When used simultaneously with indirect anticoagulants (including warfarin) it is necessary to control the coagulability of the blood.

Special instructions:

After normalization of body temperature, it is recommended to continue treatment at least 48-78 hours.

In severe pneumonia caused by Streptococcus pneumoniae, Levofloxacin may not be effective.

The introduction should be carried out for at least 60 minutes, during the introduction, palpitations and transient decreases in blood pressure may occur, and there may rarely be a collapse. With a marked decrease in blood pressure, the administration of levofloxacin is stopped.

If there is a suspected development of pseudomembranous colitis caused by Clostridium difficile, treatment with levofloxacin is canceled and appropriate therapy is prescribed.

During treatment, sunlight and artificial ultraviolet irradiation should be avoided to avoid damage to the skin (photosensitization).

When there are signs of tendinitis, pseudomembranous colitis, allergic reactions levofloxacin immediately cancel.

It should be borne in mind that the development of seizures is possible in patients with a history of brain damage (stroke, severe trauma), and the risk of hemolysis is a deficiency in glucose-6-phosphate dehydrogenase.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:Solution for infusions 5 mg / ml.

Packaging:

To 100 ml in a translucent bottle of low density polyethylene, equipped with a dust cap, with a loop at the bottom, with a calibration scale and an internal packing code on the side of the bottle. One bottle with instructions for use is put in a cardboard box. On the cardboard package valve, a sticker with the company logo is allowed to control the first opening.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Do not freeze.

Keep out of the reach of children!

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006904/09

Date of registration:28.08.2009

The owner of the registration certificate:Dr. Reddy's Laboratories Ltd.Dr. Reddy's Laboratories Ltd. India

Manufacturer: & nbsp

DR. REDDY`S LABORATORIES, LTD. India

Representation: & nbspDR REDDY'S LABORATORIS LTD. DR REDDY'S LABORATORIS LTD. India

Information update date: & nbsp11.10.2015

Illustrated instructions

Instructions

Levoleth® Р (Levolet® R)