Leobeg - instructions for use, dose, side effects, contraindications

active substance: levofloxacin hemihydrate [in terms of levofloxacin] 250 mg; Excipients: sodium chloride 450 mg, water for injection up to 50 ml, hydrochloric acid to pH 4.8, sodium hydroxide to pH 4.8.

the 100 ml package contains:

active substance: Levofloxacin hemihydrate [in terms of levofloxacin] 500 mg; Excipients: sodium chloride 900 mg, water for injection up to 100 ml, hydrochloric acid to pH 4.8, sodium hydroxide to pH 4.8.

Description:Transparent solution from yellow to greenish-yellow color.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A Fluoroquinolones

J.01.M.A.12 Levofloxacin

Pharmacodynamics:

Leobeg is a synthetic broad-spectrum antibacterial agent from the group of fluoroquinolones, containing as an active substance levofloxacin - the left-handed isomer of ofloxacin. 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 of microbial cells. Levofloxacin effective against most strains of microorganisms both in conditions in vitro and in vivo.

The degree of antibacterial activity of levofloxacin depends on the ratio of the maximum concentration in the plasma (C_ma_x) or area under the pharmacokinetic concentration-time curve and the minimum inhibitory concentration (MIC). The antibacterial spectrum of sensitivity of levofloxacin is presented below:

In vitro:

Sensitive microorganisms (MIC <2 mg / L, inhibition zone> 17 mm)

Aerobic Gram-positive microorganisms:

Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium. Enterococcus faecalis, Enterococcus spp., Listeria monocytogenes. Staphylococcus coagulase-negative methi- S(I) (coagulase-negative, methicillin-sensitive / -reservesensitive), Staphylococcus aureus methi-S (methicillin-sensitive strains), Staphylococcus epidermidis methi-S (methicillin-sensitive strains), Staphylococcus spp. CNS (coagulase-negative), Streptococci groups FROM and G, Streptococcus agalactiae. Streptococcus pneumoniae peni-I/S/R (penicillin-sensitive / -residually sensitive / -resistant), Streptococcus pyogenes, Streptococcus groups viridans peni-S/R (penicillin-sensitive / -resistant).

Aerobic Gram-negative microorganisms:

Acinetobacter baumannii, Acinetobacter spp., Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter cloacae, Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S/R (ampicillin-sensitive / -resistant), Haemophilus parainfluenzae, Helicobacter pylori. Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella spp., Moraxella catarrhalis

β+/β- (producing and non-producing beta-lactamase strains), Morganella morganii. Neisseria gonorrhoeae non PPNG/PPNG (non-producing and producing penicillinase), Neisseria meningitidis. Pasteurella canis, Pasteurella dogmatis, Pasteurella multocida, Pasteurella spp., Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Providencia spp .. Pseudomonas aeruginosa (hospital infection, embroidered Pseudomonas aeruginosa, may demand combined of therapy), Pseudomonas spp., Salmonella spp., Serratia marcescens, Serratia spp.

Anaerobic microorganisms:

Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterium spp., Veillonella spp.

Other microorganisms:

Bartonella spp., Chlamydia pneumoniae. Chlamydia psittaci. Chlamydia trachomatis, Legionella pneumophila, Legionella spp., Mycobacterium spp., Mycobacterium leprae, Mycobacterium tuberculosis. Mycoplasma hominis, Mycoplasma pneumoniae, Rickctsia spp., Ureaplasma urealyticum.

Levofloxacin moderately active (IPC = 4 mg/l; zone inhibition 16-14 mm)

Aerobic gram positive microorganisms:

Corynebacterium urealyticum, Corynebacterium xerosis. Enterococcus faecium. Staphylococcus epidermidis methi-R (methicillin-resistant), Staphylococcus haemolyticus methi-R (methicillin-resistant).

Aerobic gram-negative microorganisms:

Campylobacter jejuni / coli.

Anaerobic microorganisms:

Prevotella spp., Porphyromonas spp.

Resistant to levofloxacin microorganisms (IPC ≥ 8 mg / l; zone inhibition ≤ 13 mm)

Aerobic Gram-positive microorganisms:

Staphylococcus aureus methi-R (methicillin-resistant), Staphylococcus coagulase- negative methi-R (methicillin-resistant).

Aerobic Gram-negative microorganisms: Alcaligenes xylosoxidans.

Anaerobic microorganisms: Bacteroides thetaiotaomicron.

Other microorganisms: Mycobacterium avium.

In vivo:

The clinical efficacy of levofloxacin has been confirmed in the treatment of infections,caused by the following microorganisms:

Aerobic Gram-positive microorganisms:

Enterococcus faecalis. Staphylococcus aureus. Streptococcus pneumoniae, Streptococcus pyogenes.

Aerobic gram-negative microorganisms:

Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella (Branhamella) catarrhalis, Morganella morganii, Proteus mirabilis. Pseudomonas aeruginosa, Serratia marcescens.

Other:

Chlamydia pneumoniae, Legionella pneumophila. Mycoplasma pneumoniae.

Resistance

Resistance to levofloxacin develops as a result of a phased process of mutations of genes encoding both topoisomerases of the type II: DNA-gyrase and topoisomerase IV. Other mechanisms of resistance, such as the mechanism of influence on the penetration barriers of a microbial cell (a mechanism characteristic of Pseudomonas aeruginosa) and the mechanism of efflux (active excretion of the antimicrobial from the microbial cell) can also reduce the sensitivity of microorganisms to levofloxacin.

Due to the peculiarities of the mechanism of action of levofloxacin, there is usually no cross-resistance between levofloxacin and other antimicrobial agents.

Pharmacokinetics:

After intravenous (IV) infusion over 60 minutes of levofloxacin at a dose of 500 mg to healthy adult volunteers, the maximum plasma concentration averaged 6.2 μg / ml.

The pharmacokinetics of levofloxacin is linear in the dose range of 50-1000 mg. The equilibrium state of the concentration of levofloxacin in plasma with the administration of 500 mg of levofloxacin 1 or 2 times a day is achieved within 48 hours.

On the 10th day of intravenous administration of levofloxacin 500 mg once a day, the maximum concentration of levofloxacin in plasma was 6.4 ± 0.8 μg / ml, and the minimum concentration of levofloxacin (concentration before administration of the next dose) in plasma was 0.6 ± 0.2 μg / ml.

On the 10th day of iv administration of levofloxacin 500 mg twice daily, the maximum concentration of levofloxacin in plasma was 7.9 ± 1.1 μg / ml, and the minimum concentration of levofloxacin (concentration before administration of the next dose) in plasma was 2.3 ± 0 , 5 μg / ml.

Distribution

The connection with plasma proteins is 30-40%. The volume of distribution of levofloxacin averages 100 l after a single and repeated iv administration of 500 mg, which indicates a good penetration of levofloxacin into the organs and tissues of the human body.

Penetration into the bronchial mucosa, epithelial lining fluid, alveolar macrophages

Levofloxacin penetrates well into the bronchial mucosa, epithelial lining fluid, alveolar macrophages with penetration factors in bronchial mucosa and epithelial lining fluid, compared with plasma concentrations of 1.1-1.8 and 0.8-3, respectively.

Penetration into lung tissue

Levofloxacin well penetrates into the lung tissue with penetration factors of 2-5 compared to the concentration in the plasma.

Penetration into the alveolar fluid

Levofloxacin penetrates well into the alveolar fluid with a coefficient of penetration in comparison with the plasma concentrations of 1. When levofloxacin was administered 500 mg 1 or 2 times a day for 3 days, the maximum concentrations of levofloxacin in the alveolar fluid were achieved 2-4 hours after administration and were 4.0 and 6.7 μg / ml, respectively.

Penetration into bone tissue

Levofloxacin well penetrates into the cortical and spongy bone tissue, both in the proximal and distal parts of the femur with a coefficient of penetration (bone tissue / plasma) 0.1-3.

Penetration into the cerebrospinal fluid

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Penetration into prostate tissue

Levofloxacin penetrates well into the prostate tissue (the average ratio of prostatic / plasma concentrations was 1.84).

Concentrations in the urine

In the urine, high concentrations of levofloxacin are created, several times higher than the concentration of levofloxacin in plasma.

Metabolism

Levofloxacin is metabolized to a small extent (5% of the dose taken). Its metabolites are demethyllevofloxacin and N-oxide levofloxacin, which are excreted by the kidneys. Levofloxacin is stereochemically stable and does not undergo chiral transformations.

Excretion

After iv introduction levofloxacin relatively slowly removed from the plasma (half-life (T1/2) 6-8 hours). Excretion mainly through the kidneys (more than 85% of the dose). The total clearance of levofloxacin after a single administration of 500 mg is 175 ± 29.2 ml / min.

The plasma profile of the concentration of levofloxacin after intravenous administration is similar to that when administered orally (tablets). Therefore, oral and / or administration routes can be considered interchangeable.

Special patient groups

During clinical trials, there was no difference in the pharmacokinetics of the drug in men and women.

Pharmacokinetics in elderly patients does not differ from that in young patients, except for differences in pharmacokinetics associated with differences in creatinine clearance (CC).

With renal failure, the pharmacokinetics of levofloxacin varies. As the kidney function worsens, excretion through the kidneys and kidney clearance (ClR) decrease, and T1 / 2 increases.

Indications:

Infectious-inflammatory diseases caused by susceptible to levofloxacin microorganisms:

- community acquired pneumonia;

- complicated urinary tract infections, including pyelonephritis;

- uncomplicated urinary tract infections;

- chronic bacterial prostatitis;

- Infections of the skin and soft tissues

- for complex treatment of drug-resistant forms of tuberculosis.

Contraindications:

- Hypersensitivity to levofloxacin or other quinolones, as well as to the excipients of the drug;

- epilepsy;

- pseudo-paralytic myasthenia gravis (myasthenia gravis);

- the defeat of tendons in the previously conducted treatment with fluoroquinolones;

- children and adolescence (up to 18 years);

- pregnancy;

- the period of breastfeeding.

Carefully:

- in patients who are predisposed to develop seizures (with a history of a brain injury (stroke or severe trauma), in patients who simultaneously receive drugs that reduce the threshold of convulsive brain readiness (fenbufen, theophylline),

- deficiency of glucose-6-phosphate dehydrogenase,

- impaired renal function,

- in patients with a predisposition to lengthen the interval QT: in elderly patients, in female patients, with electrolyte imbalance (eg, hypokalemia, hypomagnesemia); congenital lengthening interval QT; with heart failure, myocardial infarction, bradycardia; while taking medications that extend the interval QT (antiarrhythmic drugs class IA and III, tricyclic antidepressants, neuroleptics, macrolides);

- in patients with diabetes mellitus receiving oral hypoglycemic agents (for example, glibenclamide) or insulin (the risk of developing hypoglycemia),

- in patients with severe adverse reactions to other fluoroquinolones, such as severe neurologic reactions (an increased risk of similar reactions with levofloxacin).

- In patients with psychoses or in patients who have a history of mental illness.

Pregnancy and lactation:

Leobeg is contraindicated for use in pregnant and lactating women, since there is a risk of damage to cartilage in the fetus and the baby.

Dosing and Administration:

A solution for Leobage drug infusions is administered slowly once or twice a day.

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

The duration of therapy depends on the type of disease. In all cases, treatment is recommended to continue for 48 to 72 hours after the disappearance of the symptoms of the disease. Treatment with the drug can not be interrupted on its own without a doctor's instructions.

Depending on the patient's condition, after several days of treatment, it is possible to switch from intravenous infusion to the same dose of the drug in tablets (given that the bioavailability of levofloxacin when taking the drug inside the tablets is 99-100%).

In case of skipping the introduction of Leobage, it is necessary to introduce the next dose as soon as possible and continue the therapy with the drug according to the recommended dosage regimen.

The recommended dose of the drug for adults with normal renal function (CK> 50 ml / min):

With community-acquired pneumonia - 500 mg once or twice a day for 7-14 days.

With complicated infections of the urinary tract, including pyelonephritis - but 500 mg once a day (in case of severe infections, an increase in dose is possible) within 7-14 days.

With pyelonephritis - 500 mg once a day for 7-10 days.

In uncomplicated urinary tract infections - 250 mg once a day for 3 days.

With chronic bacterial prostatitis - 500 mg once a day for 28 days.

In infections of the skin and soft tissues - 500 mg of levofloxacin 1-2 times a day (respectively a daily dose of 500-1000 mg of levofloxacin) - 7 to 14 days.

In the complex treatment of drug-resistant forms of tuberculosis - but 500 mg 1 -2 times a day for up to 3 months.

For patients with impaired renal function (CK <50 ml / min):

CK, ml / min	Dosing regimen
CK, ml / min	250 mg / 24 h, the first dose: 250 mg	500 mg / 24 h, first dose: 500 mg	500 mg / 12 h, the first dose of 500 mg
50-20	then: 125 mg / 24 h	then: 250 mg / 24 h	then: 250 mg / 12 h
19-10	then: 125 mg / 48 h	then: 125 mg / 24 h	then: 125 mg / 12 h
<10 (including hemodialysis and CAPD) *	then: 125 mg / 48 h	then: 125 mg / 24 h	then: 125 mg / 24 h

* No additional doses are required after hemodialysis or continuous outpatient peritoneal dialysis (CAPD).

Patients with impaired hepatic function

If there is a violation of the liver function, nc requires a special dose selection, since levofloxacin It is only slightly metabolized in the liver and excreted mainly by the kidneys.

Elderly patients

No dosage adjustment is required for elderly patients with normal renal function (see section Special instructions).

Children and teens

Leobeg is contraindicated in children and adolescents under the age of 18 (see section Contraindications).

Mode of application

The infusion solution of Leobage preparation is injected iv slowly. The duration of the infusion should be at least 30 minutes for a solution containing 250 mg of levofloxacin and at least 60 minutes for a solution containing 500 mg of levofloxacin. Depending on the patient's condition, after a few days of treatment, you can go from / in the drip to receive the same dose of the drug in a form intended for oral administration.

The infusion solution of Leobeg 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).

Solution leobeg can not be mixed with heparin or solutions that have an alkaline reaction (for example, with a solution of sodium bicarbonate).

Perform a visual inspection of the solution before administration. The solution can be used only if it is transparent from yellow to greenish-yellow without visible particles.

Grasp the top of the connecting tube.

Tear off the protective tip from the connecting tube.

Insert the needle of the infusion system into the connecting tube of the packet with twisting movements.

Hang the bag by the hole on the tripod.

During the infusion it is not necessary to protect the solution from light.

The solution is recommended to be used immediately, the unused solution is destroyed.

Side effects:

The incidence of adverse reactions is distributed as follows: Often (≥ 1/10), often (≥ 1/100, <1/10), infrequently (≥ 1/1000, <1/100), rarely (≥ 1/10000, <1/1000), rarely (<1/10000) (including individual messages), frequency unknown (according to available data, it is not possible to determine the frequency of occurrence).

Infectious and parasitic diseases

Infrequently - mycoses, development of resistance of pathogenic microorganisms.

Violations of the blood and lymphatic system

Infrequently - leukopenia (a decrease in the number of leukocytes in the peripheral blood), eosinophilia (an increase in the number of eosinophils in peripheral blood).

Rarely - thrombocytopenia (a decrease in the number of platelets in the peripheral blood), neutropenia (a decrease in the number of neutrophils in peripheral blood).

Frequency unknown - pancytopenia (decrease in the number of all elements in the peripheral blood), agranulocytosis (absence or sharp decrease in the amount of granulocytes in the peripheral blood), hemolytic anemia.

Immune system disorders

Rarely - angioedema.

Frequency unknown - hypersensitivity, anaphylactoid shock, anaphylactic shock (see section "Special instructions").

Disorders from the metabolism and nutrition

Infrequently - anorexia.

Rarely - hypoglycemia, usually in patients with diabetes mellitus (possible signs of hypoglycemia: increased appetite, increased sweating, trembling) (see section Special instructions).

Frequency unknown - hyperglycemia, hypoglycemic coma.

Disorders of the psyche

Often - insomnia.

Infrequently - anxiety, confusion, confusion.

Rarely - psychotic disorders (eg, hallucinations, paranoia), depression, agitation, sleep disturbances, nightmares.

Frequency unknown - psychotic reactions associated with suicidal thoughts or attempts and attempts to harm their own health (see section Special instructions).

Disturbances from the nervous system

Often - headache, dizziness.

Infrequently - drowsiness, tremor, dysgeusia (perversion of taste).

Rarely - cramps, paresthesia.

Frequency unknown - sensory or sensorimotor peripheral neuropathy; dyskinesia, extrapyramidal disorders, loss of taste sensations; distortion of the sense of smell, including its loss, fainting, benign intracranial hypertension.

Disturbances on the part of the organ of sight

Rarely - visual impairments, such as the vagueness of the visible image.

Frequency unknown - Transient loss of vision.

Hearing disorders and labyrinthine disorders

Infrequently - Vertigo.

Rarely - tinnitus.

Frequency unknown - Hearing loss, hearing loss.

Heart Disease

Rarely - Sinus tachycardia, palpitation.

Frequency unknown - lengthening of the interval QT, ventricular arrhythmias, ventricular tachycardia, ventricular pirouette tachycardia, which can lead to cardiac arrest (see section Special instructions, Overdose).

Vascular disorders

Often - phlebitis at the site of administration.

Rarely - lowering blood pressure.

Disturbances from the respiratory system, organs of the chest and mediastinum

Infrequently - dyspnea.

Frequency unknown - bronchospasm, allergic pneumonitis.

Disorders from the gastrointestinal tract

Often - diarrhea, vomiting, nausea.

Infrequently - abdominal pain, indigestion, flatulence, constipation.

Frequency unknown - diarrhea with an admixture of blood, which in very rare cases can indicate the development of enterocolitis, including pseudomembranous colitis, pancreatitis.

Disturbances from the liver and bile ducts

Often - increased activity of "hepatic" transaminases (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase).

Infrequently - hyperbilirubinemia.

Frequency unknown - severe liver dysfunction, including cases of acute liver failure, hepatitis, jaundice, severe hepatic insufficiency, including cases of acute liver failure, sometimes fatal, especially in patients with severe underlying disease (eg, in patients with sepsis), (see section Special instructions).

Disturbances from the skin and subcutaneous tissues

Infrequently - rash, itching, hives, hyperhidrosis.

Frequency unknown - toxic epidermal necrolysis (Lyell's syndrome), malignant exudative erythema (Stevens-Johnson syndrome), exudative erythema multiforme, photosensitivity reactions, leukocytoclastic vasculitis, stomatitis. Mucosal reactions can sometimes occur after the first dose of the drug.

Disturbances from musculoskeletal and connective tissue

Infrequently - Arthralgia, myalgia.

Rarely - defeat of tendons (see section Special instructions), including tendonitis, muscle weakness, which may be of particular importance for patients with myasthenia gravis gravis.

Frequency unknown - rhabdomyolysis, tendon rupture.This side effect can develop within 48 hours after the initiation of therapy and may be noted bilaterally, ligament rupture, muscle rupture, arthritis.

Disorders from the nochek and urinary tract

Infrequently - increased serum creatinine concentration.

Rarely - Acute renal failure (for example, caused by the development of interstitial nephritis).

Common disorders and disorders together

Often - reactions at the injection site (tenderness, skin hyperemia).

Infrequently - asthenia.

Rarely - hyperthermia.

Other side effects that may be associated with the use of fluoroquinolones: porphyria attacks in patients with porphyria.

Frequency unknown - pain (including pain in the back, chest, limbs)

Overdose:

Expected symptoms overdoses of the drug Leobage are manifested at the level of the central nervous system (confusion, dizziness, impaired consciousness and seizures as epi-seizures). In addition, gastrointestinal disorders (eg, nausea) and erosive lesions of the mucous membranes of the gastrointestinal tract can be noted. From the side of the cardiovascular system, lengthening of the interval QT.

Treatment symptomatic.It is necessary to conduct ECG monitoring to monitor the interval QT. Levofloxacin is not excreted by dialysis. There is no specific antidote.

Interaction:

There are reports of a marked decrease in the level of convulsive readiness with simultaneous use of quinolones and substances, which in turn can reduce the threshold of convulsive readiness. Equally, this also applies to the simultaneous use of quinolones, theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs. It was noted that the concentration of levofloxacin is approximately 13% higher in the presence of fenbufen compared with the values for monotherapy.

There was no effect on the pharmacokinetics of levofloxacin from calcium carbonate, digoxin, glibenclamide and ranitidine.

The use of glucocorticosteroids increases the risk of rupture of tendons.

With the simultaneous use of indirect anticoagulants (for example, warfarin), coumarin derivatives, control over the coagulation system of blood is necessary because of the possible development of severe bleeding. Removal (renal clearance) of levofloxacin is slowed by cimetidine (by 24%) and probenecid (by 34%) in view of the possible blocking of tubular secretion of levofloxacin in the nights.It should be noted that this interaction is of clinical importance, primarily for patients with impaired renal function. Simultaneous administration of levofloxacin and drugs blocking tubular secretion should be carried out with caution, especially in patients with impaired renal function.

Levofloxacin increases T1 / 2 cyclosporine by 33%. Since this increase is clinically insignificant, correction of the dose of cyclosporine when it is used simultaneously with levofloxacin is not required.

Levofloxacin, like other fluoroquinolones, should be used with caution in patients taking drugs that extend the interval QT (antiarrhythmic drugs class IA and III, tricyclic antidepressants, neuroleptics, macrolides). With the combined use of levofloxacin and hypoglycemic agents, a change in the level of glucose in the blood, for this reason, during the joint intake of this group of drugs is recommended to monitor blood glucose.

Solution for infusion Leobeg is compatible with 0.9% sodium chloride solution, 5% dextrose solution, 2.5% Ringer's solution with dextrose, combined solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).

Do not mix with heparin and solutions that have an alkaline reaction (for example sodium bicarbonate solution).

Do not mix Leobage with other medications.

Special instructions:

Treatment of hospital infections caused by certain pathogens (Pseudomonas aeruginosa), may require combination therapy. The prevalence of acquired resistance of the sown strains of microorganisms can vary depending on the geographic region and over time. In this regard, information about drug resistance in a particular country is required. For the treatment of severe infections and in the ineffectiveness of treatment, a microbiological diagnosis should be made, identifying the causative agent and determining its sensitivity to levofloxacin.

Duration of infusion

The recommended duration of IV infusion should be at least 30 minutes for a solution containing 250 mg and at least 60 minutes for a solution containing 500 mg of levofloxacin. The experience with levofloxacin shows that during the infusion, there can be increased heart rate and transient decrease in blood pressure.In rare cases, transient reduction in blood pressure can cause vascular collapse. If during the infusion of levofloxacin a pronounced decrease in blood pressure is observed, the infusion is immediately stopped.

For reasons of sterility, it is recommended to inject the solution immediately after opening the package. Before use, it is recommended to check the solution visually for visible particles. It is possible to use only a transparent solution without visible particles. The remaining amount of the solution is drained off.

Methicillin-resistant strain Staphylococcus aureus (MRSA)

Methicillin-resistant strains S.aureus most likely to have cross-resistance to fluoroquinolones, including levofloxacin. Therefore, levofloxacin therapy is not recommended in case of suspicion or in the case of confirmation of a disease caused by MRSA until the susceptibility of the microorganism to levofloxacin is confirmed.

Tendonitis and tendon rupture

In rare cases, with the introduction of Leobage, tendonitis may develop. Tendinitis (primarily, inflammation of the Achilles tendon), developed against the background of the drug, can lead to rupture of tendons.Elderly patients and patients taking glucocorticosteroids are most prone to developing tendonitis. When the drug is administered to this group of patients, to observe their condition. Patients should inform the attending physician about the appearance of symptoms of tendinitis. If suspicion of tendonitis should immediately stop treatment with Leobeg and begin appropriate treatment of the affected tendon, for example, providing him with a state of rest (see section Contraindications and Side effect).

Diseases caused by Clostridium difficile

Diarrhea, in particular a severe, persistent form with an admixture of blood, that occurs during or after the administration of the drug, may be a sign of a disease caused by Clostridium difficile. The most severe form of this disease is pseudomembranous colitis. If suspicion of pseudomembranous colitis should immediately stop the drug Leobage and immediately begin a specific antibiotic therapy (for example, intake of vancomycin). In this case, drugs that inhibit intestinal peristalsis are contraindicated.

Patients who are predisposed to develop seizures

It should be borne in mind that in patients with a history of brain damage (stroke, severe craniocerebral injury, epilepsy), the development of seizures is possible. Also, caution should be exercised when co-administering Leobeg and drugs that reduce the threshold of convulsive readiness (see section Interaction with other medicinal products). In case of seizures, Leobage should be discontinued.

Patients with deficiency of glucose-6-phosphate dehydrohease

With a deficiency of glucose-6-phosphate dehydrogenase during treatment with quinolones, there is a risk of hemolysis.

Patients with impaired function of night

Because the levofloxacin is excreted mainly by the kidneys, in patients with impaired renal function, a correction of the dosing regimen is required (see section Dosing and Administration) and control of kidney function. In the treatment of elderly patients, it should be borne in mind that patients of this group often have impaired renal function.

Hypersensitivity reactions

Levofloxacin can cause severe hypersensitivity reactions that threaten the patient's life (eg, angioedema, up to anaphylactic shock), immediately after the first injection.If these reactions develop, Leobeg should immediately stop treatment and begin appropriate therapy.

Severe bullous reactions

When taking levofloxacin, there were cases of severe bullous skin reactions, such as Stephen-Johnson syndrome or toxic epidermal necrolysis (see section "Side effect"). In case of any reactions from the skin or mucous membranes, the patient should immediately consult a doctor and do not continue the treatment until his consultation.

Hypo-and hyperglycemia

As with the use of other quinolones, when levofloxacin was used, cases of hypoglycemia and hyperglycemia were observed, usually in patients with diabetes mellitus, who received treatment with oral hypoglycemic drugs (eg, glibenclamide) or with insulin preparations. There have been reports of cases of hypoglycemic coma. Patients with diabetes are required to monitor blood glucose concentrations (see section Side effect).

Prevention of photosensitivity reactions

Although the occurrence of photosensitivity reactions during the administration of levofloxacin is very rare,It is necessary to avoid sunlight and artificial ultraviolet irradiation (solarium) during treatment and for 48 hours after the end of levofloxacin treatment to avoid damage to the skin (photosensitivity).

Superinfection

As with the use of other antibiotics, the use of levofloxacin, especially for a long time, can lead to increased reproduction of insensitive microorganisms (bacteria and fungi), which can cause a change in microflora, which is normally present in humans. As a result, superinfection may develop. Therefore, during the treatment it is obligatory to conduct a repeated assessment of the patient's condition, and. In case of development during treatment of superinfection, appropriate measures should be taken.

Patients taking indirect anticoagulants, coumarin derivatives

It is possible to increase the values of the coagulation test (prothrombin time / international normalized ratio) and / or increase bleeding time in patients taking indirect anticoagulants with levofloxacin, coumarin derivatives (for example, warfarin). It is necessary to control blood clotting in this group of patients.

Psychotic reactions

In patients taking quinolones, including levofloxacin, it is possible to develop psychotic reactions. In very rare cases, even after the administration of the first dose of levofloxacin, these reactions can turn into suicidal thoughts and behavior directed at causing harm to one's health (see section Side effect). In case of occurrence of the reactions described above, Leobeg should be discontinued and appropriate measures taken. It should be used with caution in appointing patients with psychoses or patients with a history of mental illness.

Visual disturbances

With the development of any visual impairment, an immediate consultation of the ophthalmologist is necessary.

Increase the interval QT

Use with caution in patients who have risk factors for lengthening the interval QT:

- Congenital lengthening of the interval QT.

- Simultaneous reception of drugs that extend the interval QT (for example, antiarrhythmic drugs of the class IA and III, tricyclic antidepressants, macrolides, neuroleptics)

- Disorders of electrolyte balance (eg, hypokalemia, hypomagnesemia).

- Elderly patients.

- Female Patients

- Heart diseases (eg, heart failure, myocardial infarction, bradycardia).

Peripheral Neuropathy

There have been reports of the development of sensory or sensorimotor peripheral neuropathy when taking fluoroquinolones, including when taking levofloxacin, the symptoms of which develop rapidly. If a patient develops symptoms of neuropathy, Leobeg should be discontinued in order to prevent the development of an irreversible condition of the disease.

Exacerbation of pseudo-paralytic myasthenia gravis (myasthenia gravis)

Fluoroquinolones, including levofloxacin, are characterized by neuromuscular blocking of activity and may increase muscle weakness in patients with pseudo-paralytic myasthenia gravis. In the postmarketing period, adverse reactions were observed, including pulmonary insufficiency, which required artificial respiration, and death, which were associated with the use of fluoroquinolones in patients with pseudo-paralytic myasthenia gravis. The use of levofloxacin in a patient with an established diagnosis of pseudo-paralytic myasthenia gravis is not recommended (see the "Side effect" section).

Laboratory Tests

Levofloxacin can give a false positive result for opiates, determined in urine using immunological test systems. Therefore, during the treatment with levofloxacin, more specific methods for the analysis of opiates should be used.

Levofloxacin can inhibit growth Mycobacterium tuberculosis and lead in the future to false-negative results of a bacteriological diagnosis of tuberculosis.

Violation of the function of the liver and biliary tract

reports have been received on the development of liver necrosis, including the development of fatal liver failure with levofloxacin. These phenomena were observed, first of all, in patients with a severe course of a disease (for example, sepsis) (see section Side effect). Patients should be alerted to stop treatment and seek immediate medical attention if signs and symptoms of liver damage such as anorexia, jaundice, darkening of the urine, pruritus and abdominal pain occur.

Other precautions

The sodium content in the preparation is about 154 μmol / ml (3.54 mg / ml). This should be taken into account in patients on a sodium diet and in cases where a restriction of fluid intake is required.

Effect on the ability to drive transp. cf. and fur:During drug treatment, care must be taken when driving vehicles and mechanisms 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:

For 50 or 100 ml in a polyolefin package Cryovac® with multi-layer connecting tube Cryovac®. 1 pack Cryovac® is placed in a forming bag consisting of polyester / polyester metallized / polypropylene or polyester / aluminum / polyester / polypropylene on one side and polyester ALOX/ polypropylene on the other hand. For 1.5, 10 or 20 forming packages in a cardboard box with instructions for use.

Storage conditions:

Store in the original packaging, protected from light, at a temperature of no higher than 25 ° C. After extraction from the molding bag, the solution can be stored for no more than 7 days! Keep out of the reach of children!

Shelf life:

2 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001478

Date of registration:06.02.2012

The owner of the registration certificate:Actavis PTS ehf GroupActavis PTS ehf Group Iceland

Manufacturer: & nbsp

ACS DOBFAR Info, S.A. Switzerland

Representation: & nbspAktavis, Open Company Aktavis, Open Company

Information update date: & nbsp29.09.2015

Illustrated instructions

Instructions

Leobeg (Leobeg)