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

Excipients - sodium chloride - 9.00 mg, hydrochloric acid concentrated - 1.40 mg, 10% sodium hydroxide solution - up to pH 4.8, water for injection - up to 1 ml.

Theoretical osmolarity is from 280 to 320 mOsm / kg.

Description:A clear solution of a greenish-yellow color.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A Fluoroquinolones

J.01.M.A.12 Levofloxacin

Pharmacodynamics:

Levofloxacin is a broad-spectrum antimicrobial agent group of fluoroquinolones. Levofloxacin, active substance of the preparation, is an optically active levorotatory isofloxacin - L-oxloxacin. Levofloxacin blocks the DNA-gyrase (topoisomerase II) and topoisomerase IV, disrupts supercoiling and cross-linking of DNA gaps, inhibits DNA synthesis, causes profound morphological changes in the cytoplasm, cell wall and membranes of microbial cells.

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

In vitro

Sensitive microorganisms (MPK≤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 / -modern sensitive)], Staphylococcus aureus methi-S (methicillin-sensitive), Staphylococcus epidermidis methi-S (methicillin-sensitive), Staphylococcus spp. CNS (coagulase-negative), Streptococci group C and G, Streptococcus agalactiae, Streptococcus pneumoniae peni I/S/R (penicillin-moderately sensitive / -sensitive / -resistant), Streptococcus pyogenes, Viridans streptococci 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 para influenzae, Helicobacter pylori, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella spp., Moraxella catarrhalis f+/f- (producing and non-producing beta-lactamases), Morganella morganii, Neisseria gonorrhoeae non PPNG/PPNG (non-producing and producing penicilinase), Neisseria meningitidis, Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida, Pasteurella spp., Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Providencia spp., Pseudomonas aeruginosa (hospital infections caused by Pseudomonas aeruginosa, may require combined treatment), Pseudomonas spp., Salmonella spp., Serratia marcescens, Serratia 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 t.h. Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

Moderately sensitive microorganisms (IPC = 4 mg / L, inhibition zone 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 (MIC of ≥8 mg / L, inhibition zone ≤13 mm)

- Aerobic Gram-positive microorganisms: Staphylococcus aureus methi- R (methicillin-resistant), Staphylococcus coagulase-negative methi-R (coagulase-negative methicillin-resistant).

- Aerobic Gram-negative microorganisms: Alcaligenes xylosoxidans.

- Anaerobic microorganisms: Bacteroides thetaiotaomicron.

- Other microorganisms: Mycobacterium avium.

Resistance

Resistance to levofloxacin develops as a result of a phased process of mutations of genes encoding both topoisomerases of 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 an antimicrobial agent from a 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.

Clinical efficacy (efficacy in clinical studies 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; Citrohacter freundii, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzas, Klebsiella pneumoniae, Moraxella (Branhamella) catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens.

- Other: Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae.

Pharmacokinetics:

After an intravenous 60-minute infusion of levofloxacin at a dose of 500 mg to healthy volunteers, the maximum plasma concentration (Cmax) was an average of 6.2 μg / ml.

The pharmacokinetics of levofloxacin is linear in the dosage range of 50 to 1000 mg. The equilibrium state of the concentrations of levofloxacin in the blood plasma with the administration of 500 mg of levofloxacin 1 or 2 times a day is reached within 48 hours.

On the 10th day of intravenous administration of the drug in a dose 50 mg 1 time per day Frommlevofloxacin was 6.4 ± 0.8 μg / ml, and the minimum concentration of levofloxacin (concentration before administration of the next dose) in blood plasma (Cmin) was 0.6 ± 0.2 μg / ml.

On the 10th day of intravenous administration of the drug at a dose of 500 mg twice a day Cmah was 7.9 ± 1.1 μg / ml, a Cmin was 2.3 ± 0.5 μg / ml.

Distribution.

The connection with serum proteins is 30-40%. The volume of distribution of levofloxacin averages 100 l after single and repeated intravenous 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 coefficients in the bronchial mucosa and epithelial lining fluid, compared to the concentration in the blood plasma 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 with the concentration in the blood plasma.

Penetration into the alveolar fluid

Levofloxacin penetrates well into the alveolar fluid with a coefficient of penetration of 1, compared with the concentration in the blood plasma.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 / blood plasma) 0.1-3.

Penetration into the cerebrospinal fluid.

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Penetration into the tissue of the prostate gland.

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

Concentration in the urine

In the urine, high concentrations of levofloxacin are created, several times higher than the concentration of levofloxacin in the blood 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 intravenous administration levofloxacin is excreted from the blood plasma relatively slowly (the half-life is 6-8 hours). It is usually excreted by the kidneys (85% of the administered dose). The total clearance of levofloxacin after a single administration of 500 mg was 175 ± 29.2 ml / min.

There is no significant difference in the pharmacokinetics of levofloxacin after intravenous and oral administration, indicating that these routes (oral and intravenous) are interchangeable.

Pharmacokinetics in selected patient groups.

The pharmacokinetics of levofloxacin in men and women do not differ.

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

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

Indications:

Infectious-inflammatory diseases caused by susceptible to levofloxacin microorganisms in adults:

- community acquired pneumonia;

- complicated urinary tract infections, including pyelonephritis;

- uncomplicated urinary tract infections;

- chronic bacterial prostatitis;

- infections of the skin and soft tissues;

- for the comprehensive treatment of drug-resistant forms of tuberculosis;

- prevention and treatment of anthrax in case of airborne infection.

When using Levoxime, official national recommendations on the proper use of antibacterial drugs, as well as the sensitivity of pathogenic microorganisms in a particular country, should be taken into account.

Contraindications:

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

- epilepsy;

- affections of tendons associated with taking quinolones in anamnesis;

- pregnancy and the period of breastfeeding (the risk of destruction of the cartilage growth points in the fetus or the child can not be completely ruled out);

- myasthenia gravis gravis;

- children and adolescents under 18 years of age (due to the incompleteness of skeleton growth, since the risk of damage to the cartilaginous growth points can not be completely ruled out).

Carefully:

- Patients who are predisposed to developing seizures [in patients with previous central nervous system (CNS) lesions in patients taking drugs at the same time lowering the threshold of seizure readiness of the brain, such as fenbufen, theophylline].

- In patients with latent or manifested deficiency of glucose-6-phosphate dehydrogenase (increased risk of hemolytic reactions in the treatment of quinolones).

- In patients with impaired renal function (mandatory control of kidney function, as well as correction of the dosing regimen) is required.

- In patients with known risk factors for lengthening the interval QT: in elderly patients; in female patients, in patients with uncorrected electrolyte disorders (hypokalemia, hypomagnesemia); with the syndrome of congenital lengthening of the interval QT; with diseases of the heart (heart failure, myocardial infarction, bradycardia); while taking medications that can lengthen the interval QT (antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, antipsychotics.

- In patients with diabetes mellitus,receiving oral hypoglycemic drugs, for example, glibenclamide or insulin preparations (the risk of developing hypoglycemia increases).

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

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

Pregnancy and lactation:

The drug is contraindicated for use in pregnant and lactating women.

Dosing and Administration:

A drug Levoximed intravenously drip slowly in the form of infusion. Dosing regimen is determined by the nature and severity of the infection, as well as the suspected pathogen susceptibility.

Duration of treatment varies depending on the course of the disease. As with other antibiotics, treatment with Levoxime should be continued for at least 48-72 hours after the normalization of body temperature or reliable eradication of the pathogen.

Treatment with Levoxime should not be interrupted or terminated prematurely without a doctor.

Patients with normal renal function (creatinine clearance> 50 ml / min) are recommended the following dosing regimen for treatment:

- Community-acquired pneumonia: 500 mg 1-2 times a day (respectively, the daily dose of 500-1000 mg levofloxacin), the course of treatment - 7-14 days;

- complicated urinary tract infections: 500 mg once a day (a daily dose of 500 mg of levofloxacin), the course of treatment - 7-14 days;

- pyelonephritis: 500 mg once a day (correspondingly a daily dose of 500 mg of levofloxacin), the course of treatment - 7-10 days;

- Uncomplicated urinary tract infections: 250 mg once a day (respectively, the daily dose of 250 mg of levofloxacin), the course of treatment - 3 days;

- chronic bacterial prostatitis: 500 mg once a day (corresponding to a daily dose of 500 mg levofloxacin), treatment course - 28 days;

- infections of the skin and soft tissues: 500 mg 1 - 2 times a day (respectively, the daily dose of 500 - 1000 mg levofloxacin), the course of treatment - 7-14 days;

- complex treatment of drug-resistant forms of tuberculosis: by 500 mg 1- 2 times a day (respectively a daily dose of 500 to 1000 mg of levofloxacin), course of treatment - up to 3 months;

- prevention and treatment of anthrax during airborne infection: 500 mg once a day (respectively, the daily dose of 500 mg of levofloxacin), the course of treatment - for up to 8 weeks.

Patients with impaired renal function (CK ≤50 ml / min) require a correction of the dosing regimen depending on the amount of creatinine clearance. The drug is administered according to the following scheme:

Creatinine clearance (CC)

Dosing regimen

Recommended dose: 250 mg / 24 hours

Recommended dose: 500 mg / 24 hours

Recommended dose: 500 mg / 12 hours

first dose:

250 mg

first dose:

500 mg

first dose:

500 mg

50-20 ml / min

then:

125 mg / 24 hours

then:

250 mg / 24 hours

then:

250 mg / 12 hours

19-10 ml / min

then:

125 mg / 48 hours

then:

125 mg / 24 hours

then:

125 mg / 12 hours

<10 ml / min (including hemodialysis and CAPD)

then:

125 mg / 48 hours

then:

125 mg / 24 hours

then:

125 mg / 24 hours

With hemodialysis or permanent ambulatory peritoneal dialysis (CAPD), no additional doses are required.

If there is a violation of the liver function, no special dose selection is required. levofloxacin metabolized in the liver in small measure.

For elderly patients, correction of the dosing regimen is not required, except for cases when the CK is reduced to 50 ml / min and below.

Rules for the use of a solution for infusion.

The drug is injected / drip slowly. Duration infusion of a single vial of the drug Levoximed 500 mg (100 ml with 500 mg levofloxacin) should be at least 60 minutes, and in the case of half the vial (50 ml with 250 mg levofloxacin), the duration infusion should be at least 30 minutes.

The infusion solution of the drug 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).

Infusion solution of the drug can not be mixed with heparin or solutions that have an alkaline reaction (for example, with sodium bicarbonate solution).

Depending on the patient's condition, after several days of treatment, a subsequent switch to oral levofloxacin in tablets at the same dose is possible.

If you accidentally missed the introduction of the drug, you should, as soon as possible, to enter the missed dose and continue to continue to administer the drug according to the recommended dosage regimen.

Side effects:

The following side effects are presented in accordance with the following gradations of their frequency: very frequent (≥1 / 10); frequent (≥1 / 100, <1/10); infrequent (≥1 / 1000. <1/100); Rare (≥1 / 10000, <1/1000); very rare (<1/10000) (including individual messages); unknown frequency (according to available data, it is not possible to determine the frequency of occurrence).

Heart Disease

Rare: sinus tachycardia, palpitation.

Unknown frequency (postmarketing data): interval lengthening QT, ventricular arrhythmias, ventricular tachycardia, ventricular pirouette tachycardia, which can lead to cardiac arrest.

Violations of the blood and lymphatic system

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

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

Unknown frequency (postmarketing data): pancytopenia (reduction of the number of all formed elements in the peripheral blood),agranulocytosis (absence or sharp decrease in the amount of granulocytes in the peripheral blood), hemolytic anemia.

Disturbances from the nervous system

Frequent: headache, dizziness.

Infrequent: drowsiness, tremor, dysgeusia (perversion of taste).

Rare: paresthesia, convulsions.

Unknown frequency (postmarketing data): peripheral sensory neuropathy, peripheral sensory-motor neuropathy, dyskinesia, extrapyramidal disorders, agevia (loss of taste sensations), parosmia (odor disorder, especially subjective sense of smell, objectively absent), including loss of smell, fainting, benign intracranial hypertension.

Disturbances on the part of the organ of sight

Rare: visual impairments, such as the vagueness of the visible Images.

Unknown frequency (postmarketing data): transient loss vision, uveitis.

Hearing disorders and labyrinthine disorders

Infrequent: Vertigo (feeling of deviation or twisting of one's own body or surrounding objects).

Rare: tinnitus.

Unknown frequency (postmarketing data): hearing loss, hearing loss.

Disturbances from the respiratory system, chest organs and the mediastinum

Infrequent: dyspnea.

Unknown frequency (postmarketing data): bronchospasm, allergic pneumonitis.

Disorders from the gastrointestinal tract

Frequent: diarrhea, vomiting, nausea.

Infrequent: pain in the abdomen, indigestion, flatulence, constipation.

Unknown frequency (postmarketing data): hemorrhagic diarrhea, which in very rare cases can be a sign of enterocolitis, including pseudomembranous colitis, pancreatitis.

Disorders from the kidneys and urinary tract

Infrequent: increased serum creatinine concentration.

Rare: acute renal failure (eg, due to the development of interstitial nephritis).

Hrupture of the rut and subcutaneous tissues

Infrequent: rash, itching, hives, hyperhidrosis.

Unknown frequency (postmarketing data): toxic epidermal necrolysis, Stevens-Johnson syndrome, exudative erythema multiforme, photosensitization reaction (increased sensitivity to solar and ultraviolet radiation), leukocytoclastic vasculitis, stomatitis. Reactions from the skin and mucous membranes can sometimes develop even after the administration of the first dose of the drug.

Disturbances from musculoskeletal system and connective tissue

Infrequent: arthralgia, myalgia.

Rare: damage to tendons, including tendonitis (eg, Achilles tendons), muscle weakness, which can be especially dangerous in patients with pseudo-paralytic myasthenia gravis (myasthenia gravis).

Unknown frequency (postmarketing data): rhabdomyolysis, tendon rupture (eg Achilles tendon This side effect can be observed within 48 hours after the beginning of treatment and can be bilateral), ligament rupture, muscle rupture, arthritis.

Disorders from the metabolism and nutrition

Infrequent: anorexia.

Rare: hypoglycemia, especially in patients with diabetes mellitus (possible signs of hypoglycemia: "wolfish" appetite, nervousness, perspiration, trembling).

Unknown frequency: hyperglycemia, hypoglycemic coma.

Infectious and parasitic diseases

Infrequent: fungal infections, the development of resistance of pathogenic microorganisms.

Vascular disorders

Frequent: phlebitis.

Rare: lowering of blood pressure.

General disorders and disorders at the site of administration

Frequent: reaction at the injection site (tenderness, skin hyperemia).

Infrequent: asthenia.

Rare: pyrexia (fever).

Unknown frequency: pain (including pain in the back, chest and extremities).

Immune system disorders

Rare: angioedema.

Unknown frequency (postmarketing data): anaphylactic shock, anaphylactoid shock.

Anaphylactic and anaphylactoid reactions can sometimes develop even after the administration of the first dose of the drug.

Disturbances from the liver and bile ducts

Frequent: increased activity of "hepatic" enzymes in the blood (for example, alanine aminotransferase (ALT), aspartate aminotransferase (ASAT)), an increase in the activity of alkaline phosphatase (APF) and gamma-glutamyl transferase (GGT).

Infrequent: increasing the concentration of bilirubin in the blood.

Unknown frequency (postmarketing data): severe hepatic insufficiency, including cases of development of acute hepatic insufficiency, sometimes with fatal outcome, especially in patients with severe underlying disease (eg, in patients with sepsis), hepatitis, jaundice.

Disorders of the psyche

Frequent: insomnia.

Infrequent: anxiety, confusion, confusion.

Rare: mental disorders (eg, hallucinations, paranoia), depression, agitation (agitation), sleep disturbances, nightmares.

Unknown frequency (postmarketing data): mental disorders with behavioral disorders with self-harm, including suicidal thoughts and suicidal attempts.

Other possible undesirable effects related to all fluoroquinolones:

Very rare: Attacks of porphyria (a very rare metabolic disease) in patients with porphyria.

Overdose:

Overdose Symptoms

Based on data from animal studies, the most important expected symptoms of levofloxacin overdose are symptoms from the central nervous system (impaired consciousness, including confusion, dizziness and convulsions.)

In the post-marketing use of the drug in overdose, there were effects from the central nervous system, including confusion, convulsions, hallucinations and tremors.

Nausea and erosion of the mucous membrane of the gastrointestinal tract may occur.

In clinico-pharmacological studies, carried out with doses of levofloxacin exceeding the therapeutic ones, the elongation of the interval QT.

Measures to help with overdose

In case of an overdose, careful monitoring of the patient, including ECG monitoring, is required. Treatment is symptomatic. Levofloxacin is not excreted by dialysis (hemodialysis, peritoneal dialysis and continuous ambulatory peritoneal dialysis).

There is no specific antidote.

Interaction:

Interactions requiring caution

With theophylline, fenbufen or similar drugs from the group of non-steroidal anti-inflammatory drugs, reducing the threshold of convulsive readiness of the brain

The pharmacokinetic interaction of levofloxacin with theophylline has not been revealed. However, with the simultaneous use of quinolones and theophylline, non-steroidal anti-inflammatory drugs and other drugs that reduce the threshold of convulsive brain readiness, there may be a marked decrease in the threshold of convulsive readiness of the brain.The concentration of levofloxacin with simultaneous administration of fenbufen is only increased by 13%.

With indirect anticoagulants (antagonists of vitamin K)

In patients treated with levofloxacin in combination with indirect anticoagulants (eg, warfarin), prothrombin time / international normalized relationships and / or development of bleeding, including, and severe. Therefore, with simultaneous use of indirect anticoagulants and levofloxacin, regular monitoring of blood clotting parameters is necessary.

With probenecid and cimetidine

With the simultaneous use of drugs that disrupt renal tubular secretion, such as probenecid and cimetidine, and levofloxacin should be used with caution, especially in patients with renal insufficiency. Removal (renal clearance) of levofloxacin is slowed by cimetidine by 24% and probenecid by 34%. It is unlikely that this can be of clinical significance in normal kidney function.

With cyclosporine

Levofloxacin increased T_1/2 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.

With glucocorticosteroids

Simultaneous reception of glucocorticosteroids increases the risk of rupture of tendons.

With medications that extend the interval QT

Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs that extend the range QT (for example, antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, neuroleptics).

Other

Conducted clinical and pharmacological studies to study the possible pharmacokinetic interactions of levofloxacin with calcium carbonate, digoxin, glibenclamide, ranitidine and warfarin showed that the pharmacokinetics of levofloxacin when used concomitantly with these drugs does not change sufficiently to make it clinically important.

Special instructions:

Hospital infections caused by Pseudomonas aeruginosa (Pseudomonas aeruginosa), may require combined treatment.

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 on drug resistance inspecific country; for the treatment of severe infections or in the ineffectiveness of treatment, a microbiological diagnosis should be made, isolating the pathogen and determining its sensitivity to levofloxacin.

Methicillin-resistant Staphylococcus aureus

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

Duration of infusion

It should be strictly adhered to the recommended duration of administration, which should be at least 60 min (for 100 ml infusion solution) or 30 min (for 50 ml solution). The experience with levofloxacin shows that during the infusion, there can be increased heart rate and transient decrease in blood pressure. In rare cases, there may be vascular collapse.If there is a marked decrease in blood pressure during the infusion of levofloxacin, the infusion is immediately stopped.

Patients who are predisposed to develop seizures

Like other quinolones, levofloxacin should be very careful Used in patients with a predisposition to convulsions. Such patients include patients with previous lesions of the central nervous system, such as stroke, severe craniocerebral trauma; patients simultaneously receiving drugs that reduce the threshold of convulsive brain readiness, such as fenbufen and other nonsteroidal anti-inflammatory drugs like it or other drugs that lower the threshold of convulsive readiness, such as theophylline.

Pseudomembranous colitis

Developed during or after levofloxacin treatment, diarrhea, especially severe, persistent and / or blood, may be a symptom pseudomembranous colitis, caused by Clostridium difficile. In case of suspected development of pseudomembranous colitis, treatment Levofloxacin should be discontinued immediately and immediately begin specific antibiotic therapy (Vancomycin, teicoplanin or metronidazole inside). Drugs that inhibit the intestinal peristalsis are contraindicated.

Tendonitis

Rarely observed tendonitis in the use of quinolones, including levofloxacin, can lead to the rupture of tendons, including the Achilles tendon. This side effect can develop within 48 hours after the start of treatment and can be bilateral. Older patients are more prone to tendonitis. The risk of rupture of tendons can increase with simultaneous administration of glucocorticosteroids. If suspicion of tendonitis should immediately stop treatment with Levoksimed and begin appropriate treatment of the affected tendon, for example, providing him with sufficient immobilization.

Hypersensitivity reactions

Levofloxacin can cause serious, potentially fatal, reactions hypersensitivity (angioedema, anaphylactic shock). Patients should immediately stop the injection and consult a doctor.

Severe bullous reactions

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

Disturbances from the liver and bile ducts

There have been reports of hepatic necrosis, including the development of fatal liver failure with levofloxacin, mainly in patients with severe underlying diseases, such as sepsis. Patients should be warned about the need for discontinuation of treatment and urgent medical attention in case of signs and symptoms of liver damage such as anorexia, jaundice, darkening of urine, pruritus and abdominal pain.

Patients with renal insufficiency

As levofloxacin excreted, mainly through the kidneys, in patients with impaired renal function, mandatory monitoring of kidney function is required, as well as correction of the dosing regimen. In the treatment of elderly patients, it should be borne in mind that patients of this group often have impaired renal function.

Prevention of the development of photosensitization reactions

Although photosensitization with levofloxacin is very rare, to prevent its development, patients are not recommended during treatment and within 48 hours after the end of treatment with levofloxacin without special need to be subjected to strong sunlight or artificial ultraviolet radiation (for example, to visit the solarium).

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 changes in microflora, which is normally present in humans. As a result, superinfection may develop. Therefore, during the treatment, it is mandatory to reevaluate the patient's condition, and, if developed during the treatment of superinfection, appropriate measures should be taken.

Interval lengthening QT

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

When using fluoroquinolones, including levofloxacin, caution should be exercised in patients with known risk factors for lengthening the interval QT: in patients with uncorrected electrolyte disorders (hypokalemia, hypomagnesemia); with the syndrome of congenital lengthening of the interval QT; with diseases of the heart (heart failure, myocardial infarction, bradycardia); in elderly patients; while taking medications that can lengthen the interval QT, such as antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, antipsychotics.

Elderly patients and female patients may be more sensitive to drugs that extend the interval QT. Therefore, care should be taken to use fluoroquinolones, including levofloxacin.

Patients with deficiency of glucose-6-phosphate dehydrogenase

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

Hypo-and hyperglycemia (dysglycemia)

As with the use of other quinolones, with the use of levofloxacin, cases of hyperglycaemia and hypoglycemia have been observed, especially in patients with diabetes mellitus, receiving concurrent treatment with oral hypoglycemic drugs (eg, glibenclamide) or insulin preparations. There have been reports of cases of hypoglycemic coma. Patients with diabetes are required to monitor the concentration of glucose in the blood.

Peripheral Neuropathy

In patients taking fluoroquinolones, including levofloxacin, sensory and sensory-motor peripheral neuropathy was noted, the onset of which can be rapid. If the patient has symptoms of neuropathy, the use of levofloxacin should be discontinued. This minimizes the possible risk of irreversible changes.

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,requiring artificial ventilation and fatal outcome, which were associated with the use of fluoroquinolones in patients with pseudo-paralytic myasthenia gravis. The use of levofloxacin in patients with established diagnosis of pseudo-paralytic myasthenia gravis is not recommended.

Prevention and treatment of anthrax in case of airborne infection

The use of levofloxacin in humans according to this indication is based on data on sensitivity to it Bacillus anthracis, received in research in vitro and in the experimental studies carried out on animals, as well as limited data on the use of levofloxacin in rights. The attending physicians should refer to national and / or international documents that reflect the common point of view on the treatment of anthrax.

Psychotic reactions

When using quinolones, including levofloxacin, reported the development of psychotic reactions, which in very rare cases progressed to the development of suicidal thoughts and behavioral disorders with self-harm (sometimes after the introduction of a single dose of levofloxacin).With the development of such reactions, treatment with levofloxacin should be discontinued and appropriate therapy prescribed. Caution should be used to prescribe the drug to patients with psychoses or patients who have a history of mental illness.

Visual disturbances

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

Impact on laboratory tests

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

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

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

Such side effects of levofloxacin as dizziness or vertigo, drowsiness, and visual disturbances (see the "Side effect" section) can reduce psychomotor reactions and the ability to concentrate. This may present a certain risk in situations where these the capabilities are of particular importance (for example, when driving, servicing machines and mechanisms,when performing work in an unstable situation).

Form release / dosage:

Solution for infusions 5 mg / ml.

Packaging:

For 100 ml of the drug in a colorless glass vial (type I) with a bromobutyl rubber stopper and a combined aluminum cap of the type Flip-off. One bottle together with instructions for use in a cardboard pack.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004283

Date of registration:03.05.2017

Expiration Date:03.05.2022

The owner of the registration certificate:World Medical Ilachlari Ltd. Shti.World Medical Ilachlari Ltd. Shti. Turkey

Manufacturer: & nbsp

MEFAR ILAC SANAYII, A.S. Turkey

Representation: & nbspTROKAS PHARMA LLCTROKAS PHARMA LLCRussia

Information update date: & nbsp05.06.2017

Illustrated instructions

Instructions

Levoximed (Levoximed)