Levofloxacin - instructions for use, dosage, side effects, contraindications

Excipients: lactose monohydrate 68.57 mg, microcrystalline cellulose 30.00 mg, hypromelose 10.00 mg, crospovidone 7.60 mg, magnesium stearate 7.60 mg;

sheath: film coating (polyvinyl alcohol 4,4000 mg, titanium dioxide 2,6642 mg, macrogol 2.2220 mg, talc 1.6280 mg, dye red charming 0,0748 mg, dye quinoline yellow 0.0077 mg, indigocarmine 0.0033 mg) 11.0 mg;

dosage of 500 mg:

active substance: levofloxacin hemihydrate 512.46 mg, converted to levofloxacin 500.00 mg;

Excipients: lactose monohydrate 145.84 mg, microcrystalline cellulose 51.30 mg, hypromellose 20.00 mg, crospovidone 15.20 mg, magnesium stearate 15.2 mg;

sheath: film coating (polyvinyl alcohol 8.8000 mg, titanium dioxide 5.3284 mg, macrogol 4.4440 mg, talc 3.2560 mg, red dye charming 0.1496 mg, dye quinoline yellow 0.0154 mg, indigo carmine 0.0066 mg) 22.0 mg.

Description:

Dosage of 250 mg: tablets, covered with a film shell of pink color, round, biconvex, with a risk, on the cross-section the nucleus from white with a yellowish powder to a light yellow color.

Dosage 500 mg: tablets covered with a film shell of pink color, oval, biconvex, with a risk, on the cross-section the nucleus from white with a yellowish tinge to light yellow color.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A Fluoroquinolones

J.01.M.A.12 Levofloxacin

Pharmacodynamics:

Fluoroquinolone, a broad-spectrum antimicrobial bactericide. It blocks 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 bacterial membranes. The main mechanism of development of resistance is associated with gene mutation gyr-A with the possible development of cross-resistance between levofloxacin and other fluoroquinolones. Cross-resistance between levofloxacin and antibacterial drugs of other classes usually does not arise.

Activity in vitro:

Sensitive microorganisms (minimal suppressive concentration ≤2 mg / l):

Aerobic Gram-positive microorganisms: Bacillus anthracis, Corynebacterium diphtheria, Corynebacterium jeikeium. Enterococcus spp. (at Tom number of Enterococcus faecalis), Listeria monocytogenes, Staphylococcus spp. (coagulase-negative methicillin-sensitive/moderately sensitive strains), including Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), Staphylococcus spp. (leukotoxin-containing); Streptococcus spp. groups FROM 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. (at Tom number of Acinetobacter baumannii), Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerates, Enterobacter spp. (at Tom number of Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (ampicillin-sensitive/resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (at Tom number of Klebsiella oohtwaspsa, Klebsiella pneumoniae), Moraxella catarrlialis (producing and non-reducing beta-lactamase strains), Morganella morganii, Neisseria gonorrlioeae (producing and non-reducing penicillinase strains), Neisseria meningitidis, Pasteurella spp. (a Tom number of Pasteurella canis, 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., Veillonella spp.

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

Moderately sensitive microorganisms (minimum inhibitory concentration more than or equal to 8 mg / l):

Aerobic Gram-positive microorganisms: Corynebacterium urealylicum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis (methicillin-resistant strains), Staphylococcus haemolyticus (methicillin-resistant strains).

Aerobic gram-negative microorganisms: Campylobacter jejuni, Campylobacter coli. Anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

Stable micro-organisms (minimum inhibitory concentration more than or equal to 8 mg / l):

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

Aerobic Gram-negative microorganisms: Alcaligenes xylosoxidans.

Anaerobic microorganisms: Bacteroides thetaiotaomicron.

Other microorganisms: Mycobacterium avium.

Clinical efficacy (efficacy in clinical studies for 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 catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens;

- others microorganisms: Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae.

Pharmacokinetics:

When ingested quickly and almost completely absorbed (eating little influence on speed and completeness of absorption). Bioavailability - 99%. With a single administration of 500 mg, the maximum concentration is achieved within 1-2 hours and is 5.2 ± 1.2 μg / ml. In renal failure, the decrease in clearance of levofloxacin and its excretion by the kidneys depends on the degree of decrease in the clearance of creatinine (CC). With KK 50-80 ml / min half-life (T_1/2) is 9 hours with SC 20-40 ml / min T_1/2 is 27 hours, with QC less than 20 ml / min T_1/2is 35 hours.

Connection with plasma proteins - 30-40 %. It penetrates well into the organs, tissues and body fluids: lungs, bronchial mucosa, sputum, organs of the genitourinary system, polymorphonuclear leukocytes, alveolar macrophages.

In the liver, a small portion is oxidized and / or deacetylated.

Kidney clearance - 85% of the total clearance. The half-life is 6-8 hours.

It is excreted from the body mainly by the kidneys (by glomerular filtration and tubular secretion) and by the intestine. Less than 5% of levofloxacin is excreted as metabolites.

Indications:

Infections caused by susceptible to levofloxacin pathogens:

- lower respiratory tract (exacerbation of chronic bronchitis, community-acquired pneumonia);

- ENT organs (acute sinusitis);

- urinary tract and kidneys (including acute pyelonephritis);

- skin and soft tissues (festering atheromas, abscess, boils);

- tuberculosis (complex therapy of drug-resistant forms);

chronic bacterial prostatitis.

Contraindications:

Hypersensitivity to levofloxacin, other quinolones, other components of the drug, epilepsy, tendon damage with prior quinolone treatment, pregnancy, breastfeeding period, age of 18 years, lactose intolerance, lactase deficiency, glucose-galactose malabsorption, myasthenia gravis (myasthenia gravis).

Carefully:

Elderly age (high likelihood of concomitant decline in function search), deficiency of glucose-6-phosphate dehydrogenase; in patients with psychoses or in patients with a history of mental illness; in patients with severe adverse reactions to other fluoroquinolones, such as severe neurologic reactions; in patients predisposed to developing seizures (in patients with previous lesions of the central nervous system, in patients receiving concurrent medications that reduce the threshold of convulsive brain readiness, such as fenbufen, theophylline); in patients with impaired renal function; In patients with known risk factors for lengthening the interval QT: in elderly patients, in female patients, in patients with uncorrected electrolyte disorders (eg, hypokalemia, hypomagnesemia), with the syndrome of congenital lengthening of the interval QT, with heart diseases (heart failure, myocardial infarction, bradycardia), while taking medications that can lengthen the interval QT (antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, neuroleptics); in patients with diabetes mellitus, receiving oral hypoglycemic drugs, for example, glibenclamide or insulin preparations (the risk of developing hypoglycemia increases).

Pregnancy and lactation:

See section "Contraindications".

Dosing and Administration:

Inside, before meals or at a break between meals, without chewing, squeezed enough liquid.

Dosing regimen is determined by the nature and severity of the infection, as well as the suspected pathogen susceptibility. The duration of treatment depends on the course of the disease.Given that the bioavailability of levofloxacin when taking levofloxacin in tablets is 99-100 %, in the case of transfer of the patient from intravenous infusion of levofloxacin on the taking of tablets, the treatment should be continued at the same dose that was used for intravenous infusion.

In acute sinusitis - 500 mg once a day - 10-14 days.

With an exacerbation of chronic bronchitis - 500 mg once a day - 7-10 days.

With community-acquired pneumonia - 500 mg I -2 times a day - 7-14 days.

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

With complicated infections of the urinary tract - 500 mg once a day - 7-14 days.

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

With infections of the skin and soft tissues - inside by 500 mg 1-2 times a day - 7-14 days.

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

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

Dosing regimen in patients with impaired renal function

When treating patients with impaired renal function, a dose reduction is required (see table below).

Clearance

creatinine

Dosing regimen

250 mg / 24 hours.

500 mg / 24 hours.

500 mg / 12 hours.

first dose: 250 mg

first dose: 500 mg

50 g - 20 ml / min.

then:

for 125 mg / 24 hours.

then:

250 mg / 24 hours.

then:

250 mg / 12 hours.

19g10 ml / min.

then:

for 125 mg / 48 hours.

then:

125 mg / 24 hours.

then:

125 mg / 12 hours.

<10 ml / min.

(including hemodialysis and CAPD¹)

then:

for 125 mg / 48 hours.

then:

125 mg / 24 hours.

then:

125 mg / 24 hours.

¹After hemodialysis or permanent ambulatory peritoneal dialysis (CAPD), no additional doses are required.

Dosing regimen in patients with impaired hepatic function

If the liver function is not corrected, correction of the dosing regimen is not required, since levofloxacin only slightly metabolized in the liver.

Dosage regimen in elderly patients

For elderly patients, dosage adjustment is not required, except for cases when creatinine clearance is reduced to 50 ml / min or less.

Side effects:

From the digestive system: nausea, vomiting, diarrhea (including echovirus), digestive disorders, decreased appetite, abdominal pain, pseudomembranous colitis, increased activity of "liver" transaminases, increased activity of alkaline phosphatase and gamma-glutamyltransferase, hyperbilirubinemia, hepatitis, severe hepatic insufficiency,including cases of development of acute hepatic insufficiency, sometimes with a fatal outcome, especially in patients with severe the main disease (for example, in patients with sepsis), dysbiosis, flatulence, constipation, pancreatitis, stomatitis, jaundice.

From the cardiovascular system: lowering blood pressure, cardiovascular collapse, tachycardia, lengthening of the interval QT, heart rhythm, ventricular rhythm disturbances, ventricular tachycardia, ventricular pirouette tachycardia, which can lead to cardiac arrest, benign intracranial hypertension.

From the side of metabolism: hypoglycemia (increased appetite, increased sweating), hypoglycemic coma, hyperglycemia.

From the nervous system: headaches, dizziness, weakness, fainting, snotty, insomnia, sleep disturbances, nightmares, tremors, anxiety, paresthesia, fear, hallucinations, confusion, anorexia, depression, movement disorders, convulsions, peripheral sensory neuropathy and peripheral sensory-motor neuropathy , dyskinesia, extrapyramidal disorders, anxiety, agitation, paranoia,mental disorders with behavioral disorders with self-harm, including suicidal thoughts and suicidal attempts.

From the sense organs: vertigo, ringing in the ears, visual disturbances, hearing loss, smell, taste and tactile sensitivity, transient loss of vision, hearing loss, dysgeusia, loss of taste, parasymia, including loss of smell.

From the musculoskeletal system: arthralgia, muscle weakness, myalgia, tendon rupture, tendonitis, ligament rupture, muscle rupture, arthritis.

From the urinary system: hypercreatininemia, interstitial nephritis, acute renal failure.

From the hematopoiesis: eosinophilia, hemolytic anemia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, pancytopenia, hemorrhages.

Allergic reactions: photosensitization, rash, itching and hyperemia of the skin, swelling of the skin and mucous membranes, urticaria, exudative erythema multiforme, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), bronchospasm, suffocation, angioedema, anaphylactoid shock, anaphylactic shock, allergic pneumonitis, leukocytoclastic vasculitis.

Other: asthenia, dyspnea, exacerbation of porphyritis hyperhidrosis, rhabdomyolysis, persistent fever, development of superinfection, development of resistance of pathogenic microorganisms, pain (including pain in the back, chest and extremities).

Overdose:

Symptoms drug overdose Levofloxacin manifest themselves from the central nervous system: a violation of consciousness, including confusion, dizziness, convulsions, hallucinations, tremors. In addition, it can be noted: lengthening the interval QT, gastrointestinal disorders (eg, nausea) and erosive lesions of the mucous membrane of the gastrointestinal tract.

Treatment symptomatic. In case of an overdose of Levofloxacin tablets, gastric lavage and administration of antacids for the protection of the gastric mucosa are shown, as well as monitoring of the electrocardiogram. Levofloxacin not output by dialysis. There is no specific antidote.

Interaction:

Levofloxacin increases the half-life of 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.

The effect of levofloxacin reduces drugs that depress intestinal motility, magnesium and aluminum-containing antacid drugs and iron salts (a break between intake of at least 2 hours is necessary).

Effect of the drug Levofloxacin significantly weakened by the simultaneous use of sucralfate (a means to protect the gastric mucosa). Patients committing levofloxacin and sucralfate, it is recommended to take sucralfate 2 hours after taking levofloxacin.

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

When used simultaneously with indirect anticoagulants, coumarin derivatives, control of the international normalized relationship is necessary, while simultaneous application of levofloxacin and indirect anticoagulants, prothrombin time / international normalized ratio and / or bleeding, including severe, increase were observed.

The simultaneous use of levofloxacin and oral hypoglycemic agents or insulin can lead to the development of hypoglycemia or hyperglycemia.A careful monitoring of the concentration of glucose in the blood is recommended.

With simultaneous use of drugs that disrupt the renal tubular secretion of levofloxacin, such as probenecid and cimetidip, caution should be used, especially in patients with renal insufficiency. Cimetidip and probenecid slows the withdrawal of levofloxacin by 24% and 34%, respectively. It is unlikely that this can be of clinical significance in normal kidney function.

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).

With simultaneous application didanosine (only dosage forms containing aluminum or magnesium as a buffer) reduces absorption and reduces the effect of levofloxacin (the interval between doses should be at least 2 hours). With the simultaneous use of calcium salts slightly affect the absorption of levofloxacin.

Other

The results of clinical and pharmacological studies to study possiblepharmacokinetic interactions of levofloxacin with digoxin, glibenclamide, ranitidine, warfarin showed that, when used simultaneously with these drugs, the pharmacokinetics of levofloxacin does not change sufficiently to make it clinically important.

Special instructions:

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

When levofloxacin is used, cases of photosensitization are noted. To prevent its development, patients are not recommended to undergo strong sunlight or artificial ultraviolet irradiation during treatment and within 48 hours after discontinuation of therapy.

When there are signs of tendonitis levofloxacin immediately cancel.

Hospital infections caused by Pseudomonas aeruginosa (Pseudomonas aeruginosa), may require combined treatment. The prevalence of acquired resistance of strains of microorganisms can vary depending on the geographic region and over time. In this regard, information about the resistance to levofloxacin in a particular country is required.It is required to establish a microbiological diagnosis with the isolation of the pathogen and determine its sensitivity to levofloxacin.

There is a high probability that Staphylococcus aureus (methicillin-resistant strains) will be resistant to fluoroquinolones, including levofloxacin. therefore levofloxacin It is not recommended for the treatment of established or suspected infections caused by Staphylococcus aureus (methicillin-resistant strains) in the case that laboratory tests did not confirm the susceptibility of this microorganism to levofloxacin.

As with the use of other antibiotics, the use of levofloxacin, especially for a long time, can lead to increased multiplication of insensitive microorganisms (bacteria and fungi), which can cause changes in microflora, which is normally present in humans, and, accordingly, ket lead to the development of superinfection. Therefore, during the treatment, it is necessary to reevaluate the patient's condition and, in the case of the development of superinfection, appropriate measures should be taken.

If a patient experiences diarrhea at the foyer of taking levofloxacin,inhibiting peristalsis of the intestine, are contraindicated, since it is necessary to bear in mind the possibility of developing pseudomembranous colitis. Treatment with antibacterial agents leads to a change in the normal flora of the large intestine and can lead to increased growth of clostridia. If the diagnosis of "pseudomembranous colitis" is established, it is necessary to cancel levofloxacin and begin appropriate treatment.

Fluoroquinolones, including levofloxacin, can block neuromuscular activity and increase muscle weakness in patients with pseudo-paralytic myasthenia gravis (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 myasthenia gravis Not recommended.

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

In severe community-acquired pneumonia caused by Streptococcus pneumoniae, levofloxacin may not give the optimal therapeutic effect.

In patients who use fluoroquinolones, including levofloxacin, cases of sensory and sensorimotor axonal polyneuropathy affecting small and (or) large axons are recorded, leading to paresthesia, hyposthenia, dysesthesia and weakness. Symptoms may appear soon after the onset of use and be irreversible. If the patient develops symptoms of neuropathy, including pain, burning, tingling, numbness and / or weakness or other sensitivity disorders, including tactile, pain, temperature, vibration sensitivity and a sense of position, use of the drug Levofloxacin must be discontinued immediately.

Patients should immediately stop taking the drug and consult a doctor with serious, life-threatening hypersensitivity reactions, as well as with the first manifestations of the skin or mucous membranes.

There have been reports of cases of development of psychotic reactions, which in very rare cases progressed to the development of suicidal thoughts and behavioral disorders with self-harm.In case of occurrence of similar phenomena it is necessary to stop taking levofloxacin. Use with caution levofloxacin patients with psychoses or patients who have a history of mental illness.

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

As levofloxacin is 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 (see section "Method of administration and dose"). In the treatment of elderly patients, it should be borne in mind that patients of this group often have impaired renal function (see section "Method of administration and dose"). 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. In case of signs and symptoms of liver damage such as anorexia, jaundice, darkening of urine, itching and abdominal pain, it is necessary to stop treatment with the drug. Very rare cases of lengthening of the interval have been reported QT in patients who received fluoroquinolones, including levofloxacin.

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

There have been reports of cases of hyperglycaemia and hypoglycaemia, usually in patients with diabetes mellitus, receiving concurrent treatment with oral hypoglycemic drugs (eg, glibenclamide) or insulin preparations, with levofloxacin, and cases of hypoglycemic coma.

When using levofloxacin, it should be borne in mind that 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:

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions. Consideration should be given to the potential for the development of side effects such as dizziness, vertigo, drowsiness, and visual impairment. When these undesirable phenomena appear, one should refrain from performing the above activities.

Form release / dosage:

Tablets, film-coated 250 mg, 500 mg.

Packaging:

For 5 or 10 tablets in a planar cell pack of a polyvinylchloride film and aluminum foil.

For 50 or 100 tablets in a polymer can.

For 1 circuit pack or 1 can of polymer with instructions for use in a cardboard bundle.

Storage conditions:

In a dry, protected from light 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 expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003161

Date of registration:31.08.2015 / 27.06.2016

Expiration Date:31.08.2020

The owner of the registration certificate:RAFARMA, CJSC RAFARMA, CJSC Russia

Manufacturer: & nbsp

RAFARMA, JSC Russia

Information update date: & nbsp07.03.2018

Illustrated instructions

Instructions

Levofloxacin (Levofloxacin)