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

Active substance: levofloxacin hemihydrate, which is equivalent to levofloxacin - 256.23 mg (250.00 mg); 512.46 mg (500.00 mg); 768.69 mg (750.00 mg).

Excipients: cellulose microcrystalline - 2.90 mg, 44.69 mg, 67.04 mg; crospovidone - 12.30 mg, 7.85 mg, 11.77 mg; sodium stearyl fumarate - 5.00 mg, 1.41 mg, 12.27 mg; Croscarmellose sodium - 15.38 mg, 6.15 mg, 8.30 mg; silicon dioxide colloid - 9.23 mg, 15.38 mg, 23.06 mg; maltodextrin-6.15 mg, 24.60 mg, 27.68 mg; magnesium stearate - 0.31 mg, 2.46 mg, 3.69 mg.

Sheath: Reward orange 20A2300I8 (OPADRY Orange 20A2300I8) - 7,500 mg, 15,000 mg, 22,500 mg [hydroxypropylmethylcellulose 2910 / hypromellose 6 cP (E464) -3,300 mg, 6,600 mg, 9,900 mg; titanium dioxide (E171) - 0.688 mg, 1.375 mg, 2.063 mg; talc - 1.575 mg, 3.150 mg, 4.725 mg; giprolose (hydroxypropylellogallose, clocel EE) (E463) 1.925 mg, 3.851 mg, 5.776 mg; dye sunset sunset yellow (E 110) - 0.012 mg, 0.024 mg, 0.036 mg.

Description:

Dosage of 250 mg: tablets covered with a film membrane pinkish-orange color, round biconcave. On a cut from white to light yellow color.

Dosage 500 mg and 750 mg: tablets, covered with a film membrane pinkish-orange color, oval biconvex. On a cut from white to light yellow color.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A Fluoroquinolones

J.01.M.A.12 Levofloxacin

Pharmacodynamics:

Levofloxacin 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. inhibits the synthesis of DNA, causes profound morphological changes in the cytoplasm, cell wall and membranes of sensitive microorganisms.

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

In vitro

Sensitive microorganisms (Ml IK < 2 mg / l; zone of inhibition> 17 mm)

Aerobic Gram-positive microorganisms:

Bacillus anthracis, Corynebacterium diphtheria, Corynebacterium jeikeium, Enterococcus spp. Enterococcus faecalis, Listeria monocytogenes, Staphylococcus coagulase-negative methi-S (I) (coagulase-negative methicillin-sensitive/moderate sensitive strains, at Tom number of methicillin-sensitive strains Staphylococcus aureus methi-S (methicillin-sensitive), Staphylococcus epidermidis methi-S (methicillin-sensitive), Staphylococcus spp. CNS (coagulase-negative), Streptococci groups FROM and G, Streptococcus agalactiae, Streptococcus pyogenes. Streptococcus pneumonia peni I / S / R (penicillin-sensitive/moderately sensitive / resistant), penicillin-sensitive / resistant strains Viridans streptococci peni-S/R).

Aerobic Gram-negative microorganisms:

Acinetobacter spp. (at t. h. Acinetobacter baumannii), Actinobacillus actinomycetemcomitans, Citrobacter freundii. Eikenella corrodens, Enterobacter spp. (at t. h. Enterobacter aerogenes, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus spp. (at g. h. Haemophilus ducreyi, Haemophilus parainfluenzae, ampicillin sensitive/resistant strains Haemophilus influenzae ampi-S / R ), Helicobacter pylori, Klebsiella spp. (at t. h. Klebsiella oxytoca, Klebsiella pneumoniae), Moraxella catarrhalis [)+/()- (producing and non-reducing beta-lactamase strains), Morganella morganii, Neisseria meningitidis. Neisseria gonorrhoeae non PPNG / PPNG (non-reducing and producing penicillinase), Pasteurella spp. (at t. h. Pasteurella cam's, Pasteurella dagmatis, Pasteurella multocida), Proteus mirabilis, Proteus vulgaris, Providencia spp. (at t. h. Providencia rettgeri, Providencia stuartii). Pseudomonas spp. (incl. Pseudomonas aeruginosa - hospital infections caused by Pseudomonas aeruginosa, may require combined treatment), Serratia spp. (at t. h. Serratia marcescens), Salmonella spp.

Anaerobic microorganisms:

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

Moderately sensitive microorganisms (MIC = 4 mg / L, inhibition zone = 16-14 mm)

Aerobic Gram-positive microorganisms:

Corynebacterium urealylicum. Corynebacterium xerosis, Enterococcus Faecium, Staphylococcus epidermidis methi-R (methicillin-resistant strains), Staphylococcus haemolyticus methi- R (methicillin-resistant strains).

Aerobic Gram-negative microorganisms: Campylobacter jejuni/coli.

Anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

Stable microorganisms (IPC ≥ 8 mg / L, inhibition zone ≤13 mm)

Aerobic Gram-positive microorganisms:

Staphylococcus spp. (coagulase-negative methicillin-resistant strains, including methicillin-resistant strains Staphylococcus aureus).

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 removal 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.

The clinical effectiveness (effectiveness in clinical trials in the treatment of infections caused by microorganisms listed below):

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. Others:

Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae.

Pharmacokinetics:

Absorption

After oral administration levofloxacin quickly and almost completely absorbed from the gastrointestinal tract. The intake of pesticides has little effect on the speed and completeness of absorption. Absolute bioavailability with oral administration is 99-100%. The maximum concentration in the plasma is achieved after 1-2 hours and for a dose of levofloxacin 250 mg, 500 mg and 750 mg is equal to 2.8 ug / ml, 5.2 ug / ml and 8.0 ug / ml, respectively. Pharmacokinetics of levofloxacin is linear in the range of 50 m to 1000 mg. After administration of a single dose or multiple dose absorbed drug amount directly proportional to the dose. The equilibrium concentration in plasma when receiving 500 mg of levofloxacin I or 2 times a day is reached after 48 hours.

Distribution

The average volume of distribution of levofloxacin varies from 74 to 112 liters.Binding to plasma proteins is 30-40%. It penetrates well into organs and tissues: bronchial mucosa, epithelial lining fluid, alveolar macrophages (concentration in lung tissues is 2-5 times higher than plasma concentration), pulmonary tissue, bone tissue, genitourinary system, polymorphonuclear leukocytes.

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 oral administration levofloxacin is relatively slowly excreted from the plasma (half-life of 6-8 hours). It is excreted from the body mainly by the kidneys through glomerular filtration and tubular secretion. In the unchanged form, 70% of the dose taken internally is excreted within 24 hours and 87% in 48 hours. 4% of the ingested dose is excreted intestine within 72 hours.

Pharmacokinetics separate patient groups

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

With renal failure, the pharmacokinetics of levofloxacin varies.As the kidney function decreases, excretion through the kidneys and kidney clearance decreases, and the elimination half-life increases.

Pharmacokinetics in elderly patients does not differ from that of young nazis, except for differences related to creatinine clearance.

Indications:

Bacterial infections in adults that are sensitive to levofloxacin:

- Acute bacterial sinusitis;

- exacerbation of chronic bronchitis;

- community-acquired pneumonia;

uncomplicated urinary tract infections;

- Complicated urinary tract infections (including acute pyelonephritis);

- chronic bacterial prostatitis;

- infections of the skin and soft tissues (including festering atheromas, abscess, furunculosis);

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

- prevention and treatment of anthrax during airborne infection.

Contraindications:

- Hypersensitivity to levofloxacin, other fluoroquinolones, or other components of the drug in the anamnesis;

- epilepsy;

- pseudo-paralytic myasthenia gravis (myasthenia gravis);

- tendon lesions associated with taking a fluoroquinolone in a history;

- children and adolescents under 18 years of age (due to incomplete growth of the skeleton, as the risk of damage to the cartilaginous growth points can not be completely excluded);

- Pregnancy (the risk of destruction of the cartilage growth points in the fetus can not be completely ruled out);

- lactation period (the risk of destruction of cartilage points of bone growth in a child can not be completely ruled out).

Carefully:

- predisposition to convulsive reactions (in patients with previous lesions of the central nervous system (CNS), in patients simultaneously receiving drugs that reduce the threshold of convulsive readiness of the brain (fenbufen, theophylline));

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

- renal dysfunction (monitoring of renal function, as well as correction of dosing regimens, see "Dosage and administration");

- in patients with known risk factors for lengthening the interval QT: in elderly patients (over 65 years), in female patients, in patients with uncorrected electrolyte disorders (hypokalemia, hypomagnesemia); with the syndrome of congenital lengthening interval QT; in patients with heart failure, myocardial infarction, bradycardia; while taking medications that extend the interval QT (antiarrhythmic IA and III classes, tricyclic antidepressants, neuroleptics, macrolides);

- in patients with diabetes mellitus receiving oral hypoglycemic drugs (increased risk of hypoglycemia);

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

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

Pregnancy and lactation:

Levofloxacin is contraindicated for use in pregnant women and women during breastfeeding.

Dosing and Administration:

Inside once or twice a day (every 24 or 12 hours). Tablets should be taken without chewing and drinking with a sufficient amount of water (0.5 to 1 cup). The drug can be taken before meals or at any time between meals, as eating does not affect the absorption of the drug.

The drug should be taken at least 2 hours before or 2 hours after taking medications containing magnesium and / or aluminum, iron, zinc or sucralfate (see section "Interaction with other drugs").

Given that the bioavailability of levofloxacin when receiving levofloxacin tablets is 99-100%, in the case of transfer from the patient by intravenous infusion at the reception levofloxacin tablets should continue treatment at the same dose as that used in intravenous infusion (see. "Pharmacokinetics" section) .

Skipping admission of one or several doses of the drug

If you accidentally missed taking the drug, you should take the next dose as soon as possible and continue taking the drug according to the recommended dosage regimen.

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.

Adult patients with a normal or moderately reduced function of the nights (creatinine clearance more than 50 ml / min) should be applied in accordance with the data presented in the table schemes:

Infection	Dose, mg	Multiplicity of reception in a day	Duration of treatment, days
Acute bacterial sinusitis	500	1	10-14
Acute bacterial sinusitis	750	1	5
Exacerbation of chronic bronchitis	500	1	7-10
Community-acquired pneumonia	500	1-2	7-14
Community-acquired pneumonia	750	1	5
Uncomplicated urinary tract infections Putuey	250	1	3
Complicated urinary tract infections Putuey	500	1	7-14
Complicated urinary tract infections, including acute pyelonephritis	750	1	5
Pyelonephritis	500	1	7-10
Chronic bacterial prostatitis	500	1	28
Uncomplicated infections of the skin and subcutaneous	500	1-2	7-10
Complicated infections of the skin and subcutaneous tissue	750	1	7-14
Tuberculosis (as part of complex therapy, drug-resistantandforms)	500	1-2	up to 3 months
Prevention and treatment of anthrax in case of airborne infection	500	1	up to 8 weeks

* This regimen is indicated for the treatment of community-acquired pneumonia caused by Streptococcus pneumoniae. Haemophilus influenzae. Haemophilus parainfluenzae, Mycoplasma pneumoniae. Chlamydia pneumoniae.

** This regimen is indicated for the treatment of urinary tract infections caused by Escherichia coli. Klebsiella pneumoniae, Proteus mirabilis and acute pyelonephritis caused by Escherichia coli, including cases with concomitant bacteremia.

Correction of the dose of levofloxacin in adult patients with impaired renal function (creatinine clearance less than 50 ml / min).

Dose with normal kidney function every 24 hours	Creatinine clearance from 20 to 49 ml / min	Creatinine clearance from 10 to 19 ml / min	Creatinine clearance less than 10 ml / min (including hemodialysis or continuous ambulatory peritoneal dialysis)
750 mg	750 mg every 48 hours	The initial dose of 750 mg, followed by 500 mg every 48 hours	The initial dose of 750 mg, followed by 500 mg every 48 hours
500 mg	The initial dose of 500 mg, followed by 250 mg every 24 hours	The initial dose of 500 mg, followed by 250 mg every 48 hours	The initial dose of 500 mg, followed by 250 mg every 48 hours
250 mg	No dosage adjustment required	250 mg every 48 hours for uncomplicated infections urinary tract dose adjustment is not required	No information on dose adjustment

After hemodialysis or permanent outpatient peritoneal dialysis, additional doses are not required.

If there is a violation of the liver function, dose adjustment is not required, as the volume of metabolism of levofloxacin in the liver is limited.

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

Side effects:

The following side effects are presented according to the following gradations: often (≥ 1/10), often (≥ 1/100 to <1/10), infrequently (≥ 1/1000 to <1/100), rarely (≥ 1/10000 to <1/1000), very rarely (<1/10000), frequency unspecified (it is not possible to determine the frequency of occurrence according to available data).

From the nervous system: often - headache, dizziness; infrequently - drowsiness, tremor, dysgeusia (perversion of taste); rarely - paresthesia, convulsions (see section "Special instructions"); unspecified frequency - peripheral sensory neuropathy, peripheral sensory-motor neuropathy, dyskinesia, extrapyramidal disorders, loss of taste sensations, parosmia (odor disorder, especially subjective sense of smell, objectively absent), including loss of smell, fainting, benign intracranial hypertension.

Mental Disorder: often - insomnia; infrequently - a feeling of anxiety, anxiety, confusion; rarely - mental disorders (eg, hallucinations, paranoia), depression, agitation, sleep disturbance, nightmares; frequency, unspecified - violation of the psyche with a violation of the behavior with self-harm, including suicidal thoughts and suicidal attempts.

From the side of the organ of vision: very rarely - visual impairment, such as the vagueness of the visible image; Unspecified frequency - transient loss of vision.

From the side of the hearing organ and labyrinthine disorders: infrequently - vertigo (feeling of deviation or twisting of one's own body or surrounding objects); rarely - ringing in the ears; unspecified frequency - hearing loss, hearing loss.

From the cardiovascular system: rarely - sinus tachycardia, palpitations, lowering blood pressure; unspecified frequency - interval lengthening QT, ventricular arrhythmias, ventricular tachycardia, ventricular pirouette tachycardia, which can lead to cardiac arrest (see sections "Overdose", "Special instructions").

From the side of the blood and lymphatic system: infrequently - eosinophilia, leukopenia; rarely - neutropenia, thrombocytopenia; Unspecified frequency - pancytopenia, agranulocytosis, hemolytic anemia.

From the gastrointestinal tract: often - nausea, vomiting, diarrhea; infrequently - abdominal pain, indigestion, flatulence, constipation; Unspecified frequency - hemorrhagic diarrhea, which in very rare cases can be a sign of enterocolitis, including pseudomembranous colitis (see section "Special instructions"), pancreatitis.

From the liver and bile ducts: often - increased activity of alanine aminotransferase,aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase; infrequent increase in bilirubin concentration; Unspecified frequency - 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.

From the respiratory system, organs of the thorax and mediastinum: infrequently - shortness of breath; Unspecified frequency - bronchospasm, allergic pneumonitis.

From the side of metabolism and nutrition: infrequently - anorexia; rarely - hypoglycemia (increased appetite, sweating, trembling, nervousness); unspecified frequency - hyperglycemia, hypoglycemic coma (section "Special instructions").

From the osteomuscular system and connective tissue: infrequently - arthralgia, myalgia; rarely - the defeat of tendons (for example, the Achilles tendon), including tendonitis, muscle weakness, which can be dangerous in patients with pseudo-paralytic myasthenia gravis (see the section "With caution"); Unspecified frequency - rhabdomyolysis, tendon rupture (eg Achilles tendon).This side effect can be observed within 48 hours after the start of treatment and can be bilateral in nature), ligament rupture, muscle rupture, arthritis (see section "Special instructions").

From the side of the kidneys and urinary tract: infrequently hypercreatinemia; rarely acute renal failure (eg, due to the development of interstitial nephritis).

From the skin and subcutaneous tissues: infrequently - a rash, itching, hives, hyperhidrosis; unspecified frequency - malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), photosensitivity reactions, leukocytoclastic vasculitis, stomatitis, exudative erythema multiforme. Reactions from the skin and mucous membranes, anaphylactic and anaphylactoid reactions can sometimes develop even after taking the first dose of the drug.

Infectious and parasitic diseases: infrequently - fungal infections, development of resistance of pathogenic microorganisms.

From the immune system: rarely - angioedema; Unspecified frequency - anaphylactic shock, anaphylactoid shock.

Anaphylactic and anaphylactoid reactions can sometimes be warmed up even after taking the first dose of the drug.

General disorders: infrequently - asthenia; rarely pyrexia (fever); Unspecified frequency - pain (including pain in the back, chest and extremities).

Other possible undesirable effects related to all fluoroquinolones: very rarely - porphyria attacks in patients with porphyria.

Overdose:

Symptoms: disorders of consciousness, including confusion, dizziness, convulsions, possible development of nausea, erosive lesions of the mucous membranes of the gastrointestinal tract, lengthening of the interval QT, hallucinations, tremor.

In case of an overdose, careful monitoring of the patient, including ECG monitoring, is required.

Treatment: symptomatic. In case of acute overdosage, gastric lavage and administration of antacids are indicated to protect the gastric mucosa. There is no specific antidote, dialysis is ineffective.

Interaction:

Interactions requiring caution

With preparations containing magnesium, aluminum, iron and zinc, didanosine

Preparations containing divalent or trivalent cations, such as zinc or iron salts (medicines for the treatment of anemia), magnesium and / or aluminum-containing preparations (such as antacids), didanosine (only dosage forms containing aluminum or magnesium as a buffer), it is recommended to take at least 2 hours before or 2 hours after taking the drug Levofloxacin.

Calcium salts have a minimal effect on the absorption of levofloxacin when ingested.

With sucralfate

The effect of levofloxacin is significantly weakened by simultaneous application of sucralfate. Patients receiving levofloxacin and sucralfate, it is recommended to take sucralfate 2 hours after taking levofloxacin.

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

The pharmacokinetic interaction of levofloxacin with theophylline has not been revealed. However, with simultaneous use of quinolones and theophylline, non-steroidal anti-inflammatory drugs and other drugs,reducing the threshold of convulsive readiness of the brain, possibly 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

In patients treated with levofloxacin in combination with indirect anticoagulants (eg, warfarin), there was an increase in prothrombin time / international normalized ratio and / or development of bleeding, including severe bleeding. 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, caution should be used, especially in patients with renal insufficiency. Cimetidine 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.

With cyclosporine

Levofloxacin increases the half-life of cyclosporine by 33%. Gak as it is clinically insignificant increase, the correction dose cyclosporine when applied simultaneously with levofloxacin is required.

With glucocorticosteroids

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

With drugs that extend the range of OT

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

The results of the clinical and pharmacological studies but explore possible pharmacokinetic interactions of levofloxacin with digoxin, glibenclamide, ranitidine, warfarin have shown that the pharmacokinetics of levofloxacin while the use of these drugs varies ns sufficiently to GR had clinical significance.

Special instructions:

Hospital infections caused by Pseudomonas aeruginosa (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 or in the ineffectiveness of treatment, a microbiological diagnosis should be made, isolating the pathogen and determining its sensitivity to levofloxacin.

Methicillin-resistant golden streptococcus

There is a high probability that methicillin-resistant golden streptococcus will be resistant to fluoroquinolones, including levofloxacin. therefore levofloxacin It is not recommended for treatment of established or suspected infections caused by methicillin-resistant golden streptococcus, if laboratory tests have not confirmed the susceptibility of this microorganism to levofloxacin.

Patients who are predisposed to develop seizures

Like other quinolones, levofloxacin should be used with great care in patients with a predisposition to convulsions.Such patients include patients with previous CNS lesions, 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 (see section "Interaction with other drugs").

Pseudomembranous colitis

Developed during or after levofloxacin treatment, diarrhea, especially severe, persistent and / or with blood, may be a symptom of pseudomembranous colitis caused by Clostridium difficile. In case of suspected development of pseudomembranous colitis, treatment with levofloxacin should be stopped 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. Patients of advanced age are more predisposed to the development of tendonitis. The risk of rupture of tendons can increase with simultaneous administration of glucocorticosteroids. If suspected of tendonitis should immediately stop treatment with the drug Levofloxacin and begin appropriate treatment of the affected tendon, for example, by providing him with sufficient immobilization (see the sections "Contraindications" and "Side effect").

Hypersensitivity reactions

Levofloxacin can cause serious, potentially fatal, hypersensitivity reactions (angioedema, anaphylactic shock), even with the use of initial doses (see the "Side effect" section). Patients should immediately stop taking the drug 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 (see section "Side effect"). In the case of any reactions from the skin or mucous membranes, the patient should immediately consult a doctor and do not continue treatment until he consults.

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, for example, with sepsis (see section "Side effect"). 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 by the kidneys, patients with impaired function of the night required mandatory monitoring of kidney function, 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 suffer from 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 hoursAfter the end of treatment with levofloxacin, it is necessary to undergo, without special need, strong sunlight or artificial ultraviolet irradiation (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 multiplication of insensitive microorganisms (bacteria and fungi), which can cause changes in microflora, which is normally present in humans, which can lead to the development of superinfection . 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 who received 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 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.

Older 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 (see the sections "With caution", "Method of administration and dose", "Side effect", "Overdose" and "Interaction with other medicinal products").

Patients with glucose-6-phosphate dehydrogenase deficiency

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

Hypo-and hyperglycemia (dysglycemia)

As with the use of other quinolones, when levofloxacin was used, there were cases of hypo- and hyperglycemia, usually 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 mellitus require careful monitoring of the concentration of glucose in the blood (see section "Side effect").

Peripheral neuropathy

In patients receiving fluoroquinolones, including levofloxacin, sensory and sensory-motor peripheral neuropathy was noted, the onset of which can be rapid. If the patient develops 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 post-registration period observed adverse reactions, including pulmonary failure, requesting a ventilator, and death that was associated with the use of fluoroquinolones in patients with 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).

Application in the airborne route of infection with anthrax

The use of levofloxacin in humans according to this indication is based on sensitivity data Bacillus anthracis, obtained in studies in vitro and in experimental studies conducted on animals, as well as on limited data on the use of levofloxacin in humans. 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 on 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 taking a single dose of levofloxacin (see the section "Side effect")). 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 required (see section "Adverse Effects").

Impact and 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:

Caution should be exercised when driving vehicles and engaging in other potentially hazardous activities, as some side effects of levofloxacin, such as dizziness, drowsiness, and visual impairments, can adversely affect the ability to drive vehicles and perform potentially hazardous activities requiring increased concentration and the speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 250 mg, 500 mg, 750 mg.

Packaging:

By 3, 5, 7 or 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

1 contour cell package of 3, 5, 7, 10 tablets or 2 contour packs of 5 or 7 tablets together with instructions for medical use are placed in a pack of cardboard.

Storage conditions:

At a temperature not exceeding 25 ⁰FROM.

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-003009

Date of registration:01.06.2015

The owner of the registration certificate:PHARMSTANDART-TOMSKHIMFARM, OJSC PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Manufacturer: & nbsp

PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Information update date: & nbsp28.09.2015

Illustrated instructions

Instructions

Levofloxacin (Levofloxacin)