Luffy - instructions for use, doses, side effects, contraindications

Excipients (core): cellulose microcrystalline 31,600 mg / 63,200 mg; crospovidone 5,500 mg / 11,000 mg; hypromellose 9,000 mg / 18,000 mg; talc 3,000 / 6,000 mg; sodium stearyl fumarate 4,650 mg / 9,320 mg.

Film Sheath: hypromellose 5.060 mg / 10.110 mg; Macrogol 400 1,980 mg / 3,960 mg; talc 1,900 mg / 3,810 mg; titanium dioxide 0.440 mg / 0.860 mg; ferric oxide red oxide 0.0049 mg / 0.00982 mg; ferric oxide yellow oxide 0.00014 mg / 0.00028 mg.

Description:

Dosage of 250 mg

Double-convex capsule capsules coated with a film coating from light pink to pink, with a risk on both sides. On the cross-section the nucleus is from light yellow to yellow.

Dosage 500 mg

Double-convex capsule capsules coated with a pink film cover, with a risk on both sides. On the cross-section the nucleus is from light yellow to yellow.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A Fluoroquinolones

J.01.M.A.12 Levofloxacin

Pharmacodynamics:

Luffy is a synthetic antibacterial preparation of a broad spectrum of action from the group of fluoroquinolones. As the active substance contains levofloxacin - the left-handed isomer of ofloxacin.

Levofloxacin blocks DNA-gyrase and topoisomerase IV, disrupts supercoiling and cross-linking of DNA gaps. suppresses the synthesis of DNA, causes profound morphological changes in the cytoplasm, cell wall and membranes of microbial cells. Levofloxacin is active against most strains of microorganisms in vitro and in vivo.

In vitro:

Sensitive microorganisms (minimum inhibitory concentration (MIC) ≤2 mg / ml, inhibition zone> 17 mm):

- Aerobic Gram-positive microorganisms: Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus spp. (at t. h. Enterococcus faecalis), Listeria monocytogenes, Staphylococcus coagulase-negative methi-S (I) [methicillin-sensitive/ - moderately sensitive)], Staphylococcus aureus methi-S (methicillin-sensitive), Staphylococcus epidermidis methi-S (methicillin-sensitive), Staphylococcus spp. CNS (coagulase-negative), Streptococcus spp. (groups FROM and G), Streptococcus agalactiae, Streptococcus pneumoniae peni I / S / R, (penicillin-sensitive/ moderately sensitive/-resistant), Streptococcus pyogenes, Viridans streptococci peni-S / R (penicillin-sensitive/resistant strains).

- Aerobic gram-negative microorganisms: Acinetobacter baumannii, Acinetobacter spp., Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter cloacae, Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S / R (ampicillin-sensitive / -resistant), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella spp., Moraxella catarrhalis β+/β- (Producing and non-producing beta-lactamase), Morganella morganii, Neisseria gonorrhoeae non PPNG / PPNG (producing and non-producing penicillinase), 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., Propionibacterum spp., Veilonella spp.

- Other microorganisms: Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Legionella spp, Mycobacterium spp, Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

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

- Aerobic Gram-positive microorganisms: Corynebacterium urealiticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis methi-R (methicillin-resistant), Staphylococcus haemolyticus methi-R (methicillin-resistant).

- Aerobic Gram-negative microorganisms: Campylobacter jejuni, Campylobacter coli.

- Anaerobic microorganisms: Prevotella spp, Porphyromonas spp.

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

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

Pharmacokinetics:

Absorption

Levofloxacin is rapidly and almost completely absorbed from the gastrointestinal tract. Absolute bioavailability is 99-100%.

The maximum concentration (Stach) in blood plasma with the intake of 500 mg of levofloxacin is achieved after 1-2 hours and is 5.2 ± 1.2 μg / ml. The pharmacokinetics of levofloxacin is linear in the dosage range of 50 to 1000 mg. The equilibrium state of the concentration of levofloxacin in plasma with the administration of 500 mg of levofloxacin 1 or 2 times a day is reached within 48 hours.

On the 10th day of taking 500 mg of levofloxacin 1 time per day, the maximum concentration of levofloxacin in plasma was 5.7 ± 1.4 μg / ml, and the minimum concentration of levofloxacin (concentration before taking the next dose) in plasma was 0.5 ± 0.2 mcg / ml.

On the 10th day of taking 500 mg of levofloxacin twice daily the maximum concentration of levofloxacin in plasma was 7.8 ± 1.1 μg / ml, and the minimum concentration of levofloxacin (concentration before taking the next dose) in plasma was 3.0 ± 0.9 mcg / ml.

Distribution

The connection with plasma proteins is 30-40%. After a single and repeated administration of 500 mg of levofloxacin, the volume of distribution of levofloxacin is approximately 100 liters,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

After a single dose of 500 mg of levofloxacin, the maximum concentrations of levofloxacin in the bronchial mucosa and epithelial lining fluid were achieved within 1 h or 4 h and were 8.3 μg / g and 10.8 μg / g, respectively, with coefficients of penetration into the bronchial mucosa and the fluid of the epithelial lining as compared to the concentration in the plasma of 1.1-1.8 and 0.8-3, respectively.

After 5 days of ingestion with 500 mg of levofloxacin, the average concentrations of levofloxacin 4 hours after the last administration of the drug in the epithelial lining fluid were 9.94 μg / ml and in the alveolar macrophages - 97.9 mkg / ml.

Penetration into lung tissue

Maximum concentrations in the lung tissue after oral administration of 500 mg of levofloxacin were approximately 11.3 μg / g and were achieved 4 to 6 hours after taking the drug with penetration factors of 2-5 compared to the concentration in the plasma.

Penetration into the alveolar fluid

After 3 days of 500 mg of levofloxacin 1 time or 2 times per day maximum levofloxacin concentration in the alveolar fluid are achieved within 2-4 hours after dosing and were 4.0 and 6.7 .mu.g / ml, respectively, with a penetration coefficient, as compared with plasma concentrations of 1.

Penetration into bone tissue

Levofloxacin penetrates well into the cortical and cancellous bone, as in the proximal and in the distal femur, with a coefficient of penetration (bone tissue / plasma) 0.1-3. The maximum concentration of levofloxacin in the spongy bone of the proximal femur after receiving 500 mg of the drug inside was about 15.1 g / g (after 2 hours after administration).

Penetration into the cerebrospinal fluid

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Penetration into prostate tissue

After oral administration of 500 mg of levofloxacin 1 time per day for 3 days, the average concentration of levofloxacin in the prostate tissue was 8.7 μg / g, the average ratio of prostatic / plasma concentrations was 1.84.

Concentrations in the urine

Average concentrations in the urine 8-12 hours after ingestion of doses of 150, 300 and 600 mg of levofloxacin were 44 μg / ml, 91 μg / ml and 162 μg / ml, respectively.

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 blood plasma (the half-life period is 6-8 hours). Excretion mainly through the kidneys (more than 85% of the dose). The total clearance of levofloxacin after a single dose of 500 mg was 175 ± 29.2 ml / min.

Pharmacokinetics of individual 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 differences in pharmacokinetics associated with differences in creatinine clearance (CC).

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 renal failure after a single dose of 500 mg of levofloxacin:

Creatinine clearance [ml / min]	less than 20	20-49	50-80
Kidney clearance [ml / min]	13	26	57
T_1/2[h]	35	27	9

Indications:

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

- acute sinusitis;

- exacerbation of chronic bronchitis;

- community-acquired pneumonia;

- uncomplicated urinary tract infections;

- complicated urinary tract infections (including pyelonephritis);

- chronic bacterial prostatitis;

- infections of the skin and soft tissues;

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

- prevention and treatment of anthrax during airborne infection.

When using the drug should take into account the official national recommendations for the proper use of antibacterial drugs, as well as the sensitivity of pathogenic microorganisms in a particular country.

Contraindications:

- Dhypersensitivity to levofloxacin, other fluoroquinolones, or other components of the drug;

- epilepsy;

- pseudo-paralytic myasthenia gravis (myasthenia gravis);

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

- children and adolescents under 18 years of age (due to incomplete growth of the skeleton, since 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);

- the period of breastfeeding (you can not completely exclude the risk of destruction of cartilage points of bone growth in the child).

Carefully:

- In patients who are predisposed to developing seizures (in patients with previous lesions of the nervous system (CNS), patients simultaneously receiving drugs that lower the threshold of convulsive brain readiness, such as fenbufen, theophylline).

- In patients with latent or manifested deficiency of gluco-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 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 interval QT; with heart diseases (heart failure of myocardial infarction, bradycardia); while taking medications that can lengthen the interval QT (antiarrhythmic agents IA and class III, tricyclic antidepressants, macrolides, neuroleptics).

- In patients with diabetes mellitus receiving oral hypoglycemic drugs, for example, glibenclamide or insulin (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 mental illnesses in the anamnesis.

Pregnancy and lactation:

The drug is not suitable for use in pregnant women and women during breastfeeding.

Dosing and Administration:

Inside, before meals or in the interval between meals, without chewing, squeezed with enough liquid (0.5 to 1 cup). If necessary, tablets can be broken at risk.

The drug should be taken at least 2 hours before or 2 hours after taking antacid preparations containing magnesium and / or aluminum, iron salts or sucralfate (see.section "Interaction with other medicinal products"). Given that the bioavailability of levofloxacin when ingested is 99-100%, in the case of transfer of the patient from intravenous infusion of levofloxacin to the drug in a tablet dosage form, the treatment should be continued at the same dose that was used for intravenous infusion.

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

The dosage regimen is determined by the nature and severity of the infection, as well as by the suspected pathogen susceptibility.

Duration of treatment varies depending on the course of the disease.

Recommended dosage regimen and duration of treatment in patients with normal or moderately reduced renal function (creatinine clearance - more than 50 ml / min)

- acute sinusitis: 2 tablets Lufi 250 mg or 1 tablet Luffy 500 mg once a day (respectively 500 mg levofloxacin) - 10-14 days;

- exacerbation of chronic bronchitis: 2 tablets Lufi 250 mg or 1 tablet Luffy 500 mg once a day (respectively 500 mg levofloxacin) - 7-10 days;

- Community-acquired pneumonia: 2 tablets Lufi 250 mg or 1 tablet Luffy 500 mg 1-2 times a day (respectively 500-1000 mg levofloxacin) - 7-14 days;

- Uncomplicated urinary tract infections: 1 tablet Lufi 250 mg once a day (respectively 250 mg levofloxacin) -3 days;

- complicated urinary tract infections: 2 tablets Luffy 250 mg once a day or 1 tablet Luffy 500 mg once a day (respectively 500 mg levofloxacin) - 7-14 days.

- pyelonephritis: 2 tablets Luffy 250 mg once a day or 1 tablet Luffy 500 mg once a day (respectively 500 mg levofloxacin) - 7-10 days.

- chronic bacterial prostatitis: 2 lojfi tablets 250 mg or 1 tablet Lyufi 500 mg once a day (correspondingly 500 mg levofloxacin) - 28 days.

- skin and soft tissue infections: 2 lojfi tablets 250 mg or 1 tablet Lyufi 500 mg 1-2 times a day (respectively 500-1000 mg levofloxacin) - 7-14 days.

- complex treatment of drug-resistant forms of tuberculosis: 1 tablet Lyufi 500 mg 1-2 times a day (respectively 500-1000 mg levofloxacin) - up to 3 months.

- prevention and treatment of anthrax during airborne infection: 2 lojfi tablets 250 mg or 1 tablet Lyufi 500 mg (respectively 500 mg levofloxacin) - 1 time per day for up to 8 weeks.

Dosing regimen in patients with impaired renal function

Levofloxacin is excreted primarily through the kidneys, so when treating patients with impaired renal function, it is required to reduce the dose of the drug. Relevant information on this subject is contained in the following table:

Creatinine clearance	Dosing regimen of the drug Lufi
	recommended dose for CK> 50 ml / min 250 mg / 24 hour	recommended dose for CK> 50 ml / min 500 mg / 24 hour	recommended dose for CK> 50 ml / min 500 mg / 12 h
50-20 ml / min	first dose: 250 mg then: 125 mg / 24 hour	first dose: 500 mg then: 250 mg / 24 hour	first dose: 500 mg then: 250 mg / 12 hour
19-10 ml / min	first dose: 250 mg then: 125 mg / 48 hour	first dose: 500 mg then: 125 mg / 24 hour	first dose: 500 mg then: 125 mg / 12 hour
<10 ml / min (including hemodialysis and CAPD¹	first dose: 250 mg then: 125 mg / 48 hour	first dose: 500 mg then: 125 mg / 24 hour	first dose: 500 mg then: 125 mg / 24 hour

¹= after 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 required, a special dose selection is required, since Levofloxacin is metabolized in the liver only to a very small extent.

Dosage regimen in elderly patients

For elderly patients, there is no need to change the dosage regimen, except for cases when the creatinine clearance decreases to 50 ml / min and below.

Side effects:

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

Heart Disease

Rarely: sinus tachycardia, palpitation.

Frequency unknown (postmarketing data): interval elongation QT on ECG, ventricular arrhythmias, ventricular tachycardia, ventricular pirouette tachycardia, which can lead to cardiac arrest.

Violations of the blood and lymphatic system

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

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

The frequency is unknown (postmarketing data): pancytopenia (decrease in the number of all elements in the peripheral blood), agranulocytosis (absence or sharp decrease in the number of granulocytes in the peripheral blood), hemolytic anemia.

Disturbances from the nervous system

Often: headache, dizziness.

Infrequently: drowsiness, tremor, dysgeusia (distortion of taste).

Rarely: paresthesia, convulsions.

The frequency is unknown (postmarketing data): 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 .

Disturbances on the part of the organ of sight

Very rarely: visual impairments, such as the vagueness of the visible image.

The frequency is unknown: temporary loss of vision, uveitis.

Hearing disorders and labyrinthine disorders

Infrequently: Vertigo (feeling of deflection or twisting or own body or surrounding objects).

Rarely: ringing in the ears.

The frequency is unknown (postmarketing data): hearing loss, hearing loss.

Disturbances from the respiratory system, chest and mediastinal organs

Infrequently: dyspnea

The frequency is unknown (postmarketing data): bronchospasm, allergic pneumonitis.

Disorders from the gastrointestinal tract

Often: diarrhea, vomiting, nausea.

Infrequently: abdominal pain, indigestion, flatulence, constipation.

The frequency is unknown (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: an increase in the concentration of creatinine in the blood plasma.

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

Disturbances from the skin and subcutaneous tissues

Infrequent: rash, itching, hives, hyperhidrosis.

The frequency is unknown (postmarketing data): toxic epidermal necrolysis, Stevens-Johnson syndrome, exudative erythema multiforme, photosensitivity reactions (hypersensitivity to solar and ultraviolet radiation), leukocytoclastic vasculitis, stomatitis.

Reactions from the skin and mucous membranes can sometimes develop even after taking the first dose of the drug.

Disturbances from musculoskeletal system and connective tissue

Infrequent: arthralgia, myalgia

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

The frequency is unknown (postmarketing data): rhabdomyolysis, tendon rupture (eg Achilles tendon). This side effect can be observed within 48 hours after the start of treatment and can be bilateral, a rupture of ligaments and muscles, and arthritis.

Disorders from the metabolism and nutrition

Infrequently: anorexia.

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

The frequency is unknown: hyperglycemia, hypoglycemic coma.

Infectious and parasitic diseases

Infrequently: fungal infections, development of resistance of pathogenic microorganisms.

Vascular disorders

Rarely: lowering blood pressure.

General disorders

Infrequently: asthenia.

Rarely: pyrexia (fever).

The frequency is unknown: pain, including in the back, chest and extremities.

Immune system disorders

Rarely: angioedema.

The frequency is unknown (postmarketing data): anaphylactic shock, anaphylactoid shock.

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

Disturbances from the liver and bile ducts

Often: increased activity of "hepatic" enzymes in the blood (for example, alanine aminotransferase (ALT), aspartate aminotransferase (ACT), alkaline phosphatase, gamma-glutamyltransferase (GGT)).

Infrequent: increased bilirubin concentration in the blood.

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

Disorders of the psyche

Often: insomnia.

Uncommon: a feeling of anxiety, anxiety, confusion.

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

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

Other possible undesirable effects related to all fluoroquinolones

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

Overdose:

Symptoms: nausea, erosive lesions of the mucous membrane of the gastrointestinal tract, lengthening of the interval QT, impaired consciousness, including confusion, dizziness, convulsions, hallucinations, tremors.

Treatment: In case of an overdose, careful monitoring of the patient, including ECG monitoring, is required. Treatment is symptomatic. It shows gastric lavage and antacid administration for the protection of the gastric mucosa. Levofloxacin is not excreted by dialysis (hemodialysis, peritoneal dialysis and permanent peritoneal dialysis). The specific antidote is unknown.

Interaction:

Interactions requiring caution

With iron salts, antacid agents containing magnesium and / or aluminum

It is recommended that preparations containing divalent or trivalent cations such as iron salts, antacid agents containing magnesium and / or aluminum, didanosine (only dosage forms containing aluminum or magnesium as a buffer) should be taken at least 2 hours before or 2 hours after taking Lufi tablets. Calcium salts have a minimal effect on the absorption of levofloxacin when ingested.

With sucralfate

The effect of Lufi's preparation is significantly weakened by the simultaneous use of sucralfate (a means for protecting the gastric mucosa). 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, lowering the threshold of convulsive readiness 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 that reduce 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 tsametidine

With the simultaneous use of drugs that disrupt the renal tubular secretion of levofloxacin, such as probenecid and cimetidine, care should be taken, 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 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.

With glucocorticosteroids

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

With drugs that extend the QT interval

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 from 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 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.

Patients who are predisposed to develop seizures

Like other fluoroquinolones, levofloxacin should be used with caution in patients with predisposition to developing seizures: in patients with previous lesions of the CNS (stroke, severe craniocerebral trauma), in patients receiving concomitant medications,lowering the threshold of convulsive brain readiness, such as fenbufen and other non-steroidal anti-inflammatory drugs, or other drugs such as theophylline.

Pseudomembrane colitis

Developed during or after treatment with levofloxacin, diarrhea, especially severe, persistent and / or with blood, may be a symptom of pseudomembrane 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. 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 the drug and begin appropriate treatment of the affected tendon, for example, providing him with sufficient immobilization.

Hypersensitivity reactions

Levofloxacin can cause serious, potentially fatal, hypersensitivity reactions (including angioedema, anaphylactic shock), even after taking the first dose of the drug. In these cases, stop levofloxacin and immediately consult a doctor.

Severe bullous reactions

When levofloxacin was used, cases of severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, were observed. 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 cases of liver necrosis, including the development of fatal liver failure, with the use of levofloxacin, mainly in patients with severe underlying diseases (eg sepsis).The patient should be informed that if symptoms of hepatic insufficiency (anorexia, jaundice, darkening of the urine, itching, abdominal pain) appear, discontinue treatment and consult a doctor.

Patients with renal insufficiency

As levofloxacin excreted mainly by the kidneys, in patients with impaired renal function required mandatory monitoring of kidney function, 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

When levofloxacin is used, cases of photosensitization are noted. To prevent its development, patients are not recommended to undergo, without special need, a strong sunlight or artificial ultraviolet radiation (for example, visit a solarium) during treatment and 48 hours after discontinuation of therapy.

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 the 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 it develops during the treatment of superinfection, appropriate measures should be taken.

QT interval extension

Lengthening of the interval has been reported QT when using levofloxacin in some patients.

When using levofloxacin, care should be taken in patients with predisposing to lengthen the interval QT factors: uncorrelated electrolyte disorders (hypokalemia, hypomagnesemia); congenital lengthening syndrome QT; heart disease (heart failure, myocardial infarction, bradycardia); use with other drugs that extend the interval QT (antiarrhythmic agents IA and class III, tricyclic antidepressants, macrolides, neuroleptics). Elderly patients and women may be more sensitive to drugs that extend the interval QT. Therefore, it should be used with caution in them levofloxacin.

Patients with deficiency of glucose-6-phosphate dehydrogenase

Patients with 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.

Hypoglycemia and hyperglycaemia

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

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 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 gravis)

Fluoroquinolones, including levofloxacin, can block neuromuscular activity and 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 patients with established diagnosis of myasthenia gravis gravis 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 anthracisreceived in in vitro studies and 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

Reactions from the psyche may occur even after the first use of fluoroquinolones, including levofloxacin. In very rare cases, depression or psychotic reactions progress to the occurrence of suicidal thoughts and behavior with a tendency to self-harm, including suicidal attempts.In case of development of such reactions in patients it is necessary to cancel levofloxacin and take the necessary measures. Caution should be exercised when using levofloxacin in patients with psychoses and patients with mental illness in the anamnesis.

Disturbances on the part of the organ of sight

If there is a disturbance on the part of the eye, consultation of the ophthalmologist is necessary.

With the simultaneous use of indirect anticoagulants and levofloxacin, regular monitoring of blood clotting indices is necessary.

The ability of levofloxacin to suppress growth Mycobacterium spp. can lead to false-negative results in microbiological diagnosis of tuberculosis.

In patients receiving levofloxacin, false-positive results can be obtained when determining opioids in urine.

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

Such side effects of levofloxacin as dizziness or vertigo, drowsiness, or visual impairment can impair the ability of patients to drive and engage in other potentially dangerous activities requiring increased attention and speed of psychomotor reactions.In the case of such symptoms, patients are advised to refrain from performing these activities.

Form release / dosage:

Film coated tablets, 250 mg and 500 mg.

Packaging:

5 tablets per blister of PVC film and aluminum foil (PVC / Al).

1 blister with instructions for use in a cardboard package.

Storage conditions:

Store in a 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-003664

Date of registration:06.06.2016

Expiration Date:06.06.2021

The owner of the registration certificate:Ipka Laboratories Ltd.Ipka Laboratories Ltd. India

Manufacturer: & nbsp

IPCA LABORATORIES, Ltd. India

Representation: & nbspIPKA LABORATORIES LTD. IPKA LABORATORIES LTD. India

Information update date: & nbsp21.03.2018

Illustrated instructions

Instructions

Luffie (Luffie)