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

Ingredients	Amount in tablet, mg
	250 mg		500 mg
Active substance:
Levofloxacin hemihydrate in terms of levofloxacin	250,0		500,0
Excipients:
Starch		21,275	37,55
Microcrystalline cellulose		20,00	40,00
Povidone-K30		5,00	10,00
Silica colloidal dioxide		2,50	5,00
Sodium carboxymethyl starch		10	20
Talc		2,50	5,00
Magnesium stearate		2,50	5,00
Film Sheath:
Hypromellose-15 thousand		6,50	13,00
Propylene glycol		1,50	3,00
Talc		0,50	1,00
Titanium dioxide		1,15	2,30
Iron Oxide Red Dye Oxide		0,20	0,40
Dye iron oxide yellow		0,15	0,30

Description:

250 mg tablets:

Tablets of light beige color biconcave, oblong form (caplets), covered with a film membrane, with a fault line on one side.

Tablets 500 mg:

Tablets of beige color biconcave, oblong form (caplets), film-coated, with a fault line on one side.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A Fluoroquinolones

J.01.M.A.12 Levofloxacin

Pharmacodynamics:

The preparation Lefokcin is a synthetic antibacterial preparation of a wide spectrum of action from the group of fluoroquinolones containing as an active substance levofloxacin - the left-handed isomer of ofloxacin.

Levofloxacin blocks the DNA-gyrase and topoisomerase IV,violates supercoiling and cross-linking of DNA gaps, inhibits DNA synthesis, causes profound morphological changes in the cytoplasm, cell wall and membranes of microbial cells.

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

In vitro

Sensitive microorganisms (MIC of ≤ 2 mg / ml, inhibition zone ≥ 17 mm)

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

- Aerobic Gram-negative microorganisms: Acinetobacter baumannii, Acinetobacter spp., Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter cloacae, Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S/R (ampicillin-sensitive / -resistant), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella spp., Moraxella catarrhalis |3+/(3- (producing and non-producing beta-lactamases), Morganella morganii, Neisseria gonorrhoeae non PPNG/PPNG (non-producing and 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, Propionibacterium spp., Veillonella spp.

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

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

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

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

- Anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

Resistant to levofloxacin microorganisms (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

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 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.

Clinical efficacy (effectiveness in clinical trials in the treatment of infections caused by the 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.

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

Pharmacokinetics:

Absorption

Levofloxacin is quickly and almost completely absorbed after ingestion, eating food has little effect on its absorption. Absolute bioavailability when ingested is 99-100%. After a single dose of 500 mg of levofloxacin, the maximum concentration in the blood plasma (C_m_Oh) is achieved within 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 the blood plasma with the administration of 500 mg of levofloxacin 1 or 2 times a day is reached within 48 hours.

On the 10th day of taking Lefokcin 500 mg once a day C_m_Ohlevofloxacin was 5.7 ± 1.4 μg / ml, and the minimum concentration of levofloxacin (concentration before taking the next dose) (C_min) in blood plasma was 0.5 ± 0.2 μg / ml.

On the 10th day of taking Lefokcin 500 mg twice a day C_ma_xwas 7.8 ± 1.1 μg / ml, a C_min- 3.0 ± 0.9 μg / ml.

Distribution

The connection with serum proteins is 30-40%. After a single and repeated administration of 500 mg of levofloxacin, the volume of distribution of levofloxacin is, on the average, 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 oral intake of 500 mg of levofloxacin, the maximum concentrations of levofloxacin in the bronchial mucosa and epithelial lining fluid were achieved within 1 hour or 4 hours and were 8.3 μg / g and 10.8 μg / ml, respectively,with coefficients penetration into bronchial mucosa and epithelial lining fluid, as compared with the concentration in the blood plasma components of 1.1-1.8 and 0.8-3, respectively. After 5 days of ingestion of 500 mg of levofloxacin, the average concentrations of levofloxacin 4 hours after the last drug intake in the epithelial lining fluid were 9.94 μg / ml and in alveolar macrophages 97.9 μg / ml.

Penetration into lung tissue

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

Penetration into the alveolar fluid

After 3 days of taking 500 mg of levofloxacin 1 or 2 times a day, the maximum concentrations of levofloxacin in the alveolar fluid were reached 2-4 hours after taking the drug and were 4.0 and 6.7 μg / ml, respectively, with a penetration coefficient of 1, in comparison with the concentrations in the blood plasma.

Penetration into bone tissue

Levofloxacin well adheres to cortical and spongy bone tissue, both in the proximal and distal parts of the femur, with a coefficient of penetration (bone tissue / blood plasma) of 0.1-3.The maximum concentrations of levofloxacin in the spongy bone of the proximal femur after taking 500 mg of the oral preparation were approximately 15.1 μg / g (2 hours after taking the drug).

Penetration into the cerebrospinal fluid

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Penetration into prostate tissue

After ingesting 500 mg of levofloxacin once a 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 the dose 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 ingestion levofloxacin relatively slowly excreted from the blood plasma (half-life (T1 / 2) - 6-8 hours). Excretion, mainly, through the kidneys (more than 85% of the dose taken). The total clearance of levofloxacin after a single dose of 500 mg was 175 ± 29.2 ml / min. There are no significant differences in the pharmacokinetics of levofloxacin with its intravenous administration and ingestion, which confirms that ingestion and intravenous administration are interchangeable.

Pharmacokinetics in selected patient groups

The pharmacokinetics of levofloxacin in men and women do not differ. Pharmacokinetics in elderly patients does not differ from that in young patients, except for differences in pharmacokinetics associated with differences in creatinine clearance (CC).

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

Pharmacokinetics in renal failure after a single oral intake of 500 mg of the drug Lefokcin.

CK (ml / min)	<20	20-49	50-80
ClR (ml / min)	13	26	57
T1 / 2 (h)	35	27	9

Indications:

Bacterial infections sensitive to levofloxacin 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.

Contraindications:

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

- epilepsy;

- pseudo-paralytic myasthenia gravis (myasthenia gravis);

- lesions of tendons during the previous treatment with quinolones;

- children and adolescence (up to 18 years);

- pregnancy and the period of breastfeeding.

Carefully:

- In patients who are predisposed to developing seizures [in patients with previous central nervous system (CNS) lesions, patients who receive concomitant drugs that lower the threshold for seizure preparedness of the brain, such as fenbufen, theophylline] (see "Interaction with other drugs" ").

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

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

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

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

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

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

Pregnancy and lactation:

Levofloxacin is contraindicated in pregnant and lactating women.

Dosing and Administration:

The drug Lefokcin is taken orally once or twice a day. Tablets should be swallowed without chewing and drinking with a sufficient amount of liquid (0.5 to 1 cup), can be taken before meals or between meals.

Given that the bioavailability of levofloxacin when taken orally is 99-100%, in the case of transferring the patient from intravenous infusion of levofloxacin to ingestion of the drug, continue treatment at the same dose that was used for intravenous infusion.

The admission of one or more doses of the drug

If you accidentally missed taking Lefokcin, then 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.

The recommended dosing regimen and duration of treatment in patients with normal renal function (CK> 50 mL / min)

- Acute Sinusitis: 2 tablets 250 mg or 1 tablet 500 mg once a day - 10-14 days.

- Exacerbation of chronic bronchitis: 2 tablets 250 mg or 1 tablet 500 mg once a day - 7-10 days.

- Community-acquired pneumonia: 2 tablets 250 mg or 1 tablet 500 mg 1-2 times a day-7-14 days.

- Uncomplicated urinary tract infections: 1 tablet 250 mg once a day - 3 days.

- Complicated urinary tract infections: 2 tablets 250 mg once a day or 1 tablet 500 mg once a day - 7-14 days.

- Pyelonephritis: 2 tablets 250 mg once a day or 1 tablet 500 mg once a day - 7-10 days.

- Chronic bacterial prostatitis: 2 tablets 250 mg or 1 tablet 500 mg once a day - 28 days.

- Infections of skin and soft tissues: 2 tablets 250 mg or 1 tablet 500 mg 1-2 times a day - 7-14 days.

- Complex treatment of drug-resistant forms of tuberculosis: 1 tablet 500 mg 1-2 times a day - up to 3 months.

- Prevention and treatment of anthrax during airborne infection: 2 tablets 250 mg or 1 tablet 500 mg once a day for up to 8 weeks.

Dosing regimen in patients with impaired renal function (QC≤50 ml / min) Levofloxacin is excreted mainly by the kidneys, therefore, in the treatment of patients with impaired renal function, a dose reduction is required (see table).

Clearance creatinine	250 mg / 24 hours.	500 mg / 24 hours.	500 mg / 12 hours.
	first dose:	first dose:	first dose:
	250 mg	500 mg	500 mg
50-20 ml / min.	then:	then:	then:
	for 125 mg / 24 hours.	250 mg / 24 hours.	250 mg / 12 hours.
19-10 ml / min.	then:	then:	then:
	for 125 mg / 48 hours.	125 mg / 24 hours.	125 mg / 12 hours.
<10 ml / min.	then:	then:	then:
(including	for 125 mg / 48 hours.	125 mg / 24 hours.	125 mg / 24 hours.
hemodialysis and
CAPD)

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

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.

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.

As with the use of other antimicrobials, treatment with Lefokcin 250 mg and 500 mg is recommended to continue at least 48-78 hours after the normalization of body temperature or after a reliable destruction of the pathogen.

Side effects:

The frequency of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%; The unknown frequency can not be estimated from the available data.

Heart Disease

Rarely: sinus tachycardia, palpitation.

Unknown frequency: lengthening the interval QT, ventricular arrhythmias, ventricular tachycardia, ventricular pirouette tachycardia, which can lead to cardiac arrest.

Violations of the blood and lymphatic system

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

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

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

Disturbances from the nervous system

Often: headache, dizziness.

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

Rarely: paresthesia, convulsions.

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

Vision disorders

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

Unknown frequency: transient loss of vision.

Hearing disorders and labyrinthine disorders

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

Rarely: ringing in the ears.

Unknown frequency: hearing loss, hearing loss.

Disturbances from the respiratory system, chest organs and the mediastinum

Infrequently: shortness of breath.

Unknown frequency: bronchospasm, allergic pneumonitis.

Disorders from the gastrointestinal tract

Often: diarrhea, vomiting, nausea.

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

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

Disorders from the kidneys and urinary tract

Infrequently: increased serum creatinine concentration.

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

Disturbances from the skin and subcutaneous tissues

Infrequently: rash, itching, hives, hyperhidrosis.

Unknown frequency: 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

Infrequently: arthralgia, myalgia.

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

Unknown 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), ligament rupture, muscle rupture, 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).

Unknown frequency: hyperglycemia, hypoglycemic coma.

Infectious and parasitic diseases

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

Vascular disorders

Rarely: lowering of blood pressure.

General disorders

Infrequently: asthenia.

Rarely: pyrexia (fever).

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

Immune system disorders

Rarely: angioedema.

Unknown frequency: 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 (AsAT)), increased activity of alkaline phosphatase (AP) and gamma-glutamyl transferase (GGT).

Infrequently: increasing the concentration of bilirubin in the blood.

Unknown 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.

Disorders of the psyche

Often: insomnia.

Infrequently: anxiety, confusion, confusion.

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

Unknown frequency: Mental disorders with behavioral disorders self-harm, including suicidal thoughts and suicidal attempts.

Other possible undesirable effects related to all fluoroquinolones

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

Overdose:

Symptoms of an overdose of the drug Lefokcin are manifested at the level of the central nervous system (confusion, dizziness, impaired consciousness and seizures of the type of epiprip). In addition, gastrointestinal disorders (eg, nausea) and erosive lesions of the mucosa can be noted.

In studies conducted with supra-therapeutic doses of levofloxacin, the lengthening of the interval QT.

Treatment should be focused on the symptoms. In case of an overdose, careful monitoring of the patient, including monitoring the electrocardiogram, is required. In case of acute overdosage, gastric lavage and administration of antacids are indicated to protect the gastric mucosa. Levofloxacin is not excreted by dialysis (hemodialysis, peritoneal dialysis and permanent peritoneal dialysis). Specific safener (counter material) does not exist.

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 (drugs for the treatment of anemia), magnesium and / or aluminum-containing drugs (such as antacids), didanosine (only dosage forms containing aluminum or magnesium as the buffer), it is recommended to take at least 2 hours before or 2 hours after taking the drug Lefokcin.

Calcium salts have a minimal effect on the absorption of levofloxacin upon ingestion.

With sucralfate

The effect of the drug Lefokcin significantly weakened by the simultaneous use of sucralfate (a means to protect the mucous membrane of the stomach). Patients receiving levofloxacin and sucralfate, it is recommended to take sucralfate 2 hours after taking levofloxacin.

FROM theophylline, fenbufen, or similar drugs from a group of non-steroidal anti-inflammatory drugs that reduce the threshold of convulsive brain readiness

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

The concentration of levofloxacin with simultaneous administration of fenbufen is only increased by 13%.

With indirect anticoagulants (antagonists of vitamin K)

In patients treated with levofloxacin in combination with indirect anticoagulants (eg, warfarin), prothrombin time / international normalized ratio and / or bleeding, including severe, increased. 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.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 T1 / 2 cyclosporine by 33%. Since this increase is clinically insignificant, correction of the dose of cyclosporine when it is used simultaneously with levofloxacin is not required.

With glucocorticosteroids

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

FROM 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

Clinical and pharmacological studies to study the possible pharmacokinetic interactions of levofloxacin with digoxin, glibenclamide, ranitidine, and warfarin have shown that the pharmacokinetics of levofloxacin, when used simultaneously 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 the acquired resistance of the sown strains of microorganisms can vary depending on the geographical region and over time. In this regard, information about drug resistance in a particular country is required. For the therapy of severe infections or in the ineffectiveness of treatment, a microbiological diagnosis should be made, identifying the causative agent and determining its sensitivity to levofloxacin.

Methicillin-resistant golden streptococcus

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

Patients, predisposed to the development of seizures

Like other quinolones, levofloxacin should be used with great care in patients with a predisposition to convulsions. Such patients include patients with previous lesions of the central nervous system, such as stroke, severe craniocerebral trauma; patients who simultaneously receive drugs that reduce the threshold of convulsive brain readiness, such as fenbufen and other similar Non-steroidal anti-inflammatory drugs or other drugs that lower the threshold for convulsive alertness, such as theophylline.

Pseudomembranous colitis

Developed during or after levofloxacin treatment, diarrhea, especially severe, persistent and / or 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. Older patients are more prone to tendonitis. Risk of rupture of tendons may increase with simultaneous reception of glucocorticosteroids. If suspicion of tendonitis should immediately stop treatment with Lefokcin 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 (angioedema, anaphylactic shock), even with the use of initial doses. Patients should immediately stop taking the drug and consult a doctor.

Heavy bullous reactions

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

Disturbances from the liver and bile ducts

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

Patients with renal insufficiency

As levofloxacin excreted mainly through the kidneys, in patients with impaired renal function, mandatory monitoring of kidney function is required, as well as correction of the dosing regimen (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").

Prevention of the development of photosensitization reactions

Although photosensitization with levofloxacin is very rare, it is not recommended for patients to prevent it during treatment and in48 hours after the end of treatment with levofloxacin, it is necessary to undergo, without special need, strong sunlight or artificial ultraviolet radiation (for example, to visit the solarium).

Superinfection

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

The elongation of the OT interval

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

When using fluoroquinolones, including levofloxacin, caution should be exercised in patients with known risk factors for lengthening the interval QT: in patients with uncorrected electrolyte disorders (hypokalemia, hypomagnesemia); with the syndrome of congenital lengthening of the interval QT; with diseases of the heart (heart failure, myocardial infarction, bradycardia); while taking medications that can lengthen the interval QT, such as antiarrhythmic drugs of class 1A and III, tricyclic antidepressants, macrolides, antipsychotics.

Elderly patients and female patients may be more sensitive to drugs that extend the interval QT. Therefore, care should be taken to use fluoroquinolones, including levofloxacin (see the sections "With caution", "Method of administration and dose", "Side effect" and "Overdose", "Interaction with other drugs").

Patients with deficiency of glucose-6-phosphate dehydrogenase

Patients with a latent or manifested deficiency of glucose-6-phosphate dehydrogenase have a predisposition to hemolytic reactions in the treatment 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, cases of hyperglycemia and hypoglycemia were observed, 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 are required to monitor the concentration of glucose in the blood (see section "Side effect").

Peripheral Neuropathy

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

Exacerbation of pseudo-paralytic myasthenia gravis (myasthenia gravis)

Fluoroquinolones, including levofloxacin, are characterized by neuromuscular blocking of activity and may increase muscle weakness in patients with pseudo-paralytic myasthenia gravis. In the postmarketing period, adverse reactions were observed, including pulmonary insufficiency, requiring artificial ventilation, and fatal outcome, which were associated with the use of fluoroquinolones in patients with pseudo-paralytic myasthenia gravis.The use of levofloxacin in 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 data on sensitivity to it 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 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 the "Side effect" section).

Impact on laboratory tests

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

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

Special precautions when destroying an unused preparation

There is no need for special precautions when destroying an unused preparation.

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

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

Form release / dosage:

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

Packaging:

By 3, 5, 6, 7, 10 tablets in the blister of PVC / PVDC / aluminum foil.

For 1.2, 3 or 4 blisters in a pack of cardboard along with instructions for the use of the drug for medical use.

Storage conditions:

In a dry 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:LS-001093

Date of registration:03.08.2011

Expiration Date:Unlimited

The owner of the registration certificate:Shraya Life Senses Pvt. Ltd.Shraya Life Senses Pvt. Ltd. India

Manufacturer: & nbsp

SHREYA LIFE SCIENCES, Pvt.Ltd. India

Representation: & nbspSHREYA LIFE SENENSIZ Pvt.Ltd. SHREYA LIFE SENENSIZ Pvt.Ltd. India

Information update date: & nbsp05.03.2018

Illustrated instructions

Instructions

Lefokcin (Lefokcin)