Levoflox-Routek - instructions for use, dose, side effects, contraindications

Excipients: sodium chloride 900,000 mg, disodium edetate dihydrate 5,000 mg, hydrochloric acid q.s. up to pH 3.8-5.8, water for injection up to 100 ml.

Composition per ml:

Levofoxacin hemihydrate 5,125 mg (in terms of levofloxacin) 5,000 mg.

Excipients: sodium chloride 9,000 mg, disodium edetate dihydrate 0.050 mg, hydrochloric acid q.s. up to pH 3.8-5.8, water for injection up to 1 ml.

Description:Transparent solution of light yellow or light yellow with a greenish tint of color.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A Fluoroquinolones

J.01.M.A.12 Levofloxacin

Pharmacodynamics:

Antimicrobial drug from the group of fluoroquinolones, the left-handed isomer of ofloxacin. Has a wide spectrum of antimicrobial action.

Levofloxacin 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 bacterial membranes.

Effective against most strains of microorganisms in vitro and in vivo. To levofloxacin are sensitive (minimal inhibitory concentration (MIC) is less than or equal to 2 mg / l):

aerobic Gram-positive microorganisms: Corynebacterium diphtheriae, Enterococcus spp. (at t.h. Enterococcus faecalis), Listeria monocytogenes, Staphylococcus spp. (coagulase-negative methicillin-sensitive/moderately sensitive strains), including Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), Staphylococcus spp. (leukotoxin-containing); Streptococcus spp. groups FROM and G, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-sensitive/moderately sensitive/resistant strains), Streptococcus pyogenes, Streptococcus spp. groups viridans (penicillin-sensitive/resistant strains);

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 agglomerans, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (ampicillin-sensitive/resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (at t.h. Klebsiella oxytoca, Klebsiella pneumoniae), Moraxella catarrhalis (producing and non-reducing beta-lactamase strains), Morganella morganii, Neisseria gonorrhoeae (producing and non-reducing penicillinase strains), Neisseria meningitidis, Pasteurella spp. (at t.h. Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida), Proteus mirabilis, Proteus vulgaris, Providencia spp. (at t.h. Providencia rettgeri, Providencia stuartii), Pseudomonas spp. (at t.h. Pseudomonas aeruginosa), Serratia spp. (at t.h. Serratia marcescens), Salmonella spp .;

anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterium spp., Veilonella spp.;

other microorganisms: Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella spp. (incl. Legionella pneumophila), Mycobacterium spp. (incl. Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

Moderately sensitive microorganisms (MIC is 4 mg / l):

aerobic Gram-positive microorganisms: Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis (methicillin-resistant strains), Staphylococcus haemolyticus (methicillin-resistant strains);

aerobic gram-negative microorganisms: Burkholderia cepacia, Campilobacter jejuni, Campilobacter coli;

anaerobic microorganisms: Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp., Porphyromonas spp.

Sustainable microorganisms (IPC is or more 8 mg/l):

aerobic Gram-positive microorganisms: Corynebacterium jeikeium, Staphylococcus aureus (methicillin-resistant strains), other Staphylococcus spp. (coagulase-negative methicillin-resistant strains);

aerobic gram-negative microorganisms: Alcaligenes xylosoxidans;

other microorganisms: Mycobacterium avium.

Pharmacokinetics:

Binding to proteins - 30-40%. When administered at a dose of 500 mg twice daily, cumulation can be observed to a small extent. Equilibrium concentrations are achieved 3 days after the start of application.

It penetrates well into organs and tissues: lungs, bronchial mucosa, sputum, urinary system organs, genital organs, bone tissue, prostate gland, polymorphonuclear leukocytes, alveolar macrophages.

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Average concentrations in the urine 8-12 hours after a single administration of 150, 300 or 500 mg of levofloxacin were, respectively, 44, 91 and 200 g / l.

In the liver, a small portion of levofloxacin undergoes metabolism with the formation of desmethyllevofloxacin and Nlevofloxacin oxide, which constitute <5% of the levofloxacin excreted by the kidneys.

After the administration of a single dose of 500 mg, the half-life (T1 / 2) is 6-8 hours. It is excreted mainly by the kidneys by glomerular filtration and tubular secretion. Less than 5% of levofloxacin is excreted as metabolites. Unchanged in the form of kidneys within 24 hours is deduced 70% and 48 hours - 87%.

Indications:

Infectious-inflammatory diseases caused by susceptible to levofloxacin microorganisms:

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

acute acute maxillary sinusitis;

uncomplicated urinary tract infections;

- Complicated urinary tract infections (including acute pyelonephritis);

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

- chronic bacterial prostatitis;

- complex therapy of drug-resistant forms of tuberculosis.

Contraindications:

- hypersensitivity to levofloxacin, any other component of the drug or other drugs from the quinolone group;

- epilepsy;

- damage to the tendons during the previous treatment with quinolones;

- Myasthenia gravis gravis;

- Pregnancy;

- lactation period;

- Children and adolescence (up to 18 years).

Carefully:

Elderly age (high probability of concomitant decrease in kidney function), deficiency of glucose-6-phosphate dehydrogenase, predisposition to convulsive reactions (cerebral arteriosclerosis, cerebral circulatory disorders (in history), organic diseases of the central nervous system), renal failure, congenital lengthening syndrome interval Q-T, heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (eg, hypokalemia, hypomagnesemia), diabetes mellitus, psychosis, etc.mental abnormalities in history, hepatic porphyria, simultaneous use of drugs that extend the interval Q-T (antiarrhythmic IA and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal, imidazole derivatives, some antihistamines, including antihistamines. astemizole, terfenadine, ebastine) and lowering the threshold of convulsive readiness of the brain (fenbufen, theophylline), in patients with severe adverse reactions to other fluoroquinolones (such as severe neurologic reactions), female patients.

Dosing and Administration:

The drug is administered intravenously drip. The duration of intravenous infusion of 500 mg of levofloxacin (100 ml of infusion solution) should be at least 60 minutes.

Doses are determined by the nature and severity of the infection, as well as the suspected pathogen susceptibility.

Patients with normal renal function (creatinine clearance> 50 ml / min) recommend the following dosing regimen:

- exacerbation of chronic bronchitis: 250-500 mg of levofloxacin once a day for 7-10 days;

- Community-acquired pneumonia: 500 mg of levofloxacin 1-2 times a day for 7-14 days;

- acute maxillary sinusitis: 500 mg of levofloxacin once a day for 10-14 days;

- uncomplicated urinary tract infections: 250 mg of levofloxacin once a day for 3 days;

- complicated urinary tract infections: 500 mg of levofloxacin once a day - 7-14 days;

- pyelonephritis: 500 mg of levofloxacin once a day - 7-10 days;

- skin and soft tissue infections: 500 mg of levofloxacin 1-2 times a day for 7-14 days;

- chronic bacterial prostatitis: 500 mg of levofloxacin once a day for 28 days;

- complex therapy of drug-resistant forms of tuberculosis: 500 mg of levofloxacin 1-2 times a day for up to 3 months.

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

Patients with impaired renal function (CC <50 ml / min) the following dosing regimen is recommended:

Creatinine clearance,	Dosages for intravenous administration
ml / min	recommended	recommended	recommended
	dose with KK> 50	dose with KK> 50	dose with KK> 50
	ml / min 250 mg / 24 h	ml / min - 500 mg / 24 h	ml / min - 500 mg / 12 h
	initial dose	initial dose	initial dose
	250 mg	500 mg	500 mg
50-20	Further 125 mg / 24 h	Then 250 mg / 24 h	Further 250 mg / 12 h
<19-10	Further 125 mg / 48 h	Further 125 mg / 24 h	Further 125 mg / 12 h
<10 (including when hemodialysis and permanent outpatient peritoneal dialysis)	Further 125 mg / 48 h	Further 125 mg / 24 h	Further 125 mg / 24 h

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

If the liver function is not corrected, dose adjustment is not required, since levofloxacin metabolized in the liver to an insignificant extent.

Depending on the patient's condition after a few days of treatment, it is possible to switch from intravenous drip administration to taking the same dose of the drug in a form intended for oral administration.

Side effects:

From the digestive system: stomatitis, nausea, vomiting, diarrhea (including blood), digestive disorders, abdominal pain, pseudomembranous colitis, increased activity of "liver" transaminases, hyperbilirubinemia, acute liver failure sometimes with fatal outcome, jaundice, flatulence, constipation, pancreatitis.

From the cardiovascular system: tachycardia, lengthening interval QT on a cardiogram, lowering blood pressure, vascular collapse, atrial fibrillation, palpitations,ventricular arrhythmias, ventricular pirouette tachycardia that can lead to cardiac arrest, benign intracranial hypertension.

From the side of metabolism: hypoglycemia (increased appetite, increased sweating, trembling, nervousness), hypoglycemic coma, hyperglycemia (dry mouth, thirst, increased urination, fatigue, blurred vision, dry or itchy skin, arrhythmia), increased activity of alkaline phosphatase and gamma-glutamyltransferase.

From the nervous system: headache, dizziness, fainting, drowsiness, tremor, paresthesia, seizures, peripheral sensory neuropathy, peripheral sensory-motor neuropathy, motor disorders, extrapyramidal frustration, insomnia, anxiety, confusion, hallucinations, depression, sleep disorders, nightmares, agitation, mental disorders with behavioral disorders with self-harm, including suicidal thoughts and suicidal attempts, anxiety, paranoia.

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

From the musculoskeletal system: arthralgia, myalgia, tendonitis, muscle weakness, tendon rupture, rhabdomyolysis, torn ligaments, muscle tear, arthritis.

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

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

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

Other: anorexia, asthenia, exacerbation of porphyria, photosensitivity, persistent fever, leukocytoclastic vasculitis, development of superinfection, dyspnea, hyperhidrosis, fever.

Local reactions: pain, redness at the injection site, phlebitis.

Overdose:

Symptoms: manifested primarily from the central nervous system (confusion, dizziness, impaired consciousness and convulsions).

In addition, gastrointestinal disorders (eg, nausea) and erosive lesions of the mucous membranes of the gastrointestinal tract, lengthening of the interval Q-T.
Treatment: symptomatic. Dialysis is ineffective. The specific antidote is not known.

Interaction:

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

Admission of glucocorticosteroids increases the risk of rupture of tendons (especially in the elderly).

Cimetidine and drugs that block tubular secretion, slow the withdrawal of levofloxacin.

The solution for infusion is compatible with 0.9% sodium chloride solution, 5% dextrose solution, 2.5% Ringer's solution with dextrose, combined solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).

Do not mix with heparin and solutions that have an alkaline reaction (for example, with sodium bicarbonate solution).

In patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, against the background of the administration of levofloxacin hypo- and hyperglycemic conditions are possible, therefore careful monitoring of the concentration of glucose in the blood is recommended. Levofloxacin enhances the anticoagulant activity of warfarin.

Alcohol can increase side effects from the central nervous system (dizziness, drowsiness).

Levofloxacin increases the half-life of cyclosporine.

With simultaneous application with drugs that extend the interval Q-T (antiarrhythmic IA and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal, imidazole derivatives, some antihistamines, including antihistamines. astemizole, terfenadine, ebastine) it is possible to extend the interval Q-T.

Special instructions:

When the body temperature is normal, it is recommended to continue treatment at least 48-72 h.

The recommended duration of administration should be observed: 500 mg levofloxacin (100 ml infusion solution) for at least 60 minutes. During the infusion, there may be increased heart rate, transient decrease in blood pressure, in rare cases - vascular collapse. If there is a marked decrease in blood pressure during the infusion, the administration is discontinued.

During treatment, sunlight and artificial ultraviolet irradiation should be avoided to avoid damage to the skin (photosensitization).

When there are signs of tendinitis, allergic reactions levofloxacin immediately cancel and prescribe appropriate treatment.

It should be borne in mind that in patients with predisposition to convulsive reactions (atherosclerosis of cerebral vessels, cerebral circulatory disorders (in the anamnesis), organic diseases of the central nervous system, headache a history of the brain (stroke or severe trauma)); in patients taking concomitant non-steroidal anti-inflammatory drugs, theophylline, the risk of seizures increases; when insufficiency of glucose-6-phosphate dehydrogenase is a risk of hemolysis of erythrocytes.

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 specific antibacterial therapy initiated. The use of drugs that inhibit intestinal peristalsis is contraindicated.

During treatment, alcohol should be avoided.

When used simultaneously with warfarin, careful monitoring of prothrombin time and other coagulation indices is necessary.

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

Very rare cases of lengthening of the interval have been reported Q-T 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 Q-T: elderly age; violation of electrolyte balance (hypokalemia, hypomagnesemia); congenital lengthening syndrome Q-T; heart disease (heart failure, myocardial infarction, bradycardia); simultaneous reception of drugs that can lengthen the interval Q-T.

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

As with the use of other antimicrobials, the use of levofloxacin, especially for a long time, can lead to increased reproduction of insensitive microorganisms and the development of superinfection.

There have been reports of hepatic necrosis, including the development of fatal liver failure with levofloxacin. Termination is necessary the use of the drug and urgently seek medical attention in case of signs and symptoms of liver damage such as anorexia, jaundice, darkening of urine, itching and abdominal pain. Elderly patients and female patients may be more sensitive to drugs that extend the interval QT. Therefore, it is necessary to use with caution the fluoroquinolones, including levofloxacin, in this category of patients. As with the use of other quinolones, when levofloxacin was used, cases of hyperglycaemia and hypoglycemia were observed, especially in patients with diabetes mellitus, who received treatment with oral hypoglycemic drugs 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. In the development of psychotic reactions, which in rare cases progress to the development of suicidal thoughts and behavioral disorders with self-harm, treatment with levofloxacin should be stopped and appropriate treatment should be prescribed. With the development of any visual impairment, an immediate consultation of the ophthalmologist is necessary. 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:

During the treatment period, care must be taken when driving and potentially dangerous mechanisms due to possible dizziness, drowsiness, stiffness and visual disturbances, which can lead to a slowing of the speed of psychomotor reactions and a decrease in the ability to concentrate.

Form release / dosage:Solution for infusions 5 mg / ml.

Packaging:

100 ml of the drug in a bottle of low density polyethylene with a lid of low density polyethylene.

- The bottle in a sealed polypropylene bag, along with the instructions, is placed in a cardboard box.

- The bottle in a sealed polypropylene bag together with a disposable system for intravenous administration of solutions with a built-in ventilation barrier against bacteria "Eurodream" and instructions for use are placed in a cardboard box.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the product after the date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001183

Date of registration:11.11.2011

The owner of the registration certificate:Rowecq LimitedRowecq Limited United Kingdom

Manufacturer: & nbsp

SCAN BIOTECH, Ltd. India

Representation: & nbspROUTEC LIMITEDROUTEC LIMITEDUnited Kingdom

Information update date: & nbsp30.09.2015

Illustrated instructions

Instructions

Levoflox-Routek (Levoflox-Rowtech)