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

Excipients: Dextrose anhydrous 5,000 g, hydrochloric acid q.s. to pH 3.8-5.8, sodium hydroxide q.s. up to pH 3.8-5.8, water for injection up to 100 ml. Theoretical osmolarity is about 292 mOsm / l.

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 DNA synthesis, 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 suppressing concentration (MIC) is less than or equal to 2 mg / l):

- aerobic Gram-positive microorganisms: Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus spp. (incl. 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 C 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, hospital infection, caused by Pseudomonas aeruginosa, may demand combined treatment), Serratia spp. (incl. Serratia marcescens), Salmonella spp .;

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

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

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

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

- aerobic gram-negative microorganisms: Campylobacter jejuni, Campylobacter coli;

- anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

Stable microorganisms (MIC is equal to or more than 8 mg / l):

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

- aerobic gram-negative microorganisms: Alcaligenes xylosoxidans;

- anaerobic microorganisms: Bacteroides thetaiotaomicron.

- other microorganisms: Mycobacterium avium.

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, Helicobacter pylori, Klebsiella pneumoniae, Moraxella catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens;

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

Pharmacokinetics:

After an intravenous 60-minute infusion of levofloxacin at a dose of 500 mg to healthy volunteers, the maximum plasma concentration (Cmah) was on average 6.2 μg / ml. 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.

On the 10th day of intravenous administration of levofloxacin at a dose of 500 mg once a day Cmlevofloxacin in plasma was 6.4 ± 0.8 μg / ml.

On the 10th day of intravenous administration of levofloxacin in a dose of 500 mg 2 times a day Cmlevofloxacin in plasma was 7.9 ± 1.1 μg / ml.

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 half-life (T_1/2) is 6-8 hours. It is excreted mainly by the kidneys through 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:

- community acquired pneumonia;

- uncomplicated urinary tract infections;

- complicated urinary tract infections (including pyelonephritis);

- infections of the skin and soft tissues;

- septicemia / bacteremia;

- chronic bacterial prostatitis;

- intra-abdominal infection;

- 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;
the defeat of the tendons during the previous treatment with quinolones;
pregnancy;
lactation period;
myasthenia gravis gravis,
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 (for example, hypokalemia, hypomagnesemia), diabetes mellitus, psychosis and other mental disorders in the anamnesis, 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 neurological reactions), in patients with psychoses or in patients with a history of mental illness, in 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:

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

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

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

- septicemia / bacteremia: 500 mg of levofloxacin 1-2 times a day for 10-14 days;

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

- intraabdominal infection: 500 mg of levofloxacin once a day for 7-14 days (in combination with antibacterial drugs acting on anaerobic flora);

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

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

Creatinine clearance, ml / min	Dosages for intravenous administration
	recommended dose for CK> 50 ml / min - 250 mg / 24 h	recommended dose for CK> 50 ml / min - 500 mg / 24 h	recommended dose for CK> 50 ml / min - 500 mg / 12 h
	the first dose of 250 mg	the first dose of 500 mg	the first dose of 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 hemodialysis and permanent ambulatory 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.

- As with the use of other antibiotics, treatment with levofloxacin is recommended to continue for at least 48-72 hours after normalization of body temperature or reliable eradication of the pathogen. Treatment with levofloxacin should not be interrupted or terminated prematurely without a doctor's instructions.

- Infusion solution of the drug is administered once or twice a day slowly intravenously drip. The duration of infusion of 500 mg of the drug (100 ml) should be at least 60 minutes, in the case of 250 mg (50 ml) infusion should be at least 30 minutes.

Side effects:

From the digestive system: nausea, vomiting, diarrhea (including blood), dyspepsia, flatulence, constipation, abdominal pain, pseudomembranous colitis, increased activity of "liver" transaminases, hyperbilirubinemia, severe hepatic insufficiency, including cases of acute liver failure, sometimes fatal , especially in patients with severe underlying disease (for example,in patients with sepsis), hepatitis, hemorrhagic diarrhea, which in very rare cases can be a sign of enterocolitis, pancreatitis, stomatitis, increased activity of alkaline phosphatase, gamma-glutamyltransferase, jaundice.

From the cardiovascular system: sinus tachycardia, lengthening of the interval QT on an electrocardiogram, lowering of arterial pressure, vascular collapse, palpitation, ventricular rhythm disturbances, ventricular tachycardia, ventricular pirouette tachycardia, which can lead to cardiac arrest.

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

From the nervous systemheadache, dizziness, drowsiness, tremor, paresthesia, seizures, peripheral sensory neuropathy, peripheral sensory-motor neuropathy, motor disorders, extrapyramidal disorders, insomnia, anxiety, anxiety, confusion, hallucinations, depression,sleep disturbances, nightmares, agitation, mental disorders with behavioral problems with self-harm, including suicidal thoughts and suicide attempts, syncope, benign intracranial hypertension.

From the sense organs: dysgeusia (taste distortion), loss of taste sensations, parosmia (odor disorder, especially subjective sense of smell, objectively absent), including loss of smell; visual impairments, such as blurred vision, transient loss of vision, vertigo (sense of deflection or twisting or own body or surrounding objects), ringing in the ears, hearing loss, hearing loss.

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.

Allergic reactions: itching, rash, urticaria, angioedema, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), exudative erythema multiforme, bronchospasm, allergic pneumonitis, anaphylactic shock, anaphylactoid shock.

Other: anorexia, fatigue, aggravation of porphyria, photosensitivity, persistent fever, leukocytoclastic vasculitis, development of superinfection, shortness of breath, fungal infections, pain, including back, chest and extremities.

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.

The pharmacokinetic interaction of levofloxacin with theophylline has not been revealed. The concentration of levofloxacin with simultaneous administration of fenbufen is only increased by 13%. 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.

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 of levofloxacin (100 ml of 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.The prevalence of acquired resistance of the strains of microorganisms can vary depending on the geographic region and the amount of time. In this connection, information about resistance to levofoloxacin in a particular country is required; for the treatment of severe infections or in the ineffectiveness of treatment, a microbiological diagnosis should be made, isolating the pathogen and determining its sensitivity to levofloxacin. 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.

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

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

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.

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.

As with the use of other quinolones, when levofloxacin was used, cases of hypoglycemia and hyperglycemia were observed,especially in patients with diabetes mellitus, receiving simultaneous 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.

Fluoroquinolones, including levofloxacin, can block neuromuscular activity and increase muscle weakness in patients with pseudo-paralytic myasthenia gravis. There were adverse reactions, including pulmonary insufficiency, requiring artificial ventilation, and death, which were associated with the use of fluoroquinolones in patients with pseudo-paralytic myasthenia gravis. The use of levofloxacin in patients with established diagnosis of myasthenia gravis gravis Not recommended.

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 anamnesis.

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

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, history of the brain (stroke or severe trauma)); in patients taking concomitant non-steroidal anti-inflammatory drugs, theophylline, - the risk of seizures increases; with insufficiency of glucose-6-phosphate dehydrogenase - the 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 startedspecific antibacterial therapy. 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.

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: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 attention.

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 for use, is 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-002744

Date of registration:08.12.2014

Expiration Date:08.12.2019

The owner of the registration certificate:MANAS MED, LTD MANAS MED, LTD Russia

Manufacturer: & nbsp

AISHWARYA HEALTHCARE India

Information update date: & nbsp23.09.2017

Illustrated instructions

Instructions

Aschlev (Ashlev)