Levofloxacin-Nova - instructions for use, dose, side effects, contraindications

Levofloxacin is a synthetic broad-spectrum antibacterial agent from the group of fluoroquinolones, containing as an active substance levofloxacin - the left-handed isomer of ofloxacin.

Levofloxacin blocks DNA gyrase and topoisomerase IV, disrupts 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 active against most strains of microorganisms, as in conditions in vitro, and in vivo.

In vitro:

Sensitive microorganisms (MIC of ≤2 mg / ml, zone of inhibition ≥1 7 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 / (methicillin-moderately sensitive)], Staphylococcus aureus methi-S (methicillin-sensitive), Staphylococcus epidermidis methi-S (methicillin-sensitive), Staphylococcus spp. CNS (coagulase-negative), Streptococci groups FROM and G, Streptococcus agalactiae, Streptococcus pneumoniae peni I / S / R (penicillin-sensitive / -residually sensitive / -resistant), Streptococcus pyogenes, Viridans streptococci peni-S/R (penicillin-sensitive / -resistant).

Aerobic Gram-negative microorganisms: Acinetobacter baumannil, Acinetobacter spp, Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aero genes, 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, Moraxela catarrhalis /?+//?- (producing and non-reducing beta-lactamase), Morganella morganii, Neisseria gonorrhoeae non PPNG / PPNG (non-reducing and producing penicillipase), Neisseria meningitidis, Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida, Pasteurella spp, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Providencia spp, Pseudomonas aeruginosa (hospital infection, caused by Pseudomonas aeruginosa, may demand 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, Micobacterium tuberculosis, Mycoplasma hominis, Mycoplasma pneumoniae, Ricketsia spp, Ureaplasma urealyticum.

Moderately sensitive microorganisms (IPC = 4 mg / l; zone of inhibition 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 gramogensitive microorganisms: Campilobacter jejuni/coli.

Anaerobic microorganisms: Prevotella spp, Porphyromonas spp.

Resistant to levofloxacin microorganisms (MIC of ≥ 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 gramogensitive microorganisms: Alcaligenes xylosoxidans.

Anaerobic microorganisms: Bacteroides thetaiotaomicron.

Other microorganisms: Mycobacterium avium.

Resistance

Resistance to levofloxacin develops as a result of a step-by-step process of mutations of genes encoding both topoisomerases of type II: DPC hydrase and topoisomerase IV. Other mechanisms of resistance, such as the mechanism of influence on the penetration barriers of a microbial cell (a mechanism characteristic of Pseudomonas aeruginosa) and the mechanism of efflux (active removal of the antimicrobial from the microbial cell), can also reduce the sensitivity of microorganisms to levofloxacin.

Due to the peculiarities of the mechanism of action of levofloxacin, there is usually no cross-resistance between levofloxacin and other antimicrobial agents.

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, Moraxela catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens.

Other: 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 averaged 6.2 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 blood plasma upon administration of 500 mg levofloxacin 1 or 2 times a day is achieved within 48 hours.

On the 10th day of intravenous administration of levofloxacin 500 mg once a day, the maximum concentration in the blood plasma was 6.4 + 0.8 μg / ml, and the minimum concentration of levofloxacin (concentration before administration of the next dose) in blood plasma was 0.6 + 0.2 μg / ml.

On the 10th day of intravenous administration of levofloxacin 500 mg 2 times a day, the maximum concentration in the blood plasma was 7.9 + 1.1 μg / ml,and the minimum concentration of levofloxacin (concentration before the introduction of the next dose) in the blood plasma was 2.3 + 0.5 μg / ml.

Distribution

Connection with serum proteins is 30-40%. Scope allocation of levofloxacin averages 100 l after a single and multiple intravenous administration of 500 mg, indicating good penetration levofloxacin in the organs and tissues of the human body.

Penetration into the bronchial mucosa, epithelial lining fluid, alveolar macrophages

Levofloxacin penetrates well into the bronchial mucosa, epithelial lining fluid, alveolar macrophages with penetration coefficients in the bronchial mucosa and epithelial lining fluid, in comparison with the concentration in the blood plasma of 1.1-1.8 and 0.8-3, respectively.

Penetration into lung tissue

Levofloxacin well penetrates into the lung tissue with penetration factors of 2-5, compared with the concentration in the blood plasma.

Penetration into the alveolar fluid

Levofloxacin well penetrates into the alveolar fluid with a coefficient of penetration of 1, compared with the concentrations in the blood plasma.When levofloxacin was administered 500 mg 1 or 2 times a day for 3 days, the maximum concentrations of levofloxacin in the alveolar fluid were achieved 2-4 hours after administration and were 4.0 and 6.7 μg / ml, respectively.

Penetration into bone tissue

Levofloxacin well penetrates into the cortical and spongy bone tissues, both in the proximal, hook and distal parts of the femur with a coefficient of penetration (bone tissue / blood plasma) of 0.1-3.

Penetration into the cerebrospinal fluid

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Penetration into prostate tissue

Levofloxacin well penetrates into the prostate tissue (the average ratio of prostatic / plasma concentrations was 1.84)

Concentrations in the urine

In the urine, high concentrations of levofloxacin are created, several times higher than the concentration of levofloxacin in the blood plasma.

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 intravenous administration levofloxacin is relatively slowly excreted from the blood plasma (the half-life is 6-8 hours). Excretion mainly through the kidneys (more than 85% of the dose taken). The total clearance of levofloxacin after a single administration of 500 mg is 175 + 29.2 ml / min.

There are no significant differences in the pharmacokinetics of levofloxacin with its intravenous administration and ingestion, which confirms that oral and intravenous routes of 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 decreases, and the elimination half-life increases.

Indications:

Bacterial infections caused by sensitive to levofloxacin microorganisms in adults:

- community acquired pneumonia;

- uncomplicated urinary tract infections;

- complicated urinary tract infections (including pyelonephritis);

- chronic bacterial prostatitis;

- infections of the skin and soft tissues;

- complex therapy of drug-resistant forms of tuberculosis;

- prevention and treatment of anthrax during airborne infection.

When using Levofloxacin-Nova, official national recommendations for the proper use of antibacterial drugs, as well as the sensitivity of pathogenic microorganisms in a particular country, should be taken into account (see section "Special instructions").

Contraindications:

Hypersensitivity to levofloxacin or other quinolones, as well as to drug auxiliaries, epilepsy, tendon damage with prior treatment with quinolones, pseudo-paralytic myasthenia gravis (myasthenia gravis) (see the sections "Side effects", "Special instructions"), pregnancy (the risk of destruction of the cartilage growth points in the fetus can not be ruled out completely), the period of breastfeeding (the risk of cartilage damage can not be ruled out completelypoints of bone growth in a child), children and adolescents under 18 years (due to incomplete growth of the skeleton, since the risk of damage to the cartilaginous growth points can not be ruled out completely).

Carefully:

In patients who are prone to seizures (in patients with previous central nervous system (CNS) lesions), patients taking concomitant medications that lower the threshold for seizure preparedness of the brain, such as fenbufen, theophylline) (see section "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 for kidney function, as well as correction of the dosing regimen, see "Method of application and dose ").

In patients with known risk factors for lengthening the interval QT: in elderly patients; in female patients; in patients with uncorrected electrolyte disorders (with hypoglycemia, hypomagnesemia); with the syndrome of congenital lengthening 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) (see sections "Overdose", "Interaction with other drugs", "Special instructions").

In patients with diabetes mellitus receiving treatment with 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 undesirable reactions with levofloxacin).

In patients with psychoses or in patients with a history of mental illness (see section "Special instructions").

Pregnancy and lactation:

The drug Levofloxacin-Nova is contraindicated for use in pregnant and lactating women.

Dosing and Administration:

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.As with the use of other antibiotics, treatment with the drug is recommended to continue for at least 48-78 hours after the normalization of body temperature or reliable eradication of the pathogen.

Treatment with the drug can not be interrupted or terminated prematurely without the doctor's instructions.

Depending on the patient's condition, after a few days of treatment, you can switch from intravenous infusion to the same dose of levofloxacin in tablets (due to the fact that the bioavailability of levofloxacin when taking tablets is 99-100%) (see the section "Pharmacokinetics").

If you accidentally missed the introduction of the drug, you should, as soon as possible, to enter the missed dose and continue to continue to administer the drug according to the recommended dosage regimen.

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 (daily dose of 500-1000 mg of levofloxacin) -7-14 days.

- complicated urinary tract infections: 500 mg of levofloxacin once a day (daily dose of 500 mg of levofloxacin) - 7-14 days.

- pyelonephritis: 500 mg of levofloxacin once a day (daily dose of 500 mg of levofloxacin) - 7-10 days;

- Uncomplicated urinary tract infections: 250 mg of levofloxacin once a day (daily dose of 250 mg of levofloxacin) - 3 days.

- chronic bacterial prostatitis: 500 mg levofloxacin 1 time per day (daily dose of 500 mg levofloxacin) - 28 days.

- infections of the skin and soft tissues: 500 mg of levofloxacin 1-2 times a day (daily dose of 500-1000 mg of levofloxacin) - 7-14 days.

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

- prevention and treatment of anthrax during airborne infection: 500 mg of levofloxacin once a day (daily dose of 500 mg of levofloxacin) - for up to 8 weeks.

Patients with impaired renal function (CK <50 mL / min)

Levofloxacin is excreted mainly through the kidneys, therefore, in the treatment of patients with impaired renal function, it is required to reduce the dose of the drug (see table below).

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
50-20	initial dose: 250 mg further 125 mg / 24 h	initial dose: 500 mg further 250 mg / 24 h	initial dose: 500 mg further 250 mg / 12 h
19-10	initial dose: 250 mg further 125 mg / 48 h	initial dose: 500 mg further 125 mg / 24 h	initial dose: 500 mg further 125 mg / 12 h
<10 (including hemodialysis and CAPD *)	initial dose: 250 mg further 125 mg / 48 h	initial dose: 500 mg further 125 mg / 24 h	initial dose: 500 mg further 125 mg / 24 h

* - CAPD - permanent ambulatory peritoneal dialysis

After hemodialysis or CAPD, no additional doses are required.

Dosage regimen in patients with impaired liver function

If the liver function is not corrected, correction of the dosing regimen is not required, since levofloxacin only slightly metabolized in the liver.

Dosage regimen in elderly patients

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.

Mode of application

The infusion solution of the drug is administered once or twice a day.

Infusion solution of the drug Levofloxacin-Nova 500 mg is injected SLOWLY intravenously drip.The duration of infusion of 1 bottle of a solution of the drug Levofloxacin-Nova 500 mg (100 ml with 500 mg of levofloxacin) should be at least 60 minutes, in the case of half the vial (50 ml with 250 mg of levofloxacin), the infusion should be at least 30 min. section "Special instructions").

Levofloxacin-Nova, infusion solution, 500 mg is compatible with the following infusion solutions: 0.9% sodium chloride solution, 5% dextrose solution, 2.5% Ringer's dextrose solution, combined solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).

A solution of Levofloxacin-Nova should not be mixed with heparin or solutions that have an alkaline reaction (for example sodium bicarbonate solution).

After removing the vial from the cardboard bundle, the infusion solution can be stored without light protection for more than 3 days under room lighting! - this must be confirmed!

Side effects:

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

Data obtained in clinical trials and post-marketing use of levofloxacin.

Heart Disease:

Rarely: sinus tachycardia, palpitation.

Frequency unknown: interval lengthening QT on the cardiogram, ventricular arrhythmias, ventricular tachycardia, ventricular pirouette tachycardia, which can lead to cardiac arrest.

Violations from 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).

Frequency unknown: 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.

Impaired nervous system:

Often: headache, dizziness.

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

Rarely: paresthesia, convulsions.

Frequency unknown: peripheral sensory neuropathy, peripheral sensory-motor neuropathy, dyskinesia, extrapyramidal disorders, loss of taste sensations, parosmia (odor disorder, especially subjective sensation odor, objectively absent), including benign intracranial hypertension.

Disorders from the side of the organ of vision:

Rarely: visual impairments, such as the blurring of the visible image.

Frequency unknown: transient loss of vision, uveitis.

Hearing disorders and labyrinthine disturbances:

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

Rarely: tinnitus.

Frequency unknown: hearing loss, hearing loss.

Disturbances from the respiratory system, organs of the thorax and mediastinum:

Infrequently: dyspnea.

Frequency unknown: bronchospasm, allergic pneumonitis.

Disorders from the gastrointestinal tract:

Often: diarrhea, nausea, vomiting.

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

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

Disorders from the nights 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.

Frequency unknown: toxic epidermal necrolysis, Stevens-Johnson syndrome, exudative erythema multiforme, photosensitivity reactions, leukocytoclastic vasculitis, stomatitis.

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

Disturbances from musculoskeletal system and connective tissue

Infrequently: arthralgia, myalgia.

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

Frequency unknown: rhabdomyolysis, tendon rupture (eg, Achilles tendon.This side effect can be observed within 48 hours after the start of treatment and can wear bilateral nature), ligament rupture, muscle rupture, arthritis.

Disorders from the metabolism and nutrition:

Infrequently: anorexia.

Rarely: hypoglycemia, especially in patients with diabetes mellitus (possible signs - increased appetite, sweating, trembling, nervousness).

Frequency unknown: hyperglycemia, hypoglycemic coma.

Infectious and parasitic diseases:

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

Vascular disorders:

Often: phlebitis.

Rarely: lowering of blood pressure.

General disorders and disorders at the site of administration:

Often: reaction at the injection site (tenderness, skin hyperemia).

Infrequently: asthenia.

Rarely: pyrexia (fever).

Frequency unknown: pain (including pain in the back, chest, extremities).

Impaired immune system:

Rarely: angioedema.

Frequency unknown: anaphylactic shock, anaphylactoid shock.

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

Violation of the liver and biliary tract:

Often: an increase in the activity of "hepatic" enzymes in the blood (for example, alanine aminotransferase (ALT)), aspartate aminotransferase (AST)), an increase in the activity of alkaline phosphatase (APF) and gamma-glutamyl transferase (GGT).

Infrequently: increasing the concentration of bilirubin in the blood.

Frequency unknown: 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, sleep disturbance, nightmares.

Frequency unknown: mental disorders with behavioral disorders with 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: 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 QT.

Treatment of overdose: In case of an overdose, careful monitoring of the patient, including ECG monitoring, is required. Treatment is symptomatic. Levofloxacin Not to be excreted by dialysis (hemodialysis, peritoneal dialysis and permanent ambulatory peritoneal dialysis). The specific antidote is not known.

Interaction:

Interactions requiring caution

With theophylline, fenbufen or similar drugs from the group of non-steroidal anti-inflammatory drugs and other drugs that reduce the threshold of convulsive readiness of the brain.

The pharmacokinetic interaction of levofloxacin with theophylline has not been revealed. However, with the temporary use of quinolones and theophylline, non-steroidal anti-inflammatory drugs and other drugs that lower the threshold for 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%.

FROM indirect anticoagulants (antagonists of vitamin K)

In patients who took levofloxacin in combination with indirect anticoagulants (eg, warfarin), there was an increase in prothrombin time / international normalized ratio and / or development of bleeding, including number, and heavy. Therefore, with the simultaneous use of indirect anticoagulants and Levofloxacin requires regular monitoring of blood coagulation.

With probenecid and cimetidine

With the simultaneous use of drugs that disrupt renal tubular secretion, such as probenecid and cimetidine, and levofloxacin should be used with caution, 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 medications that extend the interval QT

Levofloxacin, like other fluoroquinolones, should be used with caution in patients who use drugs that extend the range QT (e.g., antiarrhythmic agents IA and III, tricyclic antidepressants, macrolides, neuroleptics).

Other

Conducted clinical and pharmacological studies to study the possible pharmacokinetic interactions of levofloxacin with calcium carbonate, 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.

Prevalence acquired resistance of sown strains microorganisms may vary depending on the geographic region and over time. In connection with this, information about the resistance to levofloxacin in a particular country is required; for the treatment of severe infections or Ineffectiveness of treatment should be established microbiological diagnosis with the isolation of the pathogen and the definition of its sensitivity to levofloxacin.

Methicillin-resistant Staphylococcus aureus

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.

Duration of infusion

It should be strictly adhered to the recommended duration of administration, which should be at least 60 minutes (for 100 ml infusion solution) or 30 minutes (for 50 ml infusion solution). The experience with levofloxacin shows,that during the infusion, there may be increased heart rate and transient decrease in blood pressure. In rare cases, there may be vascular collapse. If there is a marked decrease in blood pressure during the infusion of levofloxacin, the infusion is immediately stopped.

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 taking concomitant medications that lower the threshold for convulsive brain readiness, such as fenbufen and other nonsteroidal anti-inflammatory drugs similar to it, or other drugs that lower the threshold for convulsive alertness, such as theophylline (see section "Interaction with other drugs").

Pseudomembranous colitis

Developed during or after levofloxacin treatment, diarrhea, especially severe, persistent and / or with blood, may be a symptom of pseudomembranous colitis caused by Clostridium difficile. In case of suspected development of pseudomembranous colitis, treatment with levofloxacin should be stopped immediately and immediately begin specific antibiotic therapy (vancomycin, teicoplanin or metronidazole inside). Drugs that inhibit the intestinal peristalsis are contraindicated.

Tendonitis

Rarely observed tendonitis in the use of quinolones, including levofloxacin, can lead to the rupture of tendons, including the Achilles tendon. This side effect can develop within 48 hours after the start of treatment and can be bilateral.

Older patients are more prone to tendonitis. The risk of rupture of tendons can increase with simultaneous admission 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 (see the sections "Contraindications" and "Side effect").

Hypersensitivity reactions

Levofloxacin can cause serious, potentially fatal hypersensitivity reactions (angioedema, anaphylactic shock).section "Side effect"). Patients should immediately stop the injection and consult a doctor.

Severe bullous reactions

When taking levofloxacin, there were cases of severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (see section "Side effect"). In 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 hepatic necrosis, including the development of fatal liver failure with levofloxacin, mainly in patients with severe underlying diseases, for example, with sepsis (see section "Side effect"). Patients should be warned about the need for discontinuation of treatment and urgent medical attention in case of signs and symptoms of liver damage such as anorexia, jaundice, darkening of the urine, pruritus, and abdominal pain.

Patients with renal insufficiency

As levofloxacin excreted mainly through the kidneys, in patients with impaired function of the nights, 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 the photosensitization reaction

Although photosensitization with levofloxacin is very rare, for prevention of its development is not recommended to patients during treatment and, within 48 hours after the end of treatment with levofloxacin, to undergo, without special need, strong sunlight or artificial ultraviolet irradiation (for example, to visit the solarium).

Superinfection

As with the use of other antibiotics, the use of levofloxacin, especially for a long time, can lead to increased 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 mandatory to reevaluate the patient's condition and, if developed during the treatment of superinfection, appropriate measures should be taken.

Interval lengthening QT

Very rare cases of lengthening of the interval have been reported QT in patients 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 elderly 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 concomitantly taking medications that can lengthen the interval QT, such as antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, antipsychotics.

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

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, levofloxacin was observed cases of development of hyperglycemia and hypoglycemia, especially in patients with sugar diabetes, receiving concurrent treatment with oral hypoglycemic drugs (eg, glibenclamide) or insulin preparations. There have been reports of cases of hypoglycemic coma. Patients with diabetes require monitoring of blood glucose concentrations (see "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 a neuromuscular blocking activity, and may increase muscle weakness in patients with pseudo-paralytic myasthenia gravis. In the period after the introduction of levofloxacin, unfavorable reactions were observed on the market, 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).

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 anthracis, received 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

When using quinolones, including levofloxacin, reported on the development of psychotic reactions, which in rare cases progressed to the development of suicidal thoughts and behavioral disorders with self-harm (sometimes after the introduction of a single dose of levofloxacin). With the development of such reactions, treatment with levofloxacin should be discontinued and appropriate treatment should be prescribed. Follows with caution in prescribing 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 using 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:

Such side effects of Levofloxacin-Nova, such as dizziness or vertigo, drowsiness, and visual impairment (see the "side effect" section), can reduce psychomotor reactions and the ability to concentrate. This can represent a certain risk in situations where these abilities are of particular importance (for example, when driving, servicing machines and mechanisms, performing work in an unstable position).

Form release / dosage:

Solution for infusions 5 mg / ml.

Packaging:

For 100 ml of the drug is placed in a bottle of high-density polyethylene. A label is attached to the vial. One bottle together with the instruction for use is placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Do not freeze.

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-004133

Date of registration:13.02.2017

Expiration Date:13.02.2022

The owner of the registration certificate:JODAS EKSPOIM, LLC JODAS EKSPOIM, LLC Russia

Manufacturer: & nbsp

NOVALEK PHARMACEITICAL, Pvt. Ltd. India

Representation: & nbspJodas Expoim, Open CompanyJodas Expoim, Open Company

Information update date: & nbsp16.03.2017

Illustrated instructions

Instructions

Levofloxacin-Nova (Levofloxacin-Nova)