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

Optically active levorotatory isofloxacin isomer - L-oxloxacin (S-(-)- enantiomer). Has a wide spectrum of antimicrobial activity. It blocks bacterial topoisomerase IV and DNA gyrase (topoisomerase II). It disrupts supercoiling and cross-linking of DNA gaps, causes profound morphological changes in the cytoplasm, cell wall. In concentrations equivalent to or exceeding the minimum inhibitory concentrations (MICs), bactericidal effects are most common. The effectiveness of ciprofloxacin depends to a large extent on the relationship between pharmacokinetic and pharmacodynamic parameters - between the maximum serum concentration (Cmax) / minimum inhibitory concentration (MIC) and between the area under the concentration-time curve (AUC) / IPC. The main mechanism of development of resistance is associated with gene mutation gyr-A with the possible development of cross-resistance between levofloxacin and other fluoroquinolones. Cross-resistance between levofloxacin and antibacterial drugs of other classes is usually not occurs.

Microorganisms sensitive in vitro

Sensitive microorganisms (MIC of no more than 2 mg / L, inhibition zone not less than 17 mm): aerobic Gram-positive microorganisms - Corynebacterium diphtheriae, Enterococcus spp., including Enterococcus faecalis, Listeria monocytogenes, Staphylococcus spp. (coagulase-negative methicillin-sensitive / leukotoxin-containing / moderately sensitive strains), including Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), 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., including Acinetobacter baumannii, Acinetobacillus actinomycetecomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter spp., including Enterobacter aero genes, Enterobacter agglomerans, Enterobacter cloacae, Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (ampicillin-sensitive / resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp., including Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis (producing and non-producing beta-lactamase strains), Morganella morganii, Neisseria gonorrhoeae (penicillinase-producing and non-producing penicillinase strains), Neisseria meningitidis, Pasteurella spp., including Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida, Proteus vulgaris, Providencia spp., including Providencia rettgeri, Providencia stuartii, Pseudomonas spp., including Pseudomonas aeruginosa, Serratia spp., including 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 pneumophila, Legionella spp., Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

Moderately sensitive microorganisms (MIC = 4 mg / L, inhibition zone not less than 16-14 mm): 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, Campylobacter jejuni, Campylobacter coli; anaerobic microorganisms Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp., Porphyromonas spp.

Stable microorganisms (MIC more than 8 mg / l, inhibition zone not less than 17 mm): aerobic Gram-positive microorganisms - Corynebacterium jeikeium, Staphylococcus aureus (methicillin-resistant strains), others Staphylococcus spp. (coagulase-negative methicillin-resistant strains); aerobic Gram-negative microorganisms - Alcaligenes xylosoxidans; other microorganisms - Mycobacterium avium.

Microorganisms sensitive in vivo

Aerobic gram-positive microorganisms: Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes.

Aerobic Gram-negative microorganisms: Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Haemophilus influenzas, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella (Branhamella) catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens.

Other: Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae.

Pharmacokinetics:

Suction

After intravenous (iv) single administration to healthy volunteers at a dose of 500 mg (infusion over 60 min) C_m_Oh was 6.2 ± 1.0 μg / ml, with a dose of 750 mg (infusion for 90 min) - 11.5 ± 4.0 μg / ml. The pharmacokinetics of levofloxacin is linear and predictable for a single and repeated intravenous administration.

Distribution

Binding to proteins - 30-40%. The average volume of distribution of levofloxacin is 89-112 l after a single and multiple IV administration at a dose of 500 mg. Cumulation at a dose of 500 mg 1 time / day is insignificant. When administered at a dose of 500 mg twice daily, cumulation may 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.

Metabolism

In the liver, a small part of levofloxacin undergoes metabolism with the formation of demethyllevofloxacin and Nlevofloxacin oxide, which is less than 5% of excreted in the urine of the drug. Levofloxacin is characterized by stereochemical stability and is not subjected to chiral transformations.

Excretion

It is excreted primarily by the kidneys (more than 85%) by glomerular filtration and tubular secretion, less than 4% is secreted by the intestine. After a single IV injection at a dose of 500 mg, the elimination half-life (T1 / 2) is 6.4 ± 0.7 hours.

Pharmacokinetics in special clinical cases

In renal failure, the decrease in clearance of the drug and its excretion by the kidneys depends on the degree of decrease in the clearance of creatinine (CC).

CK (ml / min)	less than 20	20-40	50-80
Kidney clearance (ml / min)	13	26	57
Half-life (h)	35	27	9

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to levofloxacin, including:

- community acquired pneumonia;

- Complicated urinary tract diseases, including pyelonephritis;

- infections of the skin and soft tissues.

Contraindications:

Hypersensitivity to levofloxacin, other quinolones or other components of the drug; age to 18 years; pregnancy; the period of breastfeeding; epilepsy, including in the anamnesis; lowering the threshold of convulsive activity, including with craniocerebral trauma, acute impairment - cerebral circulation, inflammatory diseases of the central nervous system; deficiency of glucose-6-phosphate dehydrogenase; lesions of tendons against the background of the previously used fluoroquinolones; peripheral neuropathy.

Carefully:

Impaired renal function (CK less than 50 ml / min); hemodialysis and peritoneal dialysis; diabetes; abnormal liver function; simultaneous reception of antiarrhythmic drugs IA and III classes, tricyclic antidepressants, macrolides; violation of electrolyte balance (hypokalemia, hypomagnesemia); elderly age; cardiovascular diseases, including chronic heart failure, myocardial infarction; interval lengthening Q-T; congenital lengthening syndrome Q-T; simultaneous use of drugs that extend the interval Q-T (tetracyclic antidepressants, antipsychotics, antifungal drugs, derivatives of imidazole, some antihistamines, incl. astemizole, terfenadine, ebastine) and lowering the threshold of convulsive readiness of the brain (fenbufen, theophylline); bradycardia; mental illness, including in the anamnesis; myasthenia gravis gravis; hepatic porphyria.

Dosing and Administration:

In the form of intravenous infusions slowly (drip) 1-2 times a day. The duration of treatment should not exceed 14 days. As with other antibiotics, treatment with Levofloxacin-Teva should be continued for at least 48-72 hours after normal body temperature.

The duration of IV infusion of the drug in a dose of 250 mg (250 mg / 50 ml solution) should be at least 30 minutes, at a dose of 500 mg (500 mg / 100 ml solution) - at least 60 minutes.

Community-acquired pneumonia

500 mg 1-2 times a day. The duration of therapy is 7-14 days.

Complicated urinary tract diseases, including pyelonephritis

250 mg once a day. In severe cases, the dose may be increased.

Duration of therapy is 7-10 days.

Infectious and inflammatory diseases of the skin and soft tissues

500 mg twice a day.Duration of therapy is 7-14 days.

Patients with impaired renal function (KK less than 50 ml / min) correction of the dosage regimen is required depending on the QC value.

Doses for patients with impaired renal function (CC less than 50 ml / min)

CK (ml / min)	Dosage for oral or intravenous administration
	250 mg / 24 h	500 mg / 24 h	500 mg / 12 h
	the first dose of 250 mg	the first dose of 500 mg	the first dose of 500 mg
50-20	then 125 mg / 24 h	then 250 mg / 24 h	then 250 mg / 12 h
19-10	then 125 mg / 48 h	then 125 mg / 24 h	then 125 mg / 12 h
less than 10 (including hemodialysis and continuous ambulatory peritoneal dialysis (CAPD)) *	then 125 mg / 48 h	then 125 mg / 24 h	then 125 mg / 24 h

* After hemodialysis or CAPD, no additional doses are required.

When a violation of liver function correction of the dose is not required.

In elderly patients dose adjustment does not require. In case of renal dysfunction, dose adjustment is performed according to the table above.

Side effects:

The incidence of adverse reactions is classified according to the recommendations of the World Health Organization: often - at least 1% and less than 10%; infrequently - not less than 0.1% and less than 1%; rarely - not less than 0.01% and less than 0.1%; very rarely - less than 0.01%, including isolated cases.

Allergic reactions: infrequently - itching, rashes, skin hyperemia, swelling of the skin and mucous membranes,hives; rarely - bronchospasm / difficulty breathing; very rarely - angioedema, anaphylactic shock, photosensitivity; in isolated cases - Stevens-Johnson syndrome, toxic epidermal necrosis (Lyell's syndrome), exudative erythema multiforme, allergic vasculitis; Anaphylactic / anaphylactoid reactions can occur on the skin and mucosa after the first dose.

From the digestive system: often - nausea, diarrhea; infrequently - anorexia, vomiting, abdominal pain, indigestion, digestive disorders, dysbacteriosis; rarely - diarrhea with blood, which in rare cases can be a symptom of enterocolitis, including pseudomembranous colitis; very rarely - hypoglycemia (increased appetite, increased sweating, trembling), especially in patients with diabetes mellitus.

Co side of the nervous system: infrequently - headache, dizziness, drowsiness, insomnia; rarely - paresthesia, tremor, anxiety, depression, psychotic reactions, agitation, confusion, convulsions, "nightmarish" dreams, anxiety, peripheral sensory neuropathy, peripheral sensory-motor neuropathy, dyskinesia,fear; very rarely - hypoesthesia, visual and hearing disorders, odor disorders (parosmia, loss of smell), taste (dysgeusia, loss of taste sensations) and tactile sensitivity, hallucinations; in isolated cases - psychotic reactions, including behavior threatening the patient's life, and suicidal thoughts and actions, extrapyramidal symptoms and other disorders of muscle coordination.

From the cardiovascular system: very rarely - lowering blood pressure, lengthening the interval QT, cardiovascular collapse, sinus tachycardia.

From the musculoskeletal system: rarely - arthralgia, myalgia, muscle weakness, tendonitis (eg Achilles tendon); very rarely - a rupture of the tendon (for example, the Achilles tendon), as for other fluoroquinolones, the appearance of the effect is possible 48 hours after the initiation of therapy and can be bilateral; in isolated cases - rhabdomyolysis.

From the liver and bile ducts: often - increased activity of "liver" transaminases; infrequently - increased bilirubin content; very rarely - hepatitis.

From the side of the kidneys and urinary tract: infrequently, an increase in serum creatinine; very rarely - acute renal failure, interstitial nephritis.

On the part of the blood system and lymphatic system: infrequently - eosinophilia, leukopenia; rarely - neutropenia, thrombocytopenia; very rarely - agranulocytosis, hemorrhage; in isolated cases - hemolytic anemia, pancytopenia.

Other: often - pain, redness and phlebitis at the injection site; infrequently - asthenia, dyspnea, growth of fungal flora and other resistant microorganisms; in isolated cases - allergic pneumonitis, fever, porphyria attacks in patients with porphyria.

Overdose:

Symptoms: confusion, dizziness, impaired consciousness and seizures like epileptic seizures, nausea, erosive lesions of the mucous membranes. In clinico-pharmacological studies with levofloxacin at doses exceeding the average therapeutic levels, an interval elongation was observed QT.

Treatment: conduct symptomatic therapy. Levofloxacin not output by dialysis. There is no specific antidote.

Interaction:

Quinolones can enhance the ability of theophylline, fenbufen and similar non-steroidal anti-inflammatory drugs (NSAIDs), lower the threshold of convulsive readiness.

The concentration of levofloxacin was 13% higher with simultaneous use with fenbufen.

Caution should be applied levofloxacin simultaneously with probenecid and cimetidine, which block tubular secretion; under their action, the removal of levofloxacin slightly slows down. This interaction has practically no clinical significance and can primarily concern patients with impaired renal function.

With simultaneous application with levofloxacin T1 / 2 cyclosporine increases by 33%.

There are reports of hypercoagulation and / or bleeding with the simultaneous use of levofloxacin with indirect anticoagulants, coumarin derivatives. It is necessary to control the international normalized relationship (INR). Simultaneous reception with glucocorticosteroids (GCS) increases the risk of developing a rupture of tendons.

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

The solution for intravenous administration 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.

Special instructions:

In severe pneumonia caused by Streptococcus pneumoniae, the use of levofloxacin may not be effective enough. Hospital infections caused by Pseudomonas aeruginosa, may require the use of combination therapy.

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

In elderly patients with levofloxacin, the incidence of tendonitis increases. The use of GCS increases the risk of rupture of tendons. If suspected of tendonitis should be immediately canceled levofloxacin and begin appropriate treatment, providing a state of rest in the area of the lesion. - Diarrhea during treatment with levofloxacin, especially severe, persistent and / or with blood, may be a symptom of pseudomembranous colitis. If suspected pseudomembranous colitis should be immediately withdrawn levofloxacin and begin appropriate treatment. In such cases, drugs that depress intestinal motility should not be used.

Levofloxacin is contraindicated in patients with epilepsy, incl. in the anamnesis. During treatment with levofloxacin, it is possible to develop an episode of seizures in patients with previous brain damage (including stroke or severe brain trauma). Convulsive readiness may also increase with simultaneous use of fenbufen, similar to it, NSAIDs or theophylline.

When applying quinolones in patients with glucose-6-phosphate dehydrogenase insufficiency, hemolysis of erythrocytes is possible.

Despite the fact that photosensitization is noted with the use of levofloxacin is very rare, patients should avoid exposure to sun or UV irradiation to prevent its development.

With the simultaneous use of levofloxacin and indirect anticoagulants, coumarin derivatives, it is necessary to monitor the state of the blood coagulation system.

When carrying out antibiotic therapy, changes in the composition of the natural microflora of the organism can be observed. For this reason, increased reproduction of bacteria and fungi resistant to the antibiotic used (secondary infection and superinfection) is possible, which in rare cases may require additional treatment. The experience with the use of other quinolones indicates that they can exacerbate porphyria. A similar effect is not excluded when using levofloxacin.

As levofloxacin excreted mainly through the kidneys, in patients with impaired function, the kidneys need to monitor the kidney function, as well as adjust the dosage regimen.

Possible lengthening interval 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: old age, electrolyte balance disorder (hypokalemia, hypomagnesemia), congenital lengthening interval syndrome Q-T, heart disease (heart failure, myocardial infarction, bradycardia), simultaneous use of drugs that can lengthen the interval Q-T.

In patients with diabetes mellitus, receiving oral hypoglycemic drugs (for example, glibenclamide) or insulin, the use of levofloxacin increases the risk of developing hypoglycemia. Such patients need control of the concentration of glucose in the blood.

In patients receiving fluoroquinolones, including levofloxacin, sensory and sensory-motor peripheral neuropathy was noted, the onset of which can be rapid. When patients develop symptoms of neuropathy, the use of levofloxacin should be stopped (minimizing the risk of irreversible changes).

Levofloxacin should be used with caution in patients with pseudo-paralytic myasthenia gravis (myasthenia gravis).

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

During treatment with levofloxacin, care should be taken when driving vehicles and controlling mechanisms due to the possibility of developing side effects from the nervous system (dizziness, drowsiness) that affect the ability to concentrate attention and the speed of psychomotor reactions.

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

Packaging:

For 100 ml of the drug in bottles of transparent colorless glass type I (Hebrew Pharm.) With plugs of bromobutyl rubber and aluminum caps equipped with a protective cover made of transparent polypropylene. 1 bottle with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature of no higher than 30 ° C in a dark place. Do not freeze. Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001219

Date of registration:16.11.2011

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Works Private, Ltd. Co. Hungary

Representation: & nbspTeva Teva Israel

Information update date: & nbsp20.09.2015

Illustrated instructions

Instructions

Levofloxacin-Teva (Levofloxacin-Teva)