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

Excipients: microcrystalline cellulose (66.40 mg / 106.80 mg), pregelatinized starch (10.00 mg / 20.00 mg), polysorbate 80 (2.50 mg / 5.00 mg), crospovidone (5.00 mg / 10 , 00 mg), talc purified (1.48 mg / 2.96 mg), silicon dioxide colloid (1.50 mg / 2.96 mg), magnesium stearate (3.50 mg / 7.00 mg).

composition of the shell: Hypromellose (3.83 mg / 5.92 mg), talc purified (0.623 mg / 0.963 mg), titanium dioxide (0.879 mg / 1.359 mg), iron oxide red (0.134 mg / 0.198 mg), iron oxide yellow oxide 0.036 mg / 0.056 mg), propylene glycol (2.933 mg / 4.533 mg), diethyl phthalate (0.365 mg / 0.566 mg).

Description:

250 mg tablets: reddish-brown, round, biconvex tablets, film-coated;

Tablets 500 mg: reddish-brown, capsular, biconvex tablets, covered with a film membrane.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A Fluoroquinolones

J.01.M.A.12 Levofloxacin

Pharmacodynamics:

Levofloxacin is a fluoroquinolone, a broad-spectrum antibacterial agent. The mechanism of action is the inhibition of bacterial topoisomerase IV and DNA gyrase (topoisomerase II), the enzymes necessary for replication, transcription,recovery and recombination of bacterial DNA.

Antimicrobial activity:

In vitro levofloxacin demonstrates broad antimicrobial activity against Gram-positive and Gram-negative microorganisms.

There is cross-resistance between levofloxacin and other fluoroquinolones, but some microorganisms resistant to other fluoroquinolones are susceptible to levofloxacin.

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

In vitro

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

- Aerobic Gram-positive microorganisms: Corynebacterium diphtheriae, Corynebacterium striatum, Enterococcus faecalis, Enterococcus spp, Listeria monocytogenes, Staphylococcus coagulase-negative methi-S(I) [methicillin-sensitive / -modern sensitive], Staphylococcus aureus methi-S, Staphylococcus epidermidis methi-S Staphylococcus spp, Streptococci group C and G, Streptococcus agalactiae, Streptococcus pneumonia peni I/S/R (penicillin-sensitive / -residually sensitive / -resistant), Streptococcus pyogenes, Viridans streptococci peni-S/R.

- Aerobic Gram-negative microorganisms: Acinetobacter baumannii, Acinetobacter spp, Acinetobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Enterobacter spp, Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S/R (ampicillin-sensitive / -resistant), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella spp, Moraxella catarrhalis P+/|3-, Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida, Pasteurella spp, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Providencia spp, Pseudomonas aeruginosa (hospital infections caused by Pseudomonas aeruginosa, may require combined treatment), Pseudomonas spp, Salmonella spp, Serratia marcescens, Serratia

- Anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp, Clostridium perfringens, Fusobacterium spp, Peptostreptococcus, Propionibacterium spp, Veilonella spp.

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

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

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

- Aerobic Gram-negative microorganisms: Burkholderia cepacia, Campylobacter jejuni/coli.

- Anaerobic microorganisms: Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp, Porphyromonas spp.

Resistant to levofloxacin microorganisms (MIC of ≥8 mg / l, inhibition zone ≤13 mm)

- Aerobic Gram-positive microorganisms: Corynebacterium jeikeium, Staphylococcus aureus methi-R, Staphylococcus coagulase-negative methi-R.

- Aerobic gram-negative microorganisms: Alcaligenes xylosoxidans.

- Anaerobic microorganisms: Bacteroides thetaiotaomicron.

- Other microorganisms: Mycobacterium avium.

Clinical efficacy (effectiveness in clinical trials in the treatment of infections caused by the microorganisms listed below)

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

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

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

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

Pharmacokinetics:

Levofloxacin is rapidly and almost completely absorbed when taken orally. The maximum concentration in the plasma is achieved 1-2 hours after ingestion and is 5.2 ± 1.2 μg / ml. The bioavailability of levofloxacin is approximately 99 %. The drug can be used regardless of food intake. It penetrates well into tissues and body fluids. The concentration of levofloxacin in the lung tissue (the maximum concentration is approximately 11.3 μg / ml and is reached in 4-5 hours) higher than in blood plasma in 2-5 times.

24-38 % the drug binds to plasma proteins. The drug is partially metabolized in the body. It is excreted mainly in the unchanged form of the kidneys (about 87 %) and 5% - in the form of inactive metabolites within 48 hours. Less than 4 % is excreted through the intestine within 72 hours. The half-life period varies from 6 to 8 hours.

Special groups of patients

Renal failure. In patients with impaired renal function, the half-life of levofloxacin from plasma is increased, which requires dose adjustment to avoid cumulation. Levofloxacin It is not eliminated from the body by hemodialysis or prolonged outpatient peritoneal dialysis.

Liver failure. The violation of liver function does not have a significant effect on the metabolism of levofloxacin.

Indications:

Infectious - inflammatory diseases caused by microorganisms sensitive to levofloxacin:

- ENT organs (including acute sinusitis);

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

- urinary tract and kidneys (including pyelonephritis);

- genital organs (including chronic bacterial prostatitis);

- skin and soft tissues (festering atheromas, abscess, furunculosis);

- intra-abdominal infection;

- tuberculosis (complex therapy of drug-resistant forms);

- septicemia / bacteremia (associated with the above indications).

Contraindications:

Individual hypersensitivity to levofloxacin, other quinolones, or individual components of the drug.

Violations of the central nervous system (epilepsy, severe form of cerebral atherosclerosis).

The defeat of the tendons during the previous treatment with quinolones.

Pregnancy and lactation.

Children and adolescence under 18 years.

Impaired renal function (creatinine clearance less than 20 ml / min).

Carefully:

Predisposition to convulsive reactions (atherosclerosis of cerebral vessels, cerebral circulatory disorders (in the anamnesis), organic diseases of the central nervous system), advanced age, deficiency of glucose-6-phosphate dehydrogenase, renal failure, congenital lengthening syndrome Q-T, heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (eg, hypokalemia, hypomagnesemia), diabetes mellitus, myasthenia gravis gravis, psychoses and other mental disorders in the anamnesis, hepatic porphyria, simultaneous reception 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).

Pregnancy and lactation:

The use of the drug is contraindicated in pregnancy. At the time of treatment should be to stop breastfeeding.

Dosing and Administration:

Inside, before meals or at a break between meals, without chewing, squeezed enough liquid.

In patients with normal renal function (creatinine clearance> 50 ml / min), the following doses are used for different indications:

	Indications		Dose	Duration (days)
1	Infectious diseases of skin and soft tissues		250-500 mg 1-2 times a day	7-14 days
2	Community-acquired pneumonia		500 mg 1-2 times a day	7-14 days
3	Exacerbation of chronic bronchitis		250-500 mg once a day	7-10 days
4	Acute maxillary sinusitis		500 mg	10-14 days
			1 time per day
5		Complicated urinary tract infections (including acute pyelonephritis)	250 mg once a day	7-10 days
6		Uncomplicated urinary tract infections	250 mg once a day	3 days
7		Intra-abdominal infection	500 mg once a day	7-14 days (in combination with antibacterial drugs acting on anaerobic flora)
8		Chronic bacterial prostatitis	500 mg once a day	28 days
9		Septicemia / bacteremia associated with the above indications	500 mg 1-2 times a day	10-14 days
10		Complex treatment of drug-resistant forms of tuberculosis	500 mg 1-2 times a day	Up to 3 months

Levofloxacin is excreted mainly by the kidneys, therefore, in the treatment of patients with impaired renal function, a dose reduction is required (see table below).

Clearance creatinine	Dosage regimen of levofloxacin
	The recommended dose for clearance of creatinine> 50 ml / min: 250 mg / 24 h	The recommended dose for clearance of creatinine> 50 ml / min: 500 mg / 24 h	The recommended dose for clearance of creatinine> 50 ml / min: 500 mg / 12 h
50-20 ml / min	The first dose: 250 mg: then 125 mg / 24 h	First dose: 500 mg: then 250 mg / 24 h	The first dose: 500 mg: then 250 mg / 12 h
19-10 ml / min	The first dose: 250 mg: then 125 mg / 48 h	First dose: 500 mg: then 125 mg / 24 h	The first dose: 500 mg: then 125 mg / 12 h
<10 ml / min (including hemodialysis and CAPD¹)	The first dose: 250 mg: then 125 mg / 48 h	First dose: 500 mg: then 125 mg / 24 h	First dose: 500 mg: then 125 mg / 24 h

¹After hemodialysis or permanent ambulatory peritoneal dialysis (CAPD), no additional doses are required.

If the liver function is not required, a special dose selection is required, since levofloxacin is metabolized in the liver only to a very small extent.

For elderly patients, there is no need to change the dosage regimen, except for cases of decreased creatinine clearance (up to 50 ml / min and below.)

Treatment with the drug is recommended to continue treatment for at least 48-78 hours after the normalization of body temperature or after a significant destruction of the pathogen. Dosing regimen is determined by the nature and severity of the infection, as well as the suspected pathogen susceptibility. The duration of therapy depends on the type of disease.

Side effects:

Determination of the frequency of adverse reactions (number of patients per total number of cases): often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100), rarely (> 1/10 000 and <1 / 1000), very rarely (<1/10 000).

From the digestive system: often - nausea, diarrhea, increased activity of "liver" transaminases. Not often - loss of appetite, vomiting, anorexia, abdominal pain, digestive disorders. Rarely, diarrhea with blood, pseudomembranous colitis; hyperbilirubinemia. Very rarely - liver reactions (eg, liver inflammation or hepatitis).

From the side of the cardiovascular system: rarely - lowering blood pressure, tachycardia. Very rarely - vascular collapse.In some cases, the lengthening of the interval QT. It is extremely rare - atrial fibrillation.

From the side of metabolism: very rarely - hypoglycemia (increased appetite, sweating, nervousness, trembling).

From the nervous system: infrequently - headache, dizziness and / or numbness, weakness, drowsiness, insomnia. Rarely - depression, anxiety, fear, hallucinations, confusion, movement disorders, convulsions, paresthesia, tremor. Very rarely - visual and hearing impairments, disorders of taste sensitivity and smell, a decrease in tactile sensitivity, peripheral sensory and sensory-motor neuropathy, ringing in the ears, agitation (agitation), "nightmarish" dreams, mental disorders with behavioral disorders with self-harm, suicidal thoughts, suicidal attempts, extrapyramidal disorders.

From the musculoskeletal system: rarely - tendon damage (including tendonitis), joint and muscle pain, Very rarely - muscle weakness, rupture of tendons (eg Achilles tendon), this side effect can be observed within 48 hours after the start of treatment and can be bilateral.In some cases - rhabdomyolysis.

From the urinary system: rarely - hypercreatininaemia. Very rarely - interstitial nephritis, acute renal failure.

From the hematopoiesis: infrequently - eosinophilia, leukopenia. Rarely - neutropenia, thrombocytopenia. Very rarely - agranulocytosis and the development of severe infections. In some cases - pancytopenia, hemolytic anemia.

Allergic reactions: infrequently - itching, flushing of the skin. Rarely, general hypersensitivity reactions (anaphylactic and anaphylactoid), such as urticaria, bronchospasm and possible severe suffocation. Very rarely - swelling of the skin and mucous membranes, a sharp decrease in blood pressure and shock, photosensitivity (increased sensitivity to sun and UV radiation), allergic pneumonitis, vasculitis. In some cases - malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).

Other: infrequently, general weakness. Very rarely - persistent fever, development of superinfection. In some cases - exacerbation of porphyria.

Overdose:Symptoms: confusion, dizziness, convulsions, gastrointestinal disorders (eg, nausea) and erosive lesions of the mucous membranes, lengthening of the interval QT.

Treatment: symptomatic, dialysis is not effective.

Interaction:

Levofloxacin increases half-life cyclosporine.

The effect of levofloxacin reduces drugs that depress intestinal motility, sucralfate, magnesium and aluminum containing antacids, iron ions, zinc in multivitamins (a break between taking these drugs and levofloxacin for at least 2 hours is necessary).

The excretion of levofloxacin slows down under the action of cimetidine, probenecid and drugs that block the tubular secretion.

Non-steroidal anti-inflammatory drugs and theophylline: when used with levofloxacin increase convulsive readiness.

Glucocorticosteroids: increase the risk of rupture of tendons.

Antidiabetic drugs: Strict control over the concentration of glucose in the blood is necessary, since there is a possibility of hyper- and hypoglycemia when used simultaneously with levofloxacin.

When used simultaneously with indirect anticoagulants, coumarin derivatives, control of the international normalized relationship is necessary. 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:

Hospital infections caused by Pseudomonas aeruginosa, may require combination therapy. As levofloxacin excreted mainly through the kidneys, in patients with impaired renal function, control over the kidney function is required, as well as correction of the dosing 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: 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 with diabetes mellitus receiving oral hypoglycemic agents (for example, glibenclamide) or insulin, when applied Levofloxacin increases the risk of developing hypoglycemia. Such patients need to monitor 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 a patient develops symptoms of neuropathy, the use of levofloxacin should be discontinued (minimizes the possible risk of irreversible changes).

The drug does not have the features of the action at the first reception or upon its cancellation.

You should not stop prematurely or temporarily discontinue the course of treatment started, and also take the medication irregularly.

If you miss a dose, you need to take the next dose of the drug as quickly as possible, then taking the drug according to the scheme established by your doctor. Do not take twice the dose of the drug.

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

During the treatment period it is necessary to refrain from engaging in potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Film coated tablets, 250 mg and 500 mg.

Packaging:

5 tablets in a blister (PVC / Aluminum).

1, 2, 5 or 10 blisters with instructions for use are placed in a cardboard pack. When packing in a Russian company (ZAO "Rafarma") 5 tablets in a blister (PVC / Aluminum), one blister along with the instruction for use is placed in a cardboard pack.

Storage conditions:

In a dry, 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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006434/08

Date of registration:11.08.2008

The owner of the registration certificate:McLeodz Pharmaceuticals Co., Ltd. McLeodz Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

MACLEODS PHARMACEUTICALS, Ltd. India

RAFARMA, JSC Russia

Representation: & nbspAdvansd Trading, OOOAdvansd Trading, OOO

Information update date: & nbsp12.10.2015

Illustrated instructions

Instructions

MACLEVO® (Maclevo®)