Левофлоксабол®

General characteristics. Structure:

Active ingredient: 5 mg of a levofloksatsin in 1 ml of solution.
Excipients: sodium chloride; dinatrium эдетат; Acidum hydrochloricum concentrated; water for injections.
 
Synthetic antibiotic of a broad spectrum of activity from group of ftorkhinolon.

Pharmacological properties:

Pharmacodynamics. Levofloxacin – a synthetic antibiotic from group of ftorkhinolon, optically active left-handed isomer of an ofloksatsin - (-) - (S) - an enantiomer. Possesses a wide range of antimicrobic action.

Inhibits DNK-girazu (topoisomerase II) and topoisomerase IV, breaks superspiralling and a stitching of DNA, suppresses DNA replication, causes profound morphological changes in cytoplasm, a cell wall and membranes of microorganisms.

Levofloxacin is highly active concerning aerobic gram-positive microorganisms: Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae (including strains, resistant to penicillin, makrolidama, tetracyclines and Trimethoprimum/sulfamethoxazole), Streptococcus pyogenes, Streptococcus agalactiae, Viridans group streptococci (Streptococcus mitis, Streptococcus sanguis, Streptococcus mutans, etc.), Streptococcus group of C, G, Bacillus anthracis, Corynebacterium diphtheriae; aerobic gram-negative microorganisms: Acinetobacter anitratus, Acinetobacter baumannii, Acinetobacter calcoaceticus, Bordetella pertussis, Citrobacter diversus, Citrobacter freundii, Enterobacter cloacae, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter sakazakii, Escherichia coli, Eikenella corrodens, Haemophilus influenzae (including the strains steady against ampicillin), Haemophilus parainfluenzae, Gardnerella vaginalis, Klebsiella pneumoniae, Klebsiella oxytoca, Morganella morganii, Moraxella catarrhalis (including the strains producing beta lactamelements), Neisseria gonorrhoeae (including the strains producing penicillinases), Neisseria meningitidis, Pasteurella multocida, Pasteurella dagmatis, Pasteurella conis, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas spp., Providencia rettgeri, Providencia stuartii, Serratia marcescens, Serratia spp., Salmonella spp.; anaerobic microorganisms: Peptostreptococcus spp. Clostridium perfringens, Prevotella melaninogenica, and also other microorganisms: Chlamydophila pneumoniae, Chlamydophila psittaci, Chlamidia trachomatis, Legionella pneumoniae, Legionella spp., Mycoplasma pneumoniae, mycobacteria (Mycobacterium tubercuosis, Mycobacterium bovis, Mycobacterium leprae), Ricketsia spp., Ureaplasma urealyticum.

Levofloxacin is moderately active concerning gram-positive microorganisms: Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium steady against Methicillinum (MR) of Staphylococcus epidermidis and Staphylococcus haemolyticus; aerobic gram-negative microorganisms: Burkholderia cepacia, Campilobacter jejuni; anaerobic microorganisms: Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp., Porphyromonas spp.

Are steady against a levofloksatsin: the majority of strains of Enterococcus faecium, Methicillinum - resistant Staphylococcus aureus and Staphylococcus epidermidis, Bacteroides fragilis, Clostridium difficile, Mycobacterium avium.
 
Pharmacokinetics. Later in/in infusion of 500 mg within 60 min. peak concentration (Cmax) are made by 6.2 mkg/ml. Communication with proteins of plasma - 30-40%. Well gets into bodies and fabrics: lungs, mucous membrane of bronchial tubes, phlegm, bodies of urinogenital system, polymorphonuclear leukocytes, alveolar macrophages. Concentration of an antibiotic in skin twice, and in lungs – from 2 to 5 times exceed serumal. Distribution volume in/in infusion of 500 mg of a levofloksatsin makes later from 74 do112 l/kg. Distribution volume after single and 500 mg of a levofloksatsin, repeated in/in infusions, makes 89-112 l. In a liver a small part of drug is oxidized and/or dezatsetilirutsya. The renal clearance makes 70% of the general clearance. T½ is 6-8 h. It is brought out of an organism preferential by kidneys by glomerular filtering and canalicular secretion. Less than 5% of a levofloksatsin are excreted in the form of metabolites. In not changed view with urine during 24 h 70% and for 48 h - 87% of the entered dose are removed; in Calais for 72 h 4% of the dose accepted inside are found.

At patients with a renal failure (the clearance of creatinine <50 ml/min.) an elimination half-life of a levofloksatsin is extended that demands dose adjustment in order to avoid cumulation of an antibiotic. The hemodialysis and peritoneal dialysis delete only an insignificant part of a levofloksatsin therefore there is no need to enter an additional dose of an antibiotic after the session of a hemodialysis or peritoneal dialysis.

Indications to use:

- acute and the exacerbations of chronic bronchitis caused by Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae or Moraxella catarrhalis;

- the pneumonia caused by Staphylococcus aureus, Streptococcus pneumoniae (including the strains steady against penicillin), Haemophilus influenzae, Haemophilus parainfluenzae, Escherichia coli, Klebsiella pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa, Serratia marcescens, Chlamydophila pneumoniae, Legionella pneumophila or Mycoplasma pneumoniae;

- the intraabdominal infections caused by Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus spp., Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Serratia marcescens, Pseudonionas aeruginosa;

- the uncomplicated and complicated infections of skin and soft tissues caused by Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis, Streptococcus agalactiae, Proteus mirabilis;

- the uncomplicated and complicated infections of urinary tract caused by Staphylococcus epidermidis, Staphylococcus saprophyticus, Enterococcus faecalis, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis or Pseudomonas aeruginosa;

- acute and exacerbations of the chronic bacterial prostatitis caused by Escherichia coli, Enterococcus faecalis or Staphylococcus epidermidis;

- septicaemia/bacteremia, connected with the indications stated above;

- complex therapy of drug resistant forms of tuberculosis.

Route of administration and doses:

^{ÏÑó«õ½«¬ßáí«½á® 500 infusion solution} of mg is entered intravenously kapelno; introduction duration - not less than 60 min.

Usual therapeutic dosages ^{of Levofloksabola®} for patients with normal function of kidneys (clearance of creatinine> of 80 ml/min.) make 500 mg each 24 hours. At heavy and life-threatening infections appoint 500 mg each 12 hours.

For clinical practice at therapy of a certain pathology it is recommended to be guided by the following doses and durations of therapy presented in the table:

Infection	Single dose	Frequency rate	Positiveness
Exacerbation of chronic bronchitis	500 mg	1 times/days	7 days *
Community-acquired pneumonia	500 mg	1 times/days	7-14 days *
Intraabdominal infection **	500 mg	1-2 times/days	7-14 days
Infections of skin and soft tissues	500 mg	1 times/days	7-10 days *
Acute pyelonephritis	500 mg	1 times/days	10 days *
Bacterial prostatitis	500 mg	1 times/days	28 days *
Sepsis	500 mg	2 times/days	10-14 days

* - step therapy is recommended;
** - it is recommended to combine with the antibacterial drugs operating on anaerobic microflora.

At patients with a renal failure the dose ^{of Levofloksabola®} should be korrigirovat depending on clearance of creatinine.

Dosing ^{of Levofloksabola®} at patients with a renal failure.

Clearance of creatinine, ml/min.	Dosing mode
	250 mg / 24 h	500 mg / 24 h	500 mg / 12 h
	first dose: 250 mg	first dose: 500 mg	first dose: 500 mg
> 50-20	then: on 125 mg each 24 h.	then: on 250 mg each 24 h.	then: on 250 mg each 12 h.
19-10	on 125 mg each 48 h.	on 125 mg each 24 h.	on 125 mg each 12 h.
<10	on 125 mg each 48 h.	on 125 mg each 24 h.	on 125 mg each 12 h.
Hemodialysis	on 125 mg each 48 h.	on 125 mg each 24 h.	on 125 mg each 12 h.
Peritoneal dialysis	on 125 mg each 48 h.	on 125 mg each 24 h.	on 125 mg each 12 h.

The bottle with ^{Levofloksabola® solution} should be protected from influence of direct sunshine.

In ^{Levofloksabola® solution} it is impossible to mix and dissolve other medicines.

For infusion ^{of Levofloksabola®} it is preferable to use separate system for in/in injections.

 

Features of use:

At treatment of patients of senile age it must be kept in mind that patients of this group often have a renal failure that demands the corresponding dose adjustment.

During infusion of a levofloksatsin the strengthened heartbeat and tranzitorny falling of arterial pressure can be observed. At the expressed falling of arterial pressure administration of drug is immediately stopped.

At a concomitant use of the drugs reducing a threshold of convulsive activity (theophylline, non-steroidal anti-inflammatory drugs - derivatives of propionic acid for treatment of rheumatic diseases) as levofloxacin can provoke an attack of spasms.

Levofloxacin extremely seldom causes a photosensitization, however the patients accepting levofloxacin are recommended not to be exposed to excessive solar or artificial ultra-violet radiation (for example, stay in the sun in the mountain area or visit of a sunbed).

At use of hinolon for patients with insufficiency glyukozo-6-fosfatdegidrogenazy hemolysis of erythrocytes therefore levofloksatsiny this category of patients should carry out treatment with extra care is possible.

At use of drug for patients with a diabetes mellitus it must be kept in mind that levofloxacin can cause a hypoglycemia.

At suspicion of antibiotikoassotsiirovanny diarrhea and pseudomembranous colitis (heavy, persistent diarrhea with or without blood impurity against the background of reception of an antibiotic) it is necessary to cancel immediately levofloxacin and to begin the corresponding treatment (metronidazole, per os Vancomycinum, enterosorbents, infusional therapy). In such cases it is impossible to apply the medicines oppressing motility of intestines.

At suspicion on a tendinitis (first of all, the Achilles tendon inflammation) it is necessary to stop treatment levofloksatsiny and to provide a condition of rest to the affected sinew.

During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding concentration of attention and speed of psychomotor reactions.

Side effects:

At use in the recommended dosages and the modes of dosing levofloxacin is well transferred.

For assessment of frequency of occurrence of side reactions use the following criteria "often" (occur at 1-10 patients from 100), "sometimes" (occur less than at 1 patient from 100), is "rare" (occur less than at 1 patient from 1000), "it is very rare" (occur less than at 1 patient from 10 000) and "in some cases" (only isolated cases are described).

Allergic reactions: sometimes - an itch and erubescence; seldom - the anaphylactic and anaphylactoid reactions (which are shown such symptoms as a small tortoiseshell, a bronchospasm, and also - in rare instances - face edemas, throats); very seldom - sudden falling of arterial pressure and shock; in some cases - Stephens-Johnson's syndrome, a toxic epidermal necrolysis (Lyell's disease) and an exudative multiformny erythema.

From skin and hypodermic cellulose: very seldom - a photosensitization.

From the alimentary system: sometimes - nausea, diarrhea, appetite loss, vomiting, abdominal pains, digestion disturbances; very seldom - diarrhea with blood impurity (in some cases it can be a symptom of pseudomembranous colitis).

From a liver: increase in activity of alaninaminotranspherase, asparaginaminotransferaza; sometimes - increase in level of bilirubin in blood serum; very seldom – hepatitis.

From a metabolism: very seldom - a hypoglycemia.

From the central and peripheral nervous system: sometimes - a headache, dizziness and/or constraint, drowsiness, sleep disorders; seldom - paresthesias in hands, a shiver, concern, conditions of fear; attacks of spasms and confusion of consciousness, psychotic reactions like hallucinations and depressions; very seldom - a vision disorder and hearing, disturbances of flavoring sensitivity and sense of smell, decrease in tactile sensitivity.

From cardiovascular system: seldom - tachycardia, falling of arterial pressure; very seldom - a vascular collapse; in some cases – lengthening of an interval of QT.

From a musculoskeletal system: seldom - joint and muscular pains; very seldom - damages of sinews, including a tendinitis, a rupture of the Achilles tendon (can have bilateral character and be shown already in 48 h after an initiation of treatment), muscular weakness (has special value for patients with a myasthenia); in some cases - рабдомиолиз.

From an urinary system: sometimes - increase in level of creatinine in blood serum; very seldom - deterioration in function of kidneys up to an acute renal failure (for example, owing to allergic reactions - intersticial nephrite).

From system of a hemopoiesis: sometimes - an eosinophilia, a leukopenia; seldom - a neutropenia, thrombocytopenia; very seldom - an agranulocytosis; in some cases - hemolitic anemia, a pancytopenia.

Others: sometimes - an adynamy; very seldom - fever, an allergic pneumonitis, a vasculitis.

Interaction with other medicines:

The concomitant use of the drugs capable to lower a threshold of convulsive readiness (theophylline, non-steroidal anti-inflammatory drugs - derivatives of propionic acid for treatment of rheumatic diseases) and a levofloksatsin can provoke an attack of spasms.

Cimetidinum and пробенецид slightly slow down renal clearance of a levofloksatsin, however, it has no clinical value.

At a concomitant use of cyclosporine and a levofloksatsin small increase in an elimination half-life of cyclosporine from a blood plasma is noted.

Levofloksabola® infusion solution is compatible from 0,9% solution of sodium chloride, 5% dextrose solution, Ringer's solution with a dextrose combined by solutions for parenteral food (amino acids, carbohydrates, electrolytes).

It is impossible to mix with the heparin, other antibiotics and solutions having alkali reaction.

Contraindications:

- hypersensitivity to a levofoloksatsin and other hinolona,
- children's and teenage age (up to 18 years),
- pregnancy,
- lactation period,
- damages of sinews at earlier carried out treatment of a hinolonama,
- epilepsy.

With care appoint:
- advanced age (high probability of the accompanying depression of function of kidneys),
- deficit glyukozo-6-fosfatdegidrogenazy,
- at patients with organic lesions of the central nervous system (a state after a stroke, brain injuries).

Overdose:

Symptoms: confusion of consciousness, dizziness and attacks of spasms, nausea, lengthening of an interval of QT, erosive damages of mucous membranes of digestive tract.
Treatment: symptomatic and infusional therapy, medical observation is shown. Badly is removed at haemo - and peritoneal dialysis therefore efficiency of these methods at acute poisoning levofloksatsiny is doubtful. The specific antidote of a levofloksatsin does not exist.

Storage conditions:

In the dry, protected from light place, at a temperature not above 25 °C. To store in the places unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 100 ml of drug in bottles (bottles) glass with a capacity of 100 ml. 1 bottle (bottle) with the application instruction is placed in a pack from a cardboard.