Levofloxabol - instructions for use, dose, side effects, contraindications

Levofloxacin is a synthetic antibiotic from the group of fluoroquinolones, the optically active levorotatory isomer of ofloxacin - (-) - (S) -enantiomer. It has a wide spectrum of antimicrobial action.

Inhibits DNA-gyrase (topoisomerase II) and topoisomerase IV, disrupts supercoiling and DNA cross-linking, suppresses DNA replication, causes profound morphological changes in the cytoplasm, cell wall and membranes of microorganisms.

Levofloxacin is highly active against aerobic Gram-positive microorganisms: Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae (including strains resistant to penicillin, macrolides, tetracyclines and trimethoprim / sulfamethoxazole), Streptococcus pyogenes, Streptococcus agalactiae, Viridans group streptococci (Streptococcus mitis, Streptococcus sanguis, Streptococcus mutans and etc.), Streptococcus groups 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 strains resistant to ampicillin), Haemophilus parainfluenzae, Gardnerella vaginalis, Klebsiella pneumoniae, Klebsiella oxytoca, Morganella morganii, Moraxella catarrhalis (including strains producing beta-l acts of aza), Neisseria gonorrhoeae (including 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,

as well as other microorganisms: Chlamydophila pneumoniae, Chlamydophila psittaci, Chlamydia trachomatis, Legionella pneumoniae, Legionella spp., Mycoplasma pneumoniae, mycobacteria (Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium leprae), Rickettsia spp., Ureaplasma urealyticum.

Levofloxacin moderately active against gram-positive microorganisms: Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, sustainable to methicillin (MR) Staphylococcus epidermidis and Staphylococcus haemolyticus,

aerobic gram-negative mikorganisms: Burkholderia cepacia, Campilobacter jejuni,

anaerobic microorganisms: Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp., Porphyromonas spp.

Stable to levofloxacin: most strains Enterococcus faecium, methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, Bacteroides fragilis, Clostridium difficile, Mycobacterium avium.

Pharmacokinetics:

After iv infusion of 500 mg for 60 min peak concentration (Cmax) is 6.2 μg / ml. The connection with plasma proteins is 30-40%. It penetrates well into organs and tissues: lungs, bronchial mucosa, sputum, organs of the genitourinary system,polymorphonuclear leukocytes, alveolar macrophages. The concentration of antibiotic in the skin is 2 times, and in the lungs - from 2 to 5 times higher than serum. The volume of distribution after IV infusion of 500 mg of levofloxacin is from 74 to 112 l / kg. The volume of distribution after a single and multiple IV infusions of 500 mg of levofloxacin is 89-112 liters. In the liver, a small portion of the drug is oxidized and / or deacetylated. Kidney clearance is 70% of the total clearance. T1 / 2 - 6-8 hours. Excreted mainly by the kidneys through glomerular filtration and tubular secretion. Less than 5% of levofloxacin is excreted as metabolites. Unchanged in the urine within 24 hours, 70% are discharged and in 87 hours 87% of the administered dose; in the stool for 72 hours 4% of the dose taken internally is detected.

In patients with renal insufficiency (creatinine clearance <50 ml / min), the half-life of levofloxacin is prolonged, which requires correction dose to avoid cumulation of the antibiotic. Hemodialysis and peritoneal Dialysis removes only a small part of levofloxacin, so there is no the need to inject an additional dose of an antibiotic after a hemodialysis session or peritoneal dialysis.

Indications:

- ABOUTand exacerbations of chronic bronchitis caused by Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae or Moraxella catarrhalis; pneumonia caused by Staphylococcus aureus, Streptococcus pneumoniae (including strains resistant to penicillin), Haemophilus influenzae, Haemophilus parainfluenzae, Escherichia coli, Klebsiella pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa, Serratia marcescens, Chlamydophila pneumoniae, Legionella pneumophila or Mycoplasma pneumoniae;

- intra-abdominal infections caused by Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus spp,, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Serratia marcescens, Pseudomonas aeruginosa;

- uncomplicated and complicated skin and soft tissue infections caused by Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis, Streptococcus agalactiae, Proteus mirabilis^-,

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

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

- septicemia / bacteremia associated with the above indications;

- complex therapy of drug-resistant forms of tuberculosis.

Contraindications:

- Hypersensitivity to levofoloxacin and other quinolones,

- children and adolescence (up to 18 years),

- pregnancy,

- lactation period,

- the lesions of tendons during the previous treatment with quinolones,

- epilepsy.

Carefully:

- Elderly age (high probability of concomitant decrease in kidney function),

- deficiency of glucose-6-phosphate dehydrogenase,

- in patients with organic lesions of the central nervous system (a condition after a stroke, a brain injury).

Dosing and Administration:

Infusion solution of Levofloxabol® 500 mg is administered intravenously drip; duration of administration - at least 60 minutes.

The usual therapeutic dosages of Levofloxabol® for patients with normal renal function (creatinine clearance> 80 ml / min) are 500 mg every 24 hours. In severe and life-threatening infections, 500 mg every 12 hours is prescribed.

For clinical practice in the treatment of certain pathologies, the following doses and the duration of therapy presented in the table are recommended:

Infection	Single dose	Multiplicity	Duration
Exacerbation of chronic bronchitis	500 mg	1 time / day	7 days*
Community-acquired pneumonia	500 mg	1 time / day	7-14 days *
Intra-abdominal infection **	500 mg	1 -2 times / day	7-14 days
Infections of the skin and soft tissues	500 mg	1 time / day	7-10 days *
Acute pyelonephritisrhythm	500 mg	1 time / day	10 days*
Bacterial pro-statutes	500 mg	1 time / day	28 days *
Sepsis	500 mg	2 times / day	10-14 days

* - step therapy is recommended;

** - it is recommended to combine with antibacterial drugs that act on anaerobic microflora.

In patients with impaired renal function, the dose of Levofloxabol® should be adjusted depending on the creatinine clearance.

Dosage of Levofloxabol® in patients with renal insufficiency.

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

The bottle with Levofloxabol® solution should be protected from direct sunlight.

Do not mix and dissolve other medicines in the Levofloxabol® solution.

For infusion of Levofloxabol®, it is preferable to use a separate system for IV infusions.

Side effects:

When used in recommended dosages and dosing regimens levofloxacin well tolerated.

To assess the incidence of adverse reactions, the following criteria are used "often" (found in 1-10 patients out of 100),"sometimes" (found in less than 1 patient out of 100), "rarely" (less than 1 in 1,000 patients), "very rare" (less than 1 in 10,000 patients) and "in some cases" ( only single cases are described).

Allergic reactions: sometimes - itching and redness of the skin; rarely - anaphylactic and anaphylactoid reactions (manifested by such symptoms as hives, bronchospasm, and - in rare cases - swelling of the face, larynx); very rarely - a sudden drop in blood pressure and shock; in some cases - Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome) and exudative erythema multiforme.

From the skin and subcutaneous tissue: very rarely photosensitization.

From the digestive system: sometimes - nausea, diarrhea, loss of appetite, vomiting, abdominal pain, digestive disorders; very rarely - diarrhea with an admixture of blood (in some cases this may be a sign of pseudomembranous colitis).

From the side of the liver: increased activity of alanine aminotransferase, asparagine aminotransferase; sometimes - an increase in the level of bilirubin in the blood serum; very rarely - hepatitis.

From the side of metabolism: very rarely - hypoglycemia.

From the central and peripheral nervous system: sometimes - headache, dizziness and / or stiffness, drowsiness, sleep disturbances; rarely - paresthesia in the hands, trembling, anxiety, states of fear; seizures and confusion, psychotic reactions such as hallucinations and depressions; very rarely - visual and hearing impairments, violations of taste sensitivity and smell, a decrease in tactile sensitivity.

From the cardiovascular system: rarely - tachycardia, a drop in blood pressure; very rarely - vascular collapse; in some cases - lengthening the interval QT.

From the musculoskeletal system: rarely joint and muscle pain; very rarely - tendon lesions, including tendonitis, Achilles tendon rupture (can be bilateral and manifest only 48 hours after the start of treatment), muscle weakness (is of particular importance for myasthenia patients); in some cases - rhabdomyolysis.

From the urinary system: sometimes - increased serum creatinine levels; very rarely - deterioration of kidney function up to acute renal failure (for example, due to allergic reactions - interstitial nephritis).

On the part of the hematopoiesis system: sometimes - eosinophilia, leukopenia; rarely - neutropenia, thrombocytopenia; very rarely - agranulocytosis; in some cases - hemolytic anemia, pancytopenia.

Other: sometimes - asthenia; very rarely - fever, allergic pneumonitis, vasculitis.

Overdose:

Symptoms: confusion, dizziness and seizures, nausea, lengthening of the interval QT, erosive lesions of the mucous membranes of the gastrointestinal tract.

Treatment: symptomatic and infusion therapy, medical supervision. Poorly removed in hemo- and peritoneal dialysis, so the effectiveness of these methods for acute levofloxacin poisoning is questionable. There is no specific antidote to levofloxacin.

Interaction:

Simultaneous reception of drugs that can lower the threshold of convulsive readiness (theophylline, non-steroidal anti-inflammatory drugs - derivatives of propionic acid for the treatment of rheumatic diseases) and levofloxacin can trigger an attack of seizures.

Cimetidine and probenecid slightly slow the renal clearance of levofloxacin, however, this has no clinical significance.

With the simultaneous administration of cyclosporine and levofloxacin, a slight increase in the half-life of cyclosporin from the blood plasma was noted. The infusion solution of Levofloxabol® is compatible with 0.9 % solution of sodium chloride, 5 % dextrose solution, Ringer's solution with dextrose, combined solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).

Do not mix with heparin, other antibiotics and solutions that have an alkaline reaction.

Special instructions:

When treating patients of senile age, it should be borne in mind that patients of this group often have a disruption of kidney function, which requires appropriate dose adjustment.

During the infusion of levofloxacin, there may be increased heart rate and transient drop in blood pressure. With a pronounced drop in blood pressure, the administration of the drug is immediately stopped.

With the simultaneous administration of drugs that reduce the threshold of convulsive activity (theophylline, non-steroidal anti-inflammatory drugs - derivatives of propionic acid for the treatment of rheumatic diseases), since levofloxacin can provoke an attack of seizures. Levofloxacin rarely causes photosensitivity, but patients receiving levofloxacin, it is recommended not to be exposed to excessive sunlight or artificial ultraviolet radiation (for example, sun exposure in the highlands or visits to the solarium).

When using quinolones in patients with glucose-6-phosphate dehydrogenase deficiency, hemolysis of red blood cells is possible, therefore treatment with levofloxacin of this category of patients should be carried out with extreme caution.

When using the drug in patients with diabetes, it should be borne in mind that levofloxacin can cause hypoglycemia.

If there is a suspicion of antibiotic-associated diarrhea and pseudomembranous colitis (severe, persistent diarrhea with or without blood admixture while taking an antibiotic), you should immediately cancel levofloxacin and begin appropriate treatment (metronidazole, vancomycin per os, enterosorbents, infusion therapy). In such cases, drugs that depress intestinal motility should not be used.

If suspicion of tendonitis (first of all, inflammation of the Achilles tendon), treatment with levofloxacin should be stopped and the resting condition of the affected tendon should be maintained.

Effect on the ability to drive transp. cf. and fur:During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring concentration of attention and speed of psychomotor reactions.

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

Packaging:

For 100 ml of the drug in bottles of glass with a capacity of 100 ml.

1 bottle (bottle) with instruction for use is placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Store in inaccessible to children.

Do not freeze.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-009887/09

Date of registration:04.12.2009 / 07.02.2018

Expiration Date:Unlimited

The owner of the registration certificate:PREBAND PFC, LLCPREBAND PFC, LLC Russia

Manufacturer: & nbsp

PREBAND PFC LLC Russia

Information update date: & nbsp07.03.2018

Illustrated instructions

Instructions

Levofloxabol® (Levofloxabol®)