Catad_pgroup Antibacterial quinolones and fluoroquinolones

Levofloxacin - instructions for use

INSTRUCTIONS
on the medical use of the drug

Registration number:

LSR-001519/08-140308

Trade name of the drug: Levofloxacin.

International non-proprietary name:

Levofloxacin.

Dosage form:

Film-coated tablets.

Compound:

Active substance:
levofloxacin - 250 mg or 500 mg (in terms of levofloxacin hemihydrate - 256.23 mg and 512.46 mg).
Excipients:
microcrystalline cellulose, hypromellose (hydroxypropyl methylcellulose), primellose (croscarmellose sodium), calcium stearate.
Shell composition:
hypromellose (hydroxypropyl methylcellulose), macrogol 4000 (polyethylene glycol, polyethylene oxide), talc, titanium dioxide, iron oxide yellow.

Description:
Tablets, film-coated yellow, round, biconvex shape. The cross section shows two layers.

Pharmacotherapeutic group:

antimicrobial agent, fluoroquinolone.

ATC code: .

Pharmacological properties
Pharmacodynamics
Levofloxacin is a synthetic broad-spectrum antibacterial drug from the group of fluoroquinolones containing levofloxacin, a levorotatory isomer of ofloxacin, as an active substance. Levofloxacin blocks DNA gyrase, disrupts supercoiling and cross-linking of DNA breaks, inhibits DNA synthesis, and causes profound morphological changes in the cytoplasm, cell wall, and membranes.
Levofloxacin is active against most strains of microorganisms both in vitro and in vivo.
Aerobic gram-positive organisms: Corynebacterium diphtheriae, Enterococcus faecalis, Enterococcus spp, Listeria monocytogenes, Staphylococcus coagulase-negative methi-S(I), Staphylococcus aureus methi-S, Staphylococcus epidermidis methi-S, Staphylococcus spp (CNS), Group C Streptococci and G, Streptococcus agalactiae, Streptococcus pneumoniae peni I/S/R, Streptococcus pyogenes, Viridans streptococci peni-S/R.
Aerobic gram-negative organisms: Acinetobacter baumannil, Acinetobacter spp, Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Enterobacter spp, Escherichia coli, Gardnerella amino-vagilis, Haemophilus influenza-Sducreyi Haemophilus parainfluenzae Helicobacter pylori Klebsiella oxytoca Klebsiella pneumoniae Klebsiella spp Moraxela catarrhalis β+/β- , Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Providencia spp, Pscudomonas aeruginosa, Pseudomonas spp, Salmonella spp, Serratia marcescens, Serratia spp.
Anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp, Clostridium perfringens, Fusobacterium spp, Peptostreptococcus, Propionibacterum 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.

Pharmacokinetics
Levofloxacin is rapidly and almost completely absorbed after oral administration. Food intake has little effect on the rate and completeness of absorption. The bioavailability of 500 mg levofloxacin after oral administration is almost 100%. After taking a single dose of 500 mg of levofloxacin, the maximum concentration is 5.2-6.9 μg / ml, the time to reach the maximum concentration is 1.3 hours, the half-life is 6-8 hours.
Communication with plasma proteins - 30-40%. It penetrates well into organs and tissues: lungs, bronchial mucosa, sputum, organs of the genitourinary system, bone tissue, cerebrospinal fluid, prostate gland, polymorphonuclear leukocytes, alveolar macrophages.
In the liver, a small part is oxidized and/or deacetylated. It is excreted from the body mainly by the kidneys by glomerular filtration and tubular secretion. After oral administration, approximately 87% of the dose taken is excreted in the urine unchanged within 48 hours, less than 4% in the feces within 72 hours.

Indications for use
Infectious and inflammatory diseases caused by susceptible microorganisms - acute sinusitis, exacerbation of chronic bronchitis, community-acquired pneumonia, complicated urinary tract infections (including pyelonephritis), uncomplicated urinary tract infections, prostatitis, infections of the skin and soft tissues, septicemia / bacteremia associated with the above indications, intra-abdominal infection.

Contraindications

hypersensitivity to levofloxacin or other quinolones;

renal failure (with creatinine clearance less than 20 ml / min. - due to the impossibility of dosing this dosage form);

epilepsy;

tendon lesions in previous treatment with quinolones;

children and adolescents (up to 18 years);

pregnancy and lactation. Carefully
The drug should be used with caution in the elderly due to the high likelihood of a concomitant decrease in kidney function, with a deficiency of glucose-6-phosphate dehydrogenase. Dosage and administration
The drug is taken orally once or twice a day. Do not chew the tablets and drink plenty of liquid (from 0.5 to 1 glass), you can take before meals or between meals. Doses are determined by the nature and severity of the infection, as well as the sensitivity of the suspected pathogen.
Patients with normal or moderately reduced renal function (creatinine clearance> 50 ml / min.) The following dosing regimen is recommended:
Sinusitis: 500 mg once a day - 10-14 days.
Exacerbation of chronic bronchitis: 250 mg or 500 mg 1 time per day for 7-10 days.
Community-acquired pneumonia: 500 mg 1-2 times a day - 7-14 days.
Uncomplicated urinary tract infections: 250 mg once a day for 3 days.
Prostatitis: 500 mg - 1 time per day - 28 days.
Complicated urinary tract infections, including pyelonephritis: 250 mg once a day for 7-10 days.
Infections of the skin and soft tissues: 250 mg 1 time per day or 500 mg 1-2 times a day - 7-14 days.
Septicemia / bacteremia: 250 mg or 500 mg 1-2 times a day - 10-14 days.
Intra-abdominal infection: 250 mg or 500 mg 1 time per day for 7-14 days (in combination with antibacterial drugs acting on the anaerobic flora).
After hemodialysis or continuous ambulatory peritoneal dialysis, no additional doses are required.
In case of impaired liver function, special dose selection is not required, since levofloxacin is metabolized in the liver only to a very small extent.
As with the use of other antibiotics, treatment with Levofloxacin tablets 250 mg and 500 mg is recommended to continue for at least 48-78 hours after normalization of body temperature or after laboratory-confirmed recovery. Side effect
The frequency of a particular side effect is determined using the following table: Allergic reactions:
Sometimes: itching and redness of the skin.
Rare: general hypersensitivity reactions (anaphylactic and anaphylactoid reactions) with symptoms such as urticaria, bronchial constriction and possibly severe suffocation.
In very rare cases: swelling of the skin and mucous membranes (for example, in the face and throat), a sudden drop in blood pressure and shock; hypersensitivity to solar and ultraviolet radiation (see "Special Instructions"); allergic pneumonitis; vasculitis.
In some cases: severe skin rashes with blistering, for example, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome) and exudative erythema multiforme. General hypersensitivity reactions may sometimes be preceded by milder skin reactions. The above reactions can develop after the first dose, a few minutes or hours after the administration of the drug. From the digestive system:
Often: nausea, diarrhea, increased activity of liver enzymes (for example, alanine aminotransferase and aspartate aminotransferase).
Sometimes: loss of appetite, vomiting, abdominal pain, indigestion.
Rare: bloody diarrhea, which in very rare cases may be a sign of intestinal inflammation and even pseudomembranous colitis (see "Special Instructions"). From the side of metabolism:
Very rarely: a decrease in the concentration of glucose in the blood, which is of particular importance for patients with diabetes mellitus; possible signs of hypoglycemia: increased appetite, nervousness, perspiration, trembling. Experience with other quinolones indicates that they can exacerbate porphyria in patients already suffering from this disease. A similar effect is not excluded when using the drug levofloxacin. From the nervous system:
Sometimes: headache, dizziness and / or numbness, drowsiness, sleep disturbances.
Rare: restlessness, paresthesia in the hands, trembling, psychotic reactions such as hallucinations and depression, agitation, convulsions and confusion.
Very rarely: impaired vision and hearing, impaired taste and smell, decreased tactile sensitivity. From the side of the cardiovascular system:
Rarely: increased heart rate, lowering blood pressure.
Very rare: (shock-like) vascular collapse.
In some cases: prolongation of the Q-T interval. From the musculoskeletal system:
Rare: tendon lesions (including tendinitis), joint and muscle pain.
Very rare: tendon rupture (eg Achilles tendon); this side effect can be observed within 48 hours after the start of treatment and may be bilateral (see "Special Instructions"); muscle weakness, which is of particular importance for patients with bulbar syndrome.
In some cases: muscle damage (rhabdomyolysis). From the urinary system:
Rarely: increased levels of bilirubin and creatinine in the blood serum.
Very rare: deterioration of kidney function up to acute renal failure, interstitial nephritis. From the side of the hematopoietic organs:
Sometimes: an increase in the number of eosinophils, a decrease in the number of leukocytes.
Rare: neutropenia; thrombocytopenia, which may be accompanied by increased bleeding.
Very rarely: agranulocytosis and the development of severe infections (persistent or recurrent fever, deterioration of health).
In some cases: hemolytic anemia; pancytopenia. Other side effects:
Sometimes: general weakness.
Very rare: fever.
Any antibiotic therapy can cause changes in the microflora, which is normally present in humans. For this reason, increased reproduction of bacteria and fungi resistant to the antibiotic used may occur, which in rare cases may require additional treatment. Overdose
Symptoms of an overdose of Levofloxacin are manifested at the level of the central nervous system (confusion, dizziness, impaired consciousness and seizures of the type of epileptic seizures). In addition, gastrointestinal disturbances (eg, nausea) and erosive lesions of the mucous membranes, prolongation of the Q-T interval may be noted.
Treatment should be symptomatic. Levofloxacin is not excreted by dialysis (hemodialysis, peritoneal dialysis and permanent peritoneal dialysis). There is no specific antidote. Interaction with other drugs
There are reports of a pronounced decrease in the threshold of convulsive readiness with the simultaneous use of quinolones and substances that, in turn, can reduce the cerebral threshold of convulsive readiness. Equally, this also applies to the simultaneous use of quinolones and theophylline.
The effect of the drug Levofloxacin is significantly weakened when used simultaneously with sucralfate. The same thing happens with the simultaneous use of magnesium or aluminum-containing antacids, as well as iron salts. Levofloxacin should be taken at least 2 hours before or 2 hours after taking these drugs. No interaction was found with calcium carbonate.
With the simultaneous use of vitamin K antagonists, monitoring of the blood coagulation system is necessary.
Elimination (renal clearance) of levofloxacin is slightly slowed down by cimetidine and probenecid. It should be noted that this interaction has practically no clinical significance. However, with the simultaneous use of drugs such as probenecid and cimetidine, blocking a certain route of excretion (tubular secretion), treatment with levofloxacin should be carried out with caution. This applies primarily to patients with limited renal function.
Levofloxacin slightly increases the half-life of cyclosporine.
Taking glucocorticosteroids increases the risk of tendon rupture. special instructions
Levofloxacin should not be used to treat children and adolescents due to the likelihood of damage to the articular cartilage.
When treating elderly patients, it should be borne in mind that patients in this group often suffer from impaired renal function (see section "Method of application and doses").
In severe pneumonia caused by pneumococci, levofloxacin may not give the optimal therapeutic effect. Hospital infections caused by certain pathogens (P. aeruginosa) may require combined treatment.
During treatment with Levofloxacin, seizures may develop in patients with previous brain damage, such as stroke or severe trauma.
Despite the fact that photosensitivity is observed with the use of levofloxacin very rarely, in order to avoid it, patients are not recommended to be exposed to strong solar or artificial ultraviolet radiation without special need.
If pseudomembranous colitis is suspected, levofloxacin should be discontinued immediately and appropriate treatment instituted. In such cases, drugs that inhibit intestinal motility should not be used.
Rarely observed with the use of the drug Levofloxacin, tendinitis (primarily inflammation of the Achilles tendon) can lead to tendon rupture. Elderly patients are more prone to tendinitis. Treatment with glucocorticosteroids likely increases the risk of tendon rupture. If tendonitis is suspected, treatment with Levofloxacin should be stopped immediately and appropriate treatment of the affected tendon should be initiated.
Patients with glucose-6-phosphate dehydrogenase deficiency (an inherited metabolic disorder) may respond to fluoroquinolones by destroying red blood cells (hemolysis). In this regard, the treatment of such patients with levofloxacin should be carried out with great caution.
Such side effects of the drug Levofloxacin as dizziness or numbness, drowsiness and visual disturbances (see also the section "Side Effects") may impair reactivity and the ability to concentrate. This may represent a certain risk in situations where these abilities are of particular importance (for example, when driving a car, when servicing machines and mechanisms, when performing work in an unstable position). Release form
Film-coated tablets, 250 mg and 500 mg. 5 or 10 tablets in a blister pack or a polymer jar.
For a dosage of 250 mg: 1 blisters or 1 jar, together with instructions for use, are placed in a cardboard pack.
For a dosage of 500 mg: 1 or 2 blister packs or 1 jar, together with instructions for use, are placed in a cardboard pack. Storage conditions
List B. In a dry, dark place, at a temperature not exceeding 25 ° C.
Keep out of the reach of children. Best before date
2 years.
Do not use after the expiration date. Terms of dispensing from pharmacies
Released by prescription. Manufacturer/organization accepting claims:
CJSC "VERTEX", Russia
Legal address: 196135, St. Petersburg, st. Tipanova, 8-100. Manufacture / address for sending consumer claims:
199026, St. Petersburg, V.O., line 24, 27-a.

To date, the fight against the resistance of pathogenic bacterial flora is considered an urgent problem of domestic and foreign pharmacology. This process is associated with a mutation in the genes of the microorganism, which is inherited. Antimicrobial resistance is increasing every year, which requires the introduction of new, and often more expensive drugs and their combinations into clinical practice. Levofloxacin, the instructions for use of which describe in detail the dosage and other aspects of administration, is not a fundamentally new antibiotic, but remains effective against a wide range of representatives of the pathogenic flora.

The quinolone class of drugs has become known relatively recently. The first drug of this group was used in 1962, it was nalidixic acid. In the 1980s, fluorine and piperazine were added to the structural formula, in the future, all medicines with this chemical composition were called fluoroquinolones. They differ from their predecessors in a wider spectrum of antimicrobial activity.

The main component of the drug Levofloxacin, instructions for use, calls the isomer of the same name of a previously synthesized antibiotic from the group of fluoroquinolones ofloxacin. Due to its effectiveness, the drug is widely used to treat infectious diseases of unknown etiology, lesions of bone, cartilage, abdominal cavity, ENT organs, and the genitourinary system. According to doctors, the drug is successfully used to prevent bacterial complications in patients with severe immunodeficiency. Levofloxacin, instructions for use confirms its action, the first-line drug for the treatment of nosocomial pneumonia.

Given the wide range of indications for admission, the medicine is available in the form of:

• solution for injections, which are administered only intravenously, with a dosage of the active ingredient 5 mg per 1 ml of injection, usually in a package of 1 ampoule or vial;
• coated tablets of 0.25 and 0.5 g;
• eye drops 0.5% in bottles of 5 and 10 ml.

The medicine is produced both under the original name and in the form of analogues under various brands, for example, Levofloxacin-Teva, Remedia, etc. The price of the medicine also depends on the country - the manufacturer. Although in some cases the high cost is justified, as this is due to the quality of the substance used to prepare the drug, the speed of action and bioavailability.

As for the principle of "work" of the drug Levofloxacin, the instructions for use describe it in insufficient detail. The active component of the antibiotic penetrates the bacterial cell membrane and affects the reproduction process by inhibiting specific enzymes. In gram-negative microorganisms, Levofloxacin inhibits the production of DNA hydrase topoisomerase II, which regulates the processes of proper DNA twisting. In gram-positive bacteria, this antibiotic from the group of fluoroquinolones blocks the activity of type IV topoisomerase, which also regulates the processes of DNA helixing.

All antibiotics - fluoroquinolones are divided into four generations depending on the spectrum of their activity. The earliest drugs affect mainly Gram-negative pathogens only and do not produce sufficiently high tissue concentrations. In the late 1980s, second-generation fluoroquinolones, active against staphylococci, appeared on the pharmaceutical market. The spectrum of action of third-generation drugs is even wider, destroying both pneumococci and intracellular pathogens.

If we talk about the activity of the antibiotic Levofloxacin, the instructions for use list the bacteria that the drug fights:

• fecal enterococcus, the most pathogenic type of enterococci, the main cause of persistent nosocomial infections of the urinary tract, myocardium and other organs;
• aureus and epidermal staphylococcus, one of the most common bacteria;
• pneumococcus, the main causative agent of meningitis and pathologies of ENT organs;
• strains of β-hemolytic streptococcus, prolonged exposure to which leads to autoimmune processes;
• the rare Streptococcus viridians, which causes endocarditis;
• various strains of enterobacter causing diseases of the digestive and urinary systems, lower respiratory tract;
• coli, considered a conditionally pathogenic bacterium, with uncontrolled reproduction can cause peritonitis, colpitis, prostatitis;
• Haemophilus influenzae, the causative agent of meningitis, pericarditis, pneumonia and other serious diseases, due to its structure is practically not destroyed by the body's own immune cells;
• Pfeiffer's stick, the cause of serious bacterial diseases of the upper and lower respiratory tract;
• Klebsiella, the main causative agent of urinary tract infections;
• legionella, a frequent "inhabitant" of contaminated air conditioner filters, the causative agent of legionellosis;
• moraxella catharalis, causes otitis media, sinusitis and other diseases of the ENT organs;
• Proteus mirabilis, often becomes the cause of the development of infections of the genitourinary system;
• Pseudomonas aeruginosa causes nosocomial infections, especially lesions of the urinary organs, soft tissues;
• chlamydophilus pneumonia, a common causative agent of respiratory infections;
• mycoplasma, is the cause of pneumonia and other lesions of the lungs and bronchial tree;
• acinetobacter, causes systemic bacterial infections of the bloodstream, ENT - organs, nervous system, musculoskeletal system;
• bacterium Borde-Jangu, the causative agent of whooping cough;
• citrobacter, often causes sepsis, meningitis, gastroenteritis, infectious pathologies of the excretory system;
• Morgan's bacterium, the causative agent of intestinal infections;
• Proteus causes bacterial diseases of the digestive tract;
• providence rettgeri, as a result of exposure to the pathogen, pathologies of the urinary system develop, resistant to other antibiotics;
• serrations, populate the respiratory and urinary tract, causing the corresponding symptoms;
• Clostridium, the causative agent of food poisoning.

This antibiotic also has a post-antibiotic effect. This is the name of the continued inhibition of bacterial growth after stopping the drug. That is why, for some diseases, an antibiotic can be taken once a day, and a reduction in the duration of treatment is also allowed.

When taken in the form of tablets, Levofloxacin quickly enters the bloodstream. The bioavailability of this antibiotic is much higher than analogues, and according to doctors, it is up to 99%. Penetrates into all affected tissues, mainly excreted by the kidneys within 1 - 2 days after ingestion.

Despite all the advantages of the drug, there are certain contraindications regarding the use of an antibiotic at an early age. In the description of clinical trials conducted on animals, there is evidence of a negative effect on the development of articular cartilage. Therefore, the prescription of the drug Levofloxacin, instructions for use, limits children and adolescents under 18 years of age.

Levofloxacin: what helps, indications and contraindications, possible side effects

The main indications for prescribing the drug are such diseases:

• lesions of ENT organs: otitis media, sinusitis;
• infections of the lower respiratory system: pneumonia, bronchitis, including exacerbations of chronic processes;
• complicated and uncomplicated lesions of the urinary system: pyelonephritis, urethritis, cystitis;
• infections of the reproductive system, including venereal: bacterial prostatitis, gonorrhea, chlamydia;
• diseases of the skin and soft tissues: festering atheromas, abscesses, boils;
• sepsis;
• eye infections;
• intra-abdominal infections, including peritonitis.

The antibacterial drug Levofloxacin from which it helps is described in detail in the annotation, it has a wide spectrum of activity against gram-negative and gram-positive pathogens.

However, like any other potent drug, this antibiotic from the fluoroquinolone group has a number of contraindications, these are:

• pregnancy;
• breastfeeding period;
• age up to 18 years (eye drops with Levofloxacin can be used in children from 1 year old);
• pseudomembranous colitis;
• epilepsy and other disorders of the central nervous system, accompanied by convulsive seizures;
• damage to tendons and connective tissues caused by previous treatment with antibiotics - quinolones;
• kidney failure;
• hypersensitivity to levofloxacin and excipients used in the manufacture of the drug.

The antibacterial agent is usually well tolerated. The occurrence of side effects is associated with the dose of the drug. But even if the doctor prescribes the drug in the maximum allowable amount, the incidence of adverse reactions does not exceed 13.5% (according to the results of clinical studies conducted in the United States).

Often, against the background of the use of the drug, disorders of the digestive tract are noted, these are:

• loss of appetite;
• pain and discomfort in the abdomen;
• nausea;
• vomit;
• constipation or vice versa, diarrhea;
• violation of the liver, which in the clinical blood test is reflected in the form of an increase in the concentration of transaminases, bilirubin and alkaline phosphatase), and the patient may complain of discomfort in the right hypochondrium;
• dysbacteriosis, in isolated cases, candidiasis of the intestine and oral cavity;
• colitis.

In 1-4% of patients, when taking Levofloxacin, the following adverse reactions from the central nervous system were noted:

• headache;
• insomnia;
• nightmares;
• sudden mood swings;
• general weakness;
• dizziness;
• anxiety, the appearance of a feeling of fear;
• in 1% of patients, doctors observed the appearance of convulsive seizures.

Side effects on the part of the skin are noted both with oral and injection administration of Levofloxacin.

Possible development:

• photodermatosis;
• rashes;
• phlebitis at the injection site or dropper.

In 1.5 - 2% of patients taking Levofloxacin, which helps the drug can consult a doctor, there are changes in the hematopoietic system. Sometimes the level of leukocytes, platelets and erythrocytes decreases (although in some cases leukocytosis and an acceleration of the erythrocyte sedimentation rate are noted, which is mistaken for a lack of effect from treatment), an increase in the concentration of eosinophils.

Lesions of the musculoskeletal system are observed in 1% of patients. They manifest as inflammation of the skeletal muscles, joint pain, damage, and sometimes rupture of the tendons. Most often, such adverse reactions are noted in older men.

If the amount of antibiotic recommended by the doctor is significantly exceeded, overdose symptoms may appear. The central nervous system reacts first. A person is in a semi-conscious state, dizziness occurs, sometimes epileptic seizures begin. Also, with an overdose of Levofloxacin, all signs of indigestion (nausea, vomiting, diarrhea) appear. On examination, erosive lesions of the intestinal mucosa are sometimes found.

Therefore, if clinical signs of an overdose appear, you should immediately consult a doctor. However, the treatment of this condition is symptomatic.

Despite the fact that this antibiotic only affects the DNA of bacteria and does not act on the body's own cells, special care must be taken when combining Levofloxacin with other drugs. So, when combined with Metronidazole, Theophylline, Imipenem and Fenbufen, the likelihood of developing seizures increases.

The effectiveness of Levofloxacin is significantly reduced when used in parallel with antacids containing iron, aluminum and manium. However, this reaction can be avoided if the antibiotic is taken two hours before or 2 hours after taking these medicines.

The use of glucocorticosteroids simultaneously with Levofloxacin increases the likelihood of tendon rupture. When an antibiotic is combined with Probenecid and other medicines against gout symptoms, it affects the pharmacokinetics of the antibacterial agent, which is associated with an increased burden on the kidneys. As a result of this interaction, symptoms of an overdose of Levofloxacin may appear. Doctors draw attention to the fact that with the simultaneous appointment with the immunosuppressant Cyclosporine, a correction of its dosage is necessary.

How to take Levofloxacin: dosage features, use during pregnancy and in childhood

Due to the broad spectrum of activity and high activity of fluoroquinolones, these drugs are a kind of heavy artillery in the treatment of bacterial infections. And uncontrolled intake of Levofloxacin can lead to the development of resistance of the pathogenic flora to the action of both this drug and other, weaker antibiotics.

As for the dosage of this remedy, it is also determined by the doctor, depending on the location of the focus of infection, the severity of the patient's condition and the severity of clinical symptoms.

• with sinusitis, tonsillitis, otitis media and other infections of the upper respiratory tract - organs: 500 mg 1 time per day for 10-14 days;
• acute bronchitis: one tablet (500 mg) 1 time per day for up to 10 days;
• with exacerbation of chronic bronchitis: 0.25 g 1 time per day, take the medicine for up to 2 weeks;
• with pneumonia: the first days of treatment, the drug is administered intravenously at 100 ml twice a day, then, with positive dynamics, the patient is transferred to oral medication at a dosage of 250-500 mg twice a day;
• with cystitis and other urinary tract infections: in severe cases of the disease, Levofloxacin is administered intravenously (50 ml) 1 time per day, or in case of uncomplicated pathology, 250 mg is administered orally once a day for 3 to 10 days;
• with bacterial infections of the epidermis and soft tissues: 100 ml twice a day intravenously, starting from the 3rd - 4th day of illness - 250 - 500 mg 1 - 2 times a day in the form of tablets for 2 weeks;
• peritonitis and other intra-abdominal lesions: 50-100 ml once a day intravenously or 250-500 mg in the form of tablets for 2 weeks, if necessary, Levofloxacin is combined with other antibiotics;
• with infections of the organs of vision: the first 2 days of therapy - 1 - 2 drops every 2 hours (except for sleep time), from 3 to 7 days of treatment - in the same dosage 4 times a day.

The use of the drug for inflammation of the prostate gland

To date, urologists agree that chronic prostatitis requires the use of antibiotics. Moreover, a course of antibiotic therapy is indicated even in the absence of pathogenic flora in the secretion of the prostate gland. Fluoroquinolones are ideal for treating prostatitis. Levofloxacin is characterized by high bioavailability and concentration in prostate tissues. In addition, unlike other potent antibiotics, this drug from the fluoroquinolone group can be used both parenterally in a hospital setting and orally, in the form of tablets for outpatient treatment.

In the USA, a clinical study was conducted regarding the effectiveness of Levofloxacin in the treatment of chronic prostatitis at a dose of 500 mg per day. Significant improvement was noted in 75% of patients. In the course of the same test, it was proved that if prostatitis occurs without the addition of chlamydial infection, the amount of Levofloxacin can be reduced to 250 mg per day.

In parallel with how to take Levofloxacin for prostatitis, non-steroidal anti-inflammatory drugs are allowed. According to the indications, the use of corticosteroids is possible, while the dose of drugs is adjusted. As for the duration of treatment, on average it is 28 days or more.

Features of use in children, during pregnancy and lactation

Levofloxacin and other antibiotics from the fluoroquinolone group were used for the treatment of children according to strict medical indications and under the supervision of doctors. After analyzing 10,000 medical records, doctors concluded that the frequency of adverse reactions does not exceed that in adults. However, data on the possible damage to the tendons in children while taking Levofloxacin have not been refuted. Therefore, pediatricians refrain from prescribing this antibiotic.

The drug is not prescribed for pregnant women. It is believed that it penetrates the placental barrier and can cause damage to the joints of the fetus. But in clinical trials on animals, such an effect of Levofloxacin has not been confirmed. There are data on the use of the drug for the treatment of 10 pregnant women with resistant abdominal infection for 2 weeks at the recommended dose. Subsequently, no pathologies of cartilage tissue were noted in newborns. The medical literature reports 130 cases of antibiotic use in the first three months of childbearing without any consequences.

Levofloxacin passes into breast milk, therefore, during treatment, feeding must be suspended. You can resume lactation no earlier than 2 to 3 days after the end of taking this fluoroquinolone.

special instructions

Like other potent antibiotics, Levofloxacin is not allowed to be dispensed in pharmacies without a doctor's prescription. However, almost all pharmacists turn a blind eye to these requirements. However, when selling, pharmacists are reminded of the dangers of self-treatment. Keep the medicine package away from children, in a cool place, protected from direct sunlight. The room temperature should not exceed 25ºС. The expiration date is 24 months from the production date.

Regardless of the dosage and duration, how to take Levofloxacin, the following rules must be observed during treatment:

• when taken orally, the tablets are drunk before meals, the drug is administered intravenously regardless of the meal;
• tablets are swallowed whole with a sufficient amount of water or unsweetened tea;
• the antibiotic affects the functioning of the nervous system, so care must be taken when driving a car or other work associated with increased concentration of attention;
• in patients who have had a stroke, the risk of convulsive syndrome increases while taking Levofloxacin;
• to reduce the risk of photodermatosis, it is recommended to minimize exposure to the open sun;
• in case of tendonitis or exacerbation of colitis, it is necessary to immediately stop taking the antibiotic;
• use Levofloxacin under medical supervision is necessary for patients with hereditary metabolic pathologies associated with impaired synthesis of 6-phosphate dehydrogenase;
• the use of eye drops may cause transient burning and tearing.

Analogues of Levofloxacin with the same composition and indications for use are the following drugs:

• Glevo (India);
• L-Optik, eye drops (Romania);
• Levoksimed (Turkey);
• Levolet (India);
• Levotek (India);
• Levoflox (India);
• Levofloxacin - Teva (Israel);
• Leflobact (Russia), in addition to the "standard" solution for infusions and tablets of 250 and 500 mg, is available in the form of capsules of 750 mg;
• Oftakviks, eye drops (Finland);
• Remedia (India);
• Tavanik (Germany), according to reviews, the most effective analogue of Levofloxacin;
• Flexid (Slovenia).

According to the opinions of doctors, Levofloxacin is the best remedy for the treatment of persistent bacterial pathologies. However, before prescribing a medicine, it is necessary to evaluate all the pros and cons. With a high risk of side effects, they try to choose a safer antibiotic. Patient reviews confirm the rapid result of treatment, and complications occur only in isolated cases.

After the doctor has painted the scheme on how to take Levofloxacin, the original drug or its analogues can be purchased at any pharmacy. According to the online pharmacy piluli.ru, a package of 10 tablets of 500 mg each costs 603 rubles, one bottle of solution for intravenous infusion costs 119 rubles. For comparison, the price of 100 ml of Tavanic (1 ampoule) is 1200 rubles, and 10 tablets of 500 mg - 949 rubles.

Recipe (international)

Rp: Levofloxacini 0.5
D.t.d: N 10 in tab.
S: 1 tablet 1 time per day 1 hour before meals.

Active substance

(Levofloxacin)

pharmachologic effect

Bactericidal, broad spectrum antibacterial.

Pharmacodynamics

Has a wide spectrum of action. Inhibits bacterial topoisomerase IV and DNA gyrase (type II topoisomerases) - enzymes necessary for replication, transcription, repair and recombination of bacterial DNA. In concentrations equivalent to or slightly higher than inhibitory concentrations, it most often has a bactericidal effect. In vitro resistance to levofloxacin resulting from spontaneous mutations is rare (10−9−10−10). Although cross-resistance has been observed between levofloxacin and other fluoroquinolones, some organisms resistant to other fluoroquinolones may be susceptible to levofloxacin.

Efficacy established in vitro and confirmed in clinical studies against gram-positive bacteria - Enterococcus faecalis, Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), Staphylococcus saprophyticus, Streptococcus pneumoniae (including multidrug-resistant strains - MDRSP*), Streptococcus pyogenes; gram-negative bacteria - Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens and other microorganisms - Chlamydia pneumoniae, Mycoplasma pneumoniae.

For most (≥90%) strains of the following microorganisms, MICs of levofloxacin (2 µg/ml or less) have been established in vitro, but the efficacy and safety of clinical use of levofloxacin in the treatment of infections caused by these pathogens has not been established in adequate and well-controlled studies: gram-positive bacteria - Staphylococcus haemolyticus, Streptococcus (group C/F), Streptococcus (group G), Streptococcus agalactiae, Streptococcus milleri, Streptococcus viridans, Bacillus anthracis; Gram - Acinetobacter lwoffii, Acinetobacter baumannii, Bordetella pertussis, Citrobacter (diversus) koseri, Citrobacter freundii, Enterobacter aerogenes, Enterobacter sakazakii, Klebsiella oxytoca, Morganella morganii, Pantoea (Enterobacter) agglomerans, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas fluorescens , Yersinia pestis; Gram-positive anaerobes - Clostridium perfringens.

May be effective against microorganisms resistant to aminoglycosides, macrolides and beta-lactam antibiotics (including penicillin).

Mode of application

For adults:

Inside, before meals or between meals, without chewing, drinking plenty of fluids.

In / in, slowly.
- With sinusitis - inside, 500 mg 1 time per day, for 10-14 days; with exacerbation of chronic bronchitis - 250-500 mg 1 time per day for 7-10 days.

With pneumonia - inside, 250-500 mg 1-2 times a day (0.5-1 g / day); in / in - 500 mg 1-2 times a day, for 7-14 days.

For urinary tract infections - inside, 250 mg 1 time per day; IV, at the same dose, 7-10 days.

For infections of the skin and soft tissues - inside, 250-500 mg 1-2 times a day; IV, 500 mg 2 times a day for 7-14 days.
- With tuberculosis - inside, 500 mg 1-2 times a day for up to 3 months. After intravenous administration, a transition to oral administration at the same dose is possible after a few days.
- In case of kidney diseases, the dose is reduced in accordance with the degree of dysfunction: with CC 20-50 ml / min - 125-250 mg 1-2 times a day, 10-19 ml / min - 125 mg 1 time in 12-48 hours , less than 10 ml / min (including hemodialysis) - 125 mg after 24 or 48 hours.
The duration of treatment should not exceed more than 14 days.

For kids: After a single intravenous injection of levofloxacin at a dose of 7 mg/kg in children aged 6 months to 16 years, the drug was eliminated faster than in adult patients.
Subsequent pharmacokinetic analysis shows that with a dosing regimen of 8 mg / kg (not more than 250 mg per dose) every 12 hours in children 6 months - 17 years old at steady state, plasma AUC0-24 and C-max values ​​\u200b\u200bcomparable to those in adult patients with a dose of levofloxacin 500 mg every 24 hours.

Indications

Infectious-inflammatory pathology that has developed as a result of infection with bacteria sensitive to levofloxacin:
. Infections of the abdominal organs;
. exacerbation of chronic bronchitis;
. community-acquired form of pneumonia;
. inflammation of the prostate gland;
. acute sinusitis;
. uncomplicated urinary tract infections;
. bacteremia / septicemia (associated with the indications given in the description);
. complicated urinary tract infections (including pyelonephritis);
. infectious pathology of soft tissues and skin.

Contraindications

Pathological conditions of the tendons after the use of other fluoroquinolones in history;
. children and adolescents (up to 18 years);
. epilepsy;
. lactation period (breastfeeding);
. pregnancy;
. individual hypersensitivity (allergy) to the components of Levofloxacin or to other quinolone derivatives. It is prescribed with caution when:
. High risk of renal failure in geriatric patients;
. deficiency of glucose-6-phosphate dehydrogenase.

Side effects

On the part of the digestive system: diarrhea, nausea, increased activity of liver enzymes, which was determined by the indicators of blood serum (often);
rarely - an increase in bilirubin in the blood serum, severe diarrhea with blood in the feces (this symptom in rare cases can be a sign of both banal and pseudomembranous colitis);
sometimes - loss or decrease in appetite, abdominal pain, vomiting, dyspeptic disorders;
very rarely - hepatitis.

Immune system: a sudden sharp decrease in blood pressure up to the development of shock, allergic pneumonitis, hypersensitivity to ultraviolet and solar radiation, vasculitis, swelling in the face and throat, other surfaces of the skin and mucous membranes (in very rare cases); skin redness and itching (sometimes); rarely - anaphylactic and anaphylactoid reactions (in the form of bronchospasm, severe suffocation, urticaria); in some cases - erythema multiforme exudative, Stevens-Johnson syndrome, Lyell's syndrome - epidermal toxic necrolysis. Sometimes general allergic manifestations were preceded by slightly milder skin reactions that appeared after taking the starting dose of Levofloxacin after a few minutes or hours.

On the part of metabolism: very rarely - a decrease in blood glucose levels with subsequent possible signs such as nervousness, "wolfish" appetite, trembling, perspiration (this must be taken into account in patients with diabetes mellitus).

From the urinary system: acute renal failure due to interstitial nephritis (very rare); rarely - an increased level of creatinine in the blood serum.

From the peripheral or central nervous system: sometimes - numbness, sleep disturbances, headache, dizziness, drowsiness; rarely - psychotic reactions (sometimes accompanied by hallucinations), tremor, anxiety, depression, various unpleasant sensations like paresthesia of the hands, confusion, psychomotor agitation, anxiety, convulsive syndrome; very rarely - impaired vision, smell, hearing, taste sensitivity, deterioration in the sensitivity of tactile receptors.

From the musculoskeletal system: tendon lesions (including tendonitis), muscle and joint pain (rarely);
tendon rupture (more often Achilles), muscle weakness (this must be taken into account in patients with bulbar syndrome) - very rarely;
in some cases - rhabdomyolysis and other muscle lesions. Achilles tendon rupture may occur during the first 2 days of Levofloxacin therapy and is usually bilateral.

From the side of the cardiovascular system: prolongation of the QT interval on the ECG (in some cases), rarely - hypotension, palpitations; very rarely - vascular collapse.

From the hemopoietic system: agranulocytosis (very rarely); sometimes - a decrease in the level of leukocytes and eosinophils according to a clinical blood test, the development of severe infections (persistent fever, relapse of fever, deterioration of health); thrombocytopenia (which may present with increased bleeding) and neutropenia (rarely); in some cases - pancytopenia or hemolytic anemia.

Other side effects: very rarely - fever, sometimes - asthenia (general weakness).

The use of Levofloxacin, as well as other antimicrobial drugs, can provoke the appearance of superinfection or secondary infection. Experience with other fluoroquinolones suggests that Levofloxacin, like other quinolone derivatives, can aggravate porphyria that the patient already has (so far, exacerbation of porphyria while taking the drug has not been registered).

Release form

Levofloxacin infusion 100 mg vials containing 0.5 g of active ingredient.
The solution in the vial is yellow-green or yellow, transparent.
Levofloxacin - 250 mg White or almost white tablets, round, coated.
The package contains 5 or 10 pieces.
Levofloxacin 500 mg white or almost white tablets, scored on one side, coated, capsule-shaped. The package contains 5 or 10 pieces.

ATTENTION!

The information on the page you are viewing was created for informational purposes only and does not promote self-treatment in any way. The resource is designed to familiarize healthcare professionals with additional information about certain medicines, thereby increasing their level of professionalism. The use of the drug "" without fail provides for a consultation with a specialist, as well as his recommendations on the method of application and dosage of the medicine you have chosen.

The antimicrobial drug Levofloxacin® belongs to the group of antibiotics - fluoroquinolones, characterized by a wide spectrum of antibacterial action. Due to the pronounced bactericidal effect, it is widely used in various fields of medical practice: in pulmonology, therapy, urology, ophthalmology, etc.

It can be administered to the body both parenterally, in the form of a solution for infusion, and orally in tablet form. Eye drops are also available for the treatment of ophthalmic bacterial infections.

However, due to the high level of toxicity, it cannot be used to treat children under 18 years of age (an exception may be cases of anthrax, purulent bronchiectasis in cystic fibrosis in patients over 16 years of age), pregnant women and several other groups of people with dysfunctions of internal organs .

Levofloxacin ® - instructions for use of tablets 500 mg and 250 mg, solution and drops

The bactericidal effect on a pathogenic microorganism is carried out due to the penetration of Levofloxacin ® into the cell and disruption of the process of its DNA formation (linking breaks and supercoiling). In addition, the drug causes irreversible destructive changes in all cellular structures - walls, membranes and cytoplasm.

The list of antibiotic-sensitive bacteria includes gram-positive diphtheria and Escherichia coli, staphylococci, pyogenic and pneumonia streptococci (as well as virids from their group). Of the gram-negative microorganisms, Neisseria, Morganella, Klebsiella, Salmonella, Pseudomonas, Escherichia, Gardnerella, and many others are sensitive to Levofloxacin.

Some anaerobes (clostridia, peptostreptococci, fusobacteria) and atypical pathogens - mycobacteria, rickettsia, legionella, chlamydia, mycoplasma, ureaplasma are also sensitive to the drug.

Pharmacological group of Levofloxacin ®

Antibiotics of the fluoroquinolone class of the third generation.

Levofloxacin ® : composition and dosage form

The active substance - levofloxacin (in Latin recipes is written Levofloxacini) belongs to the third generation of fluoroquinolone antibiotics and is a levorotatory enantiomer of the ofloxacin compound. This structural modification is twice as effective as its predecessor.

The medicine is produced by various foreign and domestic manufacturers, including the Belarusian concern Belmedpreparaty ® , the Israeli pharmaceutical company Teva ® and many others. Pharmacy chains sell the following dosage forms:

• Tablets with an active substance content of 250 or 500 mg, having a yellow color. In addition to the antibiotic, they include such formative ingredients as microcrystalline cellulose, pre- and hypromellose, calcium stearate, titanium dioxide, yellow iron oxide and macrogol. Packed tablets of 5, 7, 10 or 14 pieces per pack.
• Infusion solution with an active substance concentration of 0.5%, in addition to it containing water for injection, disodium edetate and sodium chloride. It is a clear liquid, almost colorless. Available in 100 ml bottles.
• Eye drops are similar in composition to the infusion solution. They are sold in small bottles of 5 and 10 ml, equipped with a special dropper nozzle.

Photo of the packaging of levofloxacin ® in tablets of 500 mg

The retail price for any dosage form is relatively low and depends on the specific manufacturer, variety and quantity in the package.

Prescription for Levofloxacin ® in Latin

Rp.: Levoflxacini 0.5
D.t.d. No. 10.
S. 1 tablet once a day.

What does Levofloxacin ® help with?

The scope of this antibacterial agent is very extensive. It destroys most of the most common strains of bacteria, so it can be used to treat infections of various localizations.

The solution for intravenous infusion and tablets act systemically and are prescribed to combat inflammation of the internal organs, generalized infections and purulent skin lesions. The tablet form is used mainly for sinusitis, otitis media, inflammatory processes in the lungs and bronchi.

Also, tablets are indicated for infection with pathogenic organisms of the urinary organs and the reproductive system (including prostatitis), abscesses, furunculosis. As part of complex therapy regimens, it is used to eradicate the causative agent of peptic ulcer of the duodenum and stomach - Helicobacter.

The infusion solution is administered intravenously in a hospital in case of complicated pneumonia, septic complications, anthrax, antibiotic-resistant forms of tuberculosis (in combination with other drugs), bacterial prostatitis with complications, pyoderma and bile duct infections. The basis for the appointment of eye drops are diseases caused by pathogens that are sensitive to them.

Indications for Levofloxacin ® tablets

Due to the wide spectrum of antimicrobial activity, the drug is prescribed for antibiotic therapy of infectious processes of various localization, as well as in the treatment of sepsis, peritonitis and pelvioperitonitis. Depending on the nature and severity of the pathology, one or another form of medication is used.

Tablets are indicated for infections of various organs and systems, mainly for outpatient treatment. Taken before meals to facilitate absorption and washed down with a sufficient amount of clean water (at least half a glass). Indications for the use of levofloxacin ® 500 and 250 mg:

• Acute and exacerbated chronic infections of the ENT organs (inflammation of the paranasal sinuses, otitis media).
• Abdominal abscesses.
• Inflammatory processes in the lower parts of the respiratory system (exacerbations of bronchitis and pneumonia).
• Purulent bronchiectasis in cystic fibrosis.
• Anthrax.
• Urinary tract infection (from pyelonephritis to cystitis and urethritis) in men and women.
• Uncomplicated prostatitis caused by bacteria (this form accounts for about 10% of the total number of cases and requires preliminary bacteriological laboratory testing).
• Purulent lesions of the epidermis, subcutaneous tissue and soft tissues - such as pyoderma, abscesses and furunculosis.
• Urogenital infections in adults.

They are not used in pediatrics because fluoroquinolones are quite toxic and can lead to unwanted side effects.

Levofloxacin ® solution for infusion: indications

This medicinal variety is introduced into the body through intravenous infusions when it is impossible to use tablets or in especially severe cases. This is done in a hospital, drip, that is, at a very low speed (100 ml of the drug is designed for an hour). The grounds for appointment are:

• sepsis;
• anthrax, as part of complex therapy;
• pneumonia and chronic in the acute stage with complications;
• complicated varieties of infections and bacterial;
• abdominal inflammatory processes (inflammation localized in the abdominal cavity);
• pertonitis;
• complex antibiotic therapy of especially resistant varieties of tuberculosis.

Levofloxacin ® in a dropper can be mixed with saline, Ringer's solutions and 5% dextrose. Mixing with sodium bicarbonate and heparin is unacceptable. Usually, the solution is administered until the first signs of improvement (decrease in temperature), and then the patient is transferred to the oral form of the drug in a similar dosage. In general, the duration of a course of intravenous infusion should not exceed 14 days.

Contraindications for use

Fluoroquinolones, to which this drug belongs, are characterized by increased toxicity, which determines the restrictions on their use. The negative effect of the active substance on the connective tissue has been proven, as a result of which Levofloxacin ® cannot be prescribed to the following categories of people:

• Pregnant and lactating. The drug in fairly high concentrations penetrates the placental barrier, and also enters breast milk. Therefore, during pregnancy and lactation, it is better to refrain from treatment with this antibiotic.
• Under 18 years of age. The reasons are the same as in the previous case (negative effect on the connective tissue of a growing organism). An exception may be: the need to treat anthrax or purulent bronchiectasis in cystic fibrosis in people over 16 years of age.
• With a history of epilepsy, since taking the drug increases the minimum threshold for seizure activity.
• With diagnosed tendon ruptures during previous treatment with fluoroquinolones.
• Prone to allergic reactions and hypersensitivity.
• In the case of using eye drops, age restrictions are reduced to 1 year.

In addition, the phenomena of liver or kidney failure, deficiency in the body of glucose-6-phosphate dehydrogenase and old age require caution when prescribing and using an antibiotic.

Levofloxacin ® : regimens and dosage

The use of any antibiotics should be carried out only as prescribed by the attending physician and in strict accordance with the recommendations received. Self-appointment or premature interruption of the course is fraught with complications, the addition of secondary infections and the manifestation of a pronounced side effect. In addition, individual reactions of the body to the drug are possible, up to anaphylactic shock and death.

The information provided in this section is for informational purposes only and should not be used as medical advice. The regimen and dose of the active substance depend on the type of disease and the severity of its course.

Tablets

Tablet medicines are among the most convenient to use, as they are compact and easy to take. This dosage form is used primarily for outpatient treatment, as well as in a hospital as a replacement for intravenous infusions (as the patient's condition improves).

Instructions for use Levofloxacin ® (tablets 500 and 250 mg) recommends the following regimens:

• Sinusitis of bacterial etiology in acute form is treated by taking 0.5 grams of medication per day for 2 weeks.
• For bronchitis (exacerbation of the chronic form or acute), you need to take 250 or 500 mg per day daily (dose depends on the severity of the patient's condition). The duration of antibiotic therapy is 7-14 days.
• With community-acquired pneumonia, 1 tablet of 0.5 g is prescribed once or twice a day for a period of 1-2 weeks.
• For the treatment of chronic bacterial prostatitis, a 28-day course of the drug is recommended, during which 500 mg is taken once daily.
• Skin infections and inflammatory processes of soft tissues are treated for 7 to 14 days. The daily dose in this case is 0.5-1 grams.
• Patients with urinary tract infections are prescribed 250 mg of the drug once a day for a week or 10 days.

With renal dysfunction, dosage adjustment is required according to creatinine clearance. Violation of the liver does not require adjustment. It is necessary to take an antibiotic in between meals, as food in the stomach slows down adsorption when washed down with water.

Infusion solution

Treatment with Levofloxacin ® in ampoules (vials) by intravenous infusion is carried out in a hospital. The drug is administered drip and slowly. Infusions are indicated for complicated forms of diseases, or when oral administration is impossible:

• With inflammation of the lungs, 1 or 2 droppers are placed daily, containing 500 mg of an antibiotic (that is, 1 vial). When the condition stabilizes, the patient is transferred to the tablet form of the antibiotic.
• Acute inflammatory processes in the bronchi are treated within 7-14 days. 1 infusion per day. The daily dose of the antibiotic is 0.5 grams.
• With bacterial prostatitis with complications, infusions are prescribed for 2 weeks (1 time per day, 500 mg), and then the patient is transferred to a tablet version of the drug in the same dosage.
• Pyelonephritis in the acute stage requires 3 to 10 days of daily droppers (1 bottle once a day).
• Skin infections - 1000 mg of antibiotic in two doses daily for one or two weeks.
• With sepsis, 1 or 2 vials of the drug are used daily. The duration of treatment is 7-14 days.
• In the case of anthrax and tuberculosis, 500 mg of Levofloxacin per day is used. The duration of antibiotic therapy in the first case is 3 months, and in the second - until the patient stabilizes (then it is transferred to the oral form of the drug).

As a rule, intravenous administration is indicated until the patient's condition stabilizes. Then it is advisable to replace droppers with tablets while maintaining the dosage, since the drug is equally well absorbed when used orally and parenterally.

Eye drops

This medicinal product contains 0.5% of the active substance and is used to treat bacterial eye lesions. The list of the latter includes corneal ulcer, conjunctivitis, blepharitis, chlamydial and gonorrheal invasions. A medication is usually prescribed according to the following scheme:

• 1 or 2 drops in each eye with a two-hour interval for two days;
• Further, the frequency of instillation should be 4 times a day, and the total duration of treatment should be from five to seven days.

Contraindications to the use of drops are hypersensitivity to fluoroquinolone antibiotics and benzalkonium chloride. Pregnant, lactating and children of the first year of life are also contraindicated. Side effects can be burning, pain, redness of the cornea, dry eye syndrome, pain.

Side effects of Levofloxacin ®

According to the degree of frequency of occurrence (both in clinical trials and in post-marketing studies), side effects are divided into the following categories:

• They are common, that is, from 1 to 10 people per hundred. These side effects include digestive disorders such as nausea and diarrhea. There is also an increase in the activity of the liver enzymes AST and ALT, which requires monitoring of the tests. The development of thrush is also often noted.
• Sometimes (less than one case in every 100) allergic reactions such as skin flushing and itching are noted. From the gastrointestinal tract, epigastric pain, vomiting, loss of appetite, heartburn are possible. The nervous system can react with a headache, sleep disturbances, dizziness. The composition of the blood changes: the number of eosinophils increases, and the number of leukocytes, on the contrary, decreases.
• Rare side effects, occurring less than 1 time in a thousand, include severe allergies (urticaria, bronchospasm, anaphylaxis), severe bloody diarrhea, decreased blood pressure, joint and muscle pain. The nervous system reacts with excitation, paresthesias, tremors, convulsions, confusion. On the part of the psyche, depression, hallucinations are observed. In the blood, the number of neutrophils and platelets is significantly reduced.
• Very rarely (less than 1 case per 10,000), there may be a sharp drop in blood pressure, photosensitivity, anaphylactic shock, epidermal necrolysis, exudative, disturbances in taste, hearing, vision, and tactile perception. Muscle weakness, vascular collapse, kidney failure, and tendon rupture are possible. On the part of the hematopoietic system, a reduction in the number of all formed elements is recorded.

In addition, a side effect of antibiotic therapy can be the partial death of beneficial intestinal microflora and the activation of pathogenic growth. To prevent gastrointestinal dysfunction and the development of fungal infections (for example, candidiasis), antibiotics should be combined with pre- and probiotics. It is also useful to follow a diet rich in dairy products and take multivitamin complexes to maintain immunity.

Overdose with levofloxacin ®

If the recommended dose of the tablet preparation is exceeded, responses from the central nervous system and gastrointestinal tract are observed. There are nausea, dizziness, lesions in the form of erosions on the mucous membranes of the gastrointestinal tract, confusion and convulsive seizures similar to epileptic seizures.

There is no specific antidote against Levofloxacin ®, therefore, symptomatic treatment of poisoning is carried out (gastric lavage, etc.). An overdose of eye drops is quite rare. However, if severe pain occurs, and the eyes turn red, you should rinse them with clean water and consult an ophthalmologist.

Levofloxacin ® and alcohol

It is not recommended to combine the intake of any medications with the use of alcoholic beverages. First of all, it is not recommended due to the diuretic effect of alcoholic beverages. Accelerated excretion of urine prevents the creation of the required concentration of the drug in the blood, as a result of which the effectiveness of antibiotic therapy is reduced. In addition, libations accompanied by food intake significantly slow down the absorption and assimilation of the antibiotic, again reducing the therapeutic effect.

As for Levofloxacin ® directly, here the danger of joint use with alcohol is to increase the side effects of the drug. Perhaps the development of toxic damage to the liver and nervous system.

Pregnancy

Levofloxacin ® , as well as other antibiotics of the fluoroquinolone class, should not be used to treat women who are carrying a child or breastfeeding.

This is due to the pronounced mutagenic and teratogenic effects of the drug on the fetus.

Levofloxacin ® - reviews of doctors and patients

All potent drugs undergo comprehensive clinical trials before they enter the market. For several years, the drug has been studied in terms of effectiveness and safety, as an official conclusion is given. Medicines are studied not only by the manufacturers themselves, but also by independent companies, which allows you to get the most objective assessment.

Doctors about Levofloxacin ®

Representatives of the medical community note the high antimicrobial activity of the presented antibiotic against most pathogens known today.

The medicine really successfully copes with the diseases indicated in the annotation, and the negative side effect, when used correctly, is minimal. This antibiotic is the drug of choice in the treatment of some common infections (provided there are no contraindications).

Patient opinion

On the network you can find a number of negative reviews, although in general, buyers note the high effectiveness of the drug. Complaints are reduced mainly to the occurrence of "side effects" in the form of allergies and dyspeptic disorders (nausea or diarrhea).

Despite the fairly frequent response of the gastrointestinal tract to antibiotics, more serious side effects usually do not occur. In addition, the combination of antibiotic therapy with pro- and prebiotics helps to cope with dysbacteriosis. Another undoubted advantage of Levofloxacin ® , according to reviews, is its low cost and, accordingly, availability to different categories of the population.

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Characteristics of the substance Levofloxacin

Synthetic chemotherapeutic agent, fluorinated carboxyquinolone, free from impurities S-enantiomer of the racemic compound - ofloxacin. Light yellowish-white to yellow-white crystalline powder or crystals. Molecular weight 370.38. Easily soluble in water at pH 0.6-6.7. The molecule exists as an amphion at pH values ​​corresponding to the environment of the small intestine. It has the ability to form stable compounds with ions of many metals. Ability to form chelates in vitro decreases in the following order: Al +3 >Cu +2 >Zn +2 >Mg +2 >Ca +2.

Pharmacology

pharmachologic effect- bactericidal, broad spectrum antibacterial.

Pharmacodynamics

Has a wide spectrum of action. Inhibits bacterial topoisomerase IV and DNA gyrase (type II topoisomerases) - enzymes necessary for replication, transcription, repair and recombination of bacterial DNA. In concentrations equivalent to or slightly higher than inhibitory concentrations, it most often has a bactericidal effect. In vitro resistance to levofloxacin resulting from spontaneous mutations is rare (10–9–10–10). Although cross-resistance has been observed between levofloxacin and other fluoroquinolones, some organisms resistant to other fluoroquinolones may be susceptible to levofloxacin.

Installed in vitro and clinically proven efficacy against gram-positive bacteria - Enterococcus faecalis, Staphylococcus aureus(methicillin-susceptible strains), Staphylococcus epidermidis (methicillin-susceptible strains) , Staphylococcus saprophyticus, Streptococcus pneumoniae(including multi-resistant strains - MDRSP*), Streptococcus pyogenes; gram-negative bacteria Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens and other microorganisms Chlamydia pneumoniae, Mycoplasma pneumoniae.

For most (≥90%) strains of the following microorganisms in vitro MICs of levofloxacin (2 µg/ml or less) have been established, however, the efficacy and safety of the clinical use of levofloxacin in the treatment of infections caused by these pathogens has not been established in adequate and well-controlled studies: gram-positive bacteria - Staphylococcus haemolyticus, Streptococcus(Group C/F), Streptococcus(group G), Streptococcus agalactiae, Streptococcus milleri, Streptococcus viridans, Bacillus anthracis; gram-negative bacteria Acinetobacter lwoffii Acinetobacter baumannii Bordetella pertussis Citrobacter (diversus) koseri Citrobacter freundii Enterobacter aerogenes Enterobacter sakazakii Klebsiella oxytoca Morganella morganii Pantoea (Enterobacter) agglomerans Proteus vulgaris, Yersinia pestis; Gram-positive anaerobes Clostridium perfringens.

May be effective against microorganisms resistant to aminoglycosides, macrolides and beta-lactam antibiotics (including penicillin).

* Strains with multiple antibiotic resistance ( Multi-drug resistant Streptococcus pneumoniae — MDRSP) include strains resistant to two or more of the following antibiotics: penicillin (when MIC ≥2 µg/mL), second-generation cephalosporins (eg cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole.

Clinical researches

The effectiveness of levofloxacin in the treatment community-acquired bacterial pneumonia (7-14 day dosing regimen) studied in two prospective multicenter clinical trials. In the first randomized study, which included 590 patients with community-acquired bacterial pneumonia, a comparative study was made of the effectiveness of levofloxacin at a dose of 500 mg once a day orally or intravenously for 7-14 days and cephalosporins with a total duration of treatment of 7-14 days; if the presence of an atypical causative agent of pneumonia was suspected or confirmed, patients in the comparison group could additionally receive erythromycin or doxycycline. The clinical effect (cure or improvement) on the 5-7th day after the completion of levofloxacin therapy was 95% compared to 83% in the comparison group. In the second study, which included 264 patients who received levofloxacin at a dose of 500 mg once a day orally or intravenously for 7-14 days, the clinical effect was 93%. In both studies, the efficacy of levofloxacin in the treatment of SARS caused by Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumoniae, amounted to 96, 96 and 70%, respectively. The degree of microbiological eradication in both studies was, depending on the pathogen: H.influenzae — 98%, S.pneumoniae — 95%, S. aureus — 88%, M.catarrhalis — 94%, H.parainfluenzae — 95%, K.pneumoniae — 100%.

Levofloxacin is effective for the treatment community-acquired pneumonia caused by strains of Streptococcus pneumoniae with multidrug resistance (MDRSP). After microbiological evaluation MDRSP-isolates isolated from 40 patients, it turned out that in 38 patients (95%) a clinical (recovery or improvement) and bacteriological effect was achieved after completion of levofloxacin therapy. The degree of bacteriological eradication was for different pathogens: penicillin-resistant strains - 94.1%, strains resistant to 2nd generation cephalosporins - 96.9%, strains resistant to macrolides - 96.6%, strains resistant to trimethoprim / sulfamethoxazole - 89.5%, strains resistant to tetracyclines - 100%.

The efficacy and safety of levofloxacin in community-acquired bacterial pneumonia (5-day dosing regimen) were evaluated in a double-blind, randomized, prospective, multicenter study in 528 outpatient and hospitalized adult patients with clinically and radiographically detectable mild to severe community-acquired pneumonia compared with levofloxacin 750 mg (IV or PO every day for five days) or at a dose of 500 mg IV or orally daily for 10 days. The clinical effect (improvement or recovery) was 90.9% in the levofloxacin 750 mg group and 91.1% in the 500 mg levofloxacin group. Microbiological efficacy (degree of bacteriological eradication) of a 5-day dosing regimen depending on the pathogen: S.pneumoniae — 95%, haemophilus influenzae — 100%, Haemophilus parainfluenzae — 100%, Mycoplasma pneumoniae — 96%, Chlamydophila pneumoniae — 87%.

acute bacterial sinusitis(5- and 10-14 day dosing regimens) caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, was evaluated in a double-blind, randomized, prospective, multicenter study in 780 outpatients who took levofloxacin orally once a day at a dose of 750 mg for 5 days or 500 mg for 10 days. The clinical effect of levofloxacin (complete or partial resolution of the symptoms of acute bacterial sinusitis to such an extent that further antibiotic therapy was not considered necessary) according to microbiological assessment was 91.4% in the group treated with levofloxacin at a dose of 750 mg and 88.6% in group receiving 500 mg of levofloxacin.

The effectiveness of levofloxacin in the treatment complicated urinary tract infections and acute pyelonephritis (5-day dosing regimen) was evaluated in 1109 patients in a randomized, double-blind, multicenter clinical trial in which patients received levofloxacin 750 mg IV or orally once a day for 5 days (546 patients) or ciprofloxacin 400 mg IV or 500 mg orally twice a day for 10 days (563 patients). The effectiveness of levofloxacin was assessed after 10-14 days according to the degree of bacteriological eradication and, depending on the pathogen, was: Escherichia coli — 90%, Klebsiella pneumoniae — 87%, Proteus mirabilis — 100%.

Efficacy and safety of levofloxacin in the treatment complicated urinary tract infections and acute pyelonephritis (10-day dosing regimen) evaluated during a 10-day course of treatment with levofloxacin 250 mg orally once a day in 285 patients with uncomplicated urinary tract infections, complicated urinary tract infections (mild to moderate severity) and acute pyelonephritis (mild to moderate severity) in a randomized, double-blind, multicenter clinical trial. Microbiological efficacy, measured by bacteriological eradication of microorganisms, was approximately 93%.

The efficacy of levofloxacin in infectious lesions of the skin and skin structures studied in an open randomized comparative study that included 399 patients who received levofloxacin at a dose of 750 mg / day (in / in, then inside) or the comparator for (10 ± 4.7) days. Surgical manipulations for complicated infections (excision of dead tissues and drainage) shortly before or during antibiotic therapy (as part of complex therapy) were performed in 45% of patients treated with levofloxacin and 44% of patients in the comparison group. Among patients who were under observation for 2-5 days after the end of drug therapy, the clinical effect was 116/138 (84.1%) in the group treated with levofloxacin, and 106/132 (80.3%) in the comparison group.

The efficacy of levofloxacin has also been demonstrated in a multicenter, randomized, open-label study in the treatment nosocomial pneumonia and in a multicentre, randomized, double-blind study in the treatment chronic bacterial prostatitis.

Eye drops

The clinical effect of levofloxacin in the form of 0.5% eye drops in randomized, double-blind, multicenter controlled trials in the treatment of bacterial conjunctivitis at the end of treatment (6-10 days) was 79%. The degree of microbiological eradication reached 90%.

Pharmacokinetics

Absorption. After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract, the absolute bioavailability of 500 mg and 750 mg tablets of levofloxacin is 99%. C max is achieved in 1-2 hours. When taken with food, the time to reach C max slightly increases (by 1 hour) and C max slightly decreases (by 14%), so levofloxacin can be prescribed regardless of food intake. After a single intravenous injection to healthy volunteers at a dose of 500 mg (infusion for 60 minutes), C max was (6.2 ± 1) μg / ml, at a dose of 750 mg (infusion for 90 minutes) - (11.5 ± 4) mcg/ml. The pharmacokinetics of levofloxacin is linear and predictable with single and repeated oral and/or intravenous administration. A constant plasma concentration is achieved after 48 hours when taking 500-750 mg 1 time per day. With repeated administration to healthy volunteers, the C max values ​​were: with oral administration of 500 mg / day - (5.7 ± 1.4) μg / ml, 750 mg / day - (8.6 ± 1.9) μg / ml; with intravenous administration of 500 mg / day - (6.4 ± 0.8) μg / ml, 750 mg / day - (12.1 ± 4.1) μg / ml. The plasma profile of levofloxacin concentrations after intravenous administration is similar to that after oral administration at an equivalent dose.

Distribution. The average V d is 74-112 liters after single and repeated doses of 500 and 750 mg. It is widely distributed in the tissues of the body, penetrates well into the tissue of the lungs (the concentration in the lungs is 2-5 times higher than the plasma concentration). In vitro in the concentration range corresponding to clinical values ​​​​(1-10 μg / ml), binding to plasma proteins (mainly albumin) is 24-38% and does not depend on the concentration of levofloxacin.

Metabolism and excretion. It is stereochemically stable in plasma and urine and does not convert to its enantiomer, D-ofloxacin. It is practically not metabolized in the body. It is excreted mainly unchanged in the urine (about 87% of the dose within 48 hours), small amounts - with faeces (less than 4% in 72 hours). Less than 5% is determined in the urine in the form of metabolites (desmethyl, nitric oxide), which have little specific pharmacological activity.

Terminal T 1/2 from plasma is 6-8 hours after a single or repeated oral or intravenous administration. Total Cl is 144-226 ml / min, renal Cl - 96-142 ml / min, excretion is carried out by glomerular filtration and tubular secretion. The simultaneous use of cimetidine or probenecid leads to a decrease in renal Cl by 24 and 35%, respectively, which indicates the secretion of levofloxacin by the proximal tubules. Levofloxacin crystals were not found in freshly collected urine.

Special patient groups

Age, gender, race. The pharmacokinetics of levofloxacin does not depend on the age, sex and race of patients.

After oral administration of 500 mg to healthy male volunteers, T 1/2 averaged 7.5 hours compared with 6.1 hours in women; the differences were associated with the peculiarities of the state of kidney function in men and women and had no clinical significance.

Peculiarities of pharmacokinetics depending on race were studied by covariance analysis of data from 72 subjects: 48 from Caucasians and 24 from others; no differences were found in terms of total clearance and volume of distribution.

Elderly age. The pharmacokinetics of levofloxacin in elderly patients is not significantly different if individual differences in creatinine clearance are taken into account. After a single oral dose of 500 mg of levofloxacin, T 1/2 in healthy elderly patients (66-80 years) was 7.6 hours compared with 6 hours in younger patients; the differences are due to variability in renal function and are not clinically significant. Dose adjustment in elderly patients is not required.

Renal failure. In patients with impaired renal function (Cl creatinine<50 мл/мин) значительно снижен клиренс левофлоксацина и увеличен Т 1/2 , для предотвращения кумуляции требуется коррекция дозы. Гемодиализ и длительный амбулаторный перитонеальный диализ не выводят левофлоксацин из организма и поэтому при их проведении не требуется введение дополнительных доз.

Liver failure. Pharmacokinetic studies in patients with liver disease have not been conducted. Since the metabolism of levofloxacin is negligible, no effect of liver injury on pharmacokinetics is expected.

Children. After a single intravenous injection of levofloxacin at a dose of 7 mg/kg in children aged 6 months to 16 years, the drug was eliminated faster than in adult patients. Subsequent pharmacokinetic analysis shows that with a dosing regimen of 8 mg / kg (not more than 250 mg per dose) every 12 hours in children 6 months - 17 years old at steady state, AUC 0-24 and Cmax in plasma, comparable to those in adult patients with a dose of levofloxacin 500 mg every 24 hours.

The pharmacokinetics of levofloxacin in patients with severe community-acquired pneumonia does not differ from that in healthy volunteers.

The study of the pharmacokinetics of levofloxacin in the application as 0.5% eye drops was carried out in 15 healthy adult volunteers. Plasma concentrations of levofloxacin were measured at various time intervals over a 15-day course of administration. The mean plasma concentration of levofloxacin 1 hour after instillation varied from 0.86 ng/ml on the first day to 2.05 ng/ml on the fifteenth day. Cmax of levofloxacin in plasma was 2.25 ng / ml and was reached on the 4th day after 2 days of use every 2 hours (up to 8 times a day). The Cmax of levofloxacin achieved on day 15 was more than 1000 times lower than the concentration observed after oral administration of standard doses of levofloxacin.

In studies in healthy adult volunteers (n=30), it was shown that the mean concentrations of levofloxacin in the tear film measured 4 and 6 hours after instillation were 17.0 µg/ml and 6.6 µg/ml, respectively (clinical significance unknown) .

Experimental toxicology and/or pharmacology

Levofloxacin and other fluoroquinolones have been shown to cause arthropathy in young growing animals in most species tested.

Oral administration of levofloxacin at a dose of 40 mg/kg/day in 3-month-old dogs resulted in symptomatic arthropathy and discontinuation on dosing day 8 of the planned 14 days. Minor musculoskeletal clinical effects in the absence of gross pathological or histopathological abnormalities have been observed with the lowest dose level of 2.5 mg/kg/day (approximately 0.2 times the pediatric dose based on AUC comparison). Synovitis and articular cartilage lesions have been observed at doses of 10 and 40 mg/kg (approximately 0.7 and 2.4 times the pediatric dose based on AUC comparison). Gross articular cartilage pathology and histopathological changes persisted until the end of the 18-week recovery period in dogs treated with levofloxacin at doses of 10 and 40 mg/kg/day.

In animal experiments, oral or intravenous administration of levofloxacin to immature rats and dogs resulted in an increase in cases of osteochondrosis. Histopathological examination of weight-bearing joints in immature dogs with levofloxacin revealed persistent cartilage lesions. Other fluoroquinolones also induce similar erosive changes in weight-bearing joints and other manifestations of arthropathy in immature animals of various species.

In immature dogs (aged 4-5 months), oral administration at a dose of 10 mg/kg/day for 7 days or IV at a dose of 4 mg/kg/day for 14 days led to the development of arthropathies. Oral administration of 300 mg/kg/day for 7 days or iv 60 mg/kg/day for 4 weeks caused arthropathy in immature rats.

In mice, levofloxacin produced phototoxic effects similar to, but less pronounced than, ofloxacin compared to other fluoroquinolones.

Although crystalluria has been observed in rats given intravenous administration in some studies, urinary crystals did not form in the bladder, were found only after urination, and were not associated with nephrotoxicity.

In experiments on mice, the stimulating effect of fluoroquinolones on the central nervous system was enhanced by simultaneous use with NSAIDs.

When administered rapidly intravenously to dogs at doses of 6 mg/kg or more, levofloxacin produced a hypotensive effect, presumably due to histamine release.

In research in vitro and in vivo levofloxacin within therapeutic concentrations did not have an inducing or inhibitory effect on enzyme systems, thus, no enzyme-mediated effect on the metabolism of other drugs is expected.

Carcinogenicity, mutagenicity, effect on fertility

In lifetime biological studies in rats, levofloxacin was not carcinogenic when administered orally daily for 2 years at doses up to 100 mg/kg/day (1.4 times the MRDH (750 mg) based on body surface area). Levofloxacin at any dosage regimen did not reduce the time to development of UV-induced skin tumors in albino hairless mice (Skh-1) and thus did not exhibit photocarcinogenic properties under experimental conditions. The concentration of levofloxacin in the skin tissues of hairless mice ranged from 25-42 µg/g at the maximum doses in the photocarcinogenicity study (300 mg/kg/day). For comparison, in humans, the concentration of levofloxacin in skin tissues while taking a dose of 750 mg averages 11.8 μg / g at Cmax in plasma.

Did not show mutagenic properties in the following studies: Ames test on bacteria S. Typhimurium and E. coli, test with hypoxanthine-guanine phosphoribosyltransferase of Chinese hamster ovary cells, micronucleus test in mice, dominant lethal mutation test in mice, unscheduled DNA synthesis test in rats, sister chromatid exchange test in mice. Mutagenic activity detected in tests in vitro for chromosomal aberrations (on the CHL cell line) and sister chromatid exchange (on the CHL/IU cell line).

No effect on fertility or reproductive function in rats at an oral dose of 360 mg/kg/day (4.2 times the MRHD, based on body surface area) or an IV dose of 100 mg/kg/day (in 1.2 times the MRFA, based on body surface area).

The use of the substance Levofloxacin

Levofloxacin for oral and intravenous administration is indicated for the treatment of infectious and inflammatory diseases caused by pathogens sensitive to levofloxacin in adults, incl. : community-acquired pneumonia; uncomplicated urinary tract infections; complicated urinary tract infections (including pyelonephritis); chronic bacterial prostatitis; infections of the skin and soft tissues; as part of the complex therapy of drug-resistant forms of tuberculosis; prevention and treatment of anthrax in case of airborne infection; acute sinusitis (tablets); exacerbation of chronic bronchitis (tablets); hospital pneumonia (for a dosage of tablets of 750 mg).

When using levofloxacin, one should take into account official national recommendations for the appropriate use of antibacterial agents, as well as the sensitivity of pathogenic microorganisms in a particular country (see "Special Instructions").

Levofloxacin 0.5% eye drops is indicated for the treatment of superficial bacterial eye infections caused by susceptible organisms in adults and children over 1 year of age; for the prevention of complications after surgical and laser operations on the eye.

Contraindications

For systemic use: hypersensitivity to levofloxacin or other quinolones; epilepsy; pseudoparalytic myasthenia gravis (myasthenia gravis)(see "Side effects", "Precautions"); tendon lesions when taking fluoroquinolones in history; children and adolescents under 18 years of age (due to the incomplete growth of the skeleton, since the risk of damage to cartilaginous growth points cannot be completely excluded); pregnancy (the risk of damage to the cartilaginous growth points in the fetus cannot be completely excluded); the period of breastfeeding (it is impossible to completely exclude the risk of damage to the cartilaginous growth points of bones in a child).

Eye drops: hypersensitivity to levofloxacin or other quinolones.

Application restrictions

For systemic use:

In patients predisposed to the development of seizures (in patients with previous CNS lesions, in patients simultaneously taking drugs that lower the threshold for convulsive readiness of the brain, such as fenbufen, theophylline) (see "Interaction");

In patients with latent or manifest deficiency of glucose-6-phosphate dehydrogenase (increased risk of hemolytic reactions during treatment with quinolones);

In patients with impaired renal function (mandatory monitoring of renal function is required, as well as correction of the dosing regimen);

In patients with known risk factors for QT prolongation: advanced age; female gender, uncorrected electrolyte disturbances (hypokalemia, hypomagnesemia); syndrome of congenital prolongation of the QT interval; heart disease (heart failure, myocardial infarction, bradycardia); simultaneous administration of drugs that can prolong the QT interval (class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, neuroleptics) (see "Overdose", "Interaction", "Precautions");

In patients with diabetes mellitus receiving treatment with oral hypoglycemic drugs, such as glibenclamide or insulin preparations (risk of hypoglycemia increases);

In patients with severe adverse reactions to other fluoroquinolones, such as severe neurological reactions (increased risk of similar adverse reactions when using levofloxacin);

In patients with psychosis or in patients with a history of mental illness (see "Precautions").

Eye drops: children's age (safety and efficacy have not been determined).

Use during pregnancy and lactation

Use during pregnancy is possible only if the expected effect of therapy outweighs the potential risk to the fetus (adequate, strictly controlled studies of the safety of use in pregnant women have not been conducted).

Levofloxacin was not teratogenic in rats when administered orally at a dose of 810 mg/kg/day (9.4 times the MRDH in terms of body surface area) or intravenously at a dose of 160 mg/kg/day (1. 9 times the MAFR in terms of body surface area). Oral administration to pregnant rats at a dose of 810 mg/kg/day led to an increase in the frequency of intrauterine death and a decrease in fetal body weight. In experiments on rabbits, no teratogenic effect was detected when administered orally at a dose of 50 mg / kg / day (1.1 times the MRHD in terms of body surface area) or / in the introduction at a dose of 25 mg / kg / day, which corresponds to 0.5 MRDC in terms of body surface area.

Given the results of studies with other fluoroquinolones and very limited data on levofloxacin, it can be assumed that levofloxacin may pass into the breast milk of lactating women. Due to the potential for serious adverse reactions in breastfed infants, lactating women should discontinue either breastfeeding or systemic use of levofloxacin (given the importance of the drug to the mother).

When using levofloxacin in the form eye drops care must be taken.

Side effects of the substance Levofloxacin

Serious and clinically important adverse drug reactions, which are discussed in more detail in the Precautions section, include:

Effect on tendons;

Exacerbation of pseudoparalytic myasthenia gravis ( myasthenia gravis);

Hypersensitivity reactions;

Other serious and sometimes fatal reactions;

Hepatotoxicity;

Action on the central nervous system;

- Clostridium difficile-associated diarrhea;

Peripheral neuropathy, which may be irreversible;

Prolongation of the QT interval;

fluctuations in blood glucose levels;

Photosensitivity/phototoxicity;

The development of drug resistance in bacteria.

Hypotension has been associated with rapid or intravenous bolus administration of levofloxacin. Levofloxacin should be administered slowly over 60 to 90 minutes.

Crystalluria and cylindruria have been reported with fluoroquinolones, including levofloxacin. Therefore, during treatment with levofloxacin, it is necessary to maintain adequate hydration in patients in order to avoid the formation of excessively concentrated urine.

Clinical Research Experience

Since clinical trials are conducted under a different set of conditions, the incidence of adverse reactions observed in these studies cannot be directly compared with the frequency in other clinical trials and predict the occurrence of side effects in clinical practice.

Data from 29 phase 3 pooled clinical trials (n=7537) are presented. The average age of patients is 50 years (approximately 74% of patients are under 65 years of age), 50% are male, 71% are Caucasian, and 19% are black. Patients received levofloxacin in the treatment of various infections at a dose of 750 mg 1 time per day, 250 mg 1 time per day, or 500 mg 2 times per day. The duration of therapy was usually 3-14 days (mean 10 days).

The overall frequency, type and distribution of adverse reactions were similar in patients receiving levofloxacin at a dose of 750 mg 1 time per day, compared with patients receiving 250 mg 1 time per day or 500 mg 2 times a day. Therapy was discontinued due to drug-related side effects in 4.3% of patients overall, in 3.8% of patients on 250 and 500 mg doses, and in 5.4% of patients on 750 mg. The most common side effects leading to discontinuation of the drug at doses of 250 and 500 mg were gastrointestinal complaints (1.4%), nausea (0.6%), vomiting (0.4%), dizziness (0.3%) , headache (0.2%). The most common side effects leading to discontinuation of the drug at a dose of 750 mg were gastrointestinal disorders (1.2%), nausea (0.6%), vomiting (0.5%), dizziness (0.3%), headache pain (0.3%).

The following are the side effects noted in clinical trials and observed with a frequency of> 0.1% in patients treated with levofloxacin (N=7537). The most common adverse reactions (≥3%) were nausea, headache, diarrhoea, insomnia, constipation and dizziness.

headache (6%), dizziness (3%), insomnia 1 (4%); 0.1-1% - anxiety, agitation, confusion, depression, hallucinations, nightmares 1 , sleep disturbance 1 , anorexia, unusual dreams 1 , tremor, convulsions, paresthesia, vertigo, hypertension, hyperkinesis, impaired coordination of movements, drowsiness 1 , fainting.

: 0.1-1% - anemia, arrhythmia, palpitations, cardiac arrest, supraventricular tachycardia, phlebitis, epistaxis, thrombocytopenia, granulocytopenia.

From the respiratory system: shortness of breath (1%).

From the digestive tract: nausea (7%), diarrhea (5%), constipation (3%), abdominal pain (2%), dyspepsia (2%), vomiting (2%); 0.1-1% - gastritis, stomatitis, pancreatitis, esophagitis, gastroenteritis, glossitis, pseudomembranous colitis, abnormal liver function, increased levels of liver enzymes, increased alkaline phosphatase.

From the genitourinary system: vaginitis 2 (1%); 0.1-1%: impaired renal function, acute renal failure, genital candidiasis.

: 0.1-1% - arthralgia, tendinitis, myalgia, skeletal muscle pain.

From the side of the skin: rash (2%), itching (1%); 0.1-1% - allergic reactions, edema (1%), urticaria.

Others: candidiasis (1%), reaction at the injection site (1%), chest pain (1%); 0.1-1%: hyperglycemia/hypoglycemia, hyperkalemia.

In multiple dose clinical trials, ophthalmic disorders, including cataracts and multiple lenticular lenticular opacity, have been reported in patients treated with fluoroquinolones, including levofloxacin. The relationship between these phenomena and the use of drugs has not been established.

2 N=3758 (women)

Post-marketing research

It is impossible to reliably estimate the frequency of these phenomena and the causal relationship with the use of drugs, since the reports were received spontaneously, from a population of unknown size.

From the nervous system and sensory organs: isolated reports of encephalopathy, EEG disturbances, peripheral neuropathy (may be irreversible), psychosis, paranoia, isolated reports of suicide attempts and suicidal thoughts, uveitis, visual impairment (including diplopia, decreased visual acuity, blurred vision, scotoma) , hearing loss, tinnitus, parosmia, anosmia, loss of taste, taste perversion, dysphonia, exacerbation myasthenia gravis, pseudotumor of the brain.

From the side of the cardiovascular system and blood: separate messages about torsade de pointes, prolongation of the QT interval, tachycardia, vasodilation, increased INR, prolongation of PT, pancytopenia, aplastic anemia, leukopenia, hemolytic anemia, eosinophilia.

From the digestive tract: liver failure (including fatal cases), hepatitis, jaundice.

From the side of the musculoskeletal system: tendon rupture, muscle injury including rupture, rhabdomyolysis.

From the side of the skin: bullous rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, photosensitivity/phototoxicity reactions.

Allergic reactions: hypersensitivity reactions (sometimes fatal), incl. anaphylactic / anaphylactoid reactions, anaphylactic shock, angioedema, serum sickness; isolated reports of allergic pneumonitis.

Others: leukocytoclastic vasculitis, increased activity of muscle enzymes, hyperthermia, multiple organ failure, interstitial nephritis.

When using levofloxacin in the form of 0.5% eye drops, the most commonly reported effects were: 1-3% - transient visual impairment, transient burning, pain or discomfort in the eye, sensation of a foreign body in the eye, fever, headache, pharyngitis, photophobia;<1% — аллергические реакции, отек век, сухость глаза, зуд в глазу.

Interaction

Chelated compounds: antacids, sucralfate, metal cations, multivitamins

Levofloxacin for oral administration. Magnesium and aluminum-containing antacids, sucralfate; Drugs containing metal cations (such as iron), zinc-containing multivitamins, didanosine (LF containing aluminum and magnesium), when taken orally with levofloxacin, can significantly affect the absorption of the latter in the gastrointestinal tract, leading to a decrease in its systemic level. The above drugs must be taken at least 2 hours before or 2 hours after oral administration of devofloxacin.

Levofloxacin for injection. There are no data on the interaction of IV administered fluoroquinolones with oral antacids, sucralfate, multivitamins, didanosine, or metal cations. However, none of the fluoroquinolones should be administered, incl. levofloxacin, together with any solution containing polyvalent cations, such as magnesium, through the same system for intravenous administration.

warfarin

In a clinical study in healthy volunteers, there was no significant effect of levofloxacin on C max , AUC and other pharmacokinetic parameters of R- or S-isomers of warfarin. There was also no apparent effect of warfarin on the absorption and other pharmacokinetic parameters of levofloxacin. However, in post-marketing studies, cases of an increase in the effect of warfarin have been reported when used simultaneously with levofloxacin, while the increase in PT was accompanied by episodes of bleeding. With the simultaneous use of levofloxacin and warfarin, careful monitoring of INR, PT and other indicators of coagulation is necessary, as well as monitoring for possible signs of bleeding.

Antidiabetic drugs

Fluctuations in blood glucose levels, including hyperglycemia and hypoglycemia, have been reported in patients treated simultaneously with fluoroquinolones and antidiabetic drugs. Careful monitoring of blood glucose levels is recommended when these drugs are used together.

NSAIDs

Concomitant use of NSAIDs with fluoroquinolones, including levofloxacin, may increase the risk of CNS stimulation and seizures.

Theophylline

In a clinical study in healthy volunteers, there was no significant effect of levofloxacin on plasma concentrations, AUC and other pharmacokinetic parameters of theophylline. Also, there was no visible effect of theophylline on the absorption and other pharmacokinetic parameters of levofloxacin. However, the concomitant use of theophylline with other fluoroquinolones was accompanied by an increase in T 1 / 2 and serum concentration of theophylline and a subsequent increase in the risk of theophylline-dependent adverse reactions. In this regard, it is necessary to carefully monitor the level of theophylline and appropriate dose adjustment with concomitant use of levofloxacin. Adverse reactions, incl. convulsions may occur regardless of an increase in the serum concentration of theophylline.

Cyclosporine

In a study in healthy volunteers, no clinically significant effect of levofloxacin on plasma concentrations, AUC and other pharmacokinetic parameters of cyclosporine was observed. However, increased plasma levels of ciclosporin have been reported with other fluoroquinolones. Cmax of levofloxacin was slightly lower, while Tmax and T 1/2 were slightly longer in the presence of cyclosporine, than the same parameters observed in other studies without concomitant treatment. The differences, however, are not considered clinically significant. In this regard, dose adjustment of levofloxacin or cyclosporine with their simultaneous use is not required.

Digoxin

In a clinical study involving healthy volunteers, no significant effect of levofloxacin on C max , AUC and other pharmacokinetic parameters of digoxin was found. Absorption and other pharmacokinetic parameters of levofloxacin were similar in the presence or absence of digoxin. Thus, with simultaneous use, dose adjustment of levofloxacin or digoxin is not required.

probenecid and cimetidine

In a clinical study involving healthy volunteers, no significant effect of probenecid or cimetidine on the Cmax of levofloxacin was observed. The AUC and T 1/2 values ​​of levofloxacin were higher, while the clearance values ​​were lower during combined treatment with levofloxacin with probenecid or cimetidine compared with treatment with levofloxacin alone. However, these changes are not the basis for adjusting the dose of levofloxacin when used in combination with probenecid or cimetidine.

Interactions associated with laboratory or diagnostic testing

Some fluoroquinolones, including levofloxacin, may cause false-positive urine tests for opiates when using commercially available immunoassay kits (more specific opiate tests may be needed).

Overdose

In mice, rats, dogs and monkeys, the following symptoms were observed after administration of a single high dose of levofloxacin: ataxia, ptosis, decreased locomotor activity, shortness of breath, prostration, tremor, convulsions. Doses greater than 1500 mg/kg orally and 250 mg/kg iv significantly increased mortality in rodents.

Treatment acute overdose: gastric lavage, adequate hydration. It is not excreted by hemodialysis and peritoneal dialysis.

Routes of administration

Inside, in / in, conjunctival.

Precautions for the substance Levofloxacin

Tendinopathy and tendon rupture

The use of fluoroquinolones, including levofloxacin, is associated with an increased risk of tendonitis and tendon rupture at any age. This side effect most commonly affects the Achilles tendon, and if the Achilles tendon is torn, surgery may be required. Tendonitis and rupture of the rotator cuff tendon, hand, biceps, thumb, and other tendons have also been reported. The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in elderly patients, usually over 60 years of age, in patients taking corticosteroids, and in patients with kidney, heart, and lung transplants. Factors in addition to age and corticosteroid use that may independently increase the risk of tendon rupture include increased physical activity, kidney failure, and pre-existing medical conditions such as rheumatoid arthritis. Tendonitis and tendon rupture have been reported in patients treated with fluoroquinolones who did not have the above risk factors. Tendon rupture may occur during or after completion of therapy; some cases have been reported up to several months after completion of treatment. If pain, swelling, inflammation or tendon rupture occurs, levofloxacin therapy should be discontinued. Patients should be advised to rest and avoid exertion at the first sign of tendonitis or tendon rupture, and to consult their physician for other non-quinolone antimicrobials.

Exacerbation of pseudoparalytic myasthenia gravis (myasthenia gravis)

Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with pseudoparalytic myasthenia gravis. In the post-marketing period, serious adverse reactions, including pulmonary failure requiring mechanical ventilation, and death, have been associated with the use of fluoroquinolones in patients with pseudoparalytic myasthenia gravis. The use of levofloxacin in patients with an established diagnosis of pseudoparalytic myasthenia gravis is contraindicated (see "Contraindications", "Side Effects").

Hypersensitivity reactions

It was reported about the development of severe and fatal hypersensitivity reactions and / or anaphylactic reactions while taking fluoroquinolones, incl. levofloxacin, often developing after the first dose. Some reactions have been accompanied by cardiovascular collapse, hypotension, shock, convulsions, loss of consciousness, pinching sensation, angioedema (including tongue, pharynx, glottis, or facial edema), airway obstruction (bronchospasm, shortness of breath, acute respiratory distress syndrome) , shortness of breath, urticaria, itching and other severe skin reactions. At the first manifestations of a skin rash or other hypersensitivity reactions, levofloxacin should be immediately discontinued. With the development of serious acute hypersensitivity reactions, the administration of epinephrine and other resuscitation measures may be required, including the use of oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and maintenance of airway patency (according to clinical indications) (see "Side Effects" ).

Other serious and sometimes fatal reactions

Rarely, the development of other severe and sometimes fatal reactions in patients while taking fluoroquinolones, incl. levofloxacin due to both hypersensitivity reactions and unexplained causes. These reactions occurred predominantly after repeated doses and manifested as: fever, rash or severe dermatological reactions (eg, acute epidermal necrolysis, Stevens-Johnson syndrome), vasculitis, arthralgia, myalgia, serum sickness, allergic pneumonitis, interstitial nephritis, acute renal failure , hepatitis, jaundice, acute liver necrosis or liver failure, anemia (including hemolytic and hypoplastic), thrombocytopenia (including thrombocytopenic purpura), leukopenia, agranulocytosis, pancytopenia and / or other changes in the blood.

At the first manifestations of skin rash, jaundice or any other manifestations of hypersensitivity, levofloxacin should be immediately discontinued and the necessary measures taken.

Hepatotoxicity

There was no evidence of severe levofloxacin-associated hepatotoxicity in clinical studies in more than 7,000 patients. Severe hepatotoxic reactions recorded in post-marketing observations (including acute hepatitis and fatal outcome) usually occurred within the first 14 days of treatment, most cases within 6 days, in most cases severe hepatotoxicity was not associated with hypersensitivity. The most frequent cases of fatal hepatotoxicity were observed in patients aged 65 years and older and were not associated with hypersensitivity. The use of levofloxacin should be stopped immediately if the patient develops signs and symptoms of hepatitis (see "Side Effects").

Effect on the central nervous system

Seizures, toxic psychosis, increased intracranial pressure (including pseudotumor brain) have been reported in patients treated with fluoroquinolones, incl. levofloxacin. Fluoroquinolones can also cause CNS stimulation with tremors, restlessness, anxiety, dizziness, confusion, hallucinations, paranoia, depression, insomnia, nightmares, rarely suicidal thoughts and actions; these phenomena may occur after the first dose. If these reactions occur in patients receiving levofloxacin, treatment should be discontinued and appropriate measures taken. As with other fluoroquinolones, levofloxacin should be used with caution in patients with known or suspected CNS disease that predisposes to seizures or a decrease in seizure threshold (eg, severe cerebral arteriosclerosis, epilepsy), or in the presence of other risk factors that may predispose to seizures or decreased threshold of convulsive activity (for example, some drugs, kidney dysfunction) (see "Side Effects", "Interaction").

Diarrhea associated with Clostridium difficile

About the development of diarrhea associated with Clostridium difficile, has been reported with virtually all antibacterial agents, including levofloxacin, and can range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents leads to a modification of the normal flora of the large intestine and increased growth C. difficile. Strains C. difficile, producing toxins A and B, which cause diarrhea, lead to an increased risk of mortality because these infections may be resistant to antimicrobial therapy and may require colectomy. Opportunity C. difficile-associated diarrhea should be considered in all patients who complain of diarrhea after the use of antibacterial agents. A careful anamnesis is necessary, because development C. difficile-associated diarrhea is possible within two months after the use of antibacterial drugs. If C. difficile-associated diarrhea is suspected or confirmed, stop levofloxacin and start appropriate treatment (including administration of fluids and electrolytes, protein supplements, use of antibiotics to which strains are susceptible C. difficile), as well as to conduct a surgical evaluation, if there are clinical indications (see "Side Effects").