Levofloxacin Ecolevid, 500 mg 5 pcs

Pharmacotherapeutic group: Antimicrobial agent, fluoroquinolone.

ATX code: J01MA12.

Pharmacological properties

Pharmacodnamca

Levofloxacin is a synthetic broad-spectrum antibacterial drug from the group of fluoroquinolones, containing the left-handed isomer ofloxacin as the active substance.

Levofloxacin blocks DNA-giase, disrupts superspiralization and cross-linking of DNA breaks, inhibits DNA synthesis and causes deep morphological changes in cytoplasm, cell wall and membranes of bacteria.

Levofloxacin acts bactericidally and is active against a large number of pathogens of bacterial infections both in vitro and in vivo.

Sensitive microorganisms (minimum suppressive concentration (MDC) ≤ 2 mg/L):

Aerobic gram-positive microorganisms:

Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus spp., including Enterococcus faecalis, Listeria monocytogenes, Staphylococcus spp. (coagulase-negative, methicillin-sensitive / leukotoxin-containing / moderately sensitive strains), including Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), Streptococcus spp. groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-sensitive / moderately sensitive / resistant strains), Streptococcus pyogenes, Streptococcus spp.Viridans group (penicillin-sensitive/resistant strains);

Aerobic Gram-negative microorganisms:

Acinetobacter spp., including Acinetobacter baumannii, Acinetobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter spp, including Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (ampicillin-sensitive/resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp., including Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis (beta-lactamase-producing and nonproducing strains), Morganella morganii, Neisseria gonorrhoeae (penicillinase-producing and nonproducing strains), Neisseria meningitidis, Pasteurella spp., including Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida, Proteus mirabilis, Proteus vulgaris, Providencia spp., including Providencia rettgeri, Providencia stuartii, Pseudomonas spp, including Pseudomonas aeruginosa (hospital infections caused by Pseudomonas aeruginosa may require combined treatment), Serratia spp, including Serratia marcescens, Salmonella spp.;

anaerobic microorganisms:

Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterium spp., Veillonella spp.;

other microorganisms:

Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Legionella spp., Mycobacterium spp, including Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

Moderately sensitive microorganisms (MPC = 4 mg/L):

aerobic gram-positive microorganisms:

Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis (methicillin-resistant strains), Staphylococcus haemolyticus (methicillin-resistant strains);

aerobic Gram-negative microorganisms:

Campylobacter jejuni, Campylobacter coli;

anaerobic microorganisms:

Prevotella spp., Porphyromonas spp.

Resistant microorganisms (MPC greater than 8 mg/L):

aerobic gram-positive microorganisms:

Staphylococcus aureus (methicillin-resistant strains), other Staphylococcus spp. (coagulase-negative methicillin-resistant strains);

Aerobic Gram-negative microorganisms:

Alcaligenes xylosoxidans;

anaerobic microorganisms:

Bacteroides thetaiotaomicron

other microorganisms:

Mycobacterium avium.

Clinical efficacy (effectiveness in clinical trials for infections caused by the microorganisms listed below):

aerobic gram-positive microorganisms:

Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes;

aerobic gram-negative microorganisms:

Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens;

other microorganisms:

Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae.

Levofloxacin resistance develops as a result of a stepwise process of mutations in the genes encoding both type II topoisomerases: DNA-Gyrase and topoisomerase IV. Other mechanisms of resistance, such as the mechanism of influence on the penetration barriers of the microbial cell (a mechanism characteristic of Pseudomonas aeruginosa) and the mechanism of efflux (active elimination of the antimicrobial agent from the microbial cell), may also reduce the sensitivity of microorganisms to levofloxacin.

Because of the nature of the mechanism of action of levofloxacin there is usually no cross-resistance between levofloxacin and other antimicrobial agents.

Pharmacoknetzka

Absorption

Levofloxacin is rapidly and almost completely absorbed after oral administration; food intake has little effect on its absorption. Absolute bioavailability when administered orally is 99-100%. After a single use of 500 mg of levofloxacin maximum concentration in blood plasma (Cmax) is reached within 1-2 hours and is 5.2±1.2 µg/ml. Pharmacokinetics of levofloxacin is linear in the dose range from 50 to 1000 mg. Equilibrium state of plasma concentrations of levofloxacin when administered with 500 mg of levofloxacin 1 or 2 times per day is reached within 48 hours.

On the 10th day of oral administration of Levofloxacin Ecolevid^® 500 mg once daily, the Cmax of levofloxacin was 5.7±1.4 µg/ml, and the minimum plasma concentration of levofloxacin (concentration before the next dose) (Cmin) was 0.5±0.2 µg/ml.

On day 10 of oral administration of Levofloxacin Ecolevid^® 500 mg twice daily, Cmax was 7.8±1.1 µg/ml and C min was 3.0±0.9 µg/ml.

Distribution

The binding to serum proteins is 30-40%. After single and repeated administration of 500 mg of levofloxacin the volume of distribution of levofloxacin averaged 100 l, indicating good penetration of levofloxacin into human organs and tissues.

Infiltration into the bronchial mucosa, epithelial lining fluid, alveolar macrophages

. After a single oral dose of 500 mg of levofloxacin, maximum concentrations of levofloxacin in bronchial mucosa and epithelial lining fluid were reached within 1 h or 4 h and were 8.3 µg/g and 10.8 µg/mL, respectively, with rates of penetration into bronchial mucosa and epithelial lining fluid, compared with plasma concentrations of 1.1-1.8 and 0.8-3, respectively.

After 5 days of oral administration of 500 mg of levofloxacin, mean concentrations of levofloxacin 4 hours after the last drug administration in the epithelial lining fluid were 9.94 µg/mL and in alveolar macrophages were 97.9 µg/mL.

Prevalence in pulmonary tissue

The maximum pulmonary tissue concentrations after oral administration of 500 mg of levofloxacin were approximately 11.3 µg/g and were reached 4-6 h after drug administration with penetration ratios of 2-5, compared with plasma concentrations.

Alveolar fluid penetration

After 3 days of administration of 500 mg of levofloxacin 1 or 2 times daily, maximum concentrations of levofloxacin in alveolar fluid were reached 2-4 h after drug administration and were
4.0 and 6.7 µg/mL, respectively, with a penetration coefficient of 1, compared to plasma concentrations.

Bone penetration

Levofloxacin penetrates well into cortical and cancellous bone tissue in both the proximal and distal femur, with a penetration ratio (bone tissue/plasma) of 0.1-3. Maximum levofloxacin concentrations in the cancellous bone tissue of the proximal femur following oral administration of 500 mg of the drug were approximately 15.1 µg/g (2 hours after drug administration).

Infiltration into the cerebrospinal fluid

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Infiltration into prostate tissue

. After oral administration of 500 mg of levofloxacin once daily for 3 days, the mean concentration of levofloxacin in prostate tissue was 8.7 µg/g, and the mean prostate/blood plasma concentration ratio was 1.84.

Urinary concentrations

The mean urinary concentrations 8-12 h after oral doses of 150, 300, and 600 mg of levofloxacin were 44 µg/mL, 91 µg/mL, and 162 µg/mL, respectively.

Metabolism

Levofloxacin is metabolized to a small extent (5% of the dose taken). Its metabolites are demethyllevofloxacin and levofloxacin N-oxide, which are excreted by the kidneys. Levofloxacin is stereochemically stable and does not undergo chiral transformations.

Elimation

Levofloxacin is relatively slowly eliminated from the blood plasma after oral administration (half-life (T1/2) is 6-8 hours). Excretion is mainly through the kidneys (more than 85% of the dose taken). Total clearance of levofloxacin after a single dose of 500 mg was 175±29.2 ml/minute.

There are no significant differences in the pharmacokinetics of levofloxacin when administered intravenously and when administered orally, confirming that oral and intravenous administration are interchangeable.

Pharmacokinetics in selected patient groups

The pharmacokinetics of levofloxacin do not differ in men and women.

Pharmacokinetics in elderly patients does not differ from that in younger patients, except for differences in pharmacokinetics associated with differences in creatinine clearance (CK).

In renal failure, the pharmacokinetics of levofloxacin are altered. As renal function deteriorates, renal excretion and renal clearance (CIR) decreases and T1/2 increases.

Pharmacokinetics in renal failure after a single oral administration of 500 mg of Levofloxacin Ecolevid.

Indications

Treatment of infection and inflammatory diseases caused by microorganisms sensitive to levofloxacin:

Out-of-hospital pneumonia;

Complicated urinary tract infections and pyelonephritis;

Chronic bacterial prostatitis;

Skin and soft tissue infections;

for the complex treatment of drug-resistant forms of tuberculosis;

anthrax prevention and treatment in the airborne route of infection.

Levofloxacin can be used as an alternative to other antimicrobial agents for the treatment of the following infectious and inflammatory diseases:

acute sinusitis;

exacerbation of chronic bronchitis;

uncomplicated cystitis.

When using Levofloxacin Ecolevid®, official national guidelines for the appropriate use of antibacterial agents as well as the sensitivity of pathogens in a specific country should be taken into account (see section “Special Indications”).

Active ingredient

Composition

How to take, the dosage

Ingestion. Once or twice daily. The tablets should be swallowed without chewing and with enough fluid (0.5 to 1 cup).

The drug can be taken before meals or at any time between meals, since eating has no effect on absorption of the drug (see section “Pharmacokinetics”).

The drug should be taken at least 2 hours before or 2 hours after taking drugs containing magnesium and/or aluminum, iron, zinc, or sucralfate (see section “Interaction with other medicinal products”).

Given that the bioavailability of levofloxacin when receiving Levofloxacin Ecolevid® in tablets is 99-100%, if the patient is transferred from intravenous infusion with other levofloxacin drugs, administration of Levofloxacin Ecolevid tablets® should be continued at the same dose that was used with the intravenous infusion of levofloxacin (see Pharmacokinetics and Pharmacokinetics section). See section Pharmacokinetics).

Missing one or more doses of the drug

. If you accidentally miss a dose, take the next dose as soon as possible and then continue taking Levofloxacin Ecolevid® according to the recommended dosing regimen.

Doses and duration of treatment

The dosing regimen is determined by the nature and severity of the infection and the sensitivity of the suspected pathogen. The duration of treatment varies depending on the course of the disease.

Recommended dosing regimen and duration of treatment in patients with normal renal function (CK >50 ml/min)

Acute sinusitis: 2 tablets of Levofloxacin Ecolevid® 250 mg or 1 tablet of Levofloxacin Ecolevid® 500 mg once daily (500 mg levofloxacin respectively), 10-14 days.

Exacerbation of chronic bronchitis: 2 tablets of Levofloxacin Ecolevid® 250 mg or 1 tablet of Levofloxacin Ecolevid® 500 mg once daily (respectively 500 mg of levofloxacin) –
7-10 days.

Inpatient pneumonia: 2 tablets of Levofloxacin Ecolevid® 250 mg or 1 tablet of Levofloxacin Ecolevid® 500 mg 1-2 times daily (respectively 500-1000 mg of levofloxacin) –
7-14 days.

Uncomplicated urinary tract infections: 1 tablet of Levofloxacin Ecolevid® 250 mg once daily (respectively 250 mg of levofloxacin) –
3 days.

Complicated urinary tract infections: 2 tablets of Levofloxacin Ecolevid® 250 mg once daily or 1 tablet of Levofloxacin Ecolevid® 500 mg once daily (respectively 500 mg of levofloxacin) – 7-14 days.

Pyelonephritis: 2 tablets of Levofloxacin Ecolevid® 250 mg once daily or 1 tablet of Levofloxacin Ecolevid® 500 mg once daily (respectively 500 mg of levofloxacin) – 7-10 days.

Cronic bacterial prostatitis: 2 tablets of Levofloxacin Ecolevid® 250 mg or 1 tablet of Levofloxacin Ecolevid® 500 mg once daily (500 mg of levofloxacin, respectively) – 28 days.

Infections of the skin and soft tissues: 2 tablets of Levofloxacin Ecolevid® 250 mg or 1 tablet of Levofloxacin Ecolevid® 500 mg 1-2 times daily (respectively 500-1000 mg of levofloxacin) – 7-14 days.

Comprehensive treatment of drug-resistant forms of tuberculosis: 1 tablet of Levofloxacin Ecolevid® 500 mg 1-2 times daily (respectively 500-1000 mg of levofloxacin) – up to 3 months.

Prevention and treatment of anthrax in the airborne route of infection: 2 tablets of Levofloxacin Ecolevid® 250 mg or 1 tablet of Levofloxacin Ecolevid® 500 mg (500 mg of levofloxacin, respectively) once daily for up to 8 weeks.

Dosing regimen in patients with impaired renal function (CK < 50 ml/min)

Levofloxacin is mainly excreted by the kidneys; therefore, when treating patients with impaired renal function, reduction of the drug dose is required.

Dosing regimen in patients with impaired hepatic function

The dosing regimen does not need to be adjusted if hepatic function is impaired because levofloxacin is only slightly metabolized in the liver.

Dosing regimen in elderly patients

The dosing regimen does not need to be adjusted in elderly patients unless the CK falls to 50 ml/min or lower.

Interaction

There are reports of a marked decrease in seizure threshold with concomitant use of quinolones and substances that reduce cerebral seizure threshold. This also applies to the simultaneous use of quinolones and theophylline, as well as nonsteroidal anti-inflammatory drugs – propionic acid derivatives.

Pharmacokinetic interaction of levofloxacin with theophylline has not been identified.

. Oral administration together with drugs containing bivalent and trivalent cations, such as zinc or iron salts (drugs for treatment of anemia), magnesium- and/or aluminum-containing drugs (such as antacids), didanosine (only dosage forms containing aluminum or magnesium as a buffer), leads to decreased absorption and weakened effect of levofloxacin, so it should be administered 2 hours before or 2 hours after taking the above-mentioned drugs.

Calcium salts have minimal effect on the absorption of levofloxacin when taken orally.

The effect of levofloxacin is significantly impaired with concomitant use of sucralfate (gastric mucosal protection agent). Patients receiving levofloxacin and sucralfate are recommended to take sucralfate 2 hours after taking levofloxacin.

The concentration of levofloxacin is increased by only 13% when concomitant administration of fenbufen.

Continuous use of vitamin K antagonists requires monitoring of the clotting system.

In patients treated with levofloxacin in combination with indirect anticoagulants (e.g., warfarin) an increase in prothrombin time/international normalized ratio and/or development of bleeding, including severe bleeding, was observed. Therefore, when concomitant use of indirect anticoagulants and levofloxacin, regular monitoring of blood clotting parameters is necessary.

When concomitant use of drugs that disrupt renal tubular secretion, such as probenecid and cimetidine, and levofloxacin, caution should be exercised, especially in patients with renal insufficiency. Excretion (renal clearance) of levofloxacin is slowed by 24% by cimetidine and by 34% by probenecid. This is unlikely to be clinically relevant in normal renal function.

Levofloxacin when used concomitantly with antiarrhythmic drugs of classes IA and III, tricyclic antidepressants, macrolides, neuroleptics may cause prolongation of the QT interval.

Levofloxacin increases the half-life of cyclosporine by 33%. Since this increase is clinically insignificant, there is no need to adjust the dose of cyclosporine when using it concomitantly with levofloxacin.

The use of glucocorticosteroids increases the risk of tendon rupture.

The pharmacokinetics of levofloxacin when used concomitantly with digoxin, glibenclamide, ranitidine, warfarin are not altered sufficiently to be of clinical significance.

Special Instructions

Hospital infections caused by Pseudomonas aeruginosa may require combination treatment.

Risk of developing resistance

The prevalence of acquired resistance of bacterial strains being bred may vary by geographic region and over time. This requires country-specific information on resistance to the drug. For therapy of severe infections or in case of treatment failure a microbiological diagnosis with pathogen isolation and determination of its sensitivity to levofloxacin should be established.

Methicillin-resistant Staphylococcus aureus

. There is a high probability that methicillin-resistant Staphylococcus aureus will be resistant to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of established or suspected infections caused by methicillin-resistant Staphylococcus aureus if laboratory tests have not confirmed the sensitivity of this microorganism to levofloxacin.

Loss of disability and potentially irreversible serious adverse reactions due to fluoroquinolones

. The use of fluoroquinolones, including levofloxacin, has been associated with disability and the development of irreversible serious adverse reactions from various body systems that may develop simultaneously in the same patient. Fluoroquinolone-induced adverse reactions include tendonitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and nervous system side effects (hallucinations, anxiety, depression, insomnia, headaches, and confusion). These reactions may occur within a few hours to a few weeks after the start of therapy with levofloxacin.

The development of these adverse reactions has been observed in patients of any age or without prior risk factors. If the first signs or symptoms of any serious adverse reactions occur, levofloxacin should be discontinued immediately. The use of fluoroquinolones, including levofloxacin, should be avoided in patients who have had any of these serious adverse reactions.

Patients susceptible to seizures

As with other quinolones, levofloxacin should be used with great caution in patients with a predisposition to seizures. These patients include those with previous central nervous system lesions, such as stroke, severe craniocerebral trauma; patients concomitantly taking drugs that lower the seizure threshold of the brain, such as phenbufen and other similar non-steroidal anti-inflammatory drugs or other drugs that lower the seizure threshold, such as theophylline (see section “Interaction with other medicinal products”).

The treatment with levofloxacin should be discontinued if seizures develop.

Pseudomembranous colitis

. Diarrhea that develops during or after treatment with levofloxacin, especially severe, persistent and/or with blood, may be a symptom of pseudomembranous colitis caused by Clostridium difficile. If pseudomembranous colitis is suspected, treatment with levofloxacin should be stopped immediately and specific antibiotic therapy (oral vancomycin, teicoplanin or metronidazole) started immediately. Drugs that inhibit intestinal peristalsis are contraindicated.

Tendinitis and tendon rupture

. Tendinitis is rarely seen with quinolones, including levofloxacin, which can sometimes lead to tendon rupture, including the Achilles tendon, and can be bilateral.

This side effect may develop within 48 hours of starting treatment or several months after completion of fluoroquinolone therapy.

Elderly patients are more prone to develop tendinitis; in patients taking fluoroquinolones, the risk of tendon rupture may increase with concomitant use of glucocorticosteroids. In addition, patients after transplantation have an increased risk of tendinitis, so caution is recommended when prescribing fluoroquinolones for this category of patients. In patients with impaired renal function the daily dose should be adjusted based on creatinine clearance. Patients should be advised to remain at rest at the first signs of tendinitis or tendon rupture and contact the attending physician. If tendinitis or tendon rupture is suspected, treatment with Levofloxacin Ecolevid® should be stopped immediately and appropriate treatment of the affected tendon should be initiated, for example by providing adequate immobilization (see “Contraindications” and “Side Effects”).

Hypersensitivity reactions

. Levofloxacin can cause serious, potentially fatal, hypersensitivity reactions (angioedema, anaphylactic shock), even when initial doses are used (see See section “Side effects”). Patients should immediately stop taking the drug and consult a physician.

Serious bullous reactions

. Cases of severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, have been observed with levofloxacin (see See section “Adverse effects”). If any skin or mucous membrane reactions develop, the patient should immediately consult a physician and not continue treatment until he or she has been consulted.

Disorders of the liver and biliary tract

. Cases of hepatic necrosis, including the development of hepatic failure with fatal outcome, have been reported when using levofloxacin, mainly in patients with severe underlying diseases, such as sepsis (see See section “Side effects”). Patients should be warned to discontinue treatment and seek urgent medical attention if signs and symptoms of liver damage, such as anorexia, jaundice, darkened urine, itching of the skin and abdominal pain appear.

Patients with impaired renal function

. Since levofloxacin is mainly excreted through the kidneys, patients with impaired renal function require mandatory monitoring of renal function as well as dosage regimen adjustment (see section “Dosage method. See section “Dosage and administration”). When treating elderly patients it should be taken into account that renal dysfunction is often observed in this group of patients (see section “Dosage and administration”).

Prevention of photosensitization reactions

. Although photosensitization by using levofloxacin is very rare, to prevent its development the patients are not recommended during the treatment and within 48 hours after the treatment with levofloxacin to be exposed to strong sunlight or artificial ultraviolet radiation without any special need (e.g. to visit a solarium).

Superinfection

. As with other antibiotics the use of levofloxacin, especially for a long time, may lead to increased proliferation of microorganisms insensitive to it (bacteria and fungi) which may cause changes in the microflora which is normally present in humans. As a result, superinfection may develop. Therefore, it is mandatory to reassess the patient’s condition during treatment, and if superinfection develops during treatment, appropriate measures should be taken.

QT interval prolongation

Very rare cases of QT interval prolongation have been reported in patients taking fluoroquinolones, including levofloxacin.

When using fluoroquinolones, including levofloxacin, caution should be exercised in patients with known risk factors for QT interval prolongation: In patients with uncorrected electrolyte abnormalities (with hypokalemia, hypomagnesemia); with congenital QT interval prolongation syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); and with concurrent administration of drugs that can prolong the QT interval, such as class IA and III antiarrhythmic agents, tricyclic antidepressants, macrolides, neuroleptics.

The elderly and female patients may be more sensitive to drugs that prolong the QT interval. Therefore fluoroquinolones including levofloxacin should be used with caution in these patients (see sections Caution, Dosage and administration, Adverse effects, Overdosing and Interaction with other medicinal products).

Patients with glucose-6-phosphate dehydrogenase deficiency

. Patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency have a predisposition to develop hemolytic reactions when treated with quinolones, which should be taken into account when treating with levofloxacin.

Hypo- and hyperglycemia (dysglycemia)

. As with other quinolones, cases of hyperglycemia and hypoglycemia have been observed with levofloxacin, usually in patients with diabetes mellitus receiving concomitant treatment with oral hypoglycemic agents (such as glibenclamide) or insulin drugs. Cases of hypoglycemic coma have been reported. In patients with diabetes mellitus, monitoring of blood glucose concentrations is required (see section “Side effects”).

Peripheral neuropathy

. Patients taking fluoroquinolones, including levofloxacin, have reported cases of sensory and sensory-motor peripheral neuropathy, which can have a rapid onset. If the patient develops symptoms of neuropathy, the use of levofloxacin should be discontinued. This minimizes the possible risk of developing irreversible changes.

Patients should be informed to inform their physician of any symptoms of neuropathy. Fluoroquinolones should not be prescribed in patients with a history of peripheral neuropathy.

Exacerbation of pseudoparalytic myasthenia gravis

. Fluoroquinolones, including levofloxacin, are characterized by neuromuscular conduction blocking activity and may exacerbate muscle weakness in patients with pseudoparalytic myasthenia gravis. In the post-registration period, adverse reactions, including pulmonary failure requiring artificial ventilation, and death have been observed that have been associated with fluoroquinolones in patients with pseudoparalytic myasthenia gravis. The use of levofloxacin in a patient diagnosed with pseudoparalytic myasthenia gravis is not recommended (see section “Side effects”).

Use in human anthrax

The use of levofloxacin in humans for this indication is based on sensitivity data Bacillus anthracis sensitivity data from in vitro and animal experimental studies, as well as from limited data on the use of levofloxacin in humans. Treating physicians should refer to national and/or international documents that reflect a consensus view on the treatment of anthrax.

Psychotic reactions

Psychotic reactions, including suicidal thoughts/attempts, have been reported in patients taking fluoroquinolones, including levofloxacin, sometimes after a single dose. If such reactions develop, treatment with levofloxacin should be discontinued and appropriate therapy prescribed. Caution should be exercised when prescribing the drug in patients with psychosis or patients with a history of mental illness (see section “Caution”).

Visual disturbances

In case of any visual disturbances, immediate consultation with an ophthalmologist is necessary (see section “Side effects”).

Influence on laboratory tests

In patients taking levofloxacin, urinary opioid determination may lead to false-positive results that should be confirmed by more specific methods.

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and further lead to false negatives in the bacteriological diagnosis of tuberculosis.

Influence on the ability to drive vehicles, machinery

At the time of treatment, one should refrain from driving vehicles and engaging in potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Synopsis

Contraindications

Hypersensitivity to levofloxacin, other fluoroquinolones or drug components, epilepsy, tendon involvement in previous treatment with quinolones, pregnancy, lactation, childhood and adolescence (under 18 years), myasthenia gravis.

Inborn intolerance of fructose, galactose, galactosemia, glucose-galactose malabsorption.

Because it is not possible to split the tablet in two, the drug is contraindicated in patients with impaired renal function:

In patients with a creatinine clearance of less than 50 mL/min, use with an initial dosing regimen of 250 mg/24 h is not possible;

In patients with a creatinine clearance of less than 20 mL/min, the original dosing regimen of 500 mg/24 h and 500 mg/12 h cannot be used;

In patients with a creatinine clearance of less than 10 mL/min (including hemodialysis), the dosing regimen cannot be used.

Creatinine clearance less than 10 mL/min (including in hemodialysis and continuous ambulatory peritoneal dialysis) cannot be used for all dosing regimens.

With caution

In patients predisposed to the development of seizures [in patients with previous central nervous system (CNS) lesions; in patients simultaneously taking drugs that reduce cerebral seizure threshold, such as phenbufen, theophylline] (see

In patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency (increased risk of hemolytic reactions when treated with quinolones).

In patients with known risk factors for QT interval prolongation: In elderly patients; in female patients; in patients with uncorrected electrolyte abnormalities (with hypokalemia, hypomagnesemia); with congenital QT interval prolongation syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); with concomitant administration of drugs that may prolong the QT interval (antiarrhythmic agents of class IA and III, tricyclic antidepressants, macrolides, neuroleptics) (see Sections “Overdose Overdose, Interaction with other medications, and Precautions);

In patients with diabetes mellitus receiving oral hypoglycemic medications (e.g., glibenclamide) or insulin medications (increased risk of hypoglycemia);

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

In patients with psychosis or in patients with a history of mental illness (see

In elderly patients, post-transplant patients, and concomitant use of glucocorticosteroids (increased risk of tendonitis and tendon rupture) (see section “Cautionary Note”).

Side effects

The incidence of adverse reactions is classified according to WHO guidelines: very common ≥1/10, common ≥1/100 to < 1/10, infrequent ≥1/1000 to < 1/100, rare ≥1/10000 to < 1/1000, very rare from < 1/10000, including individual cases, frequency is unknown – it was not possible to determine the incidence from the available data.

Cardiovascular system side

Rarely:Sinus tachycardia, palpitations.

Frequency unknown:long QT interval, ventricular arrhythmias, ventricular tachycardia, pirouette-type ventricular tachycardia, which may lead to cardiac arrest.

Blood and lymphatic system disorders

Infrequent: leukopenia (decreased number of leukocytes in peripheral blood), eosinophilia (increased number of eosinophils in peripheral blood).

Rarely: neutropenia (decrease in the number of neutrophils in peripheral blood), thrombocytopenia (decrease in the number of platelets in peripheral blood).

Frequency unknown:pancytopenia (decrease in the number of all the forms in peripheral blood), agranulocytosis (absence and/or a sharp decrease in the number of granulocytes in peripheral blood), hemolytic anemia.

Nervous system

Often: headache, dizziness.

Infrequent:drowsiness, tremor, dysgeusia (perversion of taste).

Rarely:paresthesia, seizures (see “Special Precautions”).

Frequency unknown:peripheral sensory neuropathy, peripheral sensory-motor neuropathy (see “Specific Indications. Special Indications, dyskinesia, extrapyramidal disorders, agueusia (loss of taste sensation), parosmia (disorder of smell sensation, especially subjective sense of smell objectively absent), including loss of smell; syncope, benign intracranial hypertension.

Visual side

Very rare:visual disturbances, such as blurring of the visible image.

Frequent unknown:Uveitis, transient vision loss.

Hearing organ and labyrinth disorders

Infrequent: Vertigo (feeling of deviation or spinning of own body or surrounding objects).

Rarely: ringing in the ears.

Frequency unknown: hearing loss, hearing loss.

Respiratory system, thoracic and mediastinal organs

Infrequent: dyspnea.

Frequency unknown: bronchospasm, allergic pneumonitis.

Gastrointestinal tract

Frequently:diarrhea, nausea, vomiting.

Infrequent: abdominal pain, flatulence, constipation, dyspepsia.

Frequency unknown:hemorrhagic diarrhea, which in very rare cases may be a sign of enterocolitis, including pseudomembranous colitis (see section “Special Instructions”), pancreatitis.

Kidney and urinary tract side

Infrequent: hypercreatininemia (increased serum creatinine concentration).

Rarely:acute renal failure (e.g., due to the development of interstitial nephritis).

Skin and subcutaneous tissue

Infrequent:rash, itching, urticaria, hyperhidrosis.

Frequency unknown:Stevens-Johnson syndrome, toxic epidermal necrolysis, exudative erythema multiforme, photosensitization reactions (hypersensitivity to sunlight and ultraviolet radiation) (see section “Special Indications”), leukocytoclastic vasculitis, stomatitis.

Skin and mucous membrane reactions may sometimes develop even after the first dose of the drug.

Musculoskeletal and connective tissue side

Infrequent:arthralgia, myalgia.

Rarely:Tendon lesions, including tendonitis (e.g., Achilles tendon), muscle weakness, which may be particularly dangerous in patients with pseudoparalytic myasthenia gravis (see “Special Precautions”).

Frequency unknown:Rhabdomyolysis, tendon rupture (e.g., Achilles tendon. This side effect may occur within 48 h after treatment initiation and may be bilateral (see also “Special Precautions”)), ligament tears, muscle tears, arthritis.

Metabolism and nutrition

Infrequent: anorexia.

Rarely:hypoglycemia, especially in patients with diabetes mellitus (possible signs of hypoglycemia: “wolfish” appetite, nervousness, sweating, trembling).

Frequency unknown:severe hypoglycemia, up to the development of hypoglycemic coma, especially in elderly patients, patients with diabetes mellitus taking oral hypoglycemic drugs or insulin (see section “Special indications”).

Infectious and parasitic diseases

Infrequent: fungal infections, development of resistance of pathogens.

vascular side

Rarely: reduction of blood pressure.

General disorders

Infrequent:asthenia.

Rarely:pyrexia (increased body temperature).

Frequency unknown:pain (including pain in the back, chest, and extremities).

immune system disorders

Rarely: angioedema.

Frequency unknown:anaphylactic shock, anaphylactoid shock.

Anaphylactic and anaphylactoid reactions may sometimes develop even after the first dose of the drug.

Hepatic and biliary tract side

Frequently: increased activity of “hepatic” enzymes in the blood (e.g., alanine aminotransferase (ALAT), aspartate aminotransferase (AsAT)), increased activity of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT).

Infrequent:increased blood bilirubin concentration.

Frequency unknown:severe liver failure, including cases of acute liver failure, sometimes with fatal outcome, especially in patients with severe underlying disease (e.g., patients with sepsis); hepatitis, jaundice.

Mental disorders

Frequently:insomnia.

Infrequent:sensation of restlessness, anxiety, confusion.

Rarely: psychiatric disorders (e.g., hallucinations, paranoia), depression, agitation (agitation), sleep disturbances, nightmares.

Frequency unknown:Psychiatric disorders with self-harm behaviors including suicidal thoughts and suicide attempts, attention disorders, disorientation, agitation, nervousness, memory disorders, delirium.

Other possible adverse effects relevant to all fluoroquinolones

Very rare: seizures of porphyria (a very rare metabolic disease) in patients with porphyria.

Overdose

Symptoms of overdose:

Based on data from animal toxicology studies, the most important expected symptoms of acute levofloxacin overdose are central nervous system symptoms (disturbances of consciousness, including confusion, dizziness, and seizures).

In post-registration use of levofloxacin in overdose, central nervous system effects including confusion, seizures, hallucinations and tremors were observed.

The development of nausea and gastrointestinal mucosal erosions may occur.

In clinical and pharmacological studies performed with doses of levofloxacin in excess of therapeutic doses, prolongation of the QT interval was observed.

Treatment of overdose:

In case of overdose, close patient monitoring is required, including electrocardiogram monitoring. Treatment is symptomatic. In case of acute overdose with the drug gastric lavage and administration of antacids to protect the gastric mucosa are indicated. Levofloxacin is not excreted by dialysis (hemodialysis, peritoneal dialysis and continuous ambulatory peritoneal dialysis). There is no specific antidote.

Pregnancy use

Similarities