Instructions for Levaxela film-coated tablets 500 mg blister No. 7
Composition
active ingredient: levofloxacin;
1 tablet contains 250 mg or 500 mg of levofloxacin in the form of levofloxacin hemihydrate;
excipients: microcrystalline cellulose, hydroxypropylcellulose, crospovidone (type A), magnesium stearate;
shell: hypromellose, titanium dioxide, macrogol 4000, sunset yellow FCF (E 110), indigo carmine, red iron oxide, yellow iron oxide – only for 500 mg.
Dosage form
Film-coated tablets.
Main physicochemical properties:
250 mg tablets: pink, oblong, biconvex tablets with a score;
500 mg tablets: orange, oblong, biconvex tablets with a score.
Pharmacotherapeutic group
Antibacterials for systemic use. Fluoroquinolones. Levofloxacin.
ATX code J01M A12.
Pharmacological properties
Pharmacodynamics.
Levofloxacin is a synthetic antibacterial agent from the fluoroquinolone group, the S(-) enantiomer of the racemic mixture of the drug ofloxacin.
Mechanism of action. Levofloxacin, as an antibacterial drug from the fluoroquinolone group, acts on the DNA gyrase and topoisomerase IV complex.
Pharmacokinetics/pharmacodynamics relationship. The degree of bactericidal activity of levofloxacin depends on the ratio of the maximum serum concentration (Cmax) or the area under the pharmacokinetic concentration-time curve (AUC) and the minimum inhibitory concentration (MIC).
Mechanism of resistance. The main mechanism of resistance is due to mutations in the gyr-A genes. In vitro, there is cross-resistance between levofloxacin and other fluoroquinolones. Due to the mechanism of action, there is usually no cross-resistance between levofloxacin and other classes of antibacterial agents.
Checkpoints
The European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommended MIC breakpoints for levofloxacin that distinguish susceptible from intermediately susceptible (moderately resistant) organisms and intermediately susceptible from resistant organisms are presented in Table 1 MIC testing (mg/L).
Table 1
Clinical MIC breakpoints for levofloxacin (version 10.0, 2020-01-01):
| Pathogen | Sensitive | Resistant |
| Enterobacteriaceae | ≤ 0.5 mg/l | > 1 mg/l |
| Pseudomonas spp. | ≤ 0.001 mg/l | > 1 mg/l |
| Acinetobacter spp. | ≤ 0.5 mg/l | > 1 mg/l |
Staphylococcus spp. Coagulase-negative staphylococci | ≤ 0.001 mg/l | > 1 mg/l |
| Enterococcus spp.1 | ≤ 4 mg/l | > 4 mg/l |
| S. pneumoniae | ≤ 0.001 mg/l | > 2 mg/l |
| Streptococcus A, B, C, G | ≤ 0.001 mg/l | > 2 mg/l |
| H. influenzae | ≤ 0.06 mg/l | > 0.06 mg/l |
| M. catarrhalis | ≤ 0.125 mg/l | > 0.125 mg/l |
| Helicobacter pylori | ≤ 1 mg/l | > 1 mg/l |
| Aerococcus sanguinicola and urinae2 | ≤ 2 mg/l | > 2 mg/l |
| Aeromonas spp. | ≤ 0.05 mg/l | > 1 mg/l |
| FC-FD (non-species related) control points | ≤ 0.5 mg/l | > 1 mg/l |
1Uncomplicated urinary tract infections only
2. Susceptibility depends on susceptibility to ciprofloxacin.
The prevalence of resistance may vary geographically and over time for selected species, and it is advisable to obtain local information on resistance, particularly when treating severe infections. As necessary, specialist advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.
| Typically sensitive species |
Aerobic Gram-positive bacteria Bacillus anthracis, Staphylococcus aureus methicillin-susceptible, Staphylococcus saprophyticus, Streptococci, group C and G, Streptococcus agalactiae, Streptococcus pneumonia, Streptococcus pyogenes. |
Aerobic Gram-negative bacteria Eikenella corrodens, Haemophilus influenza, Haemophilus para-influenzae, Klebsiella oxytoca, Moraxella catarrhalis, Pasteurella multocida, Proteus vulgaris, Providencia rettgeri. |
Anaerobic bacteria Peptostreptococcus. |
Others Chlamydophila pneumoniae, Chlamydophila psittaci, Chlamydia trachomatis, Legionella pneumophila, Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma urealyticum. |
| Species for which acquired (secondary) resistance may be problematic |
Aerobic Gram-positive bacteria Enterococcus faecalis, Staphylococcus aureus methicillin-resistant* Coagulase negative Staphylococcus spp. |
Aerobic Gram-negative bacteria Acinetobacter baumannii, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumonia, Morganella morganii, Proteus mirabilis, Providencia stuartii, Pseudomonas aeruginosa, Serratia marcescens. |
Anaerobic bacteria Bacteroides fragilis. |
Extensively resistant strains Aerobic Gram-positive bacteria Enterococcus faecium. |
* Mechanism of resistance Staphylococcus aureus is likely to be co-resistant to fluoroquinolones, including levofloxacin.
Pharmacokinetics.
Absorption
Levofloxacin is rapidly and almost completely absorbed after oral administration, with Cmax achieved within 1-2 hours. Absolute bioavailability is approximately 99-100%.
Food has almost no effect on the absorption of levofloxacin.
Steady state is achieved within 48 hours with a dosage regimen of 500 mg 1-2 times a day.
Approximately 30-40% of levofloxacin is bound to serum proteins. The mean volume of distribution of levofloxacin is approximately 100 L after single and repeated administration of a 500 mg dose, indicating its extensive distribution into body tissues.
Penetration into tissues and body fluids
Levofloxacin has the ability to penetrate the bronchial mucosa, epithelial lining fluid, alveolar macrophages, lung tissue, skin (blister contents), prostate tissue, and urine. However, levofloxacin penetrates poorly into the cerebrospinal fluid.
Biotransformation
Levofloxacin is metabolized to a very small extent, the metabolites being desmethyl-levofloxacin and levofloxacin N-oxide. These metabolites account for less than 5% of the amount of drug excreted in the urine. Levofloxacin is stereochemically stable and does not undergo chiral inversion.
Breeding
After oral and intravenous administration, levofloxacin is eliminated from the blood plasma relatively slowly (half-life is 6-8 hours). Elimination is mainly renal (more than 85% of the administered dose). The mean apparent total clearance of levofloxacin after a single 500 mg dose was 175 ± 29.2 ml/min. There is no significant difference in the pharmacokinetics of levofloxacin after oral and intravenous administration, indicating the interchangeability of these routes (oral and intravenous).
Linearity
Levofloxacin has linear pharmacokinetics in the dose range of 50 to 1000 mg.
Special patient groups
Patients with renal insufficiency
The pharmacokinetics of levofloxacin are affected by renal impairment. In renal impairment, renal excretion is slowed and clearance is reduced, and the half-life is prolonged (see Table 2).
Table 2. Pharmacokinetics in renal impairment after a single 500 mg oral dose
| Creatinine clearance (ml/min) | < 20 | 20-49 | 50-80 |
| Renal clearance (ml/min) | 13 | 26 | 57 |
| Half-life (hours) | 35 | 27 | 9 |
Elderly patients
There are no significant differences in the pharmacokinetics of levofloxacin in young and elderly patients, except for differences related to creatinine clearance.
Gender differences
Separate analyses of male and female patients demonstrated slight gender differences in the pharmacokinetics of levofloxacin. There is no evidence that these gender differences are clinically relevant.
Indication
Infections caused by microorganisms sensitive to the drug:
acute pyelonephritis and complicated urinary tract infections (see section "Special instructions for use");
chronic bacterial prostatitis;
Pulmonary anthrax: post-exposure prophylaxis and treatment (see section "Special instructions").
For the treatment of the following infections, Levaxela® should only be used when it is considered inappropriate to use antibacterial agents that are usually recommended for the treatment of such infections:
acute bacterial sinusitis;
exacerbation of chronic obstructive pulmonary disease, including bronchitis;
community-acquired pneumonia;
complicated skin and soft tissue infections;
uncomplicated cystitis (see section "Special instructions").
Levaxela® can also be used to complete a course of therapy in patients who have shown improvement during the initial use of intravenous levofloxacin.
Official recommendations on the appropriate use of antibacterial agents should be considered.
Contraindication
Hypersensitivity to levofloxacin, to other quinolones or to any ingredient of the drug;
epilepsy;
tendon damage associated with a history of fluoroquinolone use;
childhood (up to 18 years old);
pregnancy and breastfeeding.
Interaction with other medicinal products and other types of interactions
Effects of other medicinal products on levofloxacin
Iron salts, zinc salts, antacids containing magnesium or aluminum, didanosine
The absorption of levofloxacin is significantly reduced when iron salts, magnesium or aluminum antacids or didanosine (this applies only to didanosine dosage forms with aluminum or magnesium-containing buffering agents) are used simultaneously with the drug. The simultaneous use of fluoroquinolones and multivitamin preparations containing zinc reduces their absorption after oral administration. It is not recommended to use drugs containing divalent or trivalent cations, such as iron salts, zinc salts, magnesium or aluminum-containing antacids or didanosine (this applies only to didanosine dosage forms with aluminum or magnesium-containing buffering agents), within 2 hours before or after taking the drug (see section "Method of administration and dosage"). Calcium salts have a minimal effect on the absorption of levofloxacin after oral administration.
Sucralfate
Theophylline, fenbufen, or similar nonsteroidal anti-inflammatory drugs (NSAIDs)
No pharmacokinetic interaction of levofloxacin with theophylline has been identified. However, a significant decrease in the seizure threshold may occur when quinolones are administered concomitantly with theophylline, NSAIDs, and other drugs that lower the seizure threshold. Levofloxacin concentrations in the presence of fenbufen were approximately 13% higher than when levofloxacin was administered alone.
Probenecid and cimetidine
Probenecid and cimetidine have a statistically significant effect on the elimination of levofloxacin. The renal clearance of levofloxacin is reduced by 24% in the presence of cimetidine and by 34% in the presence of probenecid. This is due to the fact that both drugs are able to block the tubular secretion of levofloxacin. However, at the doses tested in the study, it is unlikely that statistically significant kinetic differences will have clinical significance. Levofloxacin should be used with caution with drugs that affect tubular secretion, such as probenecid and cimetidine, especially in patients with impaired renal function.
Other information
The following drugs have no clinically significant effect on the pharmacokinetics of levofloxacin when used concomitantly: calcium carbonate, digoxin, glibenclamide, ranitidine.
Effect of levofloxacin on other drugs
Cyclosporine
The half-life of cyclosporine increases by 33% when taken simultaneously with levofloxacin.
Vitamin K antagonists
When used concomitantly with vitamin K antagonists (e.g. warfarin), increases in coagulation tests (prothrombin time/international normalized ratio (INR)) and/or bleeding, which may be severe, have been reported. Therefore, coagulation parameters should be monitored in patients receiving concomitant vitamin K antagonists (see section 4.4).
Drugs that prolong the QT interval
Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving medicinal products known to prolong the QT interval, such as class IA and III antiarrhythmics, tricyclic antidepressants, macrolides and antipsychotics (see section 4.4 (QT interval prolongation)).
Other significant information
Levofloxacin has not been shown to affect the pharmacokinetics of theophylline (a substrate of the CYP1A2 enzyme), indicating that levofloxacin is not a CYP1A2 inhibitor.
Other types of interactions
Eating
No clinically significant interaction of Levaxela® with food has been observed, so it can be taken regardless of food intake.
Application features
Levofloxacin should be avoided in patients who have previously experienced serious adverse reactions to quinolone or fluoroquinolone-containing drugs (see section 4.8). Levofloxacin should only be initiated in these patients if no alternative treatment options are available and after careful benefit/risk assessment (see section 4.8).
Risk of resistance
Methicillin-resistant Staphylococcus aureus (MRSA) has a very high probability of being co-resistant to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of infections known or suspected to be caused by MRSA, unless laboratory tests have confirmed the susceptibility of the pathogen to levofloxacin.
Levofloxacin can be used to treat acute bacterial sinusitis and exacerbation of chronic bronchitis if these infections have been properly diagnosed.
Fluoroquinolone resistance in Escherichia coli (the most common cause of urinary tract infections) varies between countries. The local prevalence of fluoroquinolone resistance in Escherichia coli should be taken into account when prescribing fluoroquinolones.
Pulmonary anthrax: Use in humans is based on in vitro susceptibility data of Bacillus anthracis and experimental animal data, together with limited human data. Physicians should refer to national and/or international consensus guidelines for the treatment of anthrax.
Prolonged, disabling and potentially irreversible serious adverse reactions
Very rare cases of prolonged (months or years), disabling and potentially irreversible serious adverse reactions affecting various, sometimes multiple, body systems (musculoskeletal, nervous, mental and sensory) have been reported in patients treated with quinolones and fluoroquinolones, regardless of age or pre-existing risk factors. Levofloxacin should be discontinued immediately at the first signs or symptoms of any serious adverse reaction and patients should seek medical advice.
Tendonitis and tendon rupture (most commonly, but not limited to, the Achilles tendon), sometimes bilateral, may occur as early as 48 hours after starting treatment with levofloxacin and may occur even up to several months after stopping treatment. The risk of tendinitis and tendon rupture is increased in elderly patients, patients with impaired renal function, patients with organ transplantation, patients receiving daily doses of 1000 mg and those receiving concomitant corticosteroids. Therefore, concomitant use with corticosteroids should be avoided.
At the first sign of tendinitis (e.g. painful swelling, inflammation), levofloxacin treatment should be discontinued and alternative treatment considered. Appropriate treatment of the affected limb should be provided (e.g. immobilization). Corticosteroids should not be used if signs of tendinopathy are present.
Myoclonus
Cases of myoclonus have been reported in patients receiving levofloxacin (see section 4.8). The risk of myoclonus is increased in elderly patients and in patients with renal impairment unless the levofloxacin dose is adjusted according to creatinine clearance. At the first occurrence of myoclonus, levofloxacin should be discontinued immediately and appropriate treatment initiated.
Aortic aneurysm and dissection, regurgitation/valvular insufficiency
Epidemiological studies suggest an increased risk of aortic aneurysm and dissection, especially in the elderly, and of aortic and mitral valve regurgitation after the use of fluoroquinolones, especially in the elderly. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/functional insufficiency of any heart valve have been reported in patients receiving fluoroquinolones (see section 4.8).
Therefore, fluoroquinolones should only be used after careful benefit/risk assessment and after consideration of other treatment options in patients with a family history of aneurysm or congenital heart valve disease, or in patients with an existing aneurysm and/or aortic dissection or heart valve disease, or in the presence of other risk factors or conditions predisposing to:
both aortic aneurysm and dissection and regurgitation/functional insufficiency of the heart valve (e.g., connective tissue inflammation such as Marfan syndrome or vascular Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, hypertension, rheumatoid arthritis) or in addition to this
aortic aneurysm and dissection (e.g. vascular disorders such as Takayasu arteritis or giant cell arteritis, or diagnosed atherosclerosis, or Sjögren's syndrome) or in addition to this
regurgitation/functional insufficiency of the heart valve (e.g. infective endocarditis).
The risk of aortic aneurysm and dissection and rupture may also be increased in patients receiving concomitant systemic corticosteroids.
Patients should seek immediate medical attention in the emergency department if they experience sudden abdominal, chest, or back pain.
Patients should seek immediate medical attention if they experience acute shortness of breath, sudden palpitations, or develop swelling of the abdomen or lower extremities.
Diseases caused by Clostridium difficile
Diarrhea, particularly severe, persistent and/or bloody, occurring during or after treatment with levofloxacin (including within a few weeks after treatment), may be a symptom of Clostridium difficile disease. The most severe form of this disease is pseudomembranous colitis (see section "Adverse reactions"). In this regard, the physician should consider the possible presence of Clostridium difficile disease if a patient develops severe diarrhea during or after treatment with levofloxacin. If Clostridium difficile disease is suspected, levofloxacin should be immediately discontinued and appropriate treatment should be initiated as a matter of urgency. Drugs that inhibit intestinal motility are contraindicated in this case.
Patients with a tendency to seizures
Quinolones may lower the seizure threshold and precipitate seizures. Levofloxacin is contraindicated in patients with a history of epilepsy (see section 4.3). As with other quinolones, it should be used with extreme caution in patients prone to seizures and in patients receiving concomitant medications that lower the seizure threshold, such as theophylline (see section 4.5). Levofloxacin should be discontinued if a seizure occurs (see section 4.8).
Patients with glucose-6-phosphate dehydrogenase deficiency
Patients with latent or overt glucose-6-phosphate dehydrogenase deficiency may be predisposed to hemolytic reactions when treated with quinolone antibiotics. Therefore, if levofloxacin is necessary, patients should be monitored for possible hemolysis.
Patients with renal impairment
Hypersensitivity reactions
Levofloxacin can cause serious, potentially fatal hypersensitivity reactions (e.g. angioedema to anaphylactic shock), in some cases after the first dose (see section 4.8). If hypersensitivity reactions occur, patients should discontinue levofloxacin, seek medical advice immediately and initiate appropriate treatment.
Severe skin adverse reactions
Serious skin reactions such as toxic epidermal necrolysis (TEN, also known as Lyell's syndrome), Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported with levofloxacin (see section 4.8). Patients should be advised of the signs and symptoms of these serious skin reactions and monitored closely when prescribing the medicinal product. If signs and symptoms suggestive of these reactions occur, levofloxacin should be discontinued immediately and alternative treatment should be considered. If a patient develops a serious reaction such as Stevens-Johnson syndrome, TEN or DRESS with levofloxacin, the patient should not be restarted on levofloxacin.
Change in blood glucose levels
As with all quinolones, cases of changes in blood glucose levels have been reported, including both cases of hypoglycemia and cases of hyperglycemia, which are more common in the elderly, usually observed in patients with diabetes mellitus receiving concomitant therapy with an oral hypoglycemic agent (e.g. glibenclamide) or insulin. Cases of hypoglycemic coma have been reported. In patients with diabetes mellitus, careful monitoring of blood glucose levels is recommended (see section "Adverse reactions").
If a patient reports abnormal blood glucose levels, treatment should be discontinued immediately and alternative antibacterial therapy with non-fluoroquinolone drugs should be considered.
Prevention of photosensitivity
Photosensitivity has been reported with levofloxacin (see section 4.8). To prevent photosensitivity, patients are advised not to expose themselves to strong sunlight or artificial UV radiation (e.g. artificial ultraviolet light, solarium) during treatment and for 48 hours after stopping levofloxacin.
Patients receiving vitamin K antagonists
Due to the possible increase in blood coagulation parameters (prothrombin time/MCT) and/or an increase in the frequency of hemorrhagic complications in patients receiving levofloxacin in combination with a vitamin K antagonist (e.g. warfarin), coagulation test values should be monitored during concomitant use of these drugs (see section "Interaction with other medicinal products and other forms of interaction").
Psychotic reactions
Psychotic reactions have been reported in patients taking quinolones, including levofloxacin. Very rarely, these have progressed to suicidal ideation and self-harm, sometimes after only a single dose of levofloxacin (see section 4.8). If a patient develops these reactions, levofloxacin should be discontinued immediately at the first signs or symptoms of these reactions and patients should be advised to seek medical advice. Alternative non-fluoroquinolone antibacterial therapy should be considered and appropriate measures taken. Levofloxacin should be used with caution in patients with psychotic disorders or a history of psychiatric illness.
QT prolongation
Fluoroquinolones, including levofloxacin, should be used with caution in patients with known risk factors for QT prolongation, such as:
congenital or acquired long QT syndrome;
simultaneous use of drugs that have the ability to prolong the QT interval (class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotic drugs);
electrolyte imbalance (e.g. hypokalemia, hypomagnesemia);
heart disease (e.g., heart failure, myocardial infarction, bradycardia).
Elderly patients and younger women 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 "Interaction with other medicinal products and other forms of interaction", "Dosage and administration (elderly patients)", "Overdose" and "Adverse reactions").
Peripheral neuropathy
Patients who develop symptoms of neuropathy such as pain, burning, tingling, numbness or weakness while taking levofloxacin should inform their doctor before continuing treatment to prevent the development of a potentially irreversible condition (see section "Adverse reactions").
Hepatobiliary disorders
Cases of hepatic necrosis up to and including fatal hepatic failure have been reported with levofloxacin (predominantly in patients with severe underlying diseases such as sepsis) (see section 4.8). Patients should be advised to discontinue treatment and seek medical advice if signs and symptoms of liver disease such as anorexia, jaundice, dark urine, pruritus or abdominal pain occur.
Exacerbation of myasthenia gravis
Fluoroquinolones, including levofloxacin, have neuromuscular blocking effects and may exacerbate muscle weakness in patients with myasthenia gravis. In the post-marketing period, serious adverse reactions, including fatalities and conditions requiring respiratory support, have been associated with the use of fluoroquinolones in patients with myasthenia gravis. Levofloxacin is not recommended for use in patients with a history of myasthenia gravis.
Vision impairment
If any visual disturbances or adverse reactions from the visual organs occur while taking levofloxacin, you should immediately consult an ophthalmologist (see sections “Ability to affect the speed of reactions when driving vehicles or using other mechanisms” and “Adverse reactions”).
Superinfection
The use of levofloxacin, especially long-term, may lead to overgrowth of non-susceptible (resistant) microorganisms. If superinfection develops during therapy, appropriate measures should be taken.
Impact on laboratory test results
In patients treated with levofloxacin, urine opiates may give false-positive results. Positive opiates from screening tests may need to be confirmed by more specific methods.
Acute pancreatitis
Acute pancreatitis may occur in patients taking levofloxacin. Patients should be informed of the characteristic symptoms of acute pancreatitis. Patients who experience nausea, malaise, abdominal discomfort, acute abdominal pain or vomiting should seek immediate medical attention. If acute pancreatitis is suspected, levofloxacin should be discontinued; if confirmed, levofloxacin should not be restarted. Caution should be exercised in patients with a history of pancreatitis (see section 4.8).
Blood disorders
Bone marrow depression, including leukopenia, neutropenia, pancytopenia, haemolytic anaemia, thrombocytopenia, aplastic anaemia or agranulocytosis, may occur during treatment with levofloxacin (see section 4.8). If any of these disorders are suspected, blood tests should be monitored. If abnormal results are obtained, discontinuation of levofloxacin should be considered.
Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and therefore lead to false-negative results in bacteriological diagnosis of tuberculosis.
Excipients
The drug Levaxela® contains the dye sunset yellow FCF (E 110), which may cause an allergic reaction.
Use during pregnancy or breastfeeding
Due to the lack of studies and the possible damage of quinolones to articular cartilage in a growing body, levofloxacin is contraindicated during pregnancy or breastfeeding. If pregnancy is diagnosed during treatment with levofloxacin, the doctor should be informed.
Levofloxacin did not cause impaired fertility or reproductive function in animals.
Ability to influence reaction speed when driving vehicles or other mechanisms
Levofloxacin has minor or moderate influence on the ability to drive and use machines.
Some adverse reactions (e.g. dizziness/vertigo, drowsiness, visual disturbances) may impair the patient's ability to concentrate and react quickly and thus pose an increased risk in situations where these qualities are of particular importance (e.g. when driving or operating machinery).
Method of administration and doses
The drug is taken 1 or 2 times a day. The dose depends on the type and severity of the infection. The duration of treatment depends on the course of the disease.
Levaxol tablets can also be used to complete a course of therapy in patients who have shown improvement during initial treatment with intravenous levofloxacin; given the bioequivalence of the parenteral and oral forms, the same dose can be used.
Table 3
Dosage for patients with normal renal function who have creatinine clearance > 50 mL/min (depending on severity of infection)
| Indication | Dose, mg | Number receptions per day | Duration of treatment |
| Acute bacterial sinusitis | 500 | 1 time | 10-14 days |
| Exacerbation of chronic obstructive pulmonary disease of bacterial etiology, including bronchitis | 500 | 7-10 days |
| Community-acquired pneumonia | 500 | 1-2 times | 7-14 days |
| Acute pyelonephritis | 500 | 1 time | 7-10 days |
| Complicated urinary tract infections | 500 | 1 time | 7-14 days |
| Uncomplicated infections (cystitis) | 250 | 1 time | 3 days |
| Chronic bacterial prostatitis | 500 | 1 time | 28 days |
| Complicated skin and soft tissue infections | 500 | 1-2 times | 7-14 days |
| Pulmonary form of anthrax | 500 | 1 time | 8 weeks |
Special patient groups
Table 4
Dosage for patients with renal impairment with creatinine clearance ≤ 50 mL/min
| Creatinine clearance | Dosage regimen (depending on the severity of the infection and nosology) |
| 250 mg/24 hours | 500 mg/24 hours | 500 mg/12 hours |
| first dose – 250 mg | first dose – 500 mg | first dose – 500 mg |
| 50-20 ml/min | subsequent - 125 mg/24 hours | subsequent - 250 mg/24 hours | subsequent - 250 mg/12 hours |
| 19-10 ml/min | subsequent – 125 mg/ 48 hours | subsequent - 125 mg/24 hours | subsequent - 125 mg/12 hours |
| < 10 mL/min (also on hemodialysis and HAPD)1 | subsequent - 125 mg/48 hours | subsequent - 125 mg/24 hours | subsequent - 125 mg/24 hours |
1 No additional doses are required after hemodialysis or chronic ambulatory peritoneal dialysis (CHAP).
Patients with liver dysfunction
No dose adjustment is required, as levofloxacin is metabolized to a minor extent in the liver and excreted mainly by the kidneys.
Elderly patients
If renal function is not impaired, no dose adjustment is required (see section “Special warnings and precautions for use (“Tendinitis and tendon rupture” and “QT prolongation”)”).
Method of application
Levaxela® tablets should be swallowed whole, without chewing, with sufficient liquid. The tablets can be scored to adjust the dose. The tablets can be taken with or between meals. Levaxela® tablets should be taken at least 2 hours before or after taking antacids containing iron, zinc, magnesium or aluminium salts, or didanosine (this only applies to didanosine formulations with aluminium or magnesium containing buffering agents) or sucralfate, as these drugs may reduce the absorption of levofloxacin (see section “Interaction with other medicinal products and other forms of interaction”).
Children.
Levofloxacin is contraindicated in children (under 18 years of age) as damage to articular cartilage cannot be ruled out.
Overdose
Symptoms
The most important expected symptoms of levofloxacin overdose are related to the central nervous system: confusion, dizziness, impaired consciousness and seizures, hallucinations, tremor, nausea, mucosal erosion, QT prolongation, as well as gastrointestinal reactions such as nausea and mucosal erosion.
Central nervous system symptoms including confusional state, seizures, myoclonus, hallucinations and tremor have been observed in the post-marketing period.
Treatment
Treatment is symptomatic. Taking into account the possible prolongation of the QT interval, ECG monitoring is necessary due to the possible prolongation of the QT interval. In case of obvious overdose, gastric lavage is prescribed. To protect the gastric mucosa, antacids can be used.
