Eleflox (Tablets, Solution) Instructions for Use

ATC Code

J01MA12 (Levofloxacin)

Active Substance

Levofloxacin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Systemic antibacterial agents; quinolone derivatives; fluoroquinolones

Pharmacological Action

Eleflox is a synthetic broad-spectrum antibacterial drug from the fluoroquinolone group, containing Levofloxacin as the active substance – the levorotatory isomer of ofloxacin.

Levofloxacin blocks DNA gyrase, disrupts DNA supercoiling and cross-linking of breaks, inhibits DNA synthesis, and causes profound morphological changes in the cytoplasm, cell wall, and membranes of bacteria.

Levofloxacin is active against most strains of microorganisms both in vitro and in vivo.

Susceptible microorganisms (MIC ≤2 mg/L; inhibition zone ≥17 mm)

Aerobic gram-positive microorganisms: Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus spp. (including Enterococcus faecalis), Listeria monocytogenes, Staphylococcus spp. coagulase-negative methicillin-susceptible/-moderately susceptible (including Staphylococcus aureus methicillin-susceptible, Staphylococcus epidermidis methicillin-susceptible), Streptococcus spp. (groups C and G), Streptococcus agalactiae, Streptococcus pneumoniae penicillin-susceptible/-moderately susceptible/-resistant, Streptococcus pyogenes, Streptococcus spp. viridans group penicillin-susceptible/-resistant.

Aerobic gram-negative microorganisms: Acinetobacter spp. (including Acinetobacter baumannii), Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter spp. (including Enterobacter aerogenes, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampicillin-susceptible/-resistant, Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (including Klebsiella pneumoniae, Klebsiella oxytoca), Moraxella catarrhalis (beta-lactamase-producing and non-producing strains), Morganella morganii, Neisseria gonorrhoeae (non-penicillinase-producing and penicillinase-producing), Neisseria meningitidis, Pasteurella spp. (including Pasteurella multocida, Pasteurella dagmatis, Pasteurella canis), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia stuartii, Providencia rettgeri), Pseudomonas spp. (including Pseudomonas aeruginosa), Salmonella spp., Serratia spp. (including Serratia marcescens).

Hospital-acquired infections caused by Pseudomonas aeruginosa may require combined antibacterial therapy.

Anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus, Propionibacterium spp., Veillonella spp.

Other microorganisms: Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella spp. (including Legionella pneumophila), Mycobacterium spp. (including Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsiae spp., Ureaplasma urealyticum.

Moderately susceptible microorganisms (MIC = 4 mg/L; inhibition zone 14-16 mm)

Aerobic gram-positive microorganisms: Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis methicillin-resistant, Staphylococcus haemolyticus methicillin-resistant.

Aerobic gram-negative microorganisms: Campylobacter jejuni, Campylobacter coli.

Anaerobic microorganisms: Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp., Porphyromonas spp.

Resistant microorganisms (MIC ≥8 mg/L; inhibition zone ≤13 mm)

Aerobic gram-positive microorganisms: Staphylococcus aureus methicillin-resistant, other Staphylococcus spp. coagulase-negative methicillin-resistant.

Aerobic gram-negative microorganisms: Alcaligenes xylosoxidans.

Anaerobic microorganisms: Bacteroides thetaiotaomicron.

Other microorganisms: Mycobacterium avium.

Resistance

Resistance to levofloxacin develops as a result of a stepwise process of mutations in the genes encoding both type II topoisomerases: DNA gyrase and topoisomerase IV.

Other resistance mechanisms, such as the mechanism affecting the penetration barriers of the microbial cell (a mechanism characteristic of Pseudomonas aeruginosa) and the efflux mechanism (active removal of the antimicrobial agent from the microbial cell), can also reduce the sensitivity of microorganisms to levofloxacin.

Due to the peculiarities of the mechanism of action of levofloxacin, cross-resistance between levofloxacin and other antimicrobial agents is usually not observed.

Clinical efficacy (efficacy in clinical studies in the treatment of 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 (Branhamella) catarrhalis, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens.

Other: Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae.

Pharmacokinetics

Absorption

Levofloxacin is rapidly and almost completely absorbed after oral administration; food intake has little effect on its absorption.

The absolute bioavailability after oral administration is 99-100%. After a single dose of 500 mg of levofloxacin, C_max in blood plasma is reached within 1-2 hours and is 5.2±1.2 µg/ml. The pharmacokinetics of levofloxacin is linear in the dose range from 50 to 1000 mg. The steady-state concentration of levofloxacin in blood plasma when taking 500 mg of levofloxacin once or twice a day is reached within 48 hours.

On the 10th day of oral administration of levofloxacin at a dose of 500 mg once a day, C_max was 5.7±1.4 µg/ml, and the minimum concentration of levofloxacin (concentration before the next dose) (C_min) in blood plasma was 0.5±0.2 µg/ml.

On the 10th day of oral administration of levofloxacin 500 mg twice a day, C_max was 7.8±1.1 µg/ml, and C_min was 3.0±0.9 µg/ml.

Distribution

Binding to serum proteins is 30-40%. After single and repeated administration of 500 mg of levofloxacin, the V_d of levofloxacin averages 100 L, indicating good penetration of levofloxacin into the organs and tissues of the human body.

Penetration into the bronchial mucosa, epithelial lining fluid, alveolar macrophages. After a single oral dose of 500 mg of levofloxacin, C_max of levofloxacin in the bronchial mucosa and epithelial lining fluid was reached within 1 hour or 4 hours and was 8.3 µg/g and 10.8 µg/ml, respectively, with penetration coefficients into the bronchial mucosa and epithelial lining fluid, compared to the concentration in blood plasma, of 1.1-1.8 and 0.8-3, respectively.

After 5 days of oral administration of 500 mg of levofloxacin, the average concentration of levofloxacin 4 hours after the last dose of the drug in the epithelial lining fluid was 9.94 µg/ml and in alveolar macrophages – 97.9 µg/ml.

Penetration into lung tissue. C_max in lung tissue after oral administration of 500 mg of levofloxacin was approximately 11.3 µg/g and was reached 4-6 hours after drug administration with penetration coefficients of 2-5, compared to the concentration in blood plasma.

Penetration into alveolar fluid. After 3 days of taking 500 mg of levofloxacin once or twice a day, C_max of levofloxacin in alveolar fluid was reached 2-4 hours after drug administration and was 4.0 and 6.7 µg/ml, respectively, with a penetration coefficient of 1, compared to the concentration in blood plasma.

Penetration into bone tissue. Levofloxacin penetrates well into cortical and cancellous bone tissue, both in the proximal and distal parts of the femur, with a penetration coefficient (bone tissue/blood plasma) of 0.1-3.

C_max of levofloxacin in the cancellous bone tissue of the proximal femur after oral administration of 500 mg of the drug was approximately 15.1 µg/g (2 hours after drug administration).

Penetration into cerebrospinal fluid. Levofloxacin poorly penetrates into the cerebrospinal fluid.

Penetration into prostate tissue. After oral administration of 500 mg of levofloxacin once a day for 3 days, the average concentration of levofloxacin in prostate tissue was 8.7 µg/g, the average prostate/blood plasma concentration ratio was 1.84.

Concentration in urine. The average concentration in urine 8-12 hours after oral administration at doses of 150, 300 and 600 mg of levofloxacin was 44 µg/ml, 91 µg/ml and 162 µg/ml, respectively.

Metabolism

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

Excretion

After oral administration, Levofloxacin is relatively slowly eliminated from the blood plasma (T_1/2 – 6-8 hours).

Excretion is carried out mainly by the kidneys (more than 85% of the administered dose). The total clearance of levofloxacin after a single dose of 500 mg was 175±29.2 ml/min.

There are no significant differences in the pharmacokinetics of levofloxacin between its intravenous administration and oral administration. Therefore, oral administration and intravenous administration are interchangeable.

Pharmacokinetics in specific patient groups

There are no differences in the pharmacokinetics of levofloxacin between men and women.

The pharmacokinetics in elderly patients does not differ from the pharmacokinetics in young patients, except for indicators related to age-related changes in creatinine clearance.

In renal insufficiency, the pharmacokinetics of levofloxacin changes. As renal function deteriorates, renal excretion and renal clearance decrease, and T_1/2 increases.

Pharmacokinetics in renal insufficiency after a single oral dose of 500 mg of levofloxacin.

Indications

Bacterial infections sensitive to levofloxacin in adults:

• Acute sinusitis;
• Exacerbation of chronic bronchitis;
• Community-acquired pneumonia;
• Uncomplicated urinary tract infections;
• Complicated urinary tract infections (including pyelonephritis);
• Chronic bacterial prostatitis;
• Skin and soft tissue infections;
• For the complex treatment of drug-resistant forms of tuberculosis;
• Prevention and treatment of anthrax with airborne infection.

When using levofloxacin, official national recommendations for the appropriate use of antibacterial drugs, as well as the sensitivity of pathogenic microorganisms in a particular country, should be taken into account (see the “Special Instructions” section).

ICD codes

Dosage Regimen

Solution

Administered intravenously by drip. The dosage regimen is set individually, depending on the indications, clinical situation, and sensitivity of the pathogen. The duration of treatment varies depending on the course of the disease. Treatment with levofloxacin is recommended to continue for at least 48-72 hours after normalization of body temperature or reliable eradication of the pathogen.

Tablets

The drug is taken orally once or twice a day. The tablets should not be chewed and should be taken with a sufficient amount of fluid (from 0.5 to 1 glass), can be taken 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.

For patients with creatinine clearance > 50 ml/min the following dosage regimen is recommended

acute sinusitis: 500 mg once a day – 10-14 days;

exacerbation of chronic bronchitis: 500 mg once a day – 7-10 days;

community-acquired pneumonia: 500 mg once or twice a day – 7-14 days;

uncomplicated urinary tract infections: 250 mg once a day – 3 days;

complicated urinary tract infections: 500 mg once a day – 7-14 days;

pyelonephritis: 500 mg once a day – 7-10 days;

chronic bacterial prostatitis: 500 mg once a day – 28 days;

skin and soft tissue infections: 500 mg once or twice a day – 7-14 days;

complex therapy of drug-resistant forms of tuberculosis: 500 mg once or twice a day, course of treatment – up to 3 months.

prevention and treatment of anthrax with airborne infection: 500 mg once a day, course of treatment up to 8 weeks.

Dosage regimen in patients with impaired renal function

In case of impaired liver function, no special dose adjustment is required, since Levofloxacin is metabolized in the liver only to an extremely insignificant extent.

For elderly patients, no change in the dosage regimen is required, except in cases of low creatinine clearance.

As with the use of other antibiotics, treatment with the drug is recommended to continue for at least 48-72 hours after normalization of body temperature or after reliable destruction of the pathogen.

If a dose is missed, the tablet should be taken as soon as possible, until the time of the next dose is approaching. Then continue taking Eleflox according to the schedule.

Given that the bioavailability of levofloxacin when taking Eleflox tablets is almost 100%, in case of transferring a patient from intravenous infusion of Eleflox to taking tablets, treatment should be continued at the same dose that was used during intravenous infusion.

Adverse Reactions

Definition of categories of frequency of adverse effects (in accordance with WHO): very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and < 1/100), rare (≥1/10 000 and <1/1000), very rare (<1/10 000), frequency unknown (frequency cannot be estimated from available data).

Data obtained from clinical studies and post-marketing use of the drug

From the cardiovascular system rare – sinus tachycardia, palpitations; frequency unknown (post-marketing data) – QT interval prolongation, ventricular arrhythmias, ventricular tachycardia, torsades de pointes, which can lead to cardiac arrest (see sections “Overdose”, “Special Instructions”).

From the blood and lymphatic system uncommon – leukopenia (decrease in the number of leukocytes in peripheral blood), eosinophilia (increase in the number of eosinophils in peripheral blood); rare – neutropenia (decrease in the number of neutrophils in peripheral blood), thrombocytopenia (decrease in the number of platelets in peripheral blood); frequency unknown (post-marketing data) – pancytopenia (decrease in the number of all formed elements in peripheral blood), agranulocytosis (absence or sharp decrease in the number of granulocytes in peripheral blood), hemolytic anemia.

Nervous system disorders Common – headache, dizziness; Uncommon – drowsiness, tremor, dysgeusia (taste disturbance); Rare – paresthesia, convulsions (see section “Special Precautions”); Frequency not known (post-marketing data) – peripheral sensory neuropathy, peripheral sensorimotor neuropathy (see section “Special Precautions”), dyskinesia, extrapyramidal disorders, ageusia (loss of taste sensation), parosmia (disorder of smell sensation, especially a subjective sensation of a smell that is objectively absent), including loss of smell; syncope, benign intracranial hypertension.

Eye disorders Very rare – visual disturbances, such as blurred vision; Frequency not known (post-marketing data) – transient loss of vision, uveitis.

Ear and labyrinth disorders: Uncommon – vertigo (sensation of deviation or spinning of one’s own body or surrounding objects); Rare – tinnitus; Frequency not known (post-marketing data) – hearing impairment, hearing loss.

Respiratory, thoracic and mediastinal disorders Uncommon – dyspnea; Frequency not known (post-marketing data) – bronchospasm, allergic pneumonitis.

Gastrointestinal disorders Common – diarrhea, vomiting, nausea; Uncommon – abdominal pain, dyspepsia, flatulence, constipation; Frequency not known (post-marketing data) – hemorrhagic diarrhea, which in very rare cases may be a sign of enterocolitis, including pseudomembranous colitis (see section “Special Precautions”), pancreatitis.

Hepatobiliary disorders Common – increased activity of liver enzymes in the blood (e.g., ALT), (AST), increased activity of ALP and GGT (GGT); Uncommon – increased concentration of bilirubin in the blood; Frequency not known (post-marketing data) – severe hepatic failure, including cases of acute hepatic failure, sometimes with fatal outcome, especially in patients with severe underlying disease (e.g., patients with sepsis) (see section “Special Precautions”); hepatitis, jaundice.

Renal and urinary disorders Uncommon – increased serum creatinine concentration; Rare – acute renal failure (e.g., due to the development of interstitial nephritis).

Skin and subcutaneous tissue disorders Uncommon – rash, pruritus, urticaria, hyperhidrosis; Frequency not known (post-marketing data) – toxic epidermal necrolysis, Stevens-Johnson syndrome, exudative erythema multiforme, photosensitivity reactions (increased sensitivity to sunlight and UV radiation) (see section “Special Precautions”), leukocytoclastic vasculitis, stomatitis. Skin and mucous membrane reactions may sometimes develop even after the first dose of the drug.

Musculoskeletal and connective tissue disorders Uncommon – arthralgia, myalgia; Rare – tendon disorders, including tendinitis (e.g., Achilles tendon), muscle weakness, which may be particularly dangerous in patients with myasthenia gravis (see section “Special Precautions”); Frequency not known (post-marketing data) – rhabdomyolysis, tendon rupture (e.g., Achilles tendon; this adverse effect may occur within 48 hours after the start of treatment and may be bilateral (see also section “Special Precautions”)), ligament rupture, muscle rupture, arthritis.

Metabolism and nutrition disorders Uncommon – anorexia; Rare – hypoglycemia, especially in patients with diabetes mellitus (possible signs of hypoglycemia: ravenous appetite, nervousness, sweating, tremor); Frequency not known – hyperglycemia, hypoglycemic coma (see section “Special Precautions”).

Infections and infestations Uncommon – fungal infections, development of resistance of pathogenic microorganisms.

Immune system disorders Rare – angioedema; Frequency not known (post-marketing data) – anaphylactic shock, anaphylactoid shock. Anaphylactic and anaphylactoid reactions may sometimes develop even after the first dose of the drug.

Psychiatric disorders Common – insomnia; Uncommon – feeling of restlessness, anxiety, confusion; Rare – mental disorders (e.g., hallucinations, paranoia), depression, agitation, sleep disorders, nightmares; Frequency not known (post-marketing data) – psychiatric disorders with behavioral disturbances causing self-harm, including suicidal thoughts and suicide attempts.

General disorders and administration site conditions Uncommon – asthenia; Rare – pyrexia (increased body temperature); Frequency not known – pain (including back pain, chest pain and limb pain).

Other possible adverse effects related to all fluoroquinolones

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

Contraindications

• Hypersensitivity to levofloxacin or to other quinolones, as well as to excipients of the drug;
• Epilepsy;
• Tendon damage during previous treatment with quinolones;
• Childhood and adolescence (under 18 years of age) (due to incomplete skeletal growth, since the risk of damage to cartilage growth points cannot be completely excluded);
• Pregnancy and during breastfeeding (the risk of damage to cartilage growth points and the fetus and child cannot be completely excluded);
• Myasthenia gravis;
• Renal failure with CC less than 20 ml/min.
• In patients with CC less than 50 ml/min, use in the dosing regimen with an initial dose of 250 mg/24 hours is not possible;
• In patients with CC less than 20 ml/min, use in the dosing regimen with an initial dose of 500 mg/24 h and 500 mg/12 h is not possible.

With caution

• In patients predisposed to the development of seizures, in patients with previous CNS lesions, in patients simultaneously receiving drugs that lower the seizure threshold of the brain, such as fenbufen, theophylline (see section “Drug Interactions”);
• In patients with latent or manifested glucose-6-phosphate dehydrogenase deficiency (increased risk of hemolytic reactions during treatment with quinolones).
• In patients with known risk factors for QT interval prolongation: in elderly patients; in female patients, in patients with uncorrected electrolyte disturbances (with hypokalemia, hypomagnesemia); with congenital long QT syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); with simultaneous use of drugs that can prolong the QT interval (class I A and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics) (see sections “Overdose”, “Drug Interactions”, “Special Precautions”);
• In patients with diabetes mellitus receiving oral hypoglycemic drugs, for example, glibenclamide or insulin preparations (increased risk of hypoglycemia);
• 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 psychoses or in patients with a history of mental illness (see section “Special Precautions”);
• In patients with impaired renal function with CC 50-20 ml/min (also see section “Contraindications”).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Special Precautions

Hospital infections caused by Pseudomonas aeruginosa may require combination therapy.

The prevalence of acquired resistance of isolated strains of microorganisms may vary depending on the geographic region and over time. In this regard, information on drug resistance in a particular country is required. For the treatment of severe infections or in case of treatment failure, a microbiological diagnosis should be established with the isolation of the pathogen and determination of its sensitivity to levofloxacin.

When treating elderly persons, it should be borne in mind that patients in this group often suffer from impaired renal function.

Very rare cases of QT interval prolongation have been reported in patients taking fluoroquinolones, including Levofloxacin. When using levofloxacin, as well as other fluoroquinolones, caution should be exercised in patients with known risk factors for QT interval prolongation: in patients with uncorrected electrolyte disturbances (with hypokalemia, hypomagnesemia); with congenital long QT syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); with simultaneous use of drugs that can prolong the QT interval, such as class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics.

Elderly patients and female patients may be more sensitive to drugs that prolong the QT interval. Therefore, fluoroquinolones, including Levofloxacin, should be used with caution in them.

During treatment with Eleflox, the development of a seizure may occur in patients with previous brain damage, caused, for example, by stroke or severe trauma. Seizure activity may also increase with the simultaneous use of fenbufen and other NSAIDs or theophylline (see “Drug Interactions”).

Although photosensitivity is very rarely observed with the use of levofloxacin, to prevent its development, patients are not recommended to be exposed to strong sunlight or artificial ultraviolet radiation (for example, visiting a solarium) without special need during treatment and for 48 hours after the end of levofloxacin treatment.

If pseudomembranous colitis is suspected, Eleflox should be discontinued immediately and appropriate treatment should be started. Drugs that inhibit intestinal peristalsis are contraindicated in the treatment of pseudomembranous colitis.

If tendinitis is suspected, treatment with Eleflox should be stopped immediately and appropriate treatment of the affected tendon should be started, for example, by ensuring its rest.

Patients with latent or manifested glucose-6-phosphate dehydrogenase deficiency are predisposed to hemolytic reactions (destruction of red blood cells) during treatment with quinolones. In this regard, treatment of such patients with levofloxacin should be carried out with caution.

As with the use of other antibiotics, the use of levofloxacin, especially for a long time, can lead to increased reproduction of microorganisms (bacteria and fungi) that are insensitive to it, which can cause changes in the microflora that is normally present in humans. As a result, a superinfection may develop. Therefore, during treatment, it is necessary to conduct a repeated assessment of the patient’s condition, and in case of superinfection development during treatment, appropriate measures should be taken.

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, unless laboratory tests have confirmed the sensitivity of this microorganism to levofloxacin.

Levofloxacin can cause serious, potentially fatal, hypersensitivity reactions (angioedema, anaphylactic shock), even when using initial doses. Patients should immediately stop taking the drug and consult a doctor.

Cases of severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, have been observed with levofloxacin. If any skin or mucous membrane reactions occur, the patient should immediately consult a doctor and not continue treatment until consultation.

Cases of hepatic necrosis, including the development of fatal hepatic failure, have been reported with the use of levofloxacin, mainly in patients with severe underlying diseases, for example, with sepsis. Patients should be warned to discontinue treatment and seek immediate medical attention if signs and symptoms of liver damage appear, such as anorexia, jaundice, dark urine, itching and abdominal pain.

As with the use of other quinolones, cases of hyperglycemia and hypoglycemia have been observed with the use of levofloxacin, usually in patients with diabetes mellitus who are simultaneously receiving treatment with oral hypoglycemic drugs (for example, glibenclamide) or insulin preparations. Cases of hypoglycemic coma have been reported. In patients with diabetes mellitus, blood glucose concentration monitoring is required.

With the use of quinolones, including Levofloxacin, the development of psychotic reactions has been reported, which in very rare cases progressed to the development of suicidal thoughts and behavioral disorders with self-harm (sometimes after taking a single dose of levofloxacin). If such reactions develop, treatment with levofloxacin should be discontinued and appropriate therapy should be prescribed. The drug should be prescribed with caution to patients with psychoses or patients with a history of mental illness.

If any visual disturbances occur, an immediate consultation with an ophthalmologist is necessary.

In patients taking Levofloxacin, determination of opiates in urine may lead to false-positive results, which should be confirmed by more specific methods.

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and subsequently lead to false-negative results of the bacteriological diagnosis of tuberculosis.

Sensory and sensorimotor peripheral neuropathy has been observed in patients taking fluoroquinolones, including Levofloxacin, the onset of which may be rapid. If a patient develops symptoms of neuropathy, the use of levofloxacin should be discontinued. This minimizes the possible risk of irreversible changes.

Fluoroquinolones, including Levofloxacin, are characterized by neuromuscular blocking activity and may increase muscle weakness in patients with myasthenia gravis. In the post-marketing period, adverse reactions have been observed, including respiratory failure requiring mechanical ventilation, and fatal outcome, which were associated with the use of fluoroquinolones in patients with myasthenia gravis. The use of levofloxacin in a patient with an established diagnosis of myasthenia gravis is not recommended.

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

Effect on ability to drive vehicles and operate machinery

Side effects such as dizziness and drowsiness may reduce psychomotor reactions and the ability to concentrate. This may pose a certain risk in situations where these abilities are of particular importance. When driving a car, when servicing machines and mechanisms, when performing work in an unstable position, caution must be exercised.

Overdose

Symptoms: manifest mainly from the CNS (confusion, impaired consciousness, dizziness and convulsive seizures of the epileptic type). In addition, gastrointestinal disorders (e.g., nausea) and erosive lesions of the mucous membranes of the gastrointestinal tract, prolongation of the QT interval may be noted.

Treatment: symptomatic. Levofloxacin is not removed by dialysis (hemodialysis, peritoneal dialysis and continuous peritoneal dialysis). There is no specific antidote.

Due to the possible increase in the duration of the QT interval, ECG monitoring should be performed.

Drug Interactions

Quinolones in combination with drugs that lower the seizure threshold (for example, with theophylline, fenbufen and other NSAIDs) can cause a pronounced decrease in the seizure threshold.

The concentration of levofloxacin with the simultaneous use of fenbufen increases by only 13%.

The effect of the drug Eleflox is significantly weakened with simultaneous use with sucralfate. The same happens with the simultaneous use of magnesium- or aluminum-containing antacids, iron salts, didanosine (only dosage forms containing aluminum or magnesium as a buffer). Eleflox should be taken at least 2 hours before or 2 hours after taking these agents.

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

In patients receiving treatment with levofloxacin in combination with indirect anticoagulants (for example, with a vitamin K antagonist – warfarin), an increase in prothrombin time/INR and/or the development of bleeding, including severe bleeding, was observed. Therefore, with the simultaneous use of indirect anticoagulants and levofloxacin, regular monitoring of blood coagulation parameters is necessary.

The excretion (renal clearance) of levofloxacin is slightly slowed down under the influence of cimetidine and probenecid.

When combined with hypoglycemic drugs, strict monitoring of blood glucose concentration is necessary, as there is a possibility of hyper- and hypoglycemia.

Levofloxacin increases the T_1/2 of cyclosporine by 33%. Since this increase is not clinically significant, no dose adjustment of cyclosporine is required when used concomitantly with levofloxacin.

Taking corticosteroids increases the risk of tendon rupture.

Levofloxacin, like other fluoroquinolones, should be used with caution in patients taking drugs that prolong the QT interval (for example, class I A and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics).

Clinical and pharmacological studies conducted to study the possible pharmacokinetic interaction of levofloxacin with digoxin, glibenclamide, ranitidine and warfarin showed that the pharmacokinetics of levofloxacin when used simultaneously with these drugs does not change to an extent that would be of clinical significance.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.