Leflobact^® (Tablets, Solution) Instructions for Use

ATC Code

J01MA12 (Levofloxacin)

Active Substance

Levofloxacin (Rec.INN WHO registered)

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Antimicrobial agent – fluoroquinolone

Pharmacological Action

Leflobact^® is a synthetic broad-spectrum antimicrobial bactericidal drug from the fluoroquinolone group, containing Levofloxacin as the active substance – the levorotatory isomer of ofloxacin.

Compared to ofloxacin, Levofloxacin has a broader spectrum of antibacterial activity, additionally including various streptococci, including pneumococci.

Levofloxacin blocks bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, disrupts DNA supercoiling and cross-linking of breaks, inhibits DNA synthesis, causes profound morphological changes in the cytoplasm, cell wall, and membrane of microorganisms, but does not affect the enzymes of human cells.

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

Susceptible to levofloxacin (MIC <2 mg/ml)

Gram-positive aerobic microorganisms Corynebacterium diphtheriae, Enterococcus faecalis, Enterococcus spp. (except Enterococcus faecium), Listeria monocytogenes, Staphylococcus spp. coagulase-negative (methicillin-susceptible and intermediate strains), Staphylococcus aureus (methicillin-susceptible strains), Staphylococcus epidermidis (methicillin-susceptible strains), Streptococcus spp. groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-susceptible, intermediate and resistant), Streptococcus pyogenes, Streptococcus group Viridans (penicillin-susceptible and resistant).

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

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

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

Intermediate susceptibility to levofloxacin (MIC ≥4 mg/l)

Gram-positive aerobic microorganisms: Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis (methicillin-resistant strains), Staphylococcus haemolyticus (methicillin-resistant strains).

Gram-negative aerobic microorganisms Burkholderia cepacia, Campylobacter jejuni, Campylobacter coli.

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

Resistant to levofloxacin (MIC ≥ 8 mg/ml)

Gram-positive aerobic microorganisms Corynebacterium jeikeium, Staphylococcus aureus (methicillin-resistant strains), Staphylococcus spp. (coagulase-negative methicillin-resistant strains).

Gram-negative aerobic microorganisms Alcaligenes xylosoxidans.

Other microorganisms Mycobacterium avium.

Pharmacokinetics

Distribution

The pharmacokinetics of levofloxacin are linear and predictable with single and multiple administration of the drug. The plasma concentration profile of levofloxacin after intravenous administration is similar to that after oral administration of tablets. Therefore, oral and intravenous routes of administration can be considered interchangeable.

Plasma protein binding is 30-40%. It penetrates well into organs and tissues: lungs, bronchial mucosa, sputum, urinary system organs, genital organs, bone tissue, cerebrospinal fluid, prostate gland, polymorphonuclear leukocytes, alveolar macrophages.

The mean V_d of levofloxacin ranges from 89 to 112 L after single and multiple intravenous administration of 500 mg. The pharmacokinetic parameters after a single intravenous administration of levofloxacin at a dose of 500 mg are, respectively: C_max – 6.2±1 µg/ml, time to reach C_max – 1±0.1 h.

Metabolism

Levofloxacin is minimally metabolized in the liver (about 5% of the administered dose).

Excretion

T_1/2 – 6.4±0.7 h. Levofloxacin is predominantly excreted by the kidneys unchanged.

Pharmacokinetics in special clinical cases

In renal failure, the decrease in drug clearance and its renal excretion depends on the degree of reduction in creatinine clearance.

Indications

Infectious and inflammatory diseases caused by bacteria susceptible to levofloxacin

• Lower respiratory tract (community-acquired pneumonia);
• Urinary tract and kidneys (including acute pyelonephritis);
• Chronic bacterial prostatitis;
• Skin and soft tissue infections (suppurated atheromas, abscess, furuncles);
• Intra-abdominal infections;
• Septicemia/bacteremia associated with the above indications.

ICD codes

Dosage Regimen

Tablets

The drug should be taken orally before meals or between meals, without chewing, with a sufficient amount of liquid (from 0.5 to 1 glass).

For exacerbation of chronic bronchitis, 250-500 mg is prescribed once a day for 7-10 days.

For community-acquired pneumonia, 500 mg is prescribed 1-2 times a day for 7-14 days.

For sinusitis, 500 mg is prescribed once a day for 10-14 days.

For uncomplicated urinary tract infections, 250 mg is prescribed once a day for 3 days.

For complicated urinary tract infections (including pyelonephritis) – 250 mg once a day for 7-10 days.

For prostatitis, 500 mg is prescribed once a day for 28 days.

For skin and soft tissue infections, 250-500 mg is prescribed 1-2 times a day for 7-14 days.

For drug-resistant forms of tuberculosis as part of combination therapy, 500 mg is prescribed 1-2 times a day (500-1000 mg/day) for up to 3 months.

Since Levofloxacin is excreted primarily by the kidneys, when treating patients with impaired renal function, the drug dose should be reduced.

Leflobact^® in tablet form may be prescribed to continue the course of treatment for those patients who were initially prescribed intravenous administration of Leflobact^® in the form of an infusion solution and whose condition improved, allowing further oral administration of levofloxacin.

Solution

IV, drip, slowly 1-2 times a day. Doses are determined by the nature and severity of the infection, as well as the susceptibility of the suspected pathogen.

For patients with normal renal function (creatinine clearance >50 ml/min), the following dosing regimen of the drug can be recommended.

Community-acquired pneumonia 500 mg (100 ml of solution) 1-2 times a day for 7-14 days.

Uncomplicated urinary tract infections 250 mg (50 ml of solution) once a day for 3 days.

Complicated urinary tract infections (including acute pyelonephritis) 250 mg (50 ml of solution) once a day for 7-10 days.

Skin and soft tissue infections (suppurated atheromas, abscess, furuncles): 500 mg (100 ml of solution) 2 times a day for 7-14 days.

Chronic bacterial prostatitis 500 mg (100 ml of solution) once a day for 28 days.

Septicemia/bacteremia 500 mg (100 ml of solution) 1-2 times a day for 10-14 days

Intra-abdominal infection 500 mg (100 ml of solution) once a day for 7-14 days (in combination with antibacterial drugs active against anaerobic flora).

For patients with impaired renal function, adjustment of the dosing regimen is required depending on the creatinine clearance value.

¹ – no additional doses are required after hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

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.

The levofloxacin infusion solution 500 mg (100 ml) is administered intravenously by slow drip. The duration of infusion of 1 vial of levofloxacin solution 500 mg (100 ml) should be at least 60 minutes. After intravenous administration, a switch to oral administration at the same dose is possible after a few days.

Treatment with levofloxacin is recommended to be continued for at least 48-72 hours after normalization of body temperature or after confirmed eradication of the pathogen.

Adverse Reactions

From the digestive system nausea, vomiting, diarrhea, decreased appetite, abdominal pain, pseudomembranous colitis, increased activity of liver transaminases, hyperbilirubinemia, hepatitis, dysbacteriosis, severe liver failure, including cases of acute liver failure, especially in patients with severe underlying disease (e.g., sepsis).

From the cardiovascular system decreased blood pressure, vascular collapse, tachycardia, QT interval prolongation.

From the metabolism hypoglycemia (increased appetite, increased sweating, tremor), porphyria attacks.

From the nervous system headache, dizziness, weakness, drowsiness, insomnia, paresthesia, peripheral sensory and sensorimotor neuropathy, anxiety, fear, psychotic reactions, self-injurious behavior including suicidal thoughts and actions, hallucinations, confusion, depression, movement disorders, convulsions, tremor, extrapyramidal disorders, agitation, nightmares.

From the senses ageusia, dysgeusia (taste perversion), loss of taste sensation, parosmia (disorder of smell sensation, especially a subjective sensation of an objectively absent smell), including loss of smell, vertigo (a feeling of deviation or spinning of one’s own body or surrounding objects), tinnitus, hearing loss.

From the musculoskeletal system arthralgia, myasthenia, myalgia, tendon rupture, tendinitis, rhabdomyolysis.

From the urinary system hypercreatininemia, interstitial nephritis, acute renal failure.

From the hematopoietic organs eosinophilia, hemolytic anemia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, pancytopenia, hemorrhages.

Allergic reactions itching, hyperemia, swelling of the skin and mucous membranes, urticaria, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), bronchospasm, asphyxia, dyspnea, anaphylactic shock, allergic pneumonitis, vasculitis.

Local reactions phlebitis and periphlebitis.

Other exacerbation of porphyria, photosensitivity, persistent fever, development of superinfection, asthenia.

Contraindications

• Epilepsy;
• Tendon damage during previous treatment with quinolones;
• Pregnancy;
• Lactation period;
• Childhood and adolescence (under 18 years);
• Hypersensitivity (including to other quinolones).

With caution

• Elderly age, due to the high probability of concomitant decreased renal function (glucose-6-phosphate dehydrogenase deficiency);
• In patients with a history of brain damage (stroke or severe trauma) (possible development of convulsions);
• In patients with pseudoparalytic myasthenia (myasthenia gravis);
• In patients with known risk factors for QT interval prolongation;
• In patients with diabetes mellitus;
• Predisposition to convulsive reactions (cerebral vascular atherosclerosis, cerebrovascular accidents (in history);
• Organic diseases of the central nervous system;
• Renal failure;
• Congenital long QT syndrome;
• Heart disease (heart failure, myocardial infarction, bradycardia);
• Electrolyte imbalance (e.g., in hypokalemia, hypomagnesemia);
• History of psychosis and other mental disorders;
• Hepatic porphyria;
• Concomitant use of drugs that prolong the QT interval (class I A and III antiarrhythmics, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal agents, imidazole derivatives, some antihistamines, including astemizole, terfenadine, ebastine) and lower the seizure threshold of the brain (fenbufen, theophylline).

It is not recommended to prescribe Levofloxacin simultaneously with other agents that prolong the QT interval, as this increases the risk of cardiac arrhythmias.

Use in Pregnancy and Lactation

Contraindicated during pregnancy. Breastfeeding should be discontinued during treatment.

Use in Hepatic Impairment

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.

Use in Renal Impairment

For patients with impaired renal function, adjustment of the dosing regimen is required depending on the creatinine clearance value.

¹ = no additional doses are required after hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

Pediatric Use

Contraindicated in children under 18 years of age.

Geriatric Use

Use with caution in elderly patients due to the high probability of concomitant decreased renal function (glucose-6-phosphate dehydrogenase deficiency).

Special Precautions

In severe pneumonia caused by pneumococci, the therapeutic effect of Leflobact^® may be insufficient.

The duration of intravenous infusion of 500 mg (100 ml of infusion solution) should be at least 60 minutes.

During infusion, in some cases, sensations of palpitations and transient decreases in blood pressure may occur. If a pronounced decrease in blood pressure occurs, the infusion should be stopped immediately.

During treatment, it is necessary to avoid exposure to sunlight and artificial ultraviolet radiation to prevent skin damage (photosensitivity).

If signs of tendinitis, pseudomembranous colitis, or allergic reactions appear, Levofloxacin should be discontinued immediately.

It should be considered that in patients with a history of brain damage (stroke, severe trauma), seizures may develop, and in patients with glucose-6-phosphate dehydrogenase deficiency, there is a risk of hemolysis.

Since Levofloxacin is excreted mainly through the kidneys, in patients with impaired renal function, mandatory monitoring of renal function and dose regimen adjustment is required.

Very rare cases of QT interval prolongation have been reported in patients receiving fluoroquinolones, including Levofloxacin. Caution should be exercised when using fluoroquinolones, including Levofloxacin, in patients with known risk factors for QT interval prolongation: advanced age; electrolyte imbalance (hypokalemia, hypomagnesemia); congenital long QT syndrome; heart disease (heart failure, myocardial infarction, bradycardia); concurrent use of drugs that can prolong the QT interval.

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

Alcohol consumption should be avoided during treatment.

Effect on the ability to drive vehicles and operate machinery

During treatment, it is necessary to refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms confusion, dizziness, convulsions, QT interval prolongation.

Treatment symptomatic; dialysis is not effective.

Drug Interactions

During combined therapy with fenbufen and similar NSAIDs, and theophylline, the drug may lower the seizure threshold.

Corticosteroids increase the risk of tendon rupture (especially in the elderly).

The excretion of levofloxacin is slightly slowed by cimetidine and probenecid.

Levofloxacin causes a slight increase in the T_1/2 of cyclosporine from blood plasma.

Concomitant use with warfarin increases prothrombin time and the risk of bleeding (careful monitoring of INR, prothrombin time and other coagulation parameters, as well as monitoring for possible signs of bleeding, is necessary).

Ethanol may enhance central nervous system side effects (dizziness, drowsiness).

In diabetic patients receiving oral hypoglycemic agents or insulin, hypo- and hyperglycemic conditions may occur while taking levofloxacin (careful monitoring of blood glucose levels is recommended).

Concomitant use with drugs that prolong the QT interval (class I A and III antiarrhythmic drugs, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal agents, imidazole derivatives, some antihistamines, including astemizole, terfenadine, ebastine) may lead to QT interval prolongation.

The infusion solution is compatible with 0.9% sodium chloride solution, 5% dextrose (glucose) solution, 2.5% Ringer’s solution with dextrose, and combined solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).

It should not be mixed with heparin and solutions that have an alkaline reaction.

Storage Conditions

The drug should be stored in a light-protected place, out of the reach of children, at a temperature between 15°C (59°F) and 25°C (77°F).

Under room lighting, the infusion solution can be stored without light protection for no more than 3 days. Freezing is not permissible.

Shelf Life

The shelf life is 2 years.

Dispensing Status

The drug is dispensed by prescription.

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.