Leflobakt, 500 mg 10 pcs

Pharmacotherapeutic group

Antimicrobial agent – fluoroquinolone

ATX code: J01MA

Pharmacodynamics:

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

Levofloxacin blocks DNA- and topoisomerase IV disrupts superspiralization and cross-linking of DNA breaks inhibits DNA synthesis and causes deep morphological changes in cytoplasm of cell wall and microbial cell membranes. Levofloxacin is active against most strains of microorganisms in both in-vitro and in-vivo conditions.

Invitro

Sensitive microorganisms (minimum inhibitory concentration (MIC) ≤ 2 mg/l; inhibition zone ≥ 17 mm)

– Aerobic Gram-positive microorganisms: BacillusanthracisCorynebacteriumdiphtheriaeCorynebacteriumjeikeiumEnterococcusfaecalisEnterococcusspp. ListeriamonocytogenesStaphylococcuscoagulase-negativemethi-S(I) (coagulase-negative methicillin-sensitive/ moderately sensitive) Staphylococcusaureusmethi-S (methicillin-sensitive) Staphylococcusepidermidismethi-S (methicillin-sensitive) Staphylococcusspp. CNS (coagulazonegative) Streptococci group C and GStreptococcusagalactiaeStreptococcuspneumoniaepeniI/S/R (penicillin-moderately sensitive/sensitive/resistant) StreptococcuspyogenesViridansstreptococcipeniS/R (penicillin-sensitive/resistant).

– Aerobic Gram-negative microorganisms: AcinetobacterbaumanniiAcinetobacterspp. ActinobacillusactinomycetemcomitansCitrobacterfreundiiEikenellacorrodensEntero- bacteraerogenesEnterobactercloacaeEnterobacterspp. EscherichiacoliGardnerellavaginalisHaemophilusducreyiHaemophilusinfluenzaeampi-S/R (ampicillin-sensitive/resistant) HaemophilusparainfluenzaeHelicobacterpyloriKlebsiellaoxytocaKlebsiellapneumoniaeKlebsiellaspp. Moraxellacatarrhalisβ+ β- (producing and non-producing beta-lactamases) MorganellamorganiiNeisseriagonorrhoeaenonPPNG/PPNG (non-producing and producing penicillinase) NeisseriameningitidisPasteurellacanisPasteurelladagmatisPasteurellamultocidaPasteurellaspp. Proteusmira- bilisProteusvulgarisProvidenciarettgeriProvidenciastuartiiProvidenciaspp. Pseudomonasaeruginosa (hospital infections caused by Pseudomonasaeruginosa may require combined treatment) Pseudomonasspp. Salmonellaspp. Serratiamar- cescensSerratiaspp.

– Anaerobic microorganisms: BacteroidesfragilisBifidobacteriumspp. ClostridiumperfringensFusobacteriumspp. Peptostreptococcusspp. Propionibacteriumspp. Veillonellaspp.

– Other microorganisms: Bartonellaspp. ChlamydiapneumoniaeChlamydiapsittaciChlamydiatrachomatisLegionellapneumophilaLegionellaspp. Mycobacteriumspp. MycobacteriumlepraeMycobacteriumtuberculosisMycoplasmahominisMycoplasmapneumoniaeRickettsiaspp. Ureaplasmaurealyticum.

Moderately sensitive microorganisms (MPC = 4 mg/L; inhibition zone 16 – 14 mm)

– Aerobic Gram-positive microorganisms: CorynebacteriumurealyticumCorynebacteriumxerosisEnterococcusfaeciumStaphylococcusepidermidismethi-R (methicillin-resistant) Staphylococcushaemolyticusmethi-R (methicillin-resistant).

– Aerobic Gram-negative microorganisms: Campylobacterjejuni/coli.

– Anaerobic microorganisms: Prevotellaspp. Porphyromonasspp.

Levofloxacin-resistant microorganisms (MPC ≥8 mg/L; zone of inhibition ≤ 13 mm)

– Aerobic Gram-positive microorganisms: Staphylococcusaureusmethi-R (methicillin-resistant) Staphylococcuscoagulase-negativemethi-R (coagulase-negative methicillin-resistant).

– Aerobic Gram-negative microorganisms: Alcaligenesxylosoxidans.

– 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 mechanisms of resistance such as the mechanism of influence on the penetration barriers of the microbial cell (mechanism typical for Pseudomonasaeruginosa) and mechanism of efflux (active excretion of antimicrobial agent from the microbial cell) can also decrease the sensitivity of microorganisms to levofloxacin.

In view of the specific mechanism of action of levofloxacin there is usually no cross-resistance between levofloxacin and other antimicrobial agents.

Clinical efficacy (effectiveness in clinical studies in the treatment of infections caused by the microorganisms listed below):

– Aerobic Gram-positive microorganisms: EnterococcusfaecalisStaphylococcusaureusStreptococcuspneumoniaeStreptococcuspyogenes.

– Aerobic Gram-negative microorganisms: CitrobacterfreundiiEnterobactercloacaeEscherichiacoliHaemophilusinfluenzaeHaemophilusparainfluenzaeKlebsiellapneumoniaeMoraxella (Branhamella) catarrhalisMorganellamorganiiProteusmirabilisPseudomonasaeruginosaSerratiamarcescens.

– Others: Chlamydia pneumoniae Legionella pneumophila Mycoplasma pneumoniae.

Pharmacokinetics:

Absorption

Levofloxacin is quickly and almost completely absorbed after oral intake food has little effect on its absorption. Absolute bioavailability after oral administration 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 52± 12 mcg/ml. Pharmacokinetics of levofloxacin is linear in the dose range from 50 to 1000 mg. Equilibrium state of plasma concentrations of levofloxacin in administration of 500 mg of levofloxacin 1 or 2 times per day is reached within 48 hours.

On day 10 of oral administration of Lefloact® 500 mg once daily the Cmax of lovofloxacin was 57±14 mcg/ml and the minimum plasma concentration of lovofloxacin (concentration before next dose) (Cmin) was 05±02 mcg/ml.

On day 10 of oral administration of Lefloact® 500 mg twice daily the Cmax was 78±11 mcg/ml and the Cmin was 30±09 mcg/ml.

Distribution

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

Infiltration into the mucous membrane of the bronchial mucosa by the epithelial lining of alveolar macrophages

Infiltration into the mucous membrane of the bronchi by 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 83 µg/g and 108 µg/ml, respectively, with penetration rates in bronchial mucosa and epithelial lining fluid compared to plasma concentrations of 11-18 and 08-3, 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 994 µg/mL and in alveolar macrophages were 979 µg/mL.

Pulmonary tissue penetration

The maximum pulmonary tissue concentrations after oral administration of 500 mg of levofloxacin were approximately 113 µg/g and were reached 4-6 h after drug administration with penetration ratios of 2-5 compared to plasma concentrations.

Alveolar fluid penetration

After 3 days of administration of 500 mg of levofloxacin once or twice daily, maximum concentrations of levofloxacin in alveolar fluid were reached 2-4 hours after drug administration and were 40 and 67 µg/ml respectively with a penetration factor of 1 compared to the plasma concentration.

Bone penetration

Levofloxacin penetrates well into cortical and cancellous bone tissue in both proximal and distal femur with a penetration coefficient (bone tissue/plasma) of 01-3. Maximum concentrations of levofloxacin in cancellous bone tissue of proximal femur after oral administration of 500 mg of the drug were approximately 151 µg/g (2 h after drug administration).

Cerebrospinal fluid penetration

Levofloxacin does not readily penetrate into the cerebrospinal fluid.

Permeability to prostate tissue

After oral administration of 500 mg of levofloxacin once daily for 3 days, the mean concentration of levofloxacin in prostate tissue was 87 mcg/g and the mean prostate/plasma concentration ratio was 184.

Urinary concentrations

The mean urinary concentrations 8-12 hours 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 conversions.

Levofloxacin is relatively slowly eliminated from the blood plasma after oral administration (elimination 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±292 ml/min.

There are no significant differences in the pharmacokinetics of levofloxacin with intravenous versus oral administration, confirming that oral and intravenous administration are interchangeable.

Pharmacokinetics in selected patient groups

The pharmacokinetics of lsvofloxacin 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 changes. As renal function deteriorates, renal excretion and renal clearance (CIR) decreases and T1/2 increases.

Indications

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

– community-acquired pneumonia;

– complicated urinary tract infections and pyelonephritis;

– chronic bacterial prostatitis;

– infections of the skin and soft tissues;

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

– prevention and treatment of anthrax through airborne transmission.

For the treatment of the following infectious and inflammatory diseases, levofloxacin can only be used as an alternative to other antimicrobial drugs:

– acute sinusitis;

– exacerbation of chronic bronchitis;

– uncomplicated cystitis.

When using Leflobact®, official national recommendations on the proper use of antibacterial drugs should be taken into account, as well as the sensitivity of pathogenic microorganisms in a particular country (see section “Special instructions”).

Pharmacological effect

Pharmacotherapeutic group

Antimicrobial agent – fluoroquinolone

ATX code: J01MA

Pharmacodynamics:

Leflobact® is a synthetic broad-spectrum antibacterial drug from the group of fluoroquinolones containing levofloxacin, a levorotatory isomer of ofloxacin, as an active substance.

Levofloxacin blocks DNA gyrase and topoisomerase IV; disrupts supercoiling and cross-linking of DNA breaks; inhibits DNA synthesis; causes profound morphological changes in the cytoplasm, cell wall and membranes of microbial cells. Levofloxacin is active against most strains of microorganisms both in vitro and in vivo.

Invitro

Sensitive microorganisms (minimum inhibitory concentration (MIC) ≤ 2 mg/l; zone of inhibition ≥ 17 mm)

– Aerobic gram-positive microorganisms: BacillusanthracisCorynebacteriumdiphtheriaeCorynebacteriumjeikeiumEnterococcusfaecalisEnterococcusspp. ListeriamonocytogenesStaphylococcuscoagulase-negativemethi-S(I) (coagulase-negative methicillin-sensitive/moderately sensitive) Staphylococcus aureusmethi-S (methicillin-sensitive) Staphylococcus epidermidismethi-S (methicillin-sensitive) Staphylococcus spp. CNS (coagulase-negative) Streptococci group C and GStreptococcusagalactiaeStreptococcuspneumoniaepeniI/S/R (penicillin-moderately sensitive/sensitive/-resistant) StreptococcuspyogenesViridansstreptococcipeniS/R (penicillin-sensitive/-resistant).

– Aerobic gram-negative microorganisms: Acinetobacter baumanniiAcinetobacter spp. Actinobacillus actinomycetemcomitansCitrobacterfreundiiEikenellacorrodensEnterobacteraerogenesEnterobactercloacaeEnterobacterspp. EscherichiacoliGardnerellavaginalisHaemophilusducreyiHaemophilusinfluenzaeampi-S/R (ampicillin-sensitive/-resistant) HaemophilusparainfluenzaeHelicobacterpyloriKlebsiel­laoxytocaKlebsiellapneumoniaeKlebsiellaspp. Moraxellacatarrhalisβ+ β- (producing and non-producing beta-lactamases) MorganellamorganiiNeisseriagonorrhoeaenonPPNG/PPNG (non-producing and producing penicillinase) Neisseriameningitidis Pasteurellacanis Pasteurelladagmatis Pasteurellamultocida Pasteurellaspp. Proteusmira-bilisProteusvulgarisProvidenciarettgeriProvidenciastuartiiProvidenciaspp. Pseudomonasaeruginosa (hospital infections caused by Pseudomonasaeruginosa may require combination treatment) Pseudomonaspp. Salmonellasp. Serratiamar-cescensSerratiaspp..

– Anaerobic microorganisms: BacteroidesfragilisBifidobacteriumspp. Clostridium perfringens Fusobacterium spp. Peptostreptococcus spp. Propionibacterium spp. Veillonellasp.

– Other microorganisms: Bartonella spp. ChlamydiapneumoniaeChlamydiapsittaciChlamydiatrachomatisLegionellapneumophilaLegionellaspp. Mycobacterium spp. Myco­bacteriumlepraeMycobacteriumtuberculosisMycoplasmahominisMycoplasmapneumoniaeRickettsiaspp. Ureaplasmaurealyticum.

Moderately sensitive microorganisms (MIC = 4 mg/l; inhibition zone 16 – 14 mm)

– Aerobic gram-positive microorganisms: CorynebacteriumurealyticumCorynebacteriumxerosisEnterococcusfaeciumStaphylococcusepidermidismethi-R (methicillin-resistant) Staphylococcushaemolyticusmethi-R (methicillin-resistant).

– Aerobic gram-negative microorganisms: Campylobacterjejuni/coli.

– Anaerobic microorganisms: Prevotellaspp. Porphyromonas pp.

Levofloxacin-resistant microorganisms (MIC ≥ 8 mg/l; inhibition zone ≤ 13 mm)

– Aerobic gram-positive microorganisms: Staphylococcus aureusmethi-R (methicillin-resistant) Staphylococcuscoagulase-negativemethi-R (coagulase-negative methicillin-resistant).

– Aerobic gram-negative microorganisms: Alcaligenesxylosoxidans.

– Anaerobic microorganisms: Bacteroides thetaiotaomicron.

-Other microorganisms: Mycobacterium avium.

Resistance

Resistance to levofloxacin develops as a result of a step-by-step 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 influencing the penetration barriers of the microbial cell (a mechanism characteristic of Pseudomonasaeruginosa) and the mechanism of efflux (active removal of the antimicrobial agent from the microbial cell) may 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 (effectiveness in clinical studies in the treatment of infections caused by the following microorganisms):

– Aerobic gram-positive microorganisms: Enterococcus faecalis Staphylococcus aureus Streptococcus pneumoniae Streptococcus pyogenes.

– Aerobic gram-negative microorganisms: CitrobacterfreundiiEnterobactercloa­caeEscherichiacoliHaemophilusinfluenzaeHaemophilusparainfluenzaeKlebsiellapneu­moniaeMoraxella (Branhamella) catarrhalisMorganellamorganiiProteusmirabilisPseu­domonasaeruginosaSerratiamarcescens.

– Others: Chlamydia pneumoniae Legionella pneumophila Mycoplasma pneumoniae.

Pharmacokinetics:

Absorption

Levofloxacin is rapidly and almost completely absorbed after oral administration; food has little effect on its absorption. Absolute bioavailability when taken orally is 99-100%. After a single dose of 500 mg of levofloxacin, the maximum concentration in blood plasma (Cmax) is reached within 1-2 hours and is 52 ± 12 μg/ml. The pharmacokinetics of lsvofloxacin is linear over the dose range from 50 to 1000 mg. The equilibrium state of levofloxacin concentration in blood plasma when taking 500 mg of levofloxacin 1 or 2 times a day is achieved within 48 hours.

On the 10th day of oral administration of Leflobact® 500 mg 1 time per day, Cmax of lsvofloxacin was 57±14 mcg/ml and the minimum concentration of lsvofloxacin (concentration before taking the next dose) (Cmin) in blood plasma was 05±02 mcg/ml.

On the 10th day of oral administration of Leflobact® 500 mg 2 times a day, Cmax was 78±11 µg/ml and Cmin was 30±09 µg/ml.

Distribution

The binding to serum proteins is 30-40%. After a single and repeated dose of 500 mg of levofloxacin, the volume of distribution of levofloxacin averages 100 l, which indicates good penetration of levofloxacin into organs and tissues of the human body.

Penetration into the bronchial mucosa fluid of the epithelial lining alveolar macrophages

After a single oral dose of 500 mg of levofloxacin, the maximum concentrations of levofloxacin in the bronchial mucosa and epithelial lining fluid were reached within 1 hour or 4 hours and amounted to 83 μg/g and 108 μg/ml, respectively, with penetration coefficients into the bronchial mucosa and epithelial fluid compared to plasma concentrations of 11-18 and 08-3, respectively.

After 5 days of oral administration of 500 mg of levofloxacin, the average concentrations of levofloxacin 4 hours after the last dose of the drug in the fluid of the epithelial lining were 994 μg/ml and in alveolar macrophages – 979 μg/ml.

Penetration into lung tissue

Maximum concentrations in lung tissue after oral administration of 500 mg of levofloxacin were approximately 113 μg/g and were achieved 4-6 hours after administration of the drug with penetration coefficients of 2-5 compared to plasma concentrations.

Penetration into alveolar fluid

After 3 days of taking 500 mg of levofloxacin 1 or 2 times a day, the maximum concentrations of levofloxacin in the alveolar fluid were reached 2-4 hours after taking the drug and were 40 and 67 μg/ml, respectively, with a penetration coefficient of 1 compared with the concentration in the blood plasma.

Penetration into bone tissue

Levofloxacin penetrates well into cortical and cancellous bone tissue in both the proximal and distal parts of the femur with a penstration coefficient (bone tissue/blood plasma) of 01-3. The maximum concentrations of levofloxacin in the cancellous bone tissue of the proximal femur after taking 500 mg of the drug orally were approximately 151 mcg/g (2 hours after dosing).

Penetration into the cerebrospinal fluid

Levofloxacin penetrates poorly 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 87 mcg/g; the average prostate/blood plasma concentration ratio was 184.

Concentrations in urine

Mean urinary concentrations 8 to 12 hours after oral doses of 150,300 and 600 mg of levofloxacin were 44 mcg/mL, 91 mcg/mL, and 162 mcg/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.

Removal

After oral administration, levofloxacin is relatively slowly eliminated from the blood plasma (half-life (T1/2) – 6-8 hours). Excretion is predominantly through the kidneys (more than 85% of the dose taken). The total clearance of levofloxacin after a single dose of 500 mg was 175±292 ml/min.

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

Pharmacokinetics in selected patient groups

The pharmacokinetics of lsvofloxacin do not differ between men and women.

Pharmacokinetics in elderly patients do not differ from those in young patients, with the exception of differences in pharmacokinetics associated with differences in creatinine clearance (CC).

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

Special instructions

Hospital-acquired infections caused by Pseudomonas aeruginosa may require combination treatment.

The prevalence of acquired resistance in cultured strains of microorganisms may vary depending on the geographical region and over time. In this regard, information on drug resistance in a specific country is required.

For the treatment of severe infections or if treatment is ineffective, a microbiological diagnosis must be established with the isolation of the pathogen and determination of its sensitivity to levofloxacin.

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.

Patients predisposed to developing seizures

Like other quinolones, levofloxacin should be used with great caution in patients with a predisposition to seizures. Such patients include patients with previous lesions of the central nervous system such as stroke, severe traumatic brain injury; patients simultaneously receiving drugs that lower the threshold of convulsive activity of the brain such as fenbufen and other similar non-steroidal anti-inflammatory drugs or other drugs that lower the threshold of convulsive activity such as theophylline (see section “Interaction with other drugs”).

Pseudomembranous colitis

Particularly severe, persistent and/or bloody diarrhea that develops during or after treatment with levofloxacin 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 (vancomycin teicoplanin or oral metronidazole) should be started immediately. Drugs that inhibit intestinal motility are contraindicated.

Tendinitis

When using quinolones, including levofloxacin, tendinitis is rarely observed, which can sometimes lead to tendon rupture, including the Achilles tendon. This side effect can develop within 48 hours after starting treatment and can be bilateral. Elderly patients are more prone to developing tendinitis; In patients taking fluoroquinolones, the risk of tendon rupture may increase while taking glucocorticosteroids. In addition, post-transplant patients have an increased risk of developing tendinitis, so it is recommended to exercise caution when prescribing fluoroquinolones to this category of patients. If you suspect the development of tendinitis, you should immediately stop treatment with Leflobact® and begin appropriate treatment of the affected tendon, for example by ensuring sufficient immobilization (see sections “Contraindications” and “Side effects”).

Hypersensitivity reactions

Levofloxacin may cause serious, potentially fatal hypersensitivity reactions (angioedema, anaphylactic shock) even at initial doses (see Side Effects section). Patients should immediately stop taking the drug and consult a doctor.

Severe bullous reactions

When using levofloxacin, cases of the development of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been observed (see section “Side effects”) If any reactions from the skin or mucous membranes develop, the patient should immediately consult a doctor and not continue treatment until his consultation.

Disorders of the liver and biliary tract

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

Patients with impaired renal function

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

Preventing the development of photosensitivity reactions

Although photosensitivity during the use of levofloxacin develops very rarely, to prevent its development, patients are not recommended to undergo unnecessarily strong solar or artificial ultraviolet irradiation (for example, visiting a solarium) during treatment and for 48 hours after the end of treatment with levofloxacin.

Superinfection

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

QT prolongation

Very rare cases of QT 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 prolongation of the QT interval: in patients with uncorrected electrolyte disturbances (with hypokalemia and 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 and female patients may be more sensitive to drugs that prolong the QT interval. Therefore, fluoroquinolones, including levofloxacin, should be used with caution (see sections “With caution”, “Dosage and administration”, “Side effects”, “Interaction with other drugs”).

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency are predisposed to developing hemolytic reactions when treated with quinolones, which should be taken into account when treating with levofloxacin.

Hypo- and hyperglycemia (dysglycemia)

As with the use of other quinolones, cases of hyperglycemia and hypoglycemia have been observed when using levofloxacin. During therapy with levofloxacin, dysglycemia occurred more often in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, glibenclamide drugs) or insulin. When using levofloxacin in such patients, the risk of developing hypoglycemia, including hypoglycemic coma, increases. It is necessary to inform patients about the symptoms of hypoglycemia (confusion, dizziness, ravenous appetite, headache, nervousness, palpitations or increased heart rate, pallor of the skin, perspiration, trembling, weakness). If the patient develops hypoglycemia, treatment with levofloxacin should be discontinued immediately and appropriate therapy should be initiated. In these cases, it is recommended to switch to therapy with another antibiotic other than fluoroquinolones, if possible. When treating levofloxacin in elderly patients with diabetes mellitus, careful monitoring of blood glucose concentrations is recommended.

Peripheral neuropathy

Cases of sensory and sensorimotor peripheral neuropathy, the onset of which may be rapid, have been reported in patients taking fluoroquinolones including levofloxacin. If the patient develops symptoms of neuropathy, levofloxacin should be discontinued. This minimizes the possible risk of developing irreversible changes.

Exacerbation of pseudoparalytic myasthenia gravis (myasthenia gravis)

Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may increase muscle weakness in patients with myasthenia gravis. Adverse reactions, including pulmonary failure requiring mechanical ventilation and death, have been observed post-marketing with the use of fluoroquinolones in patients with myasthenia gravis. The use of levofloxacin in a patient with an established diagnosis of pseudoparalytic myasthenia gravis is not recommended (see section “Side effects”).

Use for airborne anthrax infection

The use of levofloxacin in humans for this indication is based on data on the sensitivity of Bacillus anthracis to it obtained in in vitro studies and in experimental studies conducted in animals, as well as on limited data from the use of levofloxacin in humans. Treating physicians should refer to national and/or international documents that reflect the collectively developed point of 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 taking a single dose. In case of development of any side effects from the central nervous system, including mental disorders, treatment with levofloxacin should be stopped immediately and appropriate therapy should be prescribed. In these cases, it is recommended to switch to therapy with another antibiotic other than fluoroquinolones if possible. The drug should be prescribed with caution to patients with psychosis or patients with a history of mental illness.

Visual impairment

If any visual impairment develops, immediate consultation with an ophthalmologist is necessary (see section “Side effects”).

Effect on laboratory tests

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.

Impact on the ability to drive vehicles. Wed and fur.:

Side effects of Leflobact® such as dizziness or vertigo, drowsiness and visual disturbances (see section “Side effects”) can reduce psychomotor reactions and the ability to concentrate. This may pose a certain risk in situations where these abilities are of particular importance (for example, when driving a car when servicing machines and mechanisms when performing work in an unstable position).

Active ingredient

Levofloxacin

Composition

Composition per 1 tablet:

Core composition:

Active ingredient: lsvofloxacin (in the form of levofloxacin hemihydrate) – 250 mg, 500 mg.

Excipients: calcium stearate, starch 1500, potato starch, crospovidone, povidone (low molecular weight medical polyvinylpyrrolidone 12600±2700, povidone K 17), lactose monohydrate, talc, colloidal silicon dioxide (Aerosil), microcrystalline cellulose.

Shell composition: hypromellose (hydroxypropyl methylcellulose), macrogol (polyethylene glycol 4000), titanium dioxide (titanium dioxide), tropeolin O.

Pregnancy

Levofloxacin is contraindicated for use in pregnant and breastfeeding women.

Contraindications

– Hypersensitivity to levofloxacin or other quinolones, as well as to any of the excipients of Leflobact®;

– lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

– epilepsy;

– pseudoparalytic myasthenia gravis (myasthenia gravis) (see sections “Side effects”, “Special instructions”);

– tendon damage due to a history of taking fluoroquinolones;

– childhood and adolescence up to 18 years of age (due to the incompleteness of skeletal growth, since the risk of damage to cartilaginous growth zones cannot be completely eliminated);

– pregnancy (the risk of damage to the cartilaginous growth zones of the fetus cannot be completely excluded);

– the period of breastfeeding (the risk of damage to the cartilage growth zones of bones in a child cannot be completely eliminated).

With caution:

– In patients predisposed to the development of seizures (in patients with previous lesions of the central nervous system (CNS); in patients simultaneously taking drugs that lower the threshold of convulsive activity of the brain such as fenbufen theophylline) (see section “Interaction with other drugs”);

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

– in patients with impaired renal function (mandatory monitoring of renal function is required, as well as correction of the dosage regimen, see section “Method of administration and dosage”);

– in patients with known risk factors for prolongation of the QT interval: 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); while taking medications that can prolong the QT interval (antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, antipsychotics) (see sections “Overdose”, “Interaction with other drugs”, “Special instructions”);

– in patients with diabetes mellitus receiving oral hypoglycemic drugs (for example, glibenclamide) or insulin drugs (the risk of developing hypoglycemia increases);

– in patients with severe adverse reactions to other fluoroquinolones such as severe neurological reactions (increased risk of developing similar adverse reactions when using lsvofloxacin);

– in patients with psychosis or in patients with a history of mental illness (see section “Special instructions”);

– in elderly patients, in patients after transplantation, as well as with the concomitant use of glucocorticosteroids (increased risk of tendonitis and tendon rupture) (see section “Special instructions”).

Side Effects

The side effects listed below are presented in accordance with the following gradations of frequency of their occurrence: very often (≥ 1/10); often (≥ 1/100 < 1/10); uncommon (≥ 1/1000 < 1/100); rare (≥ 1/10000 < 1/1000); very rare (<1/10000) (including isolated reports); frequency is unknown (it is not possible to determine the frequency of occurrence based on available data).

Data obtained in clinical trials and post-marketing use of the drug

Cardiac disorders: rarely – sinus tachycardia, palpitations; frequency unknown (high post-marketing data) – prolongation of the QT interval, ventricular arrhythmias, ventricular tachycardia, ventricular tachycardia of the “pirouette” type, which can lead to cardiac arrest (see sections “Overdose” “Special instructions”).

Disorders of the blood and lymphatic system: infrequently – leukopenia (decreased number of leukocytes in peripheral blood) eosinophilia (increased number of eosinophils in peripheral blood); rarely – neutropenia (decreased number of neutrophils in peripheral blood) thrombocytopenia (decreased number of platelets in peripheral blood); frequency unknown (post-marketing data) – pancytopenia (decrease in the number of all formed elements in the peripheral blood) agranulocytosis (absence or sharp decrease in the number of granulocytes in the peripheral blood) hemolytic anemia.

Nervous system disorders: often – headache, dizziness; uncommon – drowsiness, tremor, dysgeusia (taste perversion); rarely – paresthesia, convulsions (see section “Special instructions”); frequency unknown (post-marketing data) – peripheral sensory neuropathy peripheral sensorimotor neuropathy (see section “Special Instructions”) dyskinesia extrapyramidal disorders ageusia (loss of taste) parosmia (disorder of the sense of smell, especially the subjective sensation of an objectively absent smell) including loss of smell syncope increased intracranial pressure (benign intracranial hypertension psvdtumor of the brain).

Violations of the organ of vision: rarely – visual disturbances such as blurriness of the visible image; frequency unknown (post-marketing data) – transient loss of vision, uveitis.

Hearing and labyrinthine disorders: infrequently – vertigo (feeling of deviation or spinning of one’s own body or surrounding objects); rarely – ringing in the ears; frequency unknown (post-marketing data) – hearing loss, hearing loss.

Disorders of the respiratory system of the chest and mediastinum: infrequently – shortness of breath; frequency unknown (post-marketing data) – bronchospasm, allergic pneumonitis.

Gastrointestinal disorders: often – diarrhea, vomiting, nausea; uncommon – abdominal pain, dyspepsia, flatulence, constipation; frequency unknown (post-marketing data) – hemorrhagic diarrhea which in very rare cases may be a sign of enterocolitis including pseudomembranous colitis (see section “Special instructions”) pancreatitis.

Renal and urinary tract disorders: uncommon – increased serum creatinine concentration; rarely – acute renal failure (for example, due to the development of interstitial nephritis).

Disorders of the skin and subcutaneous tissues: uncommon – rash, itching, urticaria, hyperhidrosis; frequency unknown (post-marketing data) – toxic epidermal necrolysis Stevens-Johnson syndrome, exudative erythema multiforme, photosensitivity reaction (increased sensitivity to solar and ultraviolet radiation (see section “Special Instructions”), leukocytoclastic vasculitis stomatitis.

Reactions from the skin and mucous membranes can sometimes develop even after taking the first dose of the drug.

Disorders of the musculoskeletal system and connective tissue: infrequently – arthralgia, myalgia; rarely – tendon damage including tendinitis (for example, Achilles tendon), muscle weakness which can be especially dangerous in patients with myasthenia gravis (see section “Special instructions”); frequency unknown (post-marketing data) – rhabdomyolysis, tendon rupture (for example, Achilles tendon. This side effect can be observed within 48 hours after the start of treatment and can be bilateral (see also section “Special instructions”)) ligament rupture, muscle rupture, arthritis.

Metabolic and nutritional disorders: infrequently – anorexia; rarely – hypoglycemia, especially in patients with diabetes mellitus (possible signs of hypoglycemia: voracious appetite, nervousness, perspiration, trembling); frequency unknown – hyperglycemia, severe hypoglycemia up to the development of hypoglycemic coma, especially in elderly patients in patients with diabetes mellitus taking oral hypoglycemic drugs or insulin (see section “Special instructions”).

Infectious and parasitic diseases: infrequently – fungal infections, development of resistance of pathogenic microorganisms.

Vascular disorders: rarely – decreased blood pressure.

General disorders: infrequently – asthenia; rarely – pyrexia (fever); frequency unknown – pain (including pain in the back, chest and limbs).

Immune system disorders: rarely – angioedema; frequency unknown (post-marketing data) – anaphylactic shock, anaphylactoid shock. Anaphylactic and anaphylactoid reactions can sometimes develop even after taking the first dose of the drug.

Disorders of the liver and biliary tract: often – increased activity of liver enzymes in the blood (for example, alanine aminotransferase (ALT), aspartate aminotransferase (ACT)), increased activity of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT); infrequently – increased concentration of bilirubin in the blood; frequency unknown (post-marketing data) – severe liver failure including cases of acute liver failure, sometimes fatal, especially in patients with a severe underlying disease (for example, patients with sepsis) (see section “Special Instructions”) hepatitis jaundice.

Mental disorders: often – insomnia; infrequently – feeling of restlessness anxiety confusion; rarely – mental disorders (for example, hallucinations, paranoia), depression, agitation (excitement), sleep disturbances, nightmares; frequency unknown (post-marketing data) – attention disorders, disorientation, nervousness, memory impairment, delirium, mental disorders with behavioral disorders with self-harm, including suicidal thoughts and suicide attempts.

Other possible undesirable effects that apply to all fluoroquinolones: very rarely – attacks of porphyria (a very rare metabolic disease) in patients with porphyria.

Interaction

Interactions requiring caution

With preparations containing magnesium, aluminum, iron and zinc, didanosine.

Preparations containing divalent or trivalent cations such as zinc or iron salts (medicines for the treatment of anemia), magnesium and/or aluminum containing drugs (such as antacids), didanosine (only dosage forms containing aluminum or magnesium as a buffer) are recommended to be taken at least 2 hours before or 2 hours after taking Leflobact tablets.

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

With sucralfate

The effect of Leflobact® is significantly weakened by the simultaneous use of sucralfate (a drug for protecting the gastric mucosa). Patients receiving levofloxacin and sucralfate are advised to take sucralfate 2 hours after taking levofloxacin.

With theophylline, fenbufen or similar drugs from the group of non-steroidal anti-inflammatory drugs that reduce the threshold of convulsive readiness of the brain

No pharmacokinetic interaction of levofloxacin with theophylline was detected. However, with the simultaneous use of quinolones and theophylline, non-steroidal anti-inflammatory drugs and other drugs that reduce the threshold of convulsive readiness of the brain, a pronounced decrease in the threshold of convulsive readiness of the brain is possible.

The concentration of lsvofloxacin with simultaneous administration of fenbufen increases only by 13%.

With indirect anticoagulants (vitamin K antagonists)

In patients treated with lsvofloxacin in combination with indirect anticoagulants (for example, warfarin), an increase in prothrombin time/international normalized ratio and/or the development of bleeding, including severe bleeding, was observed. Therefore, with the simultaneous use of indirect anticoagulants and lsvofloxacin, regular monitoring of blood coagulation parameters is necessary.

With probenecid and cimetidine

With the simultaneous use of drugs that interfere with renal tubular secretion such as probenecid and cimetidine and levofloxacin, caution should be exercised, especially in patients with renal failure.

The elimination (renal clearance) of lsvofloxacin is slowed down by cimetidine by 24% and probenecid by 34%. This is unlikely to be of clinical significance if renal function is normal.

With cyclosporine

Levofloxacin increased the half-life of cyclosporine by 33%. Since this increase is clinically insignificant, no dose adjustment of cyclosporine is required when used concomitantly with levofloxacin.

With glucocorticosteroids

Concomitant use of glucocorticosteroids increases the risk of tendon rupture.

With drugs that prolong the QT interval

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

Others

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

Overdose

Symptoms: nausea, erosive lesions of the mucous membranes of the gastrointestinal tract (GIT), prolongation of the QT interval, confusion, dizziness, convulsions.

Treatment: gastric lavage, symptomatic dialysis is ineffective. There is no specific antidote.

Storage conditions

In a place protected from light at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life

3 years. Do not use after the expiration date stated on the package.

Manufacturer

Sintez, Russia