Roflox-Scan, 500 mg 10 pcs

Pharmacotherapeutic group

Antimicrobial agent – fluoroquinolone

ATX code

J01MA

Pharmacodynamics:

Roflox-Scan 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-giase 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 both in vitro and in vivo.

In vitro

Sensitive microorganisms (MAC ≤ 2 mg/L; zone of inhibition ≥17 mm)

– Aerobic Gram-positive microorganisms: Bacillus anthracis Corynebacterium diphtheriae Corynebacterium jeikeium Enterococcus faecalis Enterococcus spp. Listeriamonocytogenes Staphylococcus coagulase-negative methi-S(I) [coagulase-negative methicillin-sensitive/ moderately sensitive] Staphylococcus aureus methi-S (methicillin-sensitive) Staphylococcus epidermidis methi-S (methicillin-sensitive) Staphylococcus spp. CNS (coagulase-negative) Streptococci spp. C and G Streptococcus agalactiae Streptococcus pneumoniae peni I/S/R (penicillin-moderately sensitive/sensitive/resistant) Streptococcus pyogenes Viridans streptococci peni-S/R (penicillin-sensitive/resistant).

– Aerobic Gram-negative microorganisms: Acinetobacter baumannii Acinetobacter spp. Actinobacillus actinomycetemcomitans Citrobacter freundii Eikenella corrodens Enterobacter aerogenes Enterobacter cloacae Enterobacter spp. Escherichia coli Gardneirella vaginalis Haemophilus ducreyi Haemophilus influenzae ampi-S/R (ampicillin-sensitive/resistant) Haemophilus parainfluenzae Helicobacter pylori Klebsiella oxytoca Klebsiella pneumonia Klebsiella spp. Moraxella catarrhalis ß+/ß- (producing and non-producing beta-Morganella morganii Neisseria gonorrhoeae non PPNG/PPNG (non-producing and producing penicillinase) Neisseria meningitidis Pasteurelia canis Pasteurella dagmatis Pasteurella multocida Pasteurella spp Proteus mirabilis Proteus vulgaris Providencia rettgeri Providencia stuartii Providencia spp. Pseudomonas aeruginosa (hospital infections caused by Pseudomonas aeruginosa may require combined treatment) Pseudomonas spp. Salmonella spp. Serratia marcescens Serratia spp.

– 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 pneumophila Legionella spp. Mycobacterium spp. Mycobacterium leprae Mycobacterium tuberculosis Mycoplasma hominis Mycoplasma pneumoniae Rickettsia spp. Ureaplasma urealyticum.

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

– Aerobic Gram-positive microorganisms: Corynebacterium urealyticum Corynebacterium xerosis Enterococcus faecium Staphylococcus epidermidis methi-R (methicillin-resistant) Staphylococcus haemolyticus methi-R (methicillin-resistant).

– Aerobic Gram-negative microorganisms: Campylobacter jejuni/coli

– Anaerobic microorganisms: Prevotella spp. Porphyromonas spp.

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

– Aerobic gram-positive microorganisms: Staphylococcus aureus methi-R (methicillin-resistant) Staphylococcus coagulase-negative methi-R (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 mechanisms of resistance such as the mechanism of influence on the penetration barriers of the microbial cell (mechanism typical for Pseudomonas aeruginosa) 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 trials 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: Citrobacter freundii Enterobacter cloacae Escherichia coli Haemophilus influenzae Haemophilus parainfluenzae Klebsiella pneumoniae Moraxella (Branhamella) catarrhalis Morganella morganii Proteus mirabilis Pseudomonas aeruginosa Serratia marcescens.

– Others: Chlamydia pneumoniae Legionella pneumophila Mycoplasma pneumoniae.

Pharmacokinetics:

Absorption

Levofloxacin is rapidly and almost completely absorbed after ingestion food has little effect on its absorption. Absolute bioavailability when taken orally is 99-100%. After a single use of 500 mg of levofloxacin maximum concentration in blood plasma (Cmax) is reached within 1-2 hours and is 52±12 µg/ml. Pharmacokinetics of levofloxacin is linear in dose range from 50 to 1000 mg. Equilibrium state of plasma concentration of levofloxacin is reached within 48 hours when receiving 500 mg of levofloxacin 1 or 2 times per day.

On day 10 of oral administration of 500 mg of levofloxacin once daily, the Cmax of levofloxacin was 57±14 mcg/mL and the minimum plasma concentration of levofloxacin (pre-dose concentration) (Cmin) was 05±02 mcg/mL.

On day 10 of oral administration of 500 mg of levofloxacin 2 times daily, the Cmax of levofloxacin 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 administration 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, the maximum alveolar fluid concentrations of levofloxacin were reached 2-4 h after drug administration and were 40 and 67 mg/ml, respectively, with a penetration factor of 1 compared to plasma concentrations.

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 the proximal femur after 500 g of oral administration were approximately 151 µg/g (2 hours after drug administration.)

Perfusion into cerebrospinal fluid

Levofloxacin poorly penetrates 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 h after oral doses of 150,300 and 600 mg of levofloxacin were 44 µg/mL 91 µg/mL and 162 µg/mL, respectively.

Metabolism

Levofloxacin is metabolized to a small extent (5% of the dose taken). Its metabolites are demethyllevofloxacin and levofloxacin N-oxide which is excreted by the kidneys. Levofloxacin is stereochemically stable and undergoes chiral transformations.

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 levofloxacin do not differ in men and women.

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

In renal insufficiency, the pharmacokinetics of levofloxacin are altered. decreased renal function decreases renal excretion and renal clearance (ClR) and T1/2 is increased.

Pharmacokinetics in renal failure after a single oral administration of 500 mg of levofloxacin/

Indications

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

– community-acquired pneumonia;

– hospital-acquired pneumonia (for a dosage of 750 mg);

– 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 the drug Roflox-Scan, official national recommendations on the proper use of antibacterial agents should be taken into account, as well as the sensitivity of pathogenic microorganisms in a particular country.

Pharmacological effect

Pharmacotherapeutic group

Antimicrobial agent – fluoroquinolone

ATX code

J01MA

Pharmacodynamics:

Roflox-Scan 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.

In vitro

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

– Aerobic gram-positive microorganisms: Bacillus anthracis Corynebacterium diphtheriae Corynebacterium jeikeium Enterococcus faecalis Enterococcus spp. Listeria monocytogenes Staphylococcus coagulase-negative methi-S(I) [coagulase-negative methicillin-sensitive/moderately sensitive] Staphylococcus aureus methi-S (methicillin-sensitive) Staphylococcus epidermidis methi-S (methicillin-sensitive) Staphylococcus spp. CNS (coagulase negative) Streptococci spp. C and G Streptococcus agalactiae Streptococcus pneumonia peni I/S/R (penicillin-moderately sensitive/-sensitive/-resistant) Streptococcus pyogenes Viridans streptococci peni-S/R (penicillin-sensitive/-resistant).

– Aerobic gram-negative microorganisms: Acinetobacter baumannii Acinetobacter spp. Actinobacillus actinomycetemcomitans Citrobacter freundii Eikenella corrodens Enterobacter aerogenes Enterobacter cloacae Enterobacter spp. Escherichia coli Gardneirella vaginalis Haemophilus ducreyi Haemophilus influenzae ampi-S/R (ampicillin-sensitive/-resistant) Haemophilus parainfluenzae Helicobacter pylori Klebsiella oxytoca Klebsiella pneumonia Klebsiella spp. Moraxella catarrhalis ß+/ß- (producing and non-producing beta-lactamases) Morganella morganii Neisseria gonorrhoeae non PPNG/PPNG (non-producing and producing penicillinase) Neisseria meningitidis Pasteurelia canis Pasteurella dagmatis Pasteurella multocida Pasteurella spp Proteus mirabilis Proteus vulgaris Providencia rettgeri Providencia stuartii Providencia spp. Pseudomonas aeruginosa (hospital infections caused by Pseudomonas aeruginosa may require combination treatment) Pseudomonas spp. Salmonella spp. Serratia marcescens Serratia spp.

– 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 pneumophila Legionella spp. Mycobacterium spp. Mycobacterium leprae Mycobacterium tuberculosis Mycoplasma hominis Mycoplasma pneumoniae Rickettsia spp. Ureaplasma urealyticum.

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

– Aerobic gram-positive microorganisms: Corynebacterium urealyticum Corynebacterium xerosis Enterococcus faecium Staphylococcus epidermidis methi-R (methicillin-resistant) Staphylococcus haemolyticus methi-R (methicillin-resistant).

– Aerobic gram-negative microorganisms: Campylobacter jejuni/coli

– Anaerobic microorganisms: Prevotella spp. Porphyromonas spp.

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

– Aerobic gram-positive microorganisms: Staphylococcus aureus methi-R (methicillin-resistant) Staphylococcus coagulase-negative methi-R (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 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 Pseudomonas aeruginosa) 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 not usually observed.

Clinical efficacy (effectiveness 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.

– 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 plasma concentration (Cmax) is reached within 1-2 hours and is 52±12 mcg/ml. The pharmacokinetics of levofloxacin is linear in the dose range of 50 to 1000 mg. The equilibrium state of levofloxacin plasma concentration 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 500 mg of levofloxacin 1 time per day, the Cmax of levofloxacin was 57 ± 14 μg/ml and the minimum concentration of levofloxacin (concentrations before taking the next dose) in blood plasma (Cmin) was 05 ± 02 μg/ml.

On the 10th day of oral administration of 500 mg of levofloxacin 2 times a day, Cmax of levofloxacin 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 liters, 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 achieved within 1 hour or 4 hours and amounted to 83 mcg/g and 108 mcg/ml, respectively, with penetration coefficients into the bronchial mucosa and epithelial lining fluid compared with the concentration in the blood plasma of the components 11-18 and 08-3 respectively.

After 5 days of oral administration of 500 mg levofloxacin, the mean concentrations of levofloxacin 4 hours after the last dose in the epithelial lining fluid 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 mcg/g and were achieved 4-6 hours after dosing 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 concentration of levofloxacin in the alveolar fluid was reached 2-4 hours after taking the drug and amounted to 40 and 67 mg/ml, respectively, with a penetration coefficient of 1 compared with concentrations in 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 penetration 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 g 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 daily 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 undergoes chiral transformations.

Removal

After oral administration, levofloxacin is relatively slowly eliminated from the blood plasma (half-life (T1/2) – 6-8 hours). Excretion is primarily 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 levofloxacin when administered intravenously and orally, which confirms that oral administration and intravenous administration are interchangeable.

Pharmacokinetics in selected patient groups

The pharmacokinetics of levofloxacin 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. decreased renal function, renal excretion and renal clearance (ClR) decrease and T1/2 increases.

Pharmacokinetics in renal failure after a single oral dose of 500 mg levofloxacin/

Special instructions

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

Risk of developing resistance

The prevalence of acquired resistance in cultured strains of microorganisms may vary by geographic region and over time. Therefore, country-specific information on drug resistance 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.

Loss of ability to work (disability) and potential irreversible serious adverse reactions caused by taking fluoroquinolones

The use of fluoroquinolones, including levofloxacin, has been associated with disability and the development of irreversible serious adverse reactions from various body systems that can develop simultaneously in the same patient. Adverse reactions caused by fluoroquinolones include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and nervous system side effects (hallucinations, anxiety, depression, insomnia, headaches, and confusion). These reactions may develop from several hours to several weeks after starting levofloxacin therapy. The development of these adverse reactions was observed in patients of any age or without the presence of previous risk factors. If the first signs or symptoms of any serious adverse reactions occur, use of levofloxcin should be discontinued immediately. The use of fluoroquinolones, including levofloxacin, should be avoided in patients who have experienced any of these serious adverse reactions.

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 readiness of the brain such as fenbufen and other similar non-steroidal anti-inflammatory drugs or other drugs that lower the threshold of convulsive readiness such as theophylline (see section “Interaction with other drugs”).

If seizures develop, treatment with levofloxacin should be discontinued.

Pseudomembranous colitis

Diarrhea that develops during or after treatment with levofloxacin, especially severe, persistent and/or bloody, 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.

Tendonitis and tendon rupture

When using quinolones, including levofloxacin, tendinitis is rare and can sometimes lead to tendon rupture, including the Achilles tendon, and can be bilateral. This side effect may occur within 48 hours of starting treatment or several months after completion of fluoroquinolone therapy. Elderly patients are more prone to developing tendinitis; in patients taking fluoroquinolones, the risk of tendon rupture may increase with concomitant use of glucocorticosteroids. In addition, post-transplant patients have an increased risk of developing tendonitis, so it is recommended to be careful when prescribing fluoroquinolones to this category of patients. In patients with impaired renal function, the daily dose should be adjusted based on creatinine clearance.

Patients should be advised to remain calm at the first sign of tendinitis or tendon rupture and contact their healthcare provider. If you suspect the development of tendonitis or tendon rupture, you should immediately stop treatment with the drug 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

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

Disorders of the liver and biliary tract

Cases of hepatic necrosis, including fatal liver failure, 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 borne in mind 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 (bacteria and fungi) that are insensitive to it, 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); while taking medications 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” and “Overdose”, “Interaction with other drugs”).

Patients with glucose-6-phosphate dehydrogenase deficiency

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

Hypo- and hyperlycemia (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) 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, which may have a rapid onset, 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. Patients should be informed to report any symptoms of neuropathy to their healthcare provider. Fluoroquinolones should not be prescribed to patients with a history of peripheral neuropathy.

Exacerbation of pseudoparalytic myasthenia gravis (myasthenia gravis)

Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may increase muscle weakness in patients with myasthenia gravis. In the post-marketing period, adverse reactions have been observed, including pulmonary failure requiring mechanical ventilation and death, which have been associated with the use of fluoroquinolones in patients with pseudoparalytic 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 from in vitro and experimental studies 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 give a false-positive result 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 the drug Roflox-Scan 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

1 tablet contains:

Active ingredient:

levofloxacin hemihydrate 512.45 mg (in terms of levofloxacin 500.00 mg.

Excipients:

corn starch 59.25 mg;

microcrystalline cellulose 40.00 mgg;

sodium carboxymethyl starch 15.00 mg;

crospovidone 15.00 mg;

colloidal silicon dioxide 15.00 mg;

talc 10.00 mg;

hypromellose 6.80 mg;

magnesium stearate 6.50 mg.

Shell composition: film shell WT-19022P pink 6.14 mg (polyvinyl alcohol 49.00%; titanium dioxide (E 171) 21.79%; polyethylene glycol 6000 13.20%; talc 12.60%; soy lecithin 3.40%; red iron oxide dye (E 172) 0.01%)); sunset yellow dye (E 110) 0.86 mg.

Pregnancy

The drug Roflox-Scan is contraindicated for use in pregnant women and women during breastfeeding.

Contraindications

– Hypersensitivity to levofloxacin or other quinolones, as well as to any of the excipients of the Roflox-Scan drug;

– 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 cartilaginous 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 receiving drugs that lower the threshold of convulsive readiness 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 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 and hypomagnesemia); with congenital long QT syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); while taking medications that can prolong the QT interval (class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, neuroleptics) (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 hypoglycemia increases).

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

– In elderly patients in patients after transplantation and with concomitant use of glucocorticosteroids (increased risk of tendinitis and tendon rupture)

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).

Heart disorders

rarely: sinus tachycardia, palpitations.

frequency unknown: prolongation of the QT interval, ventricular arrhythmias, ventricular tachycardia, torsade de pointes (TdP), which can lead to cardiac arrest

Blood and lymphatic system disorders

uncommon: leukopenia (decrease in the number of leukocytes in the peripheral blood) eosinophilia (increase in the number of eosinophils in the peripheral blood).

rarely: neutropenia (decreased number of neutrophils in peripheral blood) thrombocytopenia (decreased number of platelets in peripheral blood).

frequency unknown: 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: peripheral sensory neuropathy peripheral sensory&motor 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 fainting increased intracranial pressure (benign intracranial hypertension pseudotumor cerebri)

Visual disorders

rarely: visual disturbances such as blurred visual images.

frequency unknown: transient vision loss, uveitis.

Hearing and labyrinth disorders

uncommon: vertigo (a feeling of deviation or spinning of one’s own body or surrounding objects).

rare: ringing in the ears.

frequency unknown: hearing loss hearing loss.

Disorders of the respiratory system of the chest and mediastinum

uncommon: shortness of breath.

frequency unknown: bronchospasm, allergic pneumonitis.

Gastrointestinal disorders

often: diarrhea, vomiting, nausea.

uncommon: abdominal pain, dyspepsia, flatulence, constipation.

frequency unknown: 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).

Skin and subcutaneous tissue disorders

uncommon: rash, itching, urticaria, hyperhidrosis.

frequency unknown: 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.

Musculoskeletal and connective tissue disorders

uncommon: arthralgia, myalgia.

rarely: tendon damage including tendonitis (eg Achilles tendon) muscle weakness which can be especially dangerous in patients with myasthenia gravis (see section “Special instructions”).

frequency unknown: 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

uncommon: anorexia.

rarely: hypoglycemia, especially in patients with diabetes mellitus (possible signs of hypoglycemia: ravenous 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

uncommon: fungal infections development of resistance of pathogenic microorganisms.

Vascular disorders

rarely: decreased blood pressure.

General disorders

uncommon: asthenia.

rarely: pyrexia (fever).

frequency unknown: pain (including pain in the back, chest and limbs).

Immune system disorders

rarely: angioedema. frequency unknown: 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 gammaglutamyltransferase (GGT).

uncommon: increased concentration of bilirubin in the blood.

frequency unknown: severe liver failure including cases of acute liver failure, sometimes fatal, especially in patients with a severe underlying disease (for example, in 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-registration data): mental disorders with behavioral disorders with self-harm including suicidal thoughts and suicidal attempts, attention disturbances, disorientation, nervousness, memory impairment, delirium.

Other possible undesirable effects relevant to all fluoroquinolones

very rare: 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 Roflox-Scan tablets.

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

With sucralfate

The effect of levofloxacin 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 levofloxacin while taking fenbufen increases only by 13%.

With indirect anticoagulants (vitamin K antagonists)

In patients treated with levofloxacin 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, when using indirect anticoagulants and levofloxacin simultaneously, regular monitoring of blood coagulation parameters is necessary.

With probenecid and cimetidine

When 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 levofloxacin 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 T1/2 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 to have clinical significance.

Overdose

Symptoms

Based on data obtained in toxicological studies conducted in animals, the most important expected symptoms of an acute overdose of levofloxacin are symptoms from the central nervous system (impaired consciousness including confusion, dizziness and convulsions).

During post-marketing use in overdose, central nervous system effects including confusion, convulsions, hallucinations and tremor have been observed.

Nausea and erosions of the gastrointestinal mucosa may develop.

In clinical and pharmacological studies conducted with doses of levofloxacin exceeding therapeutic doses, a prolongation of the QT interval was observed.

Treatment of overdose

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

Storage conditions

Store in a place protected from light at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf life

2 years.

Do not use after expiration date.

Manufacturer

Rozlex Pharm, Russia