Lefoccin, 500 mg 10 pcs

Pharmacotherapeutic group:

antimicrobial agent, fluoroquinolone

ATX code:

J01MA12

Pharmacological properties

Pharmacodynamics
Lefoccin Biox® is a synthetic broad-spectrum antibacterial agent of the group of fluoroquinolones with levofloxacin, the left-handed isomer of ofloxacin, as an 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, 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 suppressive concentration (MDC) ≤ 2mg/L; zone of inhibition ≥ 17 mm)
– aerobic Gram-positive microorganisms: Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus spp. (including Enterococcus faecalis), 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 (coagulazonegative), Streptococci group 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 spp. (including Acinetobacter baumannii), Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter spp. (including Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S/R (ampicillin-sensitive/resistant), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. Klebsiella pneumoniae, Klebsiella oxytoca), Moraxella catarrhalis β+/β- (producing and non-producing beta-lactamases), Morganella morganii, Neisseria gonorrhoeae non PPNG/PPNG (non-producing and producing penicillinase), Neisseria meningitidis, Pasteurella spp. Pasteurella multocida, Pasteurella dagmatis, Pasteurella canis), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas spp. (including Pseudomonas aeruginosa [hospital infections caused by Pseudomonas aeruginosa may require combined treatment]), Salmonella spp, Serratia spp. (including Serratia marcescens);

– 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. (including Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

Moderately sensitive 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, Campylobacter coli;

– anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

Levofloxacin-resistant microorganisms (MAC≥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), Corynebacterium jeikeium;

– 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 (a mechanism characteristic of Pseudomonas aeruginosa) and the mechanism of efflux (active elimination of the antimicrobial agent from the microbial cell), can also reduce the sensitivity of microorganisms to levofloxacin. Due to the peculiarities of the mechanism of action of levofloxacin 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 quickly and almost completely absorbed after oral administration; food has little effect on its absorption. Absolute bioavailability when administered orally is 99-100%. After a single use of 500 mg of levofloxacin maximum concentration (Cmax) in plasma is reached within 1-2 hours and is 5.2 ± 1.2 µg/ml. Pharmacokinetics of levofloxacin is linear in the dose range from 50 mg to 1000 mg. The equilibrium state of plasma concentrations of levofloxacin when receiving 500 mg of levofloxacin 1 or 2 times a day is reached within 48 hours.

On day 10 of oral levofloxacin Biox® 500 mg once daily the Cmax of levofloxacin was 5.7±1.4 µg/ml and the minimum plasma concentration of levofloxacin (concentration before the next dose) (Cmin) was 0.5±0.2 µg/ml.

On day 10 of oral administration of Lefoccin Biox® 500 mg twice daily, the Cmax in plasma was 7.8±1.1 µg/ml and the Cmin was 3.0±0.9 µg/ml.

Distribution
Binding to blood serum proteins is 30-40 %. After single and repeated oral 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.

The penetration into the bronchial mucosa, epithelial lining fluid, alveolar macrophages
. After a single oral administration of 500 mg of levofloxacin, Cmax in bronchial mucosa and epithelial lining fluid were reached within 1 h or 4 h and were 8.3 µg/g and 10.8 µg/mL, respectively, with penetration rates in bronchial mucosa and epithelial lining fluid, compared with plasma concentrations of 1.1-1.8 and 0.8-3, 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 9.94 µg/mL and in alveolar macrophages were 97.9 µg/mL.

Pulmonary tissue penetration
Cmax in pulmonary tissue after oral administration of 500 mg of levofloxacin was approximately 11.3 µg/g and was reached 4-6 h after drug administration with penetration ratios of 2-5, compared to plasma concentrations.

Alveolar fluid penetration
After 3 days of 500 mg of levofloxacin once or twice daily, the Cmax of levofloxacin in alveolar fluid was reached 2-4 hours after drug administration and was 4.0 and 6.7 µg/ml, respectively, with a penetration factor of 1, compared to plasma concentrations.

Bone penetration
Levofloxacin penetrates well into cortical and cancellous bone tissue in both the proximal and distal femur, with a penetration coefficient (bone tissue/plasma) of 0.1-3. Cmax of levofloxacin in the cancellous bone tissue of the proximal femur after oral administration of 500 mg of the drug was approximately 15.1 µg/g (2 hours after drug administration).

Cerebrospinal fluid penetration
Levofloxacin poorly penetrates into the cerebrospinal fluid.

Permeasurement in prostate tissue
After oral administration of 500 mg of levofloxacin once daily for 3 days, the mean concentration of levofloxacin in prostate tissue was 8.7 µg/g and the mean prostate/plasma concentration ratio was 1.84.

Urinary concentrations
The mean urinary concentrations 8-12 h after oral doses of 150 mg, 300 mg 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 desmethyllevofloxacin and levofloxacin N-oxide, which are excreted by the kidneys. Levofloxacin is stereochemically stable and does not undergo chiral transformations.

Elimation
After oral administration levofloxacin is relatively slowly eliminated from the blood plasma (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±29.2 ml/minute.

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

Pharmacokinetics in selected patient groups
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 failure, the pharmacokinetics of levofloxacin are altered. As renal function deteriorates, renal excretion and renal clearance (CIR) decreases and T1/2 increases.

Pharmacokinetics in renal failure after a single oral administration of 500 mg of Lefoccin Biox®.

.

Indications

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

– complicated urinary tract infections and pyelonephritis;
– chronic bacterial prostatitis;
– for the complex treatment of drug-resistant forms of tuberculosis;
– prevention and treatment of anthrax in the airborne route of infection.

Levofloxacin may be used as an alternative to other antimicrobial agents for treatment of the following infectious and inflammatory diseases:

– community-acquired pneumonia;
– complicated skin and soft tissue infections;
– acute bacterial sinusitis;
– exacerbation of chronic bronchitis;
– uncomplicated cystitis.

When using Lefoccin Biox® the official national guidelines for the appropriate use of antibacterial agents as well as the sensitivity of pathogenic microorganisms in a particular country should be taken into consideration (see section “Special indications”).

Active ingredient

Composition

Active ingredient:

Levofloxacin hemihydrate calculated in terms of Levofloxacin 500 mg

Auxiliary substances: Starch, microcrystalline cellulose, Povidone K-30, colloidal silicon dioxide, sodium carboxymethyl starch, talcum, magnesium stearate.

The film coating: Hypromellose-15 thousand, propylene glycol, talc, titanium dioxide, iron oxide red dye, iron oxide yellow dye.

How to take, the dosage

Lefoccin Biox® is taken orally once or twice a day. The tablets should be swallowed without chewing and with plenty of fluid (0.5 to 1 cup). If necessary, the tablets can be crushed into a separating groove.

Lefoccin Biox® can be taken before meals or at any time between meals because food intake does not affect absorption of the drug (see section “Pharmacokinetics”).

Lefoccin Biox® should be taken at least 2 hours before or 2 hours after taking drugs containing magnesium and/or aluminum, iron, zinc or sucralfate (see section “Interaction with other medicinal products”). Taking into account the fact that bioavailability of levofloxacin when administered orally is 99-100%, in case of changing a patient from intravenous levofloxacin infusion to oral Lefoccin Biox® administration it is necessary to continue treatment in the same dose which was used for intravenous infusion (see section “Pharmacokinetics”).

If you accidentally miss one or more doses of Lefoccin Biox®, the next dose should be taken as soon as possible and you should continue taking the drug according to the recommended dosing regimen.

Dosages and duration of treatment
The dosing regimen is determined by the nature and severity of the infection and the sensitivity of the suspected pathogen. The duration of treatment varies depending on the course of the disease.

The recommended dosing regimen and duration of treatment in patients with normal renal function (CK >50 ml/min)
– Complicated urinary tract infections: 2 tablets 250 mg once daily or 1 tablet 500 mg once daily (500 mg levofloxacin respectively) – 7-14 days.

– pyelonephritis: 2 tablets 250 mg once daily or 1 tablet 500 mg once daily (500 mg of levofloxacin, respectively) – 7-10 days.

– Chronic bacterial prostatitis: 2 tablets 250 mg or 1 tablet 500 mg once daily (500 mg of levofloxacin, respectively) – 28 days.

– Complex treatment of drug-resistant forms of tuberculosis: 1 tablet 500 mg 1-2 times per day (500-1000 mg of levofloxacin respectively) – up to 3 months.

– Prophylaxis and treatment of anthrax in case of disseminated infection: 2 tablets 250 mg or 1 tablet 500 mg (500 mg of levofloxacin, respectively) 1 time daily for up to 8 weeks.

– Community-acquired pneumonia: 2 tablets 250 mg or 1 tablet 500 mg 1-2 times daily (respectively 500-1000 mg of levofloxacin) – 7-14 days.

– Complicated skin and soft tissue infections: 2 tablets 250 mg or 1 tablet 500 mg 1-2 times daily (500-1000 mg of levofloxacin, respectively) – 7-14 days.

– Acute bacterial sinusitis: 2 tablets 250 mg or 1 tablet 500 mg 1 time per day (500 mg of levofloxacin, respectively) – 10-14 days.

– Acute exacerbation of chronic bronchitis: 2 tablets 250 mg or 1 tablet 500 mg once daily (500 mg of levofloxacin, respectively) – 7-10 days.

– Uncomplicated cystitis: 1 tablet 250 mg once daily (respectively 250 mg levofloxacin) – 3 days.

Dosing regimen in patients with impaired renal function (CK≤50 ml/min)
Levofloxacin is mainly excreted by the kidneys, so when treating patients with impaired renal function, a reduction in the dose of the drug is required (see table below).

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

The dosing regimen in patients with hepatic impairment
No special dosage adjustment is required in patients with hepatic impairment because levofloxacin is only metabolized to a very minor extent in the liver.

Dosing regimen in elderly patients
No dosing adjustment is required for elderly patients unless creatinine clearance (CK) drops to 50 ml/min or lower.

As with other antimicrobials, treatment with Lefoccin Biox® tablets 250 mg and 500 mg should be continued for at least 48-78 hours after normalization of body temperature or after reliable elimination of the pathogen.

Interaction

Cautious interactions
With drugs containing magnesium, aluminum, iron and zinc, didanosine
Medicines containing bivalent or trivalent cations such as zinc or iron salts (medicinal products for treatment of anemia), magnesium- and/or aluminum-containing drugs (such as antacids), didanosine (only medicinal forms containing aluminum or magnesium as a buffer) should be taken at least 2 hours before or 2 hours after taking Lefoccin Biox®.
Calcium salts have minimal effect on absorption of levofloxacin when taken orally.

With sucralfate
The effect of the drug LefoccinBioxx® is significantly impaired by concomitant use of sucralfate (gastric mucosal protection agent). For patients receiving levofloxacin and sucralfate it is recommended to take sucralfate 2 hours after levofloxacin administration.

With theophylline, phenbufen or similar medicinal products from the group of non-steroidal anti-inflammatory drugs (NSAIDs) that lower the cerebral threshold
No pharmacokinetic interaction of levofloxacin with theophylline was found. However, with concomitant use of quinolones and theophylline, NSAIDs and other drugs that reduce cerebral seizure threshold, a marked decrease in cerebral seizure threshold is possible.
Concentration of levofloxacin with concomitant use of fenbufen increases only by 13%.

With indirect anticoagulants (vitamin K antagonists)
In patients treated with levofloxacin in combination with indirect anticoagulants (e.g., warfarin) an increase in prothrombin time/international normalized ratio (INR) and/or development of bleeding, including severe bleeding was observed. Therefore, regular monitoring of blood clotting parameters is necessary when concomitant use of indirect anticoagulants and levofloxacin.

With probenecid and cimetidine
Caution should be exercised when concomitant use of drugs that impair renal tubular secretion, such as probenecid and cimetidine, and levofloxacin, especially in patients with renal insufficiency. Excretion (renal clearance) of levofloxacin is slowed by 24% by cimetidine and by 34% by probenecid. This is unlikely to be clinically relevant in normal renal function.

With cyclosporine
Levofloxacin increased the 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
Concurrent use of glucocorticosteroids increases the risk of tendon rupture.

With medications that prolong the QT interval
Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving medications that prolong the QT interval (such as antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, neuroleptics).

Other
Clinical and pharmacological studies to investigate possible pharmacokinetic interactions of levofloxacin with digoxin, glibenclamide, ranitidine and warfarin have shown that the pharmacokinetics of levofloxacin with these drugs does not change sufficiently to be of clinical significance.

Special Instructions

Hospital infections caused by Pseudomonas aeruginosa may require combined treatment.

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

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.

Disability (disability) and potential irreversible serious adverse reactions due to fluoroquinolones
Use of fluoroquinolones, including levofloxacin, has been associated with disability and the development of irreversible serious adverse reactions in various body systems that may develop simultaneously in the same patient. Fluoroquinolone-induced adverse reactions include tendonitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and nervous system side effects (hallucinations, anxiety, depression, insomnia, headaches, and confusion). These reactions may occur within a few hours to a few weeks after the start of therapy with levofloxacin. The development of these adverse reactions has been noted in patients of any age or without previous risk factors. If the first signs or symptoms of any serious adverse reactions occur, the use of levofloxacin should be stopped immediately. The use of fluoroquinolones, including levofloxacin, should be avoided in patients who have had any of these serious adverse reactions.

Patients susceptible to seizures
Like other quinolones, levofloxacin should be used with great caution in patients with a predisposition to seizures. Such patients include those with previous lesions of the central nervous system (CNS), such as stroke, severe craniocerebral trauma; patients simultaneously receiving drugs that lower the seizure threshold of the brain (such as theophylline; phenbufen and other non-steroidal anti-inflammatory drugs (see section “Interaction with other medicinal products”). If seizures develop, treatment with levofloxacin should be discontinued.

Pseudomembranous colitis
Diarrhea developing during or after treatment with levofloxacin, especially severe, persistent and/or with blood may be a symptom of pseudomembranous colitis caused by Clostridiumdifficile. If pseudomembranous colitis is suspected, treatment with levofloxacin should be stopped immediately and specific antibiotic therapy (oral vancomycin, teicoplanin or metronidazole) started immediately. Drugs that inhibit intestinal peristalsis are contraindicated.

Tendinitis and tendon rupture
Tendinitis, which rarely occurs with quinolones, can sometimes lead to tendon rupture, including the Achilles tendon, and can be bilateral. This side effect may develop within 48 h of treatment initiation or several months after completion of fluoroquinolone therapy. Elderly patients are more prone to develop tendinitis. In patients taking fluoroquinolones, the risk of tendon rupture may increase with concomitant use of glucocorticosteroids. In addition, patients after transplantation have an increased risk of tendinitis, so caution is recommended when prescribing fluoroquinolones for this category of patients. In patients with impaired renal function, the daily dose should be adjusted based on creatinine clearance (CK). Patients should be advised to remain at rest at the first signs of tendinitis or tendon rupture and consult their physician. If tendonitis or tendon rupture is suspected, treatment with Lefoccin Biox® should be stopped immediately and appropriate treatment of the affected tendon should be initiated, e.g. sufficient immobilization (see “Contraindications” and “Side effects”).

Hypersensitivity reactions
Levofloxacin may cause serious, potentially fatal hypersensitivity reactions (angioedema, anaphylactic shock), even when initial doses are used (see section “Side effects”). Patients should immediately stop taking the drug and consult a physician if they develop.

Serious bullous reactions
Cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been observed with levofloxacin (see section “Adverse effects”). If any skin or mucous membrane reactions develop, the patient should immediately consult a physician and do not continue treatment until he or she has been consulted.

Hepatic and biliary tract disorders
Cases of liver necrosis, including development of hepatic failure with fatal outcome, have been reported when using levofloxacin, mainly in patients with severe underlying diseases, such as sepsis (see section “Side effects”). Patients should be warned to discontinue treatment and seek urgent medical attention if signs and symptoms of liver damage, such as anorexia, jaundice, darkened urine, itching of the skin and abdominal pain appear.

Patients with impaired renal function
Since levofloxacin is mainly excreted through the kidneys, patients with impaired renal function require mandatory renal function monitoring and dosing regimen adjustment (see section “Dosage and administration”). When treating elderly patients it should be borne in mind that renal dysfunction is often observed in this group of patients (see section “Dosage and administration”).

Preventing photosensitization reactions
Although photosensitization by levofloxacin is very rare, in order to prevent its development the patients are not recommended to be exposed to intense sunlight or artificial ultraviolet radiation during the treatment and within 48 hours after treatment with levofloxacin (for example, using a solarium).

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

Long QT interval
Very rare cases of QT interval 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 QT interval prolongation: In patients with uncorrected electrolyte abnormalities (with hypokalemia, hypomagnesemia); with congenital QT interval prolongation syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); with concurrent use of drugs that can prolong the QT interval, such as class IA and III antiarrhythmic agents, tricyclic antidepressants, macrolides, neuroleptics.

The elderly and female patients may be more sensitive to drugs that prolong the QT interval. Therefore fluoroquinolones including levofloxacin should be used with caution in these patients (see sections Caution, Dosage and administration, Adverse effects, Overdosing and Interaction with other medicinal products).

Patients with glucose-6-phosphate dehydrogenase deficiency
Patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency are prone to develop hemolytic reactions when treated with quinolones and this must be taken into account when treating with levofloxacin.

Dysglycemia (hypo- and hyperglycemia)
As with other quinolones, cases of hyperglycemia and hypoglycemia have been observed with levofloxacin. During therapy with levofloxacin dysglycemia more often developed in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic agents (such as glibenclamide) or insulin drugs. When using levofloxacin in such patients the risk of hypoglycemia increases, up to hypoglycemic coma. Patients should be informed about the symptoms of hypoglycemia (confusion, dizziness, “wolfish” appetite, headache, nervousness, palpitations or increased pulse rate, pale skin, sweating, trembling, weakness). If the patient develops hypoglycemia, treatment with levofloxacin should be stopped immediately and appropriate therapy should be started. In these cases it is recommended to switch to therapy with another antibiotic other than fluoroquinolones, if possible. During treatment with levofloxacin in elderly patients and in patients with diabetes mellitus, close monitoring of blood glucose concentration is recommended.

Peripheral neuropathy
In patients taking fluoroquinolones, including levofloxacin, cases of sensory and sensory-motor peripheral neuropathy have been reported, which may have a rapid onset. If the patient develops symptoms of neuropathy, the use of levofloxacin should be discontinued. This minimizes the possible risk of developing irreversible changes.
Patients should be informed to inform their physician of the appearance of any symptoms of neuropathy. Fluoroquinolones should not be administered to patients with a history of peripheral neuropathy.

The exacerbation of pseudoparalytic myasthenia gravis
Fluoroquinolones, including levofloxacin, are characterized by neuromuscular conduction blocking activity and may increase muscle weakness in patients with pseudoparalytic myasthenia gravis. In the post-registration period, adverse reactions, including respiratory failure requiring artificial ventilation, and death have been observed that have been associated with fluoroquinolone use in patients with pseudoparalytic myasthenia gravis. The use of levofloxacin in a patient with an established diagnosis of pseudoparalytic myasthenia gravis is contraindicated (see sections “Contraindications” and “Side effects”).

The use of levofloxacin in humans for this indication is based on the data on the sensitivity of Bacillus anthracis in in vitro studies and in experimental studies conducted on animals, as well as on limited data on the use of levofloxacin in humans. Treating physicians should refer to national and/or international documents that reflect a consensus 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 a single dose. In case of development of any side effects on 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. Caution should be exercised when prescribing the drug in patients with psychosis or patients with a history of mental illness (see section “Caution”).

Aortic aneurysm and aortic dissection
According to epidemiological studies, an increased risk of aortic aneurysm and aortic dissection after fluoroquinolone use has been reported, especially in elderly patients. Therefore, fluoroquinolones should be used only after careful assessment of the benefit-risk ratio and consideration of other therapy options in patients with a family history of aortic aneurysm, or in patients with diagnosed aortic aneurysm and/or aortic dissection or in the presence of other risk factors or conditions, predisposing to the development of an aortic aneurysm or aortic dissection (e.g., Marfan syndrome, Ehlers-Danlos vascular syndrome, Takayasu arteritis, gigantocellular arteritis, Behcet’s disease, arterial hypertension, atherosclerosis) (
If there is sudden pain in the abdomen, chest or back, the patient should immediately see a physician in the emergency department.

Visual disturbances
If any visual disturbances develop, immediate consultation with an ophthalmologist is necessary (see side effects section).

Impact on laboratory tests
In patients taking levofloxacin, urinary opioid determination may lead to false positive results, which should be confirmed by more specific methods.
Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and lead to further false positive results in the bacteriological diagnosis of tuberculosis.

Side effects such as dizziness or vertigo, drowsiness and visual disturbances (see section “Adverse effects”) may decrease the speed of psychomotor reactions and the ability to concentrate. This may pose some risk in situations where these abilities are particularly important (e.g., driving a car, operating machinery, working in an unsteady position).

Contraindications

– hypersensitivity to levofloxacin, other quinolones or to other components of the preparation Lefokzin Biox®;
– epilepsy;
– myasthenia pseudoparalytica (myasthenia gravis) (see sections “Side effects” and “Indications”).
– tendon affection while using fluoroquinolones in anamnesis;
– childhood and adolescence before 18 years of age (due to unfinished skeleton growth because the risk of cartilaginous bone growth zones affection cannot be completely excluded);
– pregnancy (the risk of cartilaginous bone growth zones damage in fetus cannot be completely excluded);
– breastfeeding period (the risk of cartilaginous bone growth zones damage in baby cannot be completely excluded).

– In patients predisposed to the development of seizures (in patients with previous central nervous system (CNS) lesions, in patients simultaneously receiving drugs that reduce the threshold of seizure activity of the brain, such as phenbufen, theophylline) (see.
– In patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency (increased risk of hemolytic reactions during treatment with quinolones).
– In patients with impaired renal function (requires mandatory monitoring of renal function, as well as dosing regimen correction, see. See section “Dosage and administration”).
– In patients with known risk factors for QT interval prolongation: In elderly patients; in female patients, in patients with uncorrected electrolyte disorders (with hypokalemia, hypomagnesemia); with congenital QT interval prolongation syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); with concomitant use of drugs that may prolong the QT interval (antiarrhythmic agents of class IA and III, tricyclic antidepressants, macrolides, neuroleptics) (see sections “Overdose
– In patients with diabetes mellitus receiving oral hypoglycemic drugs such as glibenclamide or insulin drugs (increased risk of hypoglycemia).
– In patients with severe adverse reactions to other fluoroquinolones, such as severe neurological reactions (increased risk of similar adverse reactions when using levofloxacin).
– In patients with psychosis or in patients with a history of mental illness (see section “Special indications”).
– In elderly patients, in patients after transplantation, as well as in concomitant use of glucocorticosteroids (increased risk of tendinitis and tendon rupture) (see section “Cautionary Note”).
– In patients with aortic aneurysm in family history, or in patients with diagnosed aortic aneurysm and/or aortic dissection or in the presence of other risk factors or conditions, predisposing to the development of an aortic aneurysm or aortic dissection (e.g., Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, gigantocellular arteritis, Behcet’s disease, arterial hypertension, atherosclerosis) (see See section “Special Indications”).

Side effects

The frequency of side effects is classified according to World Health Organization (WHO) recommendations:

Data from clinical trials and post-registration use of levofloxacin
Infections and invasions
infrequent: Fungal infections, development of resistance of pathogens.

Blood and lymphatic system disorders
infrequent: leukopenia (decreased number of leukocytes in peripheral blood), eosinophilia (increased number of eosinophils in peripheral blood);
rarely: neutropenia (decrease in the number of neutrophils in peripheral blood), thrombocytopenia (decrease in the number of platelets in peripheral blood);
frequency unknown (post-registration data): pancytopenia (decrease in the number of all form elements in peripheral blood), agranulocytosis (absence or a sharp decrease in the number of granulocytes in peripheral blood), hemolytic anemia.

Immune system disorders
rare: angioedema;
incidence unknown (post-registration data): anaphylactic shock, anaphylactoid shock.
Anaphylactic and anaphylactoid reactions may sometimes develop even after the first dose of the drug.

Metabolic and nutritional disorders
infrequent: anorexia;
rare: hypoglycemia, especially in patients with diabetes (possible signs of hypoglycemia: “wolf” appetite, nervousness, sweating, 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 receiving insulin treatment) (see See section “Special Indications”).

Mental disorders
often: insomnia;
infrequent: anxiety, anxiety, confusion;
rarely: Psychiatric disorders (e.g., hallucinations, paranoia), depression, agitation (agitation), sleep disturbances, nightmares;
frequency unknown (post-registration data): Mental disorders with self-harm behaviors, including suicidal thoughts and suicide attempts, nervousness, memory disorders, delirium (including attention disorders, disorientation).

Overdose

Symptoms of overdose

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

In post-registration use of levofloxacin in overdose, central nervous system effects including confusion, seizures, hallucinations and tremors were observed.

The development of nausea and gastrointestinal mucosal erosions may occur.

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

Treatment

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

Pregnancy use

Similarities