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 infections and inflammatory diseases caused by microorganisms sensitive to levofloxacin:

– community-acquired pneumonia;

– complicated urinary tract infections and pyelonephritis;

– chronic bacterial prostatitis;

– skin and soft tissue infections;

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

– prevention and treatment of anthrax in the airborne route of infection.

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

– acute sinusitis;

– exacerbation of chronic bronchitis;

– uncomplicated cystitis.

When using Leflobact®, the official national guidelines for the appropriate use of antibacterial agents as well as the sensitivity of the pathogenic microorganisms in the specific country should be taken into account (see section “Cautions”).

Active ingredient

Composition

Composition per 1 tablet:

Composition of the core:

The active substance: lsvofloxacin (in the form of levofloxacin hemihydrate) – 250 mg, 500 mg.

Excillary ingredients: calcium stearate, starch 1500, potato starch, cross-spovidone, povidone (polyvinylpyrrolidone low molecular weight medical 12600±2700, povidone K 17), lactose monohydrate, talc, colloidal silicon dioxide (aerosil), microcrystalline cellulose.

The composition of the shell: hypromellose (oxypropyl methylcellulose), macrogol (polyethylene glycol 4000), titanium dioxide (titanium dioxide), tropeolin O.

How to take, the dosage

Leflobact® Tablets 250 mg or 500 mg are taken orally once or twice a day. The tablets should be swallowed without chewing and with plenty of fluid (05 to 1 cup).

The drug can be taken before meals or at any time between meals because eating has no effect on the absorption of the drug (see section on Pharmacokinetics).

The drug should be taken at least 2 hours before or 2 hours after taking preparations containing magnesium and/or aluminum iron zinc or sucralfate (see section “Interaction with other medicinal products”).

Given that the bioavailability of levofloxacin in tablet formulation of Lefloact® is 99-100% if the patient is transferred from intravenous infusion of Lefloact® to tablet formulation, treatment should continue at the same dose that was used for intravenous infusion (see section “Pharmacokinetics and drug interactions”).

If you accidentally miss one or more doses of the drug

If you accidentally miss a dose, you should take the next dose as soon as possible and continue taking Leflobac® 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.

Recommended dosing regimen and duration of treatment in patients with normal renal function (CK > 50 ml/min)

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

– Complicated urinary tract infections: 2 tablets of Lflobakt® 250 mg once daily or 1 tablet of Leflobakt® 500 mg once daily (500 mg of levofloxacin, respectively) – 7-14 days.

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

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

1 Skin and soft tissue infections: 2 tablets Leflobakt® 250 mg or 1 tablet Leflobakt® 500 mg 1 to 2 times a day (500-1000 mg of levofloxacin, respectively) – 7-14 days.

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

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

– Acute sinusitis: 2 tablets Leflobact® 250 mg or 1 tablet Leflobact® 500 mg once daily (500 mg of levofloxacin, respectively) – 10-14 days.

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

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

Dosing regimen in patients with hepatic impairment

There is no need for dosing regimen adjustment in patients with hepatic impairment because levofloxacin is only slightly metabolized in the liver.

The dosing regimen in elderly patients

In elderly patients, the dosing regimen does not need to be adjusted unless the CK falls to 50 ml/min or lower.

Interaction

Interactions requiring caution

With drugs containing magnesium-aluminum-iron and zinc didanosine.

Drugs containing bivalent or trivalent cations such as zinc or iron salts (drugs to treat anemia) magnesium- and/or aluminum-containing drugs (such as antacids) didanosine (only pharmaceutical forms containing aluminum or magnesium as a buffer) should be taken at least 2 hours before or 2 hours after taking Lefloact tablets.

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

With sucralfate

The effect of Leflobac® is significantly impaired by concomitant use of sucralfate (gastric mucosal protection agent). Patients receiving levofloxacin and sucralfate are recommended to take sucralfate 2 hours after levofloxacin administration.

With phenbufen theophylline or similar drugs from the group of non-steroidal anti-inflammatory drugs that lower the threshold of seizure readiness of the brain

Pharmacokinetic interaction of levofloxacin with theophylline was not identified. However, with concomitant use of quinolones and theophylline, nonsteroidal anti-inflammatory drugs and other drugs which decrease cerebral seizure threshold may significantly decrease cerebral seizure threshold.

The concentration of lsvofloxacin is increased by only 13% when concomitant administration of phenbufen.

With indirect anticoagulants (vitamin K antagonists)

In patients treated with lsvofloxacin in combination with indirect anticoagulants (e.g. warfarin) increased prothrombin time/international normalized ratio and/or development of bleeding, including severe. Therefore, regular monitoring of clotting parameters is necessary when concomitant use of indirect anticoagulants and lsvofloxacin.

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.

Elevation (renal clearance) of losvofloxacin is slowed by 24% by cimetidine and 34% by probenecid. This is unlikely to be clinically relevant in normal renal function.

With cyclosporine

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

With glucocorticosteroids

The concomitant use of glucocorticosteroids increases the risk of tendon rupture.

With drugs prolonging the QT interval

Levofloxacin as well as other fluoroquinolones should be used with caution in patients treated with drugs prolonging the QT interval (e.g. antiarrhythmic drugs of class IA and III tricyclic antidepressants macrolides neuroleptics).

Other

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

Special Instructions

Hospital infections caused by Pseudomonas aeruginosa may require combined treatment.

The prevalence of acquired resistance of bacterial strains may vary by geographic region and over time. This requires information about resistance to the drug in a specific country.

For therapy of severe infections or in case of ineffective treatment a microbiological diagnosis with isolation of the causative agent 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 the laboratory tests have not confirmed the sensitivity of this microorganism to levofloxacin.

Patients susceptible to seizures

Levofloxacin, like other quinolones, should be used with great caution in patients with a predisposition to seizures. This includes patients with previous central nervous system injuries such as stroke or severe traumatic brain injury; patients concomitantly taking medications which lower the seizure threshold such as phenbufen or other similar non-steroidal anti-inflammatory drugs or other drugs which lower the seizure threshold such as theophylline (see section “Interaction with other medicinal products”).

Pseudomembranous colitis

Diarrhea during or after treatment with levofloxacin of particularly 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 which inhibit intestinal peristalsis are contraindicated.

Tendinitis

Tendinitis is rarely seen with quinolones including levofloxacin and can sometimes lead to rupture of tendons including the Achilles tendon. This side effect can occur within 48 hours of starting treatment and may be bilateral. Elderly patients are more prone to the development of tendonitis; in patients taking fluoroquinolones the risk of tendon rupture may be increased 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. If tendinitis is suspected, treatment with Leflobact® should be stopped immediately and appropriate treatment of the affected tendon should be initiated, for example, by ensuring adequate immobilization (see sections “Contraindications” and “Side effects”).

Hypersensitivity reactions

Levofloxacin can 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.

Serious bullous reactions

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

Hepatic and biliary tract disorders

Hepatic necrosis including hepatic failure with fatal outcome has been reported when using levofloxacin primarily in patients with severe underlying diseases such as sepsis (see section “Adverse effects”). Patients should be advised to discontinue treatment and seek prompt medical attention if signs and symptoms of liver damage occur, such as anorexia, jaundice, darkened urine, itching and abdominal pain.

Patients with impaired renal function

Because levofloxacin is mainly excreted through the kidneys in patients with impaired renal function it is necessary to monitor renal function and adjust the dosing regimen (see section “Dosage and administration”). When treating elderly patients it should be taken into account that in this group of patients renal dysfunction is often observed (see section “Dosage and administration”).

Preventing photosensitization reactions

While photosensitization by levofloxacin is very rare to prevent its development patients are not recommended during the treatment and within 48 hours after treatment with levofloxacin to be exposed to strong sunlight or artificial ultraviolet radiation without any special need (for example, to visit a solarium).

Superinfection

As with other antibiotics levofloxacin administration especially over a prolonged period of time may lead to increased reproduction of microorganisms (bacteria and fungi) which are not sensitive to it and which may cause changes in the microflora which is normally present in humans. As a result, superinfection may develop. Therefore, it is mandatory to reassess the patient’s condition during treatment and take appropriate measures if superinfection develops during treatment.

Translongation of the QT interval

Very rare cases of prolongation of the QT interval have been reported in patients taking fluoroquinolones including levofloxacin.

With 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 QT interval such as antiarrhythmic agents class IA and III tricyclic antidepressants macrolides neuroleptics.

Elderly patients and female patients may be more sensitive to drugs that prolong the QT interval. Therefore, fluoroquinolones including levofloxacin should be used with caution (see Sections “Caution”, “Dosage and administration”, “Side effects” “Interaction with other medicines”).

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency have a predisposition to develop hemolytic reactions when treated with quinolones and this must be considered when treating with levofloxacin.

Hypo- and hyperglycemia (dysglycemia)

As with other quinolones, cases of hyperglycemia and hypoglycemia have been observed with levofloxacin. During levofloxacin therapy dysglycemia occurred more frequently in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic agents (for example, glibenclamide) or insulin. When using levofloxacin in such patients the risk of hypoglycemia up to hypoglycemic coma increases. Patients should be informed about the symptoms of hypoglycemia (confusion of consciousness, dizziness, “wolfish” appetite, headache, nervousness, palpitations or increased heart rate, pale skin, sweating, shivering, weakness). If the patient develops hypoglycemia, it is necessary to immediately stop treatment with levofloxacin and start an appropriate therapy. In these cases it is recommended to switch to therapy with other antibiotic not fluoroquinolones, if it is possible. During treatment with levofloxacin in elderly patients with diabetes mellitus close monitoring of blood glucose concentration is recommended.

Peripheral neuropathy

In patients taking fluoroquinolones including levofloxacin there have been reported cases of sensory and sensory-motor peripheral neuropathy which may have a rapid onset. If a patient develops symptoms of neuropathy the use of levofloxacin should be discontinued. This minimizes the possible risk of developing irreversible changes.

Pseudoparalytic myasthenia gravis

Fluoroquinolones including levofloxacin are characterized by blocking neuromuscular conduction activity and may increase muscle weakness in patients with pseudoparalytic myasthenia gravis. In the post-marketing period, adverse reactions including pulmonary failure requiring artificial ventilation and death have been observed that have been associated with fluoroquinolones in patients with pseudoparalytic myasthenia gravis. The use of levofloxacin in a patient with a confirmed diagnosis of pseudoparalytic myasthenia gravis is not recommended (see section “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 performed on animals, as well as on limited data on the use of levofloxacin in humans. Treating physicians should refer to national and/or international documents that reflect the consensus view of anthrax treatment.

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 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.

Visual disturbances

In case of any visual disturbances, immediate consultation with an ophthalmologist is necessary (see section on side effects).

Impact on laboratory tests

In patients taking levofloxacin, urinalysis for opiates may give false-positive results and should be confirmed by more specific methods.

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and may lead to subsequent false-negative bacteriologic diagnosis of tuberculosis.

Such side effects of Leflobact® as dizziness or vertigo drowsiness and visual disturbances (see side effects section) may impair psychomotor reactions and ability to concentrate. This may pose some risk in situations where these abilities are particularly important (e.g., driving a car when operating machinery or machines while working in an unsteady position).

Contraindications

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

– lactose intolerance glucose-galactose malabsorption;

– epilepsy;

– myasthenia gravis (myasthenia palsy) (see “Side effects of lefloxacin or other quinolones).

– tendon lesions with a history of fluoroquinolones;

– childhood and adolescence before 18 years of age (due to incomplete skeletal growth because the risk of cartilage growth zones cannot be completely excluded);

Pregnancy (we cannot completely rule out the risk of cartilage problems in the fetus);

Breast-feeding (we cannot completely rule out the risk of cartilage problems in the baby’s growth areas).

– In patients predisposed to the development of seizures (in patients with previous central nervous system (CNS) lesions; in patients simultaneously taking 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 (mandatory monitoring of renal function is required as well as dosage adjustment see sect.

– in patients with known risk factors for QT interval prolongation: in elderly female patients with unadjusted electrolyte abnormalities (with hypokalemia hypomagnesemia); with congenital QT interval prolongation syndrome; with heart disease (heart failure myocardial infarction bradycardia); in concurrent administration of drugs that can prolong the QT interval (class IA and III antiarrhythmic agents tricyclic antidepressants macrolides neuroleptics) (see

In patients with diabetes mellitus receiving oral hypoglycemic agents (e.g., glibenclamide) or insulin medications (increased risk of hypoglycemia);

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

– in patients with psychosis or in patients with a history of mental illness (see “Precautions”).

– in elderly patients after transplantation and with concomitant use of glucocorticosteroids (increased risk of tendinitis and tendon rupture) (see section “Cautionary Note”).

Side effects

The side effects listed below are presented according to the following frequency gradations: very common (≥ 1/10); common (≥ 1/100 < 1/10); infrequent (≥ 1/1000 < 1/100); rare (≥ 1/10000 < 1/1000); very rare (< 1/10000) (including individual reports); frequency unknown (no data available to determine frequency of occurrence).

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

Cardiac disorders: rare – sinus tachycardia palpitations; frequency unknown (postmarketing data) – QT interval prolongation ventricular rhythm disturbances ventricular tachycardia ventricular pirouette tachycardia that may lead to cardiac arrest (see See sections “Overdose” and “Precautions”).

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

Nervous system disorders: frequently – headache dizziness; infrequently – somnolence tremor dysgeusia (perversion of taste); rarely – paresthesia seizures (see section “Special indications”); frequency unknown (post-marketing data) – peripheral sensory neuropathy peripheral sensory-motor neuropathy (see section “Special indications”). Specific Indications) dyskinesia extrapyramidal disorders aguesia (loss of sense of taste) parosmia (disorder of sense of smell especially subjective sense of smell objectively absent) including loss of smell fainting increased intracranial pressure (benign intracranial hypertension psvdotumor brain tumor).

Visual disturbances: rare – visual disturbances such as blurred vision; frequency unknown (post-marketing data) – transient loss of vision uveitis.

Hearing and labyrinth disorders: infrequent – vertigo (feeling of deviation or spinning or own body or surrounding objects); rare – tinnitus; frequency unknown (postmarketing data) – hearing loss loss.

Respiratory system disorders of the thorax and mediastinum: infrequent – shortness of breath; frequency unknown (postmarketing data) – bronchospasm allergic pneumonitis.

Gastrointestinal disorders: frequently – diarrhea vomiting nausea; infrequent – abdominal pain dyspepsia flatulence constipation; frequency unknown (postmarketing data) – hemorrhagic diarrhea which in very rare cases may be a sign of enterocolitis including pseudomembranous colitis (see section “Indications”) pancreatitis.

Repnal and urinary tract disorders: infrequent – increase of serum creatinine concentration; rare – acute renal failure (e.g., due to interstitial nephritis).

Skin and subcutaneous tissue disorders: infrequent – rash itching urticaria hyperhidrosis; frequency unknown (post-marketing data) – toxic epidermal necrolysis Stevens-Johnson syndrome erythema exudative multiforme reactions of photosensitization (hypersensitivity to the sun and ultraviolet radiation (see sect. leukocytoclastic vasculitis stomatitis.

Skin and mucous membrane reactions may sometimes develop even after the first dose of the drug.

Musculoskeletal and connective tissue disorders: infrequent – arthralgia myalgia; rare – tendon involvement including tendinitis (e.g. Achilles tendon) muscle weakness which can be especially dangerous in patients with pseudoparalytic myasthenia gravis (see “Special Precautions”). Rhabdomyolysis – tendon rupture (e.g. Achilles tendon); frequency unknown (post-marketing data). This side effect may occur within 48 h after treatment initiation and may be bilateral (see also section “Special Precautions”)) ligament tear muscle tear arthritis.

Metabolic and nutritional disorders: infrequent – anorexia; rarely – hypoglycemia especially in patients with diabetes mellitus (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 with diabetes taking oral hypoglycemic agents or insulin (see. See section “Special Precautions”).

Infectious and parasitic diseases: infrequent – fungal infections development of resistance of pathogens.

Vascular disorders: rarely – decreased arterial pressure.

General disorders: infrequent – asthenia; rare – pyrexia (increase in body temperature); frequency unknown – pain (including back pain in the chest and extremities).

Disorders of the immune system: rare – angioedema; frequency unknown (post-marketing data) – anaphylactic shock anaphylactoid shock. Anaphylactic and anaphylactoid reactions may sometimes develop even after the first dose of the drug.

Liver and biliary tract disorders: frequent – increased activity of “hepatic” enzymes in the blood (e.g. alanine aminotransferase (ALT) aspartate aminotransferase (ACT)) increased activity of alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT); infrequent – increased blood bilirubin concentration; frequency unknown (post-marketing data) – severe hepatic failure including cases of acute hepatic failure sometimes with fatal outcome especially in patients with severe underlying disease (e.g. patients with sepsis) (see sect. (see section “Special Indications”) hepatitis jaundice.

Mental disorders: frequent – insomnia; infrequent – anxiety anxiety confusion; rare – mental disorders (e.g. hallucinations paranoia) depression agitation (agitation) sleep disorders nightmares; frequency unknown (postmarketing data) – attention disorders disorientation nervousness memory disorders delirium mental disorders with self-injurious behavior including suicidal thoughts and suicide attempts.

Other possible adverse effects related to all fluoroquinolones: very rare attacks of porphyria (a very rare metabolic disease) in patients with porphyria.

Overdose

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

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

Pregnancy use

Similarities