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Сортировка Медицина

Floxaval

levofloxacin 500 mg tablets. 

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International non-proprietary name: Levofloxacin

 

Composition

Active substance: 1 tablet contains equivalent to 250 mg, 500 mg or 750 mg of levofloxacin.

contains levofloxacin hemihydrate.

Excipients: microcrystalline cellulose, crospovidone, copovidone, anhydrous colloidal silicon dioxide,

magnesium stearate.

Coating: titanium dioxide (E171), polydextrose, hypromellose, triacetin, macrogol 8000, yellow

iron oxide (E172), red iron oxide (E172).

 

Description

Light peach or light pink, oblong, film-coated tablets with a score line on both sides.

 

Pharmacotherapeutic group

Antibacterial agent, fluoroquinolone.

ATC code: J01MA12.

 

pharmacological properties

Pharmacodynamics

Levofloxacin is a broad-spectrum antibacterial agent for oral and intravenous use belonging to the fluoroquinolone group. Levofloxacin has a bactericidal effect by affecting the DNA-DNA-gyrase complex (bacterial topoisomerase II) and topoisomerase IV of bacteria.

Microbiology

Levofloxacin is resistant to a wide range of gram-positive and gram-negative microorganisms.

Levofloxacin is usually bactericidal at concentrations close to or slightly above inhibitory concentrations.

In vitro resistance to levofloxacin caused by spontaneous mutations is very rare. However, cross-resistance between levofloxacin and other fluoroquinolones is possible.

Levofloxacin has been shown to affect the following pathogens in both in vitro and clinical studies.

Aerobic gram-positive microorganisms: Enterococcus faecalis, Staphylococcus aureus (methicillin-susceptible strains), Staphylococcus epidermidis (methicillin-susceptible strains), Staphylococcus saprophyticus, Streptococcus pneumoniae (including multidrug-resistant strains), Streptococcus pyogenes;_cc781905-5cde-3194-bb3b -136bad5cf58d_

Aerobic Gram-negative: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens;

Other microorganisms: Chlamydia pneumoniae, Mycoplasma pneumoniae.

The effectiveness of levofloxacin against the following microorganisms has been demonstrated in vitro, but has not been determined in clinical studies:

Aerobic gram-positive: Staphylococcus haemolyticus, Streptococcus (C/F group), Streptococcus (G group), Streptococcus agalactiae, Streptococcus milleri, streptococci from the Viridans group;

Aerobic gram-negative: Acinetobacter baumannii, Acinetobacter lwoffii, Bordetella pertussis, Citrobacter (diversus) koseri, Citrobacter freundii, Enterobacter aerogenes, Enterobacter sakazaki, Klebsiella oxytoca, Morganella morganii, Pantoea (Enterobacter) agglomerans, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas flourescens ;

Anaerobic gram-positive: Clostridium perfringens.

Pharmacokinetics

Levofloxacin is quickly and completely absorbed after oral administration. The maximum concentration in the blood plasma is reached 1-2 hours after oral administration. Absolute bioavailability is about 99-100%. The pharmacokinetics of levofloxacin are linear and predictable in single or repeated oral or intravenous dosing regimens. Steady-state concentrations are achieved 48 hours after taking doses of 500 mg or 750 mg per day. Levofloxacin coated tablets are recommended to be taken 1 hour before or 2 hours after food intake, as co-administration of levofloxacin at a dose of 500 mg with food prolongs the time to reach the maximum concentration by 1 hour, and the maximum concentration in the plasma after taking the tablets is 14%, that of the oral solution. decreases by 25% after admission. Since the pharmacokinetics of levofloxacin are similar and comparable when administered orally and intravenously in the same doses, it is possible to switch from one dosage form to another.

Levofloxacin is stereochemically stable in plasma and urine and is not metabolically converted to its enantiomer. After oral administration, 87% of the dose is excreted unchanged in the urine within 48 hours, and 4% of the dose is excreted in the feces within 72 hours. Levofloxacin undergoes negligible metabolism and is mainly excreted unchanged in the urine. The half-life of levofloxacin is approximately 6-8 hours after oral and intravenous administration of single and repeated doses.  

Instructions for use

Floxaval coated tablets are indicated for the following infections caused by microorganisms sensitive to levofloxacin in adults:

  • Acute sinusitis

  • Exacerbation of chronic bronchitis

  • Community-acquired pneumonia

  • Complicated infections of the urinary system, including pyelonephritis

  • Chronic bacterial prostatitis

  • Skin and soft tissue infections

 

Contraindications

Hypersensitivity to levofloxacin or other antibacterial agents from the quinolone group, as well as auxiliary substances included in their composition.

Epilepsy.

Tendon damage previously associated with the use of an antibacterial agent from the fluoroquinolone group.

Use in children and adolescents.

Pregnancy and lactation period.

 

Special instructions and precautions

Combination with other antibiotics may be required in nosocomial infections caused by P. aeruginosa.

If severe persistent and/or bloody diarrhea occurs during or after treatment, the possibility of Clostridium difficile-associated pseudomembranous enterocolitis should be considered. If this is suspected, treatment with levofloxacin tablets should be stopped immediately and appropriate supportive and/or specific treatment should be initiated without delay. In this clinical situation, drugs that slow intestinal peristalsis are contraindicated.

When using antibacterial agents from the fluoroquinolone group, tendinitis is rarely possible, and Achilles tendon rupture in individual cases. This unpleasant manifestation can appear 48 hours after the start of treatment and can be bilateral. The risk of tendinitis and tendon rupture is higher in elderly patients and those taking corticosteroids. Therefore, it is important to observe such patients during the use of levofloxacin tablets. If tendinitis is suspected, treatment should be discontinued immediately and appropriate treatment (ie, immobilization of the injured tendon) initiated.

As with other fluoroquinolones, Floxaval coated tablets should be used with caution in patients prone to seizures associated with previous head injury, with fenbufen or similar non-steroidal anti-inflammatory drugs, or with anticonvulsant drugs such as theophylline.

It should be used with caution in patients with glucose-6-phosphate dehydrogenase deficiency, as hemolytic reactions have been reported during the use of quinolone antibacterial agents in this group of patients. 

In case of renal insufficiency, the dose of levofloxacin tablets is adjusted taking into account creatinine clearance.

Although photosensitization has been observed very rarely during the use of levofloxacin, patients are not advised to expose themselves to strong sunlight or artificial ultraviolet light such as solariums.

Some of the side effects observed during treatment with levofloxacin tablets may impair the ability to concentrate and react, which may pose a certain risk, especially when driving vehicles and operating machinery. 

As with the use of other quinolones, changes in blood glucose levels, including symptomatic hyper- or hypoglycemia, have been reported in patients with diabetes who are simultaneously using oral hypoglycemic agents (glyburide/glibenclamide) or insulin. Blood glucose levels should be carefully monitored in these patients. If a hypoglycemic reaction occurs in a patient treated with levofloxacin, the treatment should be stopped immediately and appropriate treatment should be instituted.

Serious and sometimes fatal hypersensitivity reactions and/or anaphylactic shock have been reported during treatment with quinolones, including levofloxacin. Such reactions often appear after the first dose. Some reactions may be accompanied by cardiovascular collapse, hypotension/shock, convulsions, loss of consciousness, burning sensation in the skin, angioneurotic edema, dyspnea, urticaria, pruritus, and other serious skin reactions. At the first appearance of skin rash or other symptoms of hypersensitivity, treatment with levofloxacin should be stopped immediately. Severe acute hypersensitivity reactions may require epinephrine, as well as oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and other resuscitative measures, including airway patency.

As during treatment with other antibiotics, levofloxacin, especially long-term use, can lead to an increase in resistant microorganisms. Therefore, the patient's condition is taken into account during retreatment. Appropriate measures should be taken if superinfection occurs during treatment.

Levofloxacin may cause QT prolongation syndrome or torsades de pointes. Do not use if congenital QT interval prolongation or torsades de pointes is diagnosed or suspected.

Care should be taken during its use in patients receiving treatment with vitamin K antagonists.

Methicillin-resistant staphylococci aureus are usually resistant to levofloxacin. Therefore, if methicillin-resistant Staphylococcus aureus is suspected, levofloxacin should not be prescribed without laboratory sensitivity testing.

Levofloxacin should be stopped immediately if vision problems occur during treatment.

 

Interaction with other drugs

Antacids, sucralfate, iron salts, multivitamin preparations

Although complexation with divalent cations is less than with other quinolones, co-administration of levofloxacin tablets with iron salts, sucralfate, multivitamin preparations containing metal cations (such as iron) and zinc, and antacids containing magnesium and aluminum may adversely affect the absorption of levofloxacin from the gastrointestinal tract and may cause lower than expected concentrations. Preparations containing these substances are recommended to be taken 2 hours before or 2 hours after taking levofloxacin tablets.

Theophylline

The interaction of levofloxacin with theophylline has not been reported. The simultaneous use of other quinolones with theophylline can lead to a decrease in the plasma concentration of theophylline, a prolongation of its half-life and an increase in the risk of side effects in this group of patients. When theophylline is used together with levofloxacin, it is important to strictly monitor the theophylline level and make the appropriate correction of the dose. Adverse effects, including seizures, are possible regardless of whether or not the theophylline dose is reduced.

Warfarin

During the conducted clinical studies, interaction between levofloxacin and warfarin was not noted. However, post-marketing studies have reported potentiation of the effects of warfarin when co-administered with levofloxacin. At this time, along with bleeding, prothrombin time was also prolonged. Careful monitoring of prothrombin time, international normalized ratio (INR) and other relevant coagulation tests is important during co-administration of levofloxacin and warfarin. Because of the possibility of bleeding, patients should be monitored.

Cyclosporine

Cmax and Ke  during the combined use of levofloxacin with ciclosporin are slightly reduced, Tmax and t ½ are lower than when they are used separately. However, since the difference is clinically insignificant, there is no need to adjust the dose of either ciclosporin or levofloxacin.   

Digoxin

Interactions between levofloxacin and digoxin were not observed during the conducted studies. For this reason, there is no need to adjust the dose of either levofloxacin or digoxin when levofloxacin is used together with digoxin.

Probenecid and cimetidine

During the conducted clinical studies, when levofloxacin was used with probenecid and cimetidine, the AUC and t½ indicators increased by 27-38% and 30%, and the CL/F and CL indicators decreased by 21-35%, when the rate and amount of absorption did not change compared to the use of levofloxacin alone. Although these indicators are statistically significant, they are not enough to correct the dose of levofloxacin when used together with probenecid and cimetidine.

QSIAV

The risk of CNS stimulation and convulsions may increase when NSAIDS are used together with quinolones, including levofloxacin.

Antidiabetic drugs

Changes in blood glucose levels, including hyperglycemia and hypoglycemia, are possible during the simultaneous use of quinolones with antidiabetic agents, therefore, patients who use antidiabetic agents and levofloxacin are advised to strictly monitor the level of glucose in the blood.

 

Use during pregnancy and lactation

Pregnancy

It should not be used in pregnant women as there are not enough studies.

Lactation period

In the absence of well-controlled studies, it should not be used during lactation.

 

Effects on the ability to drive vehicles and other potentially dangerous mechanisms

Some side effects observed during treatment with levofloxacin (such as dizziness, drowsiness, visual disturbances) can weaken the ability to concentrate and the copy of psychomotor reactions. When those reactions are observed, patients are not recommended to drive vehicles and other mechanisms.

 

Method of use and dosage

Floxaval coated tablets are taken 1 or 2 times a day. The dose is adjusted depending on the type of infection, severity and sensitivity of the suspected pathogen.

The duration of treatment depends on the course of the disease. Floxaval coated tablets are taken inside without chewing, with enough liquid. It is allowed to divide the tablets if there is a need for dose correction. Tablets can be taken 1 hour before or 2 hours after food intake. Tablets should be taken 2 hours before or 2 hours after taking iron salts, antacids or sucralfate to avoid reduced absorption of floxaval coated tablets.

Dosage regimen in patients with normal renal function (creatinine clearance >50 ml/min)

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Additional information on special groups of patients

Patients with renal failure

Since it is excreted through the kidneys, the dose should be adjusted in patients with renal failure.

Dosing regimen depending on the severity of infection in patients with renal failure

(creatinine clearance ≤50 ml/min):

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*No additional dose is required after hemodialysis or continuous ambulatory peritoneal dialysis.

 

Patients with liver failure

Since levofloxacin undergoes negligible hepatic metabolism and is mainly excreted by the kidneys, no dose adjustment is necessary.

Elderly patients

No dose adjustment is necessary in elderly patients with normal renal function.

Pediatric patients

It is not used in children and adolescents under 18 years of age, as articular cartilage damage is not excluded.

 

Side effects

The frequency of occurrence of side effects is classified as follows: very often (≥1/10); often (from ≥1/100 to <1/10); sometimes (≥1/1000 to <1/100); rarely (≥1/10,000 to <1/1,000); very rarely (<1/10000); the frequency of occurrence is unknown (it cannot be determined based on the available data).

Infections and infestations

Sometimes: fungal infections (and proliferation of other resistant microorganisms).

Blood and lymphatic system

Sometimes: leukopenia, eosinophilia.

Rare: neutropenia, thrombocytopenia.

Very rare: agranulocytosis.

Not known: pancytopenia, hemolytic anemia.

To the immune system

Very rare: anaphylactic shock.

Anaphylactic and anaphylactoid reactions can sometimes occur after the first dose.

Not known: hypersensitivity reactions.

To metabolism and nutrition

Sometimes: anorexia.

Very rare: hypoglycemia, especially in those with diabetes.

Mental disorders

Sometimes: insomnia, nervousness.

Rare: psychotic disorders, depression, confusion, alertness, agitation.

Very rare: psychotic reactions with suicidal behavior, hallucinations, including suicidal thoughts or actions.

To the nervous system

Sometimes: dizziness, insomnia, drowsiness.

Rare: paresthesias, tremor, convulsions.

Very rare: sensory and sensorimotor peripheral neuropathies, taste and smell disorders.

To the organ of vision

Very rare: visual impairment.

To the organ of hearing and the labyrinth system

Sometimes: dizziness.

Very rare: hearing impairment.

Not known: tinnitus.

To the cardiovascular system

Rare: tachycardia, hypotension.

Not known: QT interval prolongation on ECG.

To respiratory, thoracic organs and intermural organs

Rare: bronchospasm, dyspnea.

Very rare: allergic pneumonitis.

To the gastrointestinal system

Often: diarrhea, nausea.

Sometimes: vomiting, abdominal pain, dyspepsia, flatulence, constipation.

Rare: bloody diarrhea, which may be a symptom of enterocolitis, including pseudomembranous colitis.

To the hepatobiliary system

Often: increased level of liver enzymes (ALT, AST, alkaline phosphatase, QGT);

Rare: increased level of bilirubin in blood plasma;

Very rare: hepatitis.

Not known: jaundice and severe impairment of liver function, including acute liver failure.

To the skin and subcutaneous adipose tissue

Sometimes: rash, itching.

Infrequently: uvula;

Very rare: angioneurotic edema, photosensitizing reactions.

Not known: toxic epidermal necrolysis, Stevens-Johnson syndrome, multiform exudative erythema, hyperhidrosis. Skin and mucous membrane reactions may occur after the first dose.

To the musculoskeletal system, connective tissue

Rare: damage to tendons, including tendinitis (eg Achilles tendonitis), arthralgia, myalgia.

Very rare: tendon rupture may occur within 48 hours of starting treatment and may be bilateral, muscle weakness (may be of particular importance in patients with myasthenia gravis).

Not known: rhabdomyolysis.

To the kidney and urinary tract

Sometimes: increased level of creatinine in blood plasma.

Very rare: acute renal failure (e.g. associated with interstitial nephritis).

General disorders and local reactions

Sometimes: asthenia.

Very rare: fever.

Not known: pain (including pain in the back, chest and limbs)

Other undesirable manifestations associated with the use of fluoroquinolones:

  • extrapyramidal symptoms and other disorders of muscle coordination;

  • hypersensitivity vasculitis;

  • porphyria attacks in patients with porphyria.

Consult a doctor if unwanted effects occur.

 

Overdose

Levofloxacin tablets have a low potential for acute toxic effects. Expected symptoms of acute overdose include confusion/impairment of consciousness by the central nervous system, dizziness, tremors, convulsions, nausea and erosion of the gastric mucosa by the gastrointestinal system. Prolongation of the QT interval was noted during clinical-pharmacological studies with supratherapeutic doses of levofloxacin.

In case of acute overdose, the patient should be under supervision, an ECG examination should be performed.

Treatment: the stomach should be washed and emptied and symptomatic treatment should be carried out. Antacids can be used to protect the stomach lining. Levofloxacin is not removed by hemodialysis, peritoneal dialysis and permanent ambulatory peritoneal dialysis. There is no specific antidote.

 

Release form

250 mg, 500 mg or 750 mg coated tablets.

5, 7, 10, 50 or 70 tablets, in blisters.

Floxaval 500 mg coated tablets

10 tablets, in a blister. 1 blister is packed in a cardboard box together with a leaflet.

 

Storage conditions 

It should be stored at a temperature not higher than 25°C, in a dry place, protected from light and out of the reach of children.

 

Shelf life

3 years.

Do not use after the expiration date.

 

Condition of release from pharmacy

It is released on the basis of a prescription.

 

Manufacturer and holder of registration card

Delorbis Pharmaceuticals Ltd, Cyprus.

17, Athinon street, Ergates Industrial Area, 2643 Ergates, PO Box 28629, 2081 Lefkosia, Cyprus.

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