Floracid^® (Tablets) Instructions for Use

ATC Code

J01MA12 (Levofloxacin)

Active Substance

Levofloxacin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Systemic antibacterial agents; quinolone derivatives; fluoroquinolones

Pharmacological Action

A synthetic broad-spectrum antibacterial agent from the fluoroquinolone group, the levorotatory isomer of ofloxacin. Levofloxacin blocks DNA gyrase and topoisomerase IV, disrupts DNA supercoiling and cross-linking of breaks, inhibits DNA synthesis, and causes profound morphological changes in the cytoplasm, cell wall, and membranes of microbial cells.

Levofloxacin is active against most strains of microorganisms both in vitro and in vivo.

Aerobic Gram-positive microorganisms Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus spp. (including Enterococcus faecalis), Listeria monocytogenes, Staphylococcus coagulase-negative methi-S(I), Staphylococcus aureus methi-S, Staphylococcus epidermidis methi-S, Staphylococcus spp. (CNS), Streptococcus groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae peni I/S/R, Streptococcus pyogenes, Streptococcus viridans peni-S/R.

Aerobic Gram-negative microorganisms Acinetobacter spp. (including Acinetobacter baumannii), Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter spp. (including Enterobacter aerogenes, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S/R, Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp. (including Klebsiella oxytoca, Klebsiella pneumoniae), Moraxella catarrhalis (β+/β-), Morganella morganii, Neisseria gonorrhoeae non-PPNG/PPNG, Neisseria meningitidis, Pasteurella spp. (including Pasteurella dagmatis, Pasteurella multocida, Pasteurella canis), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas aeruginosa, Pseudomonas spp. (including Pseudomonas aeruginosa), 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 spp. (including Legionella pneumophila), Mycobacterium spp. (including Mycobacterium leprae, Mycobacterium tuberculosis), Mycoplasma hominis, Mycoplasma pneumoniae, Ricketsia spp., Ureaplasma urealyticum.

Moderately susceptible microorganisms aerobic Gram-positive microorganisms – Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis methi-R, Staphylococcus liaemolyticus methi-R; aerobic Gram-negative microorganisms – Campylobacter jejuni, Campylobacter coli; anaerobic microorganisms – Prevotella spp., Porphyromonas spp.

Microorganisms resistant to levofloxacin aerobic Gram-positive microorganisms – Staphylococcus aureus methi-R, Staphylococcus coagulase-negative methi-R, Corynebacterium jeikeium; aerobic Gram-negative microorganisms – Alcaligenes xylosoxidans; anaerobic microorganisms – Bacteroides thetaiotaomicron; other microorganisms – Mycobacterium avium.

Pharmacokinetics

Levofloxacin is rapidly and almost completely absorbed after oral administration; food intake has little effect on absorption. The absolute bioavailability after oral administration is 99-100%. After a single 500 mg dose, C_max in plasma is reached within 1-2 hours and is 5/2+1/2 µg/ml. The pharmacokinetics of levofloxacin are linear in the dose range from 50 to 1000 mg. C_ss of levofloxacin in plasma when taken at a dose of 500 mg once or twice daily is reached within 48 hours. Plasma protein binding is 30-40%. After single and repeated administration of a 500 mg dose, the V_d of levofloxacin averages 100 L, indicating good penetration of levofloxacin into organs and tissues.

Levofloxacin is metabolized to a small extent (5% of the administered dose). Its metabolites are demethyllevofloxacin and N-oxide levofloxacin, which are excreted by the kidneys. Levofloxacin is eliminated from plasma relatively slowly, T_1/2 is 6-8 hours. Excretion is primarily via the kidneys (more than 85% of the administered dose). The total clearance of levofloxacin after a single 500 mg dose was 175±29.2 ml/min.

In renal insufficiency, the pharmacokinetics of levofloxacin change. As renal function deteriorates, urinary excretion and renal clearance decrease, and T_1/2 increases.

Indications

Treatment of infectious and inflammatory diseases caused by microorganisms sensitive to levofloxacin: community-acquired pneumonia; complicated urinary tract infections and pyelonephritis; chronic bacterial prostatitis; skin and soft tissue infections; for the complex treatment of drug-resistant forms of tuberculosis; prophylaxis and treatment of anthrax with airborne infection.

For the treatment of the following infectious and inflammatory diseases, Levofloxacin may be used as an alternative to other antimicrobial drugs: acute sinusitis, exacerbation of chronic bronchitis; uncomplicated cystitis.

ICD codes

Dosage Regimen

Administer orally with a full glass of water. Take tablets at the same time each day, with or without food. Maintain adequate hydration during treatment.

For community-acquired pneumonia, the recommended dose is 500 mg once daily for 7-14 days.

For complicated urinary tract infections and acute pyelonephritis, the recommended dose is 250 mg once daily for 10 days.

For chronic bacterial prostatitis, the recommended dose is 500 mg once daily for 28 days.

For skin and soft tissue infections, the recommended dose is 500 mg once or twice daily for 7-14 days.

For acute sinusitis, the recommended dose is 500 mg once daily for 10-14 days.

For exacerbation of chronic bronchitis, the recommended dose is 500 mg once daily for 7 days.

For uncomplicated cystitis, the recommended dose is 250 mg once daily for 3 days.

For inhalational anthrax (post-exposure), the recommended dose is 500 mg once daily for 60 days.

For drug-resistant tuberculosis, use as part of a combination regimen; the dose is typically 500-750 mg once daily.

Adjust the dosage regimen in patients with renal impairment. For creatinine clearance 20-49 ml/min, administer 250 mg as an initial dose, then 250 mg every 24 hours. For creatinine clearance 10-19 ml/min, administer 250 mg as an initial dose, then 250 mg every 48 hours.

Do not crush or chew the tablets. Complete the entire prescribed course of therapy, even if symptoms improve. If a dose is missed, take it as soon as remembered unless it is almost time for the next dose. Do not double the dose.

Adverse Reactions

From the cardiovascular system rarely – sinus tachycardia, palpitations, decreased BP; frequency unknown – QT interval prolongation, ventricular arrhythmias, ventricular tachycardia, torsades de pointes, which can lead to cardiac arrest.

From the hematopoietic system infrequently – leukopenia, eosinophilia; rarely – neutropenia, thrombocytopenia; frequency unknown – pancytopenia, agranulocytosis, hemolytic anemia.

From the nervous system often – headache, dizziness; infrequently – drowsiness, tremor, dysgeusia; rarely – paresthesia, convulsions; frequency unknown – peripheral sensory neuropathy, peripheral sensorimotor neuropathy, dyskinesia, extrapyramidal disorders, ageusia, parosmia, including loss of smell, syncope, benign intracranial hypertension.

Mental disorders often – insomnia; infrequently – feeling of anxiety, confusion; rarely – mental disorders (hallucinations, paranoia), depression, agitation, sleep disorders, nightmares; frequency unknown – mental disorders with behavioral disorders causing self-harm, including suicidal thoughts and suicide attempts.

From the organ of vision rarely – visual disturbances such as blurred vision; frequency unknown – transient loss of vision, uveitis.

From the organ of hearing and labyrinthine disorders infrequently – vertigo; rarely – tinnitus; frequency unknown – hearing loss, hearing impairment.

From the respiratory system infrequently – dyspnea; frequency unknown – bronchospasm, allergic pneumonitis.

From the digestive system often – diarrhea, vomiting, nausea; infrequently – anorexia, abdominal pain, dyspepsia, flatulence, constipation; frequency unknown – hemorrhagic diarrhea, which in very rare cases may be a sign of enterocolitis, including pseudomembranous colitis, pancreatitis.

From the liver and biliary tract often – increased ALT, AST, ALP, GGT activity; infrequently – increased blood bilirubin concentration; frequency unknown – severe liver failure, including cases of acute liver failure (sometimes fatal), especially in patients with severe underlying disease (e.g., sepsis); hepatitis, jaundice.

From the urinary tract infrequently – increased serum creatinine concentration; rarely – acute renal failure (e.g., due to interstitial nephritis).

From the skin and subcutaneous tissues infrequently – rash, itching, urticaria, hyperhidrosis; frequency unknown – toxic epidermal necrolysis, Stevens-Johnson syndrome, exudative multiforme erythema, photosensitivity reactions (increased sensitivity to solar and UV radiation), leukocytoclastic vasculitis, stomatitis.

From the immune system rarely – angioedema; frequency unknown – anaphylactic shock, anaphylactoid shock.

From the musculoskeletal system infrequently – arthralgia, myalgia; rarely – tendon damage, including tendinitis (e.g., Achilles tendon), muscle weakness, which can be particularly dangerous in patients with myasthenia gravis; frequency unknown – rhabdomyolysis, tendon rupture (e.g., Achilles tendon), ligament rupture, muscle rupture, arthritis.

From metabolism rarely – hypoglycemia, especially in patients with diabetes mellitus; frequency unknown – hyperglycemia, hypoglycemic coma.

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

General reactions infrequently – asthenia; rarely – pyrexia; frequency unknown – pain (including back, chest, limb pain); very rarely – porphyria attacks in patients already suffering from this disease.

Contraindications

Hypersensitivity to levofloxacin or other quinolones; epilepsy; myasthenia gravis; history of tendon lesions associated with fluoroquinolone use; pregnancy, breastfeeding period; age under 18 years.

With caution in patients predisposed to seizures (in patients with previous CNS lesions, in patients simultaneously receiving drugs that lower the seizure threshold of the brain, such as fenbufen, theophylline; in patients with latent or manifested glucose-6-phosphate dehydrogenase deficiency (increased risk of hemolytic reactions during quinolone treatment); in patients with impaired renal function (mandatory monitoring of renal function and dosage regimen adjustment is required); in patients with known risk factors for QT interval prolongation (in elderly patients; in women; in patients with uncorrected electrolyte disturbances (with hypokalemia, hypomagnesemia); with congenital long QT syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); with simultaneous use of drugs that can prolong the QT interval (class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics); in patients with diabetes mellitus receiving oral hypoglycemic drugs (e.g., glibenclamide) or insulin (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 psychoses or patients with a history of mental illness; in elderly patients, in patients after transplantation, as well as with concomitant use of corticosteroids (increased risk of tendinitis and tendon rupture).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

In case of impaired liver function, no dosage regimen adjustment is required.

Use in Renal Impairment

Should be used with caution in patients with impaired renal function.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Should be used with caution in elderly patients.

Special Precautions

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

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

There is a high probability that methicillin-resistant strains of 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 strains of Staphylococcus aureus, unless laboratory tests have confirmed the sensitivity of this microorganism to levofloxacin.

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

Like other quinolones, Levofloxacin should be used with great caution in patients predisposed to seizures: in patients with previous CNS lesions, such as stroke, severe traumatic brain injury; in patients simultaneously receiving drugs that lower the seizure threshold of the brain, such as fenbufen and other similar NSAIDs, as well as other drugs that lower the seizure threshold, such as theophylline. If seizures develop, levofloxacin treatment should be discontinued.

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

When using quinolones, including Levofloxacin, tendinitis is rarely observed, which can sometimes lead to tendon rupture, including the Achilles tendon. This side effect may develop within 48 hours of starting treatment and may be bilateral. Elderly patients are more prone to developing tendinitis; in patients taking fluoroquinolones, the risk of tendon rupture may increase with the simultaneous use of corticosteroids. In addition, patients after transplantation have an increased risk of developing tendinitis, so caution is recommended when prescribing fluoroquinolones to this category of patients.

Levofloxacin may cause serious, potentially life-threatening hypersensitivity reactions (angioedema, anaphylactic shock), even with the initial doses. Patients should immediately discontinue the drug and consult a doctor.

Cases of severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, have been observed with the use of levofloxacin. If any skin or mucous membrane reactions develop, the patient should immediately consult a doctor and not continue treatment until consultation with a specialist.

Cases of liver necrosis, including the development of fatal liver failure, have been reported with the use of levofloxacin, mainly in patients with severe underlying diseases, such as sepsis. The patient should be warned to discontinue treatment and seek urgent medical attention if signs and symptoms of liver damage appear, such as anorexia, jaundice, dark urine, itching, and abdominal pain.

Since Levofloxacin is excreted primarily by the kidneys, in patients with impaired renal function, mandatory monitoring of renal function and dose regimen adjustment is required. When treating elderly patients, it should be considered that this patient group often has impaired renal function.

Although photosensitivity develops very rarely with the use of levofloxacin, to prevent its development, patients are not recommended to undergo intense sunlight or artificial UV radiation (for example, use tanning beds) during treatment and for 48 hours after finishing treatment with levofloxacin.

As with the use of other antibiotics, the use of levofloxacin, especially over a long period, can lead to the overgrowth of microorganisms (bacteria and fungi) non-susceptible to it, which can cause changes in the microflora normally present in humans, potentially resulting in a superinfection. Therefore, during treatment, a repeated assessment of the patient’s condition should be performed, and if a superinfection develops during treatment, appropriate measures should be taken.

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

Patients with latent or manifested glucose-6-phosphate dehydrogenase deficiency have a predisposition to developing hemolytic reactions when treated with quinolones, which should be taken into account when treating with levofloxacin.

As with the use of other quinolones, cases of hyperglycemia and hypoglycemia have been observed with the use of levofloxacin, usually in diabetic patients receiving simultaneous treatment with oral hypoglycemic drugs (e.g., glibenclamide) or insulin. Cases of hypoglycemic coma have been reported. Blood glucose monitoring is required in diabetic patients.

Cases of sensory and sensorimotor peripheral neuropathy have been reported in patients receiving fluoroquinolones, including Levofloxacin, the onset of which can be rapid. If a patient develops symptoms of neuropathy, the use of levofloxacin should be discontinued. This minimizes the potential risk of irreversible changes. Patients should be informed of the need to report any symptoms of neuropathy to their treating physician. Fluoroquinolones should not be prescribed to patients with a history of peripheral neuropathy.

Fluoroquinolones, including Levofloxacin, are characterized by neuromuscular blocking activity and can exacerbate muscle weakness in patients with myasthenia gravis. Adverse reactions, including respiratory failure requiring ventilatory support and fatal outcome, have been associated with the use of fluoroquinolones in patients with myasthenia gravis. The use of levofloxacin in a patient with an established diagnosis of myasthenia gravis is not recommended.

The use of levofloxacin for the prophylaxis and treatment of inhalational anthrax is based on in vitro susceptibility data for Bacillus anthracis and on limited human use data. The treating physician should refer to national and/or international consensus documents regarding the treatment of anthrax.

Psychotic reactions, including suicidal thoughts/attempts, have been noted in patients taking fluoroquinolones, including Levofloxacin, sometimes after a single dose. If such reactions develop, treatment with levofloxacin should be discontinued and appropriate therapy instituted. The drug should be prescribed with caution to patients with psychosis or patients with a history of mental illness.

If any visual disturbances occur, an immediate consultation with an ophthalmologist is necessary.

In patients using Levofloxacin, urine opiate tests may yield false-positive results, which should be confirmed by more specific methods.

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis, which may subsequently lead to false-negative results in the bacteriological diagnosis of tuberculosis.

Effect on the Ability to Drive and Operate Machinery

Side effects such as dizziness or vertigo, drowsiness, and visual disturbances may reduce psychomotor reactions and the ability to concentrate. This may pose a certain risk in situations where these abilities are particularly important (e.g., when driving a car, operating machinery, or working in an unstable position).

Drug Interactions

Drugs containing divalent or trivalent cations, such as zinc or iron salts, magnesium- and/or aluminum-containing preparations, didanosine (only dosage forms containing aluminum or magnesium as a buffer), are recommended to be taken at least 2 hours before or 2 hours after taking levofloxacin.

The effect of levofloxacin is significantly reduced with the simultaneous use of sucralfate. Patients receiving Levofloxacin and sucralfate are advised to take sucralfate 2 hours after taking levofloxacin.

With the simultaneous use of quinolones and theophylline, NSAIDs and other drugs that lower the seizure threshold of the brain, a pronounced decrease in the seizure threshold of the brain is possible.

In patients receiving Levofloxacin in combination with indirect anticoagulants (e.g., warfarin), an increase in prothrombin time/INR and/or the development of bleeding, including severe bleeding, was observed. Therefore, with the simultaneous use of indirect anticoagulants and levofloxacin, regular monitoring of blood coagulation parameters is necessary.

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

Concomitant use of corticosteroids increases the risk of tendon rupture.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.