Levofloxacin-Stada (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

Antimicrobial agent – fluoroquinolone

Pharmacological Action

Levofloxacin is a synthetic broad-spectrum antibacterial drug from the fluoroquinolone group, containing Levofloxacin as the active substance – the levorotatory isomer of ofloxacin.

Levofloxacin blocks DNA gyrase, disrupts DNA supercoiling and cross-linking of breaks, inhibits DNA synthesis, and causes profound morphological changes in the cytoplasm, cell wall, and membranes of bacteria.

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

Aerobic Gram-positive microorganisms: Corynebacterium diphtheriae, Enterococcus spp. (including Enterococcus faecalis), Listeria monocytogenes, Staphylococcus spp. (coagulase-negative, methicillin-sensitive, methicillin-intermediate), including methicillin-sensitive, methicillin-intermediate Staphylococcus aureus, methicillin-sensitive, methicillin-intermediate Staphylococcus epidermidis, Streptococcus spp. groups C and G, Streptococcus agalactiae, penicillin-sensitive/intermediate/resistant Streptococcus pneumoniae, Streptococcus pyogenes, penicillin-intermediate/resistant Streptococcus spp. of the viridans group.

Aerobic Gram-negative microorganisms: Acinetobacter spp., (including Acinetobacter baumannii), Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter spp. (including Enterobacter agglomerans, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, ampicillin-sensitive/resistant Haemophilus influenzae, Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp., Klebsiella oxytoca, Klebsiella pneumoniae, Beta-lactamase-producing and Beta-lactamase-non-producing Moraxella catarrhalis, Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella spp., Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Pseudomonas spp. (including Pseudomonas aeruginosa), Salmonella spp., Serratia spp., including Serratia marcescens.

Anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., 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.

Aerobic Gram-positive microorganisms: Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis (methicillin-resistant strains), Staphylococcus haemolyticus (methicillin-resistant strains).

Aerobic Gram-negative microorganisms: Burkholderia cepacia, Campylobacter jejuni, Campylobacter coli.

Anaerobic microorganisms: Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp., Porphyromonas spp.

Resistant microorganisms.

Aerobic Gram-positive microorganisms: Corynebacterium jeikeium, Staphylococcus aureus (methicillin-resistant strains), other Staphylococcus spp. (coagulase-negative methicillin-resistant strains).

Aerobic Gram-negative microorganisms: Alcaligenes xylosoxidans.

Other microorganisms: Mycobacterium avium.

Pharmacokinetics

Levofloxacin is rapidly and almost completely absorbed after oral administration. Food intake has little effect on the rate and extent of absorption. The bioavailability of 500 mg of levofloxacin after oral administration is almost 100%.

After a single dose of 500 mg of levofloxacin, the maximum concentration is 5.2 µg/ml, the time to reach maximum concentration is 1.3 hours, and the half-life is 6-8 hours.

Plasma protein binding is 30-40%. It penetrates well into organs and tissues: lungs, bronchial mucosa, sputum, genitourinary organs, bone tissue, cerebrospinal fluid, prostate gland, polymorphonuclear leukocytes, alveolar macrophages.

A small part is oxidized and/or deacetylated in the liver. It is excreted from the body mainly by the kidneys through glomerular filtration and tubular secretion. After oral administration, approximately 87% of the administered dose is excreted by the kidneys unchanged within 48 hours, and less than 4% is excreted through the intestines within 72 hours.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to levofloxacin

• Acute sinusitis;
• Exacerbation of chronic bronchitis;
• Community-acquired pneumonia;
• Complicated urinary tract infections (including pyelonephritis);
• Uncomplicated urinary tract infections;
• Chronic bacterial prostatitis;
• Skin and soft tissue infections;
• Intra-abdominal infection;
• Tuberculosis (as part of combination therapy for drug-resistant forms).

ICD codes

Dosage Regimen

Tablets

Orally, 1 or 2 times a day (every 24 or 12 hours).

Do not chew the tablets and drink them with a sufficient amount of liquid (from 0.5 to 1 glass), take before meals or between meals. Doses are determined by the nature and severity of the infection, as well as the sensitivity of the suspected pathogen.

For patients with normal or moderately impaired renal function (creatinine clearance > 50 ml/min), the following dosing regimen is recommended

Acute sinusitis 500 mg once a day – 10-14 days.

Exacerbation of chronic bronchitis 250 mg or 500 mg once a day – 7-10 days.

Community-acquired pneumonia 500 mg 1-2 times a day – 7-14 days.

Uncomplicated urinary tract infections 250 mg once a day – 3 days.

Chronic bacterial prostatitis 500 mg – once a day – 28 days.

Complicated urinary tract infections, including pyelonephritis 250 mg once a day – 7-10 days.

Skin and soft tissue infections 250 mg once a day or 500 mg 1-2 times a day -7-14 days.

Intra-abdominal infection 500 mg once a day – 7-14 days (in combination with antibacterial drugs active against anaerobic flora).

Tuberculosis (as part of combination therapy for drug-resistant forms) 500 mg 1-2 times a day for up to 3 months.

In patients with impaired renal function, the interval between doses of the drug should be increased and a lower dose should be used. With creatinine clearance (CC) 50-20 ml/min, the first dose is 500 mg in the first 24 hours, then 250 mg 1 or 2 times a day, depending on the pathogen, localization and severity of the infection.

After hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), no additional doses are required.

In case of impaired liver function, no special dose adjustment is required, since Levofloxacin is metabolized in the liver to a small extent.

For elderly patients, no change in the dosing regimen is required, except in cases of low creatinine clearance.

Treatment with levofloxacin is recommended to be continued for at least 48-72 hours after normalization of body temperature or after reliable eradication of the pathogen. If a dose is missed, the tablet should be taken as soon as possible without waiting for the next scheduled dose. Then maintain equal time intervals between doses – 24 hours (for a once-daily regimen) or 12 hours (for a twice-daily regimen).

Adverse Reactions

The frequency of a particular side effect is determined using the following table

Skin reactions and general hypersensitivity reactions

Uncommon: itching and redness of the skin.

Rare: general hypersensitivity reactions (anaphylactic and anaphylactoid reactions) with symptoms such as urticaria, bronchospasm and possibly severe suffocation.

In very rare cases: swelling of the skin and mucous membranes (for example, in the face and pharynx), sudden drop in blood pressure and shock; increased sensitivity to sunlight and ultraviolet radiation (see Special Instructions); allergic pneumonitis; vasculitis.

In isolated cases: severe skin rashes with blistering, for example, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome) and exudative multiform erythema. General hypersensitivity reactions may sometimes be preceded by milder skin reactions. The reactions mentioned above may develop after the first dose within a few minutes or hours after administration of the drug.

Effect on the gastrointestinal tract and metabolism

Common: nausea, diarrhea, dysbacteriosis.

Uncommon: loss of appetite, vomiting, abdominal pain, indigestion.

Rare: hemorrhagic diarrhea (bloody diarrhea), which in very rare cases may be a sign of intestinal inflammation and even pseudomembranous colitis (see Special Instructions).

Very rare: drop in blood sugar levels (hypoglycemia), which is of particular importance for patients suffering from diabetes mellitus; possible signs of hypoglycemia: “ravenous” appetite, nervousness, sweating, trembling. Experience with other quinolones indicates that they can cause exacerbation of porphyria (a very rare metabolic disease) in patients already suffering from this disease. A similar effect cannot be excluded when using the drug Levofloxacin.

Effect on the nervous system

Uncommon: headache, dizziness and/or numbness, vertigo (sensation of deviation or spinning of one’s own body or surrounding objects), drowsiness, sleep disturbances, insomnia.

Rare: depression, anxiety, psychotic reactions (e.g., with hallucinations), paresthesia, tremor, psychomotor agitation, agitation, confusion, convulsions, anxiety, fear.

Very rare: dysgeusia (taste perversion), loss of taste sensation, parosmia (disorder of smell sensation, especially a subjective sensation of an objectively absent smell), including loss of smell, visual and hearing impairments, hearing loss, tinnitus, decreased tactile sensitivity.

Frequency not known: peripheral sensory neuropathy, peripheral sensorimotor neuropathy, dyskinesia, nightmares, extrapyramidal disorders, mental disorders with behavioral disorders with self-harm, including suicide attempts.

Effect on the cardiovascular system

Rare: palpitations, decreased blood pressure. Very rare: (shock-like) vascular collapse. In isolated cases: QT interval prolongation.

Effect on muscles, tendons and bones

Rare: tendon lesions (including tendinitis), joint and muscle pain.

Very rare: tendon rupture (e.g., Achilles tendon); this side effect may occur within 48 hours after the start of treatment and may be bilateral (see Special Instructions); muscle weakness, which is of particular importance for patients with pseudoparalytic myasthenia gravis.

In isolated cases: muscle lesions (rhabdomyolysis).

Effect on the liver and kidneys

Common: increased activity of liver enzymes (e.g., ALT and AST).

Rare: increased levels of bilirubin and creatinine in the blood serum (a sign of impaired liver or kidney function).

Very rare: hepatic reactions (e.g., liver inflammation); deterioration of kidney function up to acute renal failure, for example, due to allergic reactions (interstitial nephritis).

Frequency not known: severe liver failure, including cases of acute liver failure, especially in patients with severe underlying disease (e.g., sepsis).

Effect on the blood

Uncommon: increased number of eosinophils, decreased number of leukocytes.

Rare: neutropenia; thrombocytopenia, which may be accompanied by increased bleeding, hemorrhages.

Very rare: agranulocytosis and the development of severe infections (persistent or recurrent fever, deterioration of general condition).

In isolated cases: hemolytic anemia; pancytopenia.

Other side effects

Uncommon: general weakness (asthenia).

Very rare: fever.

Any antibiotic therapy can cause changes in the microflora (bacteria and fungi) that are normally present in humans. For this reason, increased proliferation of bacteria and fungi resistant to the antibiotic used (secondary infection and superinfection) may occur, which in rare cases may require additional treatment.

Contraindications

• Epilepsy;
• Tendon lesions during previous treatment with quinolones;
• Childhood and adolescence (up to 18 years);
• Pregnancy and lactation;
• Hypersensitivity to levofloxacin, to other quinolones, other components of the drug.

With caution

Predisposition to convulsive reactions (cerebral vascular atherosclerosis, cerebrovascular accidents (including history), organic diseases of the central nervous system), renal failure, congenital long QT syndrome, heart failure, myocardial infarction, bradycardia, electrolyte imbalance (hypokalemia, hypomagnesemia), elderly age (over 65 years), diabetes mellitus, severe myasthenia gravis, psychoses and other mental disorders (including history), hepatic porphyria, simultaneous use of drugs that prolong the QT interval (class IA and III antiarrhythmics, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal agents, imidazole derivatives, some antihistamines, including astemizole, terfenadine, ebastine), simultaneous use of drugs that lower the seizure threshold (fenbufen, theophylline), cimetidine, probenecid, glucose-6-phosphate dehydrogenase deficiency.

Use in Pregnancy and Lactation

The use of the drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

In case of impaired liver function, no special dose adjustment is required, since Levofloxacin is metabolized in the liver to a small extent.

Use in Renal Impairment

In patients with impaired renal function, the interval between doses of the drug should be increased and a lower dose should be used. With CC 50-20 ml/min, the first dose is 500 mg in the first 24 hours, then 250 mg 1 or 2 times a day, depending on the pathogen, localization and severity of the infection.

After hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), no additional doses are required.

Pediatric Use

Contraindication: childhood and adolescence (up to 18 years).

Geriatric Use

For elderly patients, no change in the dosing regimen is required, except in cases of low creatinine clearance.

When treating elderly patients, it should be borne in mind that patients in this group often suffer from impaired renal function.

Special Precautions

Levofloxacin should not be used to treat children and adolescents due to the probability of damage to the articular cartilage.

Since Levofloxacin is excreted mainly by the kidneys, in patients with impaired renal function, mandatory monitoring of renal function and dosage regimen adjustment is required.

When treating elderly patients, it should be borne in mind that patients in this group often suffer from impaired renal function.

Very rare cases of QT interval prolongation have been reported in patients receiving fluoroquinolones, including Levofloxacin. Caution should be exercised when using fluoroquinolones, including Levofloxacin, in patients with known risk factors for QT interval prolongation: elderly age; electrolyte imbalance (hypokalemia, hypomagnesemia); congenital long QT syndrome; myocardial infarction, heart failure, bradycardia; simultaneous use of drugs that can prolong the QT interval.

In patients with diabetes mellitus receiving oral hypoglycemic agents, such as glibenclamide, or insulin, the use of quinolones increases the risk of hypoglycemia. Such patients require blood glucose monitoring.

Sensory and sensorimotor neuropathy has been observed 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.

Levofloxacin should be used with caution in patients with pseudoparalytic myasthenia gravis.

In severe pneumonia caused by Streptococcus pneumoniae, Levofloxacin may not provide optimal therapeutic effect. Hospital-acquired infections caused by certain pathogens (Pseudomonas aeruginosa) may require combination therapy.

During treatment with Levofloxacin-Stada, a seizure may develop in patients with previous brain damage, caused, for example, by stroke or severe trauma. Seizure threshold may also increase with simultaneous use of fenbufen, similar non-steroidal anti-inflammatory drugs or theophylline (see “Interactions”).

Although photosensitivity is very rarely observed with the use of levofloxacin, to avoid it, patients are not recommended to be exposed to strong sunlight or artificial ultraviolet radiation.

If pseudomembranous colitis is suspected, Levofloxacin should be discontinued immediately and appropriate treatment initiated. In such cases, drugs that inhibit intestinal motility should not be used.

Tendinitis (primarily inflammation of the Achilles tendon), rarely observed with the use of Levofloxacin, can lead to tendon rupture. Elderly patients are more prone to tendinitis. Treatment with glucocorticosteroids (“cortisone drugs”) is likely to increase the risk of tendon rupture. If tendinitis is suspected, treatment with Levofloxacin should be stopped immediately and appropriate treatment of the affected tendon should be initiated, for example, by ensuring its rest (see “Contraindications” and “Side Effects”).

Patients with glucose-6-phosphate dehydrogenase deficiency (a hereditary metabolic disorder) may react to fluoroquinolones with destruction of red blood cells (hemolysis). In this regard, treatment of such patients with levofloxacin should be carried out with caution.

Such side effects of Levofloxacin-Stada as dizziness or numbness, drowsiness and visual disturbances (see also the section “Side Effects”) can slow down psychomotor reactions and the ability to concentrate. This may pose a certain risk in situations where these abilities are of particular importance (for example, when driving a car, when servicing machines and mechanisms, when performing work in an unstable position). Alcohol consumption is not recommended during treatment with levofloxacin.

Overdose

Symptoms nausea, erosive lesions of the gastrointestinal mucosa, QT interval prolongation, confusion, dizziness, convulsions.

Treatment symptomatic, gastric lavage, intake of antacids; dialysis is ineffective. A specific antidote is not known.

Drug Interactions

There are reports of a significant decrease in the seizure threshold with the simultaneous use of quinolones and substances that, in turn, can lower the cerebral seizure threshold. The same applies to the simultaneous use of quinolones and theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs (agents for the treatment of rheumatic diseases).

The effect of Levofloxacin is significantly reduced when used simultaneously with sucralfate (an agent for protecting the gastric mucosa), drugs that inhibit intestinal motility. The same thing happens with the simultaneous use of magnesium- or aluminum-containing antacid agents (drugs for the treatment of heartburn and gastralgia), as well as iron salts (agents for the treatment of anemia). Levofloxacin should be taken at least 2 hours before or 2 hours after taking these agents. No interaction was found with calcium carbonate.

With simultaneous use with indirect anticoagulants, coumarin derivatives, vitamin K antagonists, monitoring of INR (international normalized ratio) is necessary.

With simultaneous use of drugs that prolong the QT interval (class IA and III antiarrhythmics, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungals, imidazole derivatives, some antihistamines, including astemizole, terfenadine, ebastine), QT prolongation is possible.

The excretion (renal clearance) of levofloxacin is slightly slowed down by the action of cimetidine and probenecid. It should be noted that this interaction has practically no clinical significance. Nevertheless, with the simultaneous use of drugs such as probenecid and cimetidine, which block a certain excretion pathway (tubular secretion), treatment with levofloxacin should be carried out with caution. This applies primarily to patients with reduced renal function.

Levofloxacin slightly increases the half-life of cyclosporine. The use of glucocorticosteroids increases the risk of tendon rupture.

Storage Conditions

In a dry place, protected from light, at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

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.