Glevo, 500 mg 25 pcs.

Pharmacological action – broad spectrum antimicrobial, bactericidal.

Pharmacodynamics

Glevo (levofloxacin) is a broad spectrum antimicrobial bactericidal agent of fluoroquinolones group. It blocks DNA-enzyme (topoisomerase II) and topoisomerase IV, breaks superspiralization and cross-linking of DNA breaks, inhibits DNA synthesis, causes deep morphological changes in cytoplasm, cell wall and membranes.

The following aerobic gram-positive organisms are sensitive to the drug: Corynebacterium diphtheriae, Enterococcus faecalis, Enterococcus spp, Listeria monocytogenes, Staphylococcus coagulase-negative methicillin-sensitive and methicillin-moderately sensitive, Staphylococcus aureus methicillin-sensitive, Staphylococcus epidermidis methicillin-sensitive, Staphylococcus spp, Streptococci group C and G, Streptococcus agalactiae, Streptococcus pneumoniae penicillin-sensitive/moderately sensitive/resistant, Streptococcus pyogenes and Viridans penicillin-moderately sensitive/resistant; aerobic gram-negative microorganisms: Acinetobacter baumannii, Acinetobacter spp, Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Enterobacter spp, Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampicillin-sensitive/resistant, Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella spp, Moraxella catarrhalis β+/β-, Morganella morganii, Neisseria gonorrhoeae (non-penicillinase producing/penicillinase producing), Neisseria meningitidis, Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida, Pasteurella spp, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Providencia spp, Pseudomonas aeruginosa, Pseudomonas spp., Salmonella spp., Serratia marcescens, Serratia spp.; 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 leprae, Mycobacterium tuberculosis, Mycobacterium spp., Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.

Pharmacokinetics

In oral administration it is quickly and almost completely absorbed (eating has little effect on the speed and completeness of absorption). Bioavailability is 99%. Tmax is 1-2 h; when administered in 250 and 500 mg, Cmax in blood is 2.8 and 5.2 mcg/ml, respectively. The binding to plasma proteins is 30-40%.

It penetrates well into organs and tissues – lungs, bronchial mucosa, sputum, urogenital organs, polymorphonuclear leukocytes, alveolar macrophages.

In the liver, a small portion is oxidized and/or deacetylated. Renal clearance is 70% of total clearance. T1/2 is 6-8 hours. It is eliminated mainly by the kidneys through glomerular filtration and tubular secretion. Less than 5% of levofloxacin is excreted as metabolites. During 24 hours 70% is eliminated unchanged by the kidneys and during 48 hours – 87%; during 72 hours in the intestine it is eliminated 4% of the dose taken orally.

Indications

Urinary tract infections, Skin infections, Sinusitis, Respiratory tract infections, Tuberculosis, Lung inflammation (pneumonia), Boils, Bronchitis, Prostatitis, Haymorrhitis

Bacterial infections sensitive to levofloxacin in adults:

– acute sinusitis;

– exacerbation of chronic bronchitis;

– community-acquired pneumonia;

– Uncomplicated urinary tract infections;

– Complicated urinary tract infections (including acute pyelonephritis);

– chronic bacterial prostatitis;

– skin and soft tissue infections;

– septicemia/bacteremia associated with the above indications;

– abdominal infections;

– complex treatment of drug-resistant forms of tuberculosis.

Active ingredient

Levofloxacin

Composition

1 film-coated tablet contains:

active ingredient:

levofloxacin (as hemihydrate) – 500.00 mg,

excipients: MCC; starch; povidone (K30); crosspovidone; magnesium stearate; avicel pH 101 (MCC),

film coating: hypromellose; macrogol (polyethylene glycol 6000); dibutyl phthalate; talc; titanium dioxide; iron oxide red dye; iron oxide yellow dye (tablets, 500 mg).

How to take, the dosage

Orally, 1 or 2 times a day, without chewing and with plenty of fluid (0.5 to 1 cup), can be taken 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.

Patients with normal or moderately reduced renal function (creatinine Cl >50 ml/min) are recommended the following dosing regimen of the drug.

Sinusitis: 500 mg once daily for 10-14 days.

The exacerbation of chronic bronchitis: 250 or 500 mg once daily for 7-10 days.

Out-of-hospital pneumonia: 500 mg 1 or 2 times a day – 7-14 days.

Uncomplicated urinary tract infections: 250 mg once daily for 3 days.

Prostatitis: 500 mg once a day – 28 days.

Complicated urinary tract infections, including pyelonephritis: 250 mg once daily for 7-10 days.

Infections of the skin and soft tissues: 250-500 mg 1-2 times a day – 7-14 days.

Intra-abdominal infection: 500 mg once daily for 7-14 days (in combination with antibacterials acting on anaerobic flora).

Additional doses are not required after hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

In patients with hepatic impairment no special dose selection is required because levofloxacin is only metabolized to a very minor extent in the liver.

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

As with other antibacterials, treatment with Glevo, film-coated tablets is recommended to continue for at least 48-78 hours after normalization of body temperature or reliable eradication of the pathogen.

If the drug is missed, take the tablet as soon as possible before the next appointment is approaching. Then continue taking the drug according to the regimen.

Interaction

Increases T1/2 of cyclosporine.

The effect of the drug is reduced by drugs that inhibit intestinal motility: sucralfate, aluminum/magnesium-containing antacids and iron salts (a break of at least 2 hours between doses is necessary).

NSAIDs, theophylline increase seizure activity.

The GCS increases the risk of tendon rupture.

Cimetidine and drugs that block tubular secretion slow excretion.

Hypoglycemic drugs: close monitoring of blood glucose levels is necessary because there is a possibility of hyper- and hypoglycemia when used concomitantly with levofloxacin.

Special Instructions

Although levofloxacin is more soluble than other quinolones, patients should be adequately hydrated.

At the time of treatment, sunlight and artificial UV exposure should be avoided to avoid damage to the skin (photosensitization).

In case of signs of tendinitis, pseudomembranous colitis, levofloxacin should be stopped immediately and appropriate therapy should be prescribed.

It should be noted that patients with a history of brain damage (stroke, severe trauma) may have seizures; with insufficiency of glucose-6-phosphate dehydrogenase the risk of hemolysis increases.

Impact on the ability to drive vehicles and operate machinery. During treatment, caution should be exercised when driving motor transport and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Contraindications

– hypersensitivity to levofloxacin and other fluoroquinolones;

– epilepsy;

– tendonitis in previous treatment with quinolones;

– pregnancy;

– lactation period;

– childhood and adolescence under 18 years of age.

With caution: advanced age (high probability of concomitant decreased renal function); glucose-6-phosphate dehydrogenase deficiency.

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; unknown frequency (no data available to determine incidence).

Data from clinical trials of levofloxacin

Cardiac: rare – sinus tachycardia; unknown frequency – QT interval prolongation.

Blood and lymphatic system disorders: 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); unknown frequency – pancytopenia (decrease of all forms in peripheral blood), agranulocytosis (absence or acute decrease of granulocytes in peripheral blood), hemolytic anemia.

Nervous system disorders: Frequent – headache, dizziness; infrequent – somnolence, tremor, dysgeusia (perversion of taste); rare – paresthesia, seizures; unknown frequency – peripheral sensory neuropathy, peripheral sensory-motor neuropathy, dyskinesia, extrapyramidal disorders, loss of taste sensation, parosmia (disorder of sense of smell, especially subjective sense of smell, objectively absent) including loss of smell.

Visually: very rare – visual disturbances such as blurred vision.

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

Respiratory system, chest and mediastinum organs: infrequent – shortness of breath; unknown frequency – bronchospasm, allergic pneumonitis.

Gastrointestinal disorders: frequent – diarrhea, vomiting, nausea; infrequent – abdominal pain, dyspepsia; unknown frequency – hemorrhagic diarrhea which in very rare cases may be a sign of enterocolitis, including pseudomembranous colitis.

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

Skin and subcutaneous tissue disorders: infrequent – rash, pruritus, urticaria, unknown frequency – toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme exudative, photosensitization reactions (hypersensitivity to sunlight and UV radiation), leukocytoclastic vasculitis. Skin and mucous membrane reactions may sometimes develop even after the first dose of the drug.

Skeletal-muscular system and connective tissue disorders: Infrequent – arthralgia, myalgia; rare – tendon involvement, including tendonitis (e.g., Achilles tendon), muscle weakness, which may be particularly dangerous in patients with pseudoparalytic myasthenia gravis; unknown frequency – rhabdomyolysis, tendon rupture (e.g., Achilles tendon). This side effect can be observed within 48 h after treatment start and is bilateral.

Metabolism and nutrition: infrequent – anorexia; rarely – hypoglycemia, especially in patients with diabetes mellitus (possible signs of hypoglycemia: wolf appetite, nervousness, sweating, trembling).

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

Vascular disorders: rarely – decreased BP.

General disorders: infrequent – asthenia; rarely – pyrexia (increase in body temperature).

The immune system: rare – angioedema; unknown frequency – anaphylactic shock, anaphylactoid shock. Anaphylactic and anaphylactoid reactions may sometimes develop even after the first dose of the drug.

Hepatic and biliary tract disorders: frequent – increased activity of liver enzymes in blood (e.g. ALT, AST); infrequent – increased concentration of bilirubin in blood; unknown frequency – severe liver failure, including cases of acute liver failure, especially in patients with severe underlying disease (e.g. sepsis), hepatitis.

Mental disorders: frequent – insomnia; infrequent – anxiety, confusion; rare – mental disorders (e.g., with hallucinations), depression, agitation (agitation), sleep disorders, nightmares; unknown frequency – mental disorders with behavioral disorders with self-harm, including suicidal thoughts and suicide attempts.

Other possible adverse effects relevant to all fluoroquinolones

Very rare – attacks of porphyria (a very rare metabolic disease) in patients already suffering from this disease.

Overdose

Symptoms: nausea, gastrointestinal mucosal erosions, prolonged QT interval, confusion, dizziness, seizures.

Treatment: symptomatic, dialysis is ineffective.

Similarities

Signicef, Tavanic, Oftavix, Flexid, Levolet R, Levofloxacin-Teva, Glevo, Haileflox, Leflobakt, L-Optik Rompharm, Levofloxacin, Korfecin