Levolet R, 5 mg/ml 100 ml

Pharmacological action – broad spectrum antimicrobial, bactericidal.

Pharmacodynamics

Blocks DNA-Giase (topoisomerase II) and topoisomerase IV, breaks superspiralization and cross-linking of DNA breaks, inhibits DNA synthesis, causes profound morphological changes in the cytoplasm, cell wall and membranes.

Levofloxacin is active against the following strains of microorganisms, both in vitro and in vivo.

Sensitive microorganisms (minimum suppressive concentration – MAC – ≤2 mg/ml)

Aerobic Gram-positive microorganisms: Corynebacterium diphtheriae, Enterococcus faecalis, Enterococcus spp, Listeria monocytogenes, Staphylococcus coagulase-negative methi-S(I) (methicillin-sensitive/moderately sensitive strains), Staphylococcus aureus methi-S (methicillin-sensitive strains), Staphylococcus epidermidis methi-S (methicillin-sensitive strains), Staphylococcus spp. (CNS – leukotoxin-containing), Streptococci of groups C and G (including Streptococcus agalactiae, Streptococcus pneumoniae peni-S/I/R (penicillin-sensitive / moderately sensitive / resistant strains), Streptococcus pyogenes, Viridans streptococci peni-S/R (penicillin-sensitive / resistant strains).

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

Moderately susceptible microorganisms (MPC ≥4 mg/l)

Aerobic Gram-positive microorganisms: Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis methi-R (methicillin-resistant strains), Staphylococcus haemolyticus methi-R (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 (MPC ≥8 mg/L)

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

Aerobic Gram-negative microorganisms: Alcaligenes xylosoxidans.

Other microorganisms: Mycobacterium avium.

Pharmacokinetics

The pharmacokinetics of levofloxacin with single and multiple administration of the drug has a linear character. Plasma concentration profile of levofloxacin after intravenous administration is similar to that of tablets. Therefore, oral and intravenous routes of administration may be considered interchangeable.

After single and multiple intravenous administration at a dose of 500 mg, the Vd of levofloxacin is 89 to 112 liters. After an hour’s infusion of 500 mg levofloxacin in healthy volunteers the mean value of Cmax in plasma was (6.2±1) mcg/ml, Tmax was (1±0.1) hours.

In oral administration it is quickly and almost completely absorbed (food intake has little effect on the speed and completeness of absorption). Bioavailability – 99%. Tmax is 1-2 h; when administered in 250 and 500 mg the average Cmax 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.

Extracted from the body mainly by the kidneys through glomerular filtration and tubular secretion. After a single 500 mg intravenous injection the T1/2 is (6.4±0.7) hours, when taking tablets the T1/2 is 6-8 hours. Renal clearance is 70% of total clearance. Less than 5% of levofloxacin is excreted as metabolites. In urine over 24 hours 70% of the administered dose is found unchanged, and over 48 hours – 87%. In feces over a period of 72 hours 4% of the administered dose is detected. In renal insufficiency, the decrease in clearance of the drug and its excretion by the kidneys depends on the degree of decrease in Cl creatinine.

Indications

Infectious-inflammatory diseases of mild to moderate severity, caused by pathogens sensitive to the drug:

– community-acquired pneumonia;

– drug-resistant forms of tuberculosis (as part of complex therapy);

– Complicated kidney and urinary tract infections, including pyelonephritis;

– Uncomplicated urinary tract infections;

– Prostatitis, including bacterial

– septicemia/bacteremia associated with the above indications;

– intra-abdominal infection.

Active ingredient

Composition

How to take, the dosage

Internal, intravenous.

The doses are determined by the nature and severity of the infection and the sensitivity of the suspected pathogen.

For both dosage forms

In community-acquired pneumonia: 500 mg 1-2 times a day. The course of treatment is 7-14 days.

Uncomplicated urinary tract infections: 250 mg once daily. The course of treatment is 3 days.

Complicated urinary tract infections (including pyelonephritis): 250 mg once daily. The course of treatment is 7-10 days.

Prostatitis, including bacterial: 500 mg once daily. The course of treatment is 28 days.

Septicemia/bacteremia: 500 mg 1 to 2 times a day. The course of treatment is 10-14 days.

Intra-abdominal infection: 500 mg once daily. The course of treatment is 7-14 days, in combination with antibacterials acting on anaerobic flora.

In combination therapy of drug-resistant forms of tuberculosis: 500 mg once or twice a day (500-1000 mg of levofloxacin daily), depending on the disease severity and the therapy scheme applied. The course of treatment is up to 3 months.

In patients with normal or mildly impaired renal function (Cl creatinine >50 ml/min) dosing regimen adjustment is not required.

Patients with impaired renal function require dosing adjustment depending on creatinine Cl value.

Performance in impaired liver function. No special dosage formulation is required in patients with hepatic impairment because levofloxacin is only slightly metabolized in the liver.

Levolet®P in the form of infusion solution is administered by IV dropwise, slowly. The duration of the drug administration in dose of 500 mg (100 ml of infusion solution/500 mg of levofloxacin) should be at least 60 min. Levolet®P solution is compatible with the following infusion solutions: 0.9% sodium chloride solution, 5% dextrose solution, 2.5% Ringer’s solution with dextrose, combined solutions for parenteral nutrition (aminoacids, carbohydrates and electrolytes). The drug solution should not be mixed with heparin or solutions with an alkaline reaction (e.g. sodium bicarbonate solution).

In case of positive dynamics of the clinical condition of the patient after a few days of treatment it is possible to switch from IV drops administration to oral administration of the drug at the same dose.

The duration of treatment, depending on the course of the disease, is no more than 14 days (except for bacterial prostatitis). As with other antibiotics, treatment with Levolet®P is recommended to be continued for at least 48-72 hours after body temperature normalization or after reliable eradication of the pathogen.

Interaction

Increases the T1/2 of cyclosporine.

NSAIDs, theophylline increase seizure activity, GCS increase the risk of tendon rupture.

Cimetidine and drugs that block tubular secretion slow excretion.

In addition for film-coated tablets

The completeness of absorption is reduced by drugs that inhibit intestinal motility, sucralfate, antacid drugs containing aluminum and magnesium salts, as well as drugs containing iron salts (a break of at least 2 hours between doses is necessary).

In addition for infusion solution

When used concomitantly with indirect anticoagulants (including warfarin) it is necessary to control blood clotting.

Special Instructions

Treatment with levofloxacin is recommended to continue for at least 48-72 hours after normalization of body temperature or after reliable eradication of the pathogen. During treatment it is necessary to avoid sunlight and artificial UV irradiation in order to avoid skin damage (photosensitization). In case of signs of tendinitis, pseudomembranous colitis levofloxacin should be immediately discontinued.

It should be noted that patients with a history of brain damage (stroke, severe traumatic brain injury) may experience seizures; with glucose-6-phosphate dehydrogenase deficiency there is a risk of hemolysis.

In severe pneumonia caused by Streptococcus pneumoniae, levofloxacin may be ineffective.

Intravenous administration should be carried out for at least 60 minutes; palpitations and transient BP decrease may be noted during administration; collapse may occur rarely. In case of marked BP decrease levofloxacin administration should be stopped. If pseudomembranous colitis due to Clostridium difficile is suspected, treatment with levofloxacin should be discontinued and an appropriate therapy should be prescribed.

Impact on the ability to drive a car or perform work requiring an increased rate of physical and mental reactions. During treatment, caution should be exercised when driving motor vehicles and engaging in other potentially hazardous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

– hypersensitivity to excipients of the drug;

– epilepsy;

– history of tendon lesions associated with taking quinolones;

– childhood and adolescence under 18 years of age;

– pregnancy;

– lactation (breastfeeding) period.

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

Side effects

The incidence of side effects is classified according to frequency of occurrence: often (1-10%); sometimes (less than 0.1-1%); rarely (0.01-0.1%); very rarely (less than 0.01%), including individual reports.

The blood system and blood forming organs: sometimes – eosinophilia, leukopenia; rarely – neutropenia, thrombocytopenia; very rarely – marked agranulocytosis; in some cases – hemolytic anemia, pancytopenia.

The digestive system: frequently – nausea, diarrhea, increased ALT, ACT, dysbiosis; sometimes – loss of appetite, vomiting, abdominal pain, digestive disorders, hyperbilirubinemia; rarely – diarrhea with blood (in very rare cases it can be a sign of intestinal inflammation or pseudomembranous colitis); very rarely – hepatitis.

Systems: rare – tachycardia, decreased blood pressure; very rare – vascular collapse; in rare cases – prolongation of QT interval.

The central and peripheral nervous system: sometimes – headache, dizziness, stiffness of movements, drowsiness, sleep disturbance; rarely – paresthesias in the hands, trembling, anxiety, states of fear, seizures, confusion; very rarely – psychotic reactions like hallucinations and depression, movement disorders.

Sensory organs: very rarely – disorders of vision and hearing, smell, taste and tactile sensitivity.

Metabolism disorders: very rarely – hypoglycemia (manifested by a sharp increase in appetite, nervousness, sweating, trembling); in individual cases – exacerbation of porphyria.

Urinary system disorders: rarely – hypercreatininemia; very rarely – deterioration of renal function up to and including acute renal failure (e.g., due to allergic reactions – interstitial nephritis).

Muscular system disorders: rare – tendon disorders (including tendinitis), joint and muscle pain; very rare – tendon ruptures (including Achilles, which may be bilateral and appear within 48 hours after treatment start), muscle weakness (of particular importance for myasthenic patients); rhabdomyolysis in rare cases.

Allergic reactions: sometimes – itching and redness of the skin; rarely – anaphylactic and anaphylactoid reactions (manifested by symptoms such as urticaria, bronchospasm and possible severe choking, and in rare cases – swelling of the face, larynx); very rarely – a sharp decrease in BP, anaphylactic shock; in some cases – Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome) and erythema exudative multiforme, allergic pneumonitis, vasculitis.

Dermatological reactions: very rare – photosensitization.

Others: sometimes – asthenia; very rare – persistent fever, development of superinfection.

Additional for infusion solution

Local reactions: often – pain, redness, phlebitis.

Overdose

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

Treatment: symptomatic, dialysis is ineffective.

Similarities