active ingredient: clarithromycin; 1 tablet contains clarithromycin 250mg or 500mg
auxiliary substances: corn starch, corn starch, magnesium stearate, silicon dioxide colloidal, talc, microcrystalline cellulose, sodium croscarmellose, sodium lauryl sulfate, hypromellose, titanium dioxide (E 171) dye: yellow sunset FCF (e 110) (dosage 250 mg) or tartrazin (e 102) (dosage 500 mg) .
Basic physico-chemical properties: film-coated tablets: 250 mg-round shape, from light orange to orange color, with chamfer; 500 mg-oblong shape, yellow color, with chamfer, with notch. On the surface of the tablets allowed marbling. The cross - section view shows two layers.
Pharmacological group. Antimicrobial agents for systemic use. Macrolides.
ATC code J01F A09.
Pharmacodynamics. Clarithromycin is a semi-synthetic antibiotic of the macrolide group. Antibacterial action of clarithromycin is determined by its binding to 50S-ribosomal subunit of sensitive bacteria and inhibition of protein biosynthesis. The drug shows high efficacy in vitro against a broad spectrum of aerobic and anaerobic gram-positive and gram-negative organisms, including nosocomial strains. The minimum suppressive concentrations (MPC) of clarithromycin are usually 2 times lower than MPC of erythromycin. Clarithromycin in vitro is highly effective against Legionella pneumophila and Mycoplasma pneumoniae. Acts bactericidal Helicobacter pylori, clarithromycin activity is higher in neutral pH than in acidic pH. In vitro and in vivo data indicate high efficacy of clarithromycin in clinically significant strains of mycobacteria. Studies in vitro have shown that Enterobacteriaceae and Pseudomonas strains, as well as gram-negative bacteria that do not produce lactose, are insensitive to clarithromycin. Clarithromycin is active in vitro and in clinical practice for most strains of the following microorganisms:
aerobic gram-positive microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes;
aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Legionella pneumophila;
other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae (TWAR), Helicobacter pylori;
Mycobacterium: Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium avium complex (MAC), which includes Mycobacterium avium, Mycobacterium intracellulare.
Beta-lactamases of microorganisms do not affect the effectiveness of clarithromycin.
Most of the methicillin - and oxazolepropionic strains of staphylococci not sensitive to clarithromycin.
Clarithromycin is active in vitro against most strains of such microorganisms, but the clinical efficacy and safety of its use have not been established.
Aerobic gram-positive microorganisms: Streptococcus agalactiae, Streptococcus spp. (groups C, F, G, Viridans)
aerobic gram-negative microorganisms: Bordetella pertussis, Pasteurella multocida;
anaerobic gram-positive microorganisms: Clostridium perfringens, Peptococcus niger, and Propionibacterium acnes;
anaerobic gram-negative microorganisms: Bacteriodes melaninogenicus;
other microorganisms: Chlamydia trachomatis;
spirochetes: Borrelia burgdorferi, Treponema pallidum;
Campylobacter: Campylobacter jejuni.
Clarithromycin has a bactericidal effect against several strains of bacteria: Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae, Helicobacter pylori and Campylobacter spp.
The main metabolite of clarithromycin in the human body is microbiologically active 14-hydroxyclarithromycin (14-on-clarithromycin). For most microorganisms, the microbiological activity of the metabolite is the same or 1-2 times weaker than the parent substance, except for Haemophilus influenzae, against which the effectiveness of the metabolite is 2 times higher. In vitro and in vivo, the parent substance and its main metabolite exhibit either an additive or synergistic effect against Haemophilus influenzae, depending on the strain of the microbe.
Pharmacokinetics. Clarithromycin is rapidly and well absorbed in the digestive tract after oral administration of the drug in the form of tablets. Microbiologically active metabolite 14-ON-clarithromycin is formed by the metabolism of the first pass. Clarithromycin can be used with or without food since food does not affect the bioavailability of clarithromycin tablets. Food slightly delays the onset of clarithromycin absorption and the formation of a 14-on-metabolite. Pharmacokinetics clarithromycin nonlinear, but the equilibrium concentration is achieved within 2 days of the drug. In the application of 250 mg 2 times a day for 15-20% of the unchanged form is excreted in the urine. At a dose of 500 mg 2 times a day withdrawal of the drug with urine intensively (about 36%). 14-on-clarithromycin is the main metabolite excreted in the urine in the amount of 10-15% of the dose. A large part of the remainder of the dose excreted in the feces, mainly in the bile. 5-10% of the parent compound in the feces.
When applying clarithromycin 500 mg 3 times a day clarithromycin concentrations in blood plasma increased compared to a dose of 500 mg 2 times a day.
Clarithromycin concentrations in tissues several times higher than the concentration of the drug in the blood. Elevated concentrations were found in tonsillar and pulmonary tissues. Clarithromycin at therapeutic doses in 80% associated with blood plasma proteins. Clarithromycin penetrates the mucous membrane of the stomach. The content of clarithromycin in the mucous membrane and gastric tissue is higher in the application of clarithromycin with omeprazole than in monotherapy clarithromycin.
Treatment of infections caused by susceptible to clarithromycin microorganisms:
infections of the lower respiratory tract (bronchitis, acute lobar pneumonia and primary atypical pneumonia)
infections of the upper respiratory tract, i.e. nose and throat (pharyngitis, tonsillitis), and infection of the paranasal sinuses;
infections of skin and soft tissues (impetigo, folliculitis, erysipeloid, furunculosis, infected wounds)
disseminated or localized mycobacterial infections caused by Mycobacterium avium or Mycobacterium intracellulare . Localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum or Mycobacterium kansasii ;
eradication of Helicobacter pylori in patients with duodenal ulcer during inhibition of hydrochloric acid secretion (clarithromycin vs. H. pylori at neutral pH is higher than at acid pH)
acute and chronic odontogenic infections.
Hypersensitivity to the components of the drug, to other macrolide antibiotics. The simultaneous use of cisapride, pimozide, terfenadine, astemizole (this can lead to prolonged QT interval and development of cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation and piruetas ventricular tachycardia (torsades de pointes)), ergot alkaloids (e.g. ergotamine, dihydroergotamine (since this may lead to ergotoxine)), inhibitors of HMG-COA reductase inhibitor (statin), which is largely metabolized by CYP3A4 (lovastatin or simvastatin) (increased risk of myopathy, including rhabdomyolysis), oral midazolam. Patients with a history of Qt prolongation or ventricular arrhythmias, including pirouette ventricular tachycardia. Hypokalemia (risk of PROLONGATION of Qt interval). Severe hepatic insufficiency and concomitant renal insufficiency. Concomitant use of clarithromycin (and other strong CYP3A4 inhibitors) with colchicin in patients with renal or hepatic insufficiency.
Interaction with other medicinal products and other forms of interaction
Clarithromycin does not interact with oral contraceptives.
The use of the following drugs is strictly contraindicated due to the possible development of severe consequences of interaction.
Cisapride, pimozide, astemizole, terfenadine. The increase in the level of cisapride, pimozide and