Klacid granules d / prig.suspenz.d / pr. Inside 250mg / 5ml, 70ml

• Infectious and inflammatory diseases caused by microorganisms sensitive to clarithromycin: lower respiratory tract infections (such as bronchitis, pneumonia);

• upper respiratory tract infections (such as pharyngitis, sinusitis);

• infections of the skin and soft tissues (such as folliculitis, inflammation of the subcutaneous tissue, erysipelas);

• disseminated or localized mycobacterial infections caused by Mycobacterium avium and Mycobacterium intracellulare; localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum and Mycobacterium kansasii; acute otitis media

For oral administration.

The finished suspension can be taken regardless of food intake, including with milk.

Preparation for use: water is gradually added to the vial to the mark and shaken to obtain 60 ml or 100 ml of a suspension containing 125 mg of clarithromycin in 5 ml.

The finished suspension can be stored for 14 days at room temperature (15 to 30 ? C).

Before each use, the suspension should be shaken well.

The recommended daily dose of clarithromycin suspension for non-mycobacterial infections in children is 7.5 mg / kg 2 times a day (maximum - 500 mg 2 times a day).

The usual duration of treatment is 5-10 days, depending on the pathogen and the severity of the condition.

In children with disseminated or localized mycobacterial infections (M. Avium, M. intracellulare, M. chelonae, M. fortuitum, M. kansasii), the recommended daily dose of clarithromycin is 7.5-15 mg / kg 2 times a day and should not exceed the maximum dose of 500 mg 2 times a day. In children with CC less than 30 ml / min / 1.73 m2, the dose of clarithromycin should be halved

Granules for preparation of suspension for oral administration in the form of granular powder from white to light yellow color, with a fruity aroma; shaking with water forms an opaque suspension from white to light yellow, with a fruity aroma.

5 ml ready-made suspension.

clarithromycin 250 mg

Excipients: carbomer (carbopol 974P) - 150 mg, povidone K90 - 35 mg, silicon dioxide - 10 mg, maltodextrin - 238.1 mg, sucrose - 2276.2 mg, titanium dioxide - 35.7 mg, xanthan gum - 3.8 mg, fruit flavor - 35.7 mg, potassium sorbate - 20 mg, citric acid - 4.24 mg, hypromellose phthalate - 304.2 mg, castor oil - 32.1 mg.

• Hypersensitivity to clarithromycin, macrolides and other components of the drug;

• simultaneous administration of clarithromycin with the following drugs: astemizole, cisapride, pimozide, terfenadine (see the section 'Interaction with other medicinal products');

• simultaneous administration of clarithromycin with ergot alkaloids, for example, ergotamine, dihydroergotamine (see the section 'Interaction with other medicinal products');

• concomitant administration of clarithromycin with oral midazolam (see section 'Interaction with other medicinal products');

• concomitant use of clarithromycin with HMG-CoA reductase inhibitors (statins), which are largely metabolized by the CYP3A4 isoenzyme (lovastatin or simvastatin), due to an increased risk of myopathy, including rhabdomyolysis (see section 'Interaction with other medicinal products');

• concomitant administration of clarithromycin with colchicine (see the section 'Interaction with other medicinal products');

• concomitant use of clarithromycin with ticagrelor or ranolazine; a history of prolongation of the QT interval (congenital or acquired registered prolongation of the QT interval) or ventricular arrhythmias, including ventricular tachycardia of the 'pirouette' type (see sections 'Special instructions' and 'Interaction with other medicinal products');

• hypokalemia (risk of lengthening the QT interval);

• severe hepatic impairment, concurrent with renal impairment;

• a history of cholestatic jaundice / hepatitis, developed with the use of clarithromycin (see section 'Special instructions');

• congenital fructose intolerance, sucrase-isomaltase deficiency, glucose-galactose malabsorption syndrome; porphyria; breastfeeding period

Pharmacodynamics:

Clarithromycin is a semisynthetic antibiotic of the macrolide group and has an antibacterial effect, interacting with the 50S ribosomal subunit of sensitive bacteria and inhibiting protein synthesis. Clarithromycin has shown high in vitro activity against standard and isolated bacterial cultures. It is highly effective against many aerobic and anaerobic, gram-positive and gram-negative microorganisms. Clarithromycin is highly effective in vitro against Legionella pneumophila, Mycoplasma pneumoniae and Helicobacter (Campilobacter) pylori. Enterobacteriaceae and Pseudomonas as well as other non-lactose-degrading Gram-negative bacteria are insensitive to clarithromycin. It has been shown that clarithromycin has an antibacterial effect against the following pathogens:aerobic gram-positive microorganisms - Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes; aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainftuenzae, Moraxella catarrhalis, Legionella pneumophila, Neisseria gonorrhoeae; other microorganisms - Mycoplasma pneumoniae, Chlamydia pneumoniae (TWAR), Chlamydia trachomatis; mycobacteria - Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum; Mycobacterium avium complex (MAC) - a complex including: Mycobacterium avium, Mycobacterium intracellulare. Beta-lactamase production has no effect on clarithromycin activity. Most strains of staphylococci resistant to methicillin and oxacillin are also resistant to clarithromycin. Helicobacter pylori.The sensitivity of H. pylori to clarithromycin was studied on H. pylori isolates isolated from 104 patients prior to initiation of drug therapy. In 4 patients, clarithromycin-resistant strains of H. pylori were isolated, in 2 - strains with intermediate resistance, in the remaining 98 patients, H. pylori isolates were sensitive to clarithromycin. Clarithromycin has an effect in vitro against most strains of the following microorganisms (however, the safety and efficacy of using clarithromycin in clinical practice has not been confirmed by clinical studies and its practical significance remains unclear): aerobic gram-positive microorganisms - Streptococcus agalactiae, Streptococci (groups C, F, G), Viridans group streptococci; aerobic gram-negative microorganisms - Bordetella pertussis, Pasteurella multocida;anaerobic gram-positive microorganisms - Clostridium perfringens, Peptococcus niger, Propionibacterium acnes; anaerobic gram-negative microorganisms - Bacteroides melaninogenicus; spirochetes - Borrelia burgdorferi, Treponema pallidum; campylobacter - Campylobacter jejuni. The main metabolite of clarithromycin in the human body is a microbiologically active metabolite - 14-hydroxyclarithromycin (14-OH-clarithromycin).

The microbiological activity of the metabolite is the same as that of the original substance, or 1Ц2 times weaker in relation to most microorganisms. The exception is H. influenzae, for which the efficiency of the metabolite is 2 times higher. The parent substance and its main metabolite have either an additive or a synergistic effect on H. influenzae in vitro and in vivo, depending on the culture of bacteria. Susceptibility Studies Quantitative methods that require measuring the diameter of the microbial growth inhibition zone provide the most accurate estimates of the sensitivity of bacteria to antimicrobial agents. One of the recommended susceptibility testing uses discs impregnated with 15 µg clarithromycin (Kirby-Bauer diffusion test);the test results are interpreted depending on the diameter of the zone of inhibition of the growth of the microorganism and the value of the MIC of clarithromycin. The MIC value is determined by the method of medium dilution or diffusion into agar. Laboratory tests give one of 3 results: persistent - the infection can be considered as resistant to treatment with this drug; moderately sensitive - the therapeutic effect is ambiguous, and a possible increase in dosage may lead to sensitivity; sensitive - the infection may be considered treatable with clarithromycin.and possibly increased dosage may result in sensitivity; sensitive - the infection may be considered treatable with clarithromycin.and possibly increased dosage may result in sensitivity; sensitive - the infection may be considered treatable with clarithromycin.

Pharmacokinetics:

The drug is rapidly absorbed in the gastrointestinal tract. The absolute bioavailability is about 50%. With repeated administration of a dose of the drug, cumulation was not detected, and the nature of metabolism in the human body did not change. Eating food immediately before taking the drug increased the bioavailability of the drug by an average of 25%. Clarithromycin can be used before or during meals. In vitro In in vitro studies, the binding of clarithromycin to blood plasma proteins is 70% at a concentration of 0.45 to 4.5 ?g / ml. At a concentration of 45 ?g / ml, binding is reduced to 41%, probably as a result of saturation of the binding sites. This is observed only at concentrations that are many times higher than the therapeutic one. Healthy When prescribing clarithromycin at a dose of 250 mg 2 times a day, the maximum Css of clarithromycin and 14-hydroxyclarithromycin in plasma was reached after 2Ц3 days and was 1 and 0,6 ?g / ml, respectively. T1 / 2 of the original drug and its main metabolite was 3Ц4 and 5Ц6 hours, respectively. When clarithromycin was administered at a dose of 500 mg 2 times a day, the maximum Css of clarithromycin and 14-hydroxyclarithromycin in plasma was achieved after taking the 5th dose and was average 2.7-2.9 and 0.88-0.83 ?g / ml, respectively. T1 / 2 of the original drug and its main metabolite were 4.5-4.8 hours and 6.9-8.7 hours, respectively. In the equilibrium state, the level of 14-hydroxyclarithromycin does not increase in proportion to the doses of clarithromycin, and T1 / 2 of clarithromycin and its main metabolite increases with increasing dose. The nonlinear nature of the pharmacokinetics of clarithromycin is associated with a decrease in the formation of 14-OH- and N-demethylated metabolites when using higher doses,which indicates the nonlinearity of clarithromycin metabolism at high doses. With urine, about 37.9% is excreted after taking 250 mg and 46% after taking 1200 mg of clarithromycin, through the intestines - about 40.2 and 29.1%, respectively. Clarithromycin and its 14-OH metabolite are well distributed in tissues and body fluids. After oral administration of clarithromycin, its content in the cerebrospinal fluid remains low (with normal BBB permeability 1Ц2% of the serum level). The content in the tissues is usually several times higher than the content in the blood serum.After oral administration of clarithromycin, its content in the cerebrospinal fluid remains low (with normal BBB permeability 1Ц2% of the serum level). The content in the tissues is usually several times higher than the content in the blood serum.After oral administration of clarithromycin, its content in the cerebrospinal fluid remains low (with normal BBB permeability 1Ц2% of the serum level). The content in the tissues is usually several times higher than the content in the blood serum.

Liver dysfunction

In patients with moderate to severe hepatic impairment, but with preserved renal function, clarithromycin dose adjustment is not required. Css in blood plasma and systemic clearance of clarithromycin do not differ between patients of this group and healthy patients. The Css of 14-hydroxyclarithromycin in people with impaired liver function is lower than in healthy people.

Impaired renal function

In case of impaired renal function, the minimum and maximum levels of clarithromycin in the blood plasma, T1 / 2, AUC of clarithromycin and 14-OH metabolite increase. The elimination constant and urinary excretion decrease. The degree of change in these parameters depends on the degree of impaired renal function.

Elderly patients

In elderly patients, the level of clarithromycin and its 14-OH-metabolite in the blood was higher, and excretion was slower than in the group of young people. It is believed that changes in pharmacokinetics in elderly patients are associated primarily with changes in creatinine clearance and functional state of the kidneys, and not with the age of patients. Patients with mycobacterial infections of Css clarithromycin and 14-OH-clarithromycin in patients with HIV infection who received clarithromycin in usual doses (500 mg 2 times a day) were similar to those in healthy people. However, when using clarithromycin at the higher doses that may be required to treat mycobacterial infections, antibiotic concentrations can be significantly higher than usual. In patients with HIV infection who took clarithromycin at a dose of 1000 and 2000 mg / day in 2 divided doses,Css were usually 2Ц4 and 5Ц10 ?g / ml, respectively. When using the drug in higher doses, an increase in T1 / 2 was observed compared to that in healthy people who received clarithromycin in normal doses. The increase in plasma concentrations and the duration of T1 / 2 when prescribing clarithromycin in higher doses is consistent with the known nonlinearity of the drug's pharmacokinetics. Combined treatment with omeprazole Clarithromycin 500 mg 3 times a day in combination with omeprazole at a dose of 40 mg / day increases the T1 / 2 and AUC0-24 of omeprazole. In all patients receiving combination therapy, compared with those receiving omeprazole alone, there was an 89% increase in AUC0-24 and a 34% increase in T1 / 2 of omeprazole. In clarithromycin, Cmax, Cmin and AUC0-8 increased by 10, 27 and 15%, respectively, compared with the datawhen clarithromycin alone was used without omeprazole. In the steady state, the concentration of clarithromycin in the gastric mucosa 6 hours after administration in the group receiving the combination was 25 times higher than those in the group receiving clarithromycin alone. The concentration of clarithromycin in the stomach tissues 6 hours after taking 2 drugs was 2 times higher than the data obtained in the group of patients who received only clarithromycin.

Application for pregnancy and children:

the use of clarithromycin during pregnancy (especially in the first trimester) is possible only when there is no alternative therapy, and the potential benefit to the mother outweighs the potential risk to the fetus. If necessary, taking during lactation, breastfeeding should be discontinued

Side effects:

allergic reactions: rash; from the nervous system: headache, insomnia; on the part of the skin: intense sweating; from the digestive system: diarrhea, vomiting, dyspepsia, nausea, abdominal pain; from the senses: dysgeusia; on the part of the cardiovascular system: vasodilation; laboratory parameters: abnormal liver function test

Overdose:

in case of an overdose, the unabsorbed drug should be removed from the gastrointestinal tract (gastric lavage, intake of activated charcoal, etc.) and symptomatic therapy should be carried out. Hemodialysis and peritoneal dialysis do not significantly affect the concentration of clarithromycin in serum, which is typical for other drugs of the macrolide group.

Influence on the ability to drive vehicles and mechanisms:

care should be taken when driving vehicles and machinery, given the potential for dizziness, vertigo, confusion and disorientation that may occur while taking this drug

Interaction with other medicinal products:

antiarrhythmic drugs (quinidine and disopyramide): it is possible that ventricular tachycardia of the 'pirouette' type may occur with the combined use of clarithromycin and quinidine or disopyramide. With the combined use of clarithromycin and oral hypoglycemic agents (for example, sulfonylurea derivatives) and / or insulin, severe hypoglycemia may occur. Indirect anticoagulants: when warfarin and clarithromycin are taken together, bleeding is possible, a marked increase in INR and prothrombin time

Special instructions:

possible development of cross-resistance to clarithromycin and other antibiotics of the macrolide group, as well as lincomycin and clindamycin. Clarithromycin should be administered to pregnant women with careful risk-benefit assessment, especially during the first three months of pregnancy.

Carefully:

moderate to severe renal failure; liver failure of moderate and severe degree; patients with coronary artery disease (CHD), severe heart failure, hypomagnesemia, conduction disorders, or clinically significant bradycardia; diabetes mellitus (the drug contains sucrose)