Product Overview
Structure
1 coated tablet contains:
active substance:
clarithromycin 500 mg,
Excipients:
croscarmellose sodium,
sodium lauryl sulfate,
microcrystalline cellulose,
povidone (medical polyvinylpyrrolidone low molecular weight),
magnesium stearate,
colloidal silicon dioxide (aerosil),
hypromellose (hydroxypropyl methylcellulose),
macrogol (polyethylene glycol 6000),
titanium dioxide
hyprolose (hydroxypropyl cellulose),
quinoline yellow dye,
vanillin.
pharmachologic effect
Pharmacotherapeutic group:
antibiotic, macrolide.
Pharmacodynamics:
Clarithromycin is a second-generation bacteriostatic antibiotic from the broad-spectrum macrolide group. It disrupts the synthesis of protein of microorganisms (binds to the 50S subunit of the ribosome membrane of the microbial cell). It acts on extra- and intracellularly located pathogens. Active against:
Streptococcus agalactiae (Streptococcus pyogenes, Streptococcus viridans, Streptococcus pneumoniae), Haemophilus influenzae (parainfluenzae), Haemophilus ducreyi, Neisseria gonorrhoeae, Neisseria meningitidis, Listeria monocytogenes, Legionella pneumophila, Mycoplasma pneumoniae, Helicobacter pylori (Campilobacter), Campilobacter jejuni, Chlamidia pneumoniae, Moraxella catarrhalis, Bordetella pertussis, Propionibacterium acne, Mycobacterium avium, Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium marinom, Staphylococcus aureus, Ureaplasma urealyticum, Toxoplasma gondii, Corynebacterium spp., Borrelia burgdorferi, Pasteurella multocida, some anaerobes (Eubacterium spp., Peptococcus spp., Propionibacterium spp., Clostridium perfringens, Bacteroides melaninogenicus), is less active against Mycobacterium tuberculosis.
Pharmacokinetics:
Absorption is fast. Food slows down absorption, without significantly affecting bioavailability. Communication with plasma proteins - more than 90%. After a single dose, 2 peaks of the maximum concentration of the drug in plasma are recorded.
The second peak is due to the ability of the drug to concentrate in the gallbladder, followed by gradual or rapid entry into the intestines and absorption. The time to reach the maximum concentration of the drug in blood plasma with oral administration of 250 mg is 1-3 hours.
After oral administration, 20% of the dose taken is rapidly hydroxylated in the liver by the cytochrome CYP3A4, CYP3A5 and CYP3A7 enzymes to form the main metabolite, β-14-hydroxyclarithromycin, with pronounced antimicrobial activity against Haemophilus influenzae.
It is an inhibitor of isoenzymes CYP3A4, CYP3A5 and CYP3A7.
With regular intake of 250 mg / day, the equilibrium concentrations of the unchanged drug and its main metabolite are 1 and 0.6 μg / ml, respectively; the elimination half-life is 3-4 hours and 5-6 hours, respectively. When the dose is increased to 500 mg / day, the equilibrium concentration of the unchanged drug and its metabolite in plasma is 2.7-2.9 and 0.83-0.88 μg / ml, respectively; the half-life is 4.8-5 hours and 6.9-8.7 hours, respectively.
At therapeutic concentrations, it accumulates in the lungs, skin and soft tissues (in them, concentrations are 10 times higher than the level in blood serum).
It is excreted by the kidneys and intestines (20-30% - in unchanged form, the rest - in the form of metabolites). With a single dose of 250 mg and 1200 mg, 37.9 and 46% are excreted by the kidneys, 40.2 and 29.1%, respectively, by the intestines.
Indications
- Lower respiratory tract infections (including bronchitis, pneumonia).
- Infections of the upper respiratory tract (including pharyngitis, sinusitis).
- Infections of the skin and soft tissues (including folliculitis, erysipelas).
- Mycobacterial infections caused by Mycobacterium avium and Mycobacterium intracellulare. Localized infections caused by Mycobacterium fortuitum and Mycobacterium kansasii.
- Prevention of the spread of infection caused by the Mycobacterium avium complex (MAC infection) in HIV-infected patients with a CD4 lymphocyte count of not more than 100 / μl.
- Eradication of Helicobacter pylori in order to reduce the recurrence rate of gastric ulcer and duodenal ulcer.
- Odontogenic infections.
Pregnancy and lactation
The use of the drug during pregnancy (II and III trimesters) is possible only if the intended benefit to the mother outweighs the potential risk to the fetus.
Clarithromycin is excreted in breast milk, so if it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.
Contraindications
Hypersensitivity to drugs of the macrolide group;
Simultaneous administration of clarithromycin with the following drugs: astemizole, cisapride, pimozide and terfenadine;
Porphyria
Pregnancy (I trimester);
Lactation period
· Children's age up to 12 years.
Precautions: Renal and / or liver failure. Against the background of taking drugs metabolized by the liver, it is recommended to measure their concentration in the blood.
Side effects
From the side of the nervous system: headache, dizziness, anxiety, fear, insomnia, "nightmare" dreams; rarely - disorientation, hallucinations, psychosis, depersonalization, confusion.
From the digestive system: nausea, vomiting, gastralgia, diarrhea, stomatitis, glossitis, increased activity of "liver" transaminases, cholestatic jaundice, rarely - pseudomembranous enterocolitis.
From the sensory organs: tinnitus, taste change (dysgeusia); in isolated cases - hearing loss that occurs after discontinuation of the drug.
On the part of the hemopoietic organs and hemostatic system: rarely - thrombocytopenia (unusual bleeding, hemorrhage).
Allergic reactions: skin rash, itching, malignant exudative erythema (Stevens-Johnson syndrome), anaphylactoid reactions.
Other: development of microorganism resistance.
Interaction
The simultaneous use of clarithromycin with cisapride, pimozide, terfenadine, astemizole, as this leads to an increase in the concentration of these drugs in blood plasma by 2-3 times, which can cause a prolongation of the QT interval, disturbance of the heart rhythm, including ventricular tachycardia, ventricular fibrillation.
With simultaneous administration, clarithromycin increases the concentration in the blood of drugs metabolized in the liver with the help of cytochrome P450 enzymes: indirect anticoagulants, carbamazepine, theophylline, triazolam, midazolam, cyclosporine, vinblastine, disopyramide, phenytoinapinapamapolapolazolapamapolapolazolapamapolazolapovalapolazolapovalapolazolapovolapolazolapovalapolazolapovolapolazolapovolapolazolapovalapolazolapovalapolazolapovalapolazolapovalapolazolapovalapolazolapovalapolazolapovalapolazolapovalapolapovalapolazolapovalapolazolapovolapastigolapastin simvolapolazolapamyolapolazolapastigalovolapolazolapamyolapasta acids, cilostazol, methylprednisolone, omeprazole, quinidine, ergot alkaloids, sildenafil, tacrolimus.
With the simultaneous administration of clarithromycin and zidovudine in HIV-infected patients, a decrease in the equilibrium concentration of zidovudine was noted (an interval of at least 4 hours is required between the use of drugs).
With the simultaneous use of ritonavir (200 mg every 8 hours) and clarithromycin (500 mg every 12 hours), the metabolism of clarithromycin slows down (Cmax of clarithromycin increased by 31%, Cmin - by 182%, AUC - by 77%). A significant slowdown in the formation of 14-hydroxyclarithromycin was noted.
When taking ritonavir, clarithromycin should not be prescribed at a dose of more than 1 g per day. In this case, patients without impaired renal function do not need to adjust the dose of clarithromycin. This is of great importance in the case of the use of such a combination in patients with impaired renal function: in patients with creatinine clearance from 30 to 60 ml / min, the dose of clarithromycin is reduced by 50% (up to 500 mg once a day).
Perhaps the development of cross-resistance between clarithromycin, lincomycin and clindamycin.
How to take, course of administration and dosage
Inside, adults and children over 12 years old - 250-500 mg 2 times a day. The duration of treatment is 6-14 days.
In the treatment of infections caused by Mycobacterium avium, 500 mg is prescribed orally 2 times a day. The duration of treatment is 6 months or more.
To eradicate Helicobacter pylori in patients with peptic ulcer and duodenal ulcer, clarithromycin is prescribed 250-500 mg twice a day as part of combination therapy. The duration of treatment is 7-14 days.
In patients with chronic renal failure (creatinine clearance less than 30 ml / min or serum creatinine concentrations more than 3.3 mg / 100 ml) - 250 mg / day (once), in severe infections - 250 mg 2 times a day. The maximum duration of treatment in patients of this group is 14 days.
Overdose
Symptoms: nausea, vomiting, diarrhea, headache, confusion.
Treatment: gastric lavage and symptomatic treatment. Hemodialysis and peritoneal dialysis do not lead to a significant change in the concentration of clarithromycin in serum.
Special instructions
In the presence of chronic liver diseases, regular monitoring of serum enzymes is necessary.
It is prescribed with caution against the background of drugs metabolized by the liver (it is recommended to measure their concentration in the blood).
In the case of joint administration with warfarin or other indirect anticoagulants, it is necessary to control prothrombin time.
It is necessary to pay attention to the possibility of cross-resistance between clarithromycin and other macrolide antibiotics, as well as lincomycin and clindamycin.
With prolonged or repeated use of the drug, superinfection (the growth of insensitive bacteria and fungi) is possible.
Release form
Yellow coated tablets are biconvex, oblong with rounded edges, with a risk.
Two layers are visible on the cross section, the inner layer is white or almost white.
