Description
Release form
film-coated sustained-release tablets
Packing
14 pcs.
Pharmacological action
Pharmacological action – antibacterial.
Pharmacodynamics
Macrolide bacteriostatic second-generation antibiotic from the broad-spectrum macrolide group. It disrupts the synthesis of protein of microorganisms (binds to the 50S subunit of the membrane of the ribosome of the microbial cell).
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 (Campylobacter) pylori, Campylobacter jejuni, Chlamidia pneumoniae (trachomatis), Moraxella (Branhamella) catarrhalis, Toramlium pomissermspomifermspomifermspomifermspomifermspompomifermspompomifermspompomifermspomporypherms burgdorferi, Treponema pallidum, Pasteurella multocida, some anaerobes (Eubacterium spp., Peptococcus spp., Propionibacterium spp., Clostridium perfringens, Bacteroides melaninogenicus) and all mycobacteria except M.tuberculosis.
The main metabolite of clarithromycin in the human body is the microbiologically active metabolite 14-hydroxyclarithromycin. The microbiological activity of the metabolite is the same as that of the starting substance, or 1-2 times weaker with respect to most microorganisms. An exception is H.influenzae, for which the metabolite is 2 times more effective. The starting material and its main metabolite have either an additive or synergistic effect against H. influenzae in vitro and in vivo, depending on the culture of the bacteria.
Pharmacokinetics of
Clarithromycin is metabolized in the liver cytochrome P4503A (CYP3A) system. Absolute bioavailability is about 50%. With repeated administration of the drug, cumulation was not detected and the nature of the metabolism in the human body does not change.
Clarithromycin binds to plasma proteins by 70% at a concentration of 0.45 to 4.5 μg / ml. At a concentration of 45 μg / ml, binding decreases to 41%, probably as a result of saturation of the binding sites. This is observed only at concentrations many times higher than therapeutic.
Ingestion of sustained-release clarithromycin at a dose of 500 mg per day helps maintain equilibrium plasma levels of maximum concentrations of clarithromycin and 14-hydroxyclarithromycin. The equilibrium Cmax of clarithromycin and 14-hydroxyclarithromycin in plasma are 1.3 and 0.48 μg / ml, respectively. T1 / 2 of the initial drug and its main metabolite are respectively 5.3 and 7.7 hours. When taking prolonged-acting clarithromycin, at a dose of 1000 mg per day (2 tablets of 500 mg), the equilibrium levels of Cmax of clarithromycin and 14-hydroxyclarithromycin are an average of 2.4 and 0.67 μg / ml, respectively. T1 / 2 of the initial drug and its main metabolite are 5.8 and 8.9 hours, respectively. The Tmax value when taking doses of 500 and 1000 mg per day is about 6 hours. At equilibrium, the level of 14-hydroxyclarithromycin does not increase in proportion to the doses of clarithromycin, and T1 / 2 of clarithromycin and its main metabolite increase with increasing dose. The non-linear nature of the pharmacokinetics of clarithromycin is associated with a decrease in the formation of 14-hydroxylated and N-demethylated metabolites when using higher doses, which indicates the non-linearity of clarithromycin metabolism when taking high doses.
With urine, about 40% of the dose of clarithromycin is excreted, through the intestines – about 30%.
Clarithromycin and 14-hydroxyclarithromycin are widely distributed in tissues and body fluids. After oral administration of clarithromycin, its content in the cerebrospinal fluid remains low (with normal BBB permeability – 1-2% of the level in the blood serum). The content in tissues is usually several times higher than the content in blood serum.
Impaired liver function. In patients with moderate and severe impairment of the functional state of the liver, but with preserved renal function, dose adjustment of clarithromycin is not required. The equilibrium concentration in plasma and systemic clearance of clarithromycin does not differ in patients of this group and healthy patients. The equilibrium concentration level of 14-hydroxyclarithromycin in people with impaired liver function is lower than in healthy people.
Impaired renal function. With impaired renal function, the minimum and maximum plasma clarithromycin, T1 / 2, AUC of clarithromycin and 14-hydroxyclarithromycin increase. The elimination constant and urinary excretion are reduced. The degree of change in these parameters depends on the degree of impaired renal function.
Elderly patients. In elderly patients, the levels of clarithromycin and 14-hydroxyclarithromycin in the blood were higher, and excretion was slower than in a 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 the patients.
Indications
Treatment of infectious diseases caused by susceptible microorganisms: lower respiratory tract infections (bronchitis, pneumonia)
upper respiratory tract infections (pharyngitis, sinusitis), otitis
infections of the skin and soft tissues (folliculitis, erysipelatous inflammation) localized mycobacterial infections caused by Mycobacterium avium and Mycobacterium intracellulare. Localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum and Mycobacterium kansasii.
elimination H. pylori and a decrease in the frequency of relapse of a duodenal ulcer associated with H. pylori.
Use during pregnancy and lactation
Safety of clarithromycin during pregnancy and lactation has not been established. Therefore, during pregnancy, clarithromycin is prescribed only in the absence of alternative therapy, if the intended benefit outweighs the potential risk to the fetus.
Special instructions
In the presence of chronic liver diseases, regular monitoring of serum enzymes is necessary.
With caution is prescribed against the background of drugs metabolized by the liver (it is recommended to measure their concentration in the blood).
In the case of co-administration with warfarin or other indirect anticoagulants, it is necessary to control PV.
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, the development of superinfection is possible (re-infection with the same pathogens against the background of a developed disease).
Children under 12 years of age are recommended to use Klabax ® in the form of granules for the preparation of a suspension for oral administration, at 125 or 250 mg / 5 ml.
Composition of
clarithromycin 500 mg
excipients: hypromellose lactose monohydrate MCC povidone silicon dioxide colloidal sodium stearyl fumarate talc magnesium stearate
film coating: dye Opadry yellow 20H52875 dyngol tin yellow hyprome 24%)
ink composition: black ink Opacode-S-1-17734 (shellac 45% (20% esterified) in SD-45 alcohol, black iron oxide, n-butanol, propylene glycol, methanol, isopropanol *, ammonium hydroxide 28%)
* evaporates during the manufacturing process
Dosage and administration
Inside, with food, without breaking, without chewing, swallowing whole.
Adults and children 12 years of age and older usually 500 mg once daily. In severe cases, the dose is increased to 500 mg 2 times a day.
Duration of treatment is 7-14 days.
For patients with creatinine Cl 30-60 ml / min, only in severe infections, a dose of 500 mg once a day is possible (i.e., a 50% reduction in the daily dose).
Drug interaction
With a simultaneous administration, it increases the blood concentration of drugs metabolized in the liver by the enzymes of cytochrome P450 – indirect anticoagulants, carbamazepine, theophylline, astemizole, cisapride, terfenadine (2 3 times), triazolamide, disazolam, disazolam, cyclamide , phenytoin, rifabutin, lovastatin, digoxin, ergot alkaloids, etc.
Rare cases of acute skeletal muscle necrosis have been reported, coinciding in time with the simultaneous administration of clarithromycin and hydroxymethylglutaryl-CoA reductase inhibitors – lovastatin and simvastatin.
There are reports of an increase in the concentration of digoxin in the plasma of patients receiving both digoxin and clarithromycin tablets. In such patients, it is necessary to constantly monitor the content of digoxin in the serum in order to avoid digital intoxication.
Clarithromycin can reduce the clearance of triazolam and, thus, increase its pharmacological effects with the development of drowsiness and confusion.
The simultaneous use of clarithromycin and ergotamine (ergot derivatives) can lead to acute ergotamine intoxication, manifested by severe peripheral vasospasm.
Co-administration of zidovudine orally with adult HIV-infected patients and clarithromycin tablets may decrease the equilibrium concentrations of zidovudine. Considering that clarithromycin probably alters the absorption of zidovudine administered simultaneously inside, this interaction can be largely avoided by taking clarithromycin and zidovudine at different hours of the day (with an interval of at least 4 hours).
With the simultaneous administration of clarithromycin and ritonavir, serum concentrations of clarithromycin increase. Dose adjustment of clarithromycin in these cases in patients with normal renal function is not required. However, in patients with Cl creatinine from 30 to 60 ml / min, the dose of clarithromycin should be reduced by 50%, and with Cl creatinine less than 30 ml / min, prolonged-release clarithromycin tablets should not be prescribed. Such patients are prescribed quick release clarithromycin of 250 or 500 mg. With simultaneous treatment with ritonavir, clarithromycin should not be prescribed in doses above 1 g / day.
Overdose
Symptoms: probably gastrointestinal symptoms (nausea, vomiting, diarrhea) headache, confusion.
Treatment: Immediate gastric lavage and symptomatic treatment. Hemodialysis and peritoneal dialysis do not lead to a significant change in serum clarithromycin levels.
Storage Conditions
In a dark place at a temperature not exceeding 25 ° C.
Shelf life
2 years.
Deystvuyushtee substance
Clarithromycin
Pharmacy terms
Prescription
Dosage form
tablets prolong.
