Composition, form of production and packaging
The tablets covered with a film covering of pink color, round, biconcave, with an embossing "РЎ 127" on one side.
1 tab.
clopidogrel hydrogen sulfate 97.875 mg,
which corresponds to the content of clopidogrel 75 mg
Excipients: microcrystalline cellulose (Avicel PH 112) - 211.125 mg, mannitol - 58 mg, croscarmellose sodium - 12 mg, silicon dioxide colloid - 2 mg, magnesium stearate - 4 mg.
The composition of the shell: opadrai pink 03B54202 (hypromellose - 62.5%, titanium dioxide - 30.6%, macrogol-400 - 6.25%, iron oxide red oxide - 0.65%) - 13.475 mg.
10 pieces. - blisters (3) - packs of cardboard.
10 pieces. - blisters (10) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
A specific inhibitor of platelet aggregation, has a coronary expansive effect. Selectively reduces the binding of ADP to platelet receptors and the activation of GPIIb / IIIa receptors by ADP, thereby weakening platelet aggregation.
Reduces platelet aggregation caused by other agonists, preventing their activation by released ADP, does not affect the activity of phosphodiesterase (PDE).Irreversibly binds to ADP-receptor platelets, which remain immune to stimulation of ADP throughout the life cycle (about 7 days).
The inhibition of platelet aggregation is observed 2 hours after taking the drug (40% inhibition) at an initial dose of 400 mg. The maximum effect (60% suppression of aggregation) develops after 4-7 days of constant admission in a dose of 50-100 mg / day. Antiaggregant effect persists throughout the life span of platelets (7-10 days).Aggregation of platelets and bleeding time return to the baseline, on average, 5 days after cessation of treatment.
In the presence of an atherosclerotic lesion, the vessel interferes with the development of atherothrombosis regardless of the localization of the vascular process (cerebrovascular, cardiovascular or peripheral lesions).
PHARMACOKINETICS
Suction and distribution
Absorption and bioavailability are high; the concentration in the plasma is low and after 2 hours after the intake it does not reach the measurement limit (0.025 Ојg / l).Clopidogrel and the main metabolite bind reversibly to plasma proteins (98% and 94%, respectively).
Metabolism
Metabolised in the liver. The main metabolite is an inactive derivative of carboxylic acid, which accounts for about 85% of the compound circulating in the plasma. Cmax metabolite, after repeated oral administration of clopidogrel at a dose of 75 mg, is achieved after 1 hour and is about 3 mg / l. Clopidogrel is a precursor of the active substance. Its active metabolite, a thiol derivative, is formed by oxidizing clopidogrel to 2-oxo-clopidogrel and subsequent hydrolysis. The oxidative process is regulated, first of all, by cytochrome P450 2B6 and 3A4 isoenzymes, and, to a lesser extent, 1A1, 1A2 and 1C19. The active thiol metabolite quickly and irreversibly binds to platelet receptors, thereby suppressing platelet aggregation. This metabolite is not detected in plasma.
Excretion
It is excreted by the kidneys - 50%, the intestines - 46% (within 120 hours after administration). T 1/2 of the main metabolite after a single and repeated intake - 8 hours. Concentrations of kidney metabolites - 50%.
Pharmacokinetics in special clinical cases
After taking clopidogrel at a dose of 75 mg / day in patients with severe kidney disease (SC 5-15 ml / min), the concentration of the main metabolite in the plasma is lower than in patients with moderate kidney disease (QC from 30 to 60 ml / min) and healthy individuals. Although the inhibitory effect on ADP-induced platelet aggregation was reduced (25%), compared to the same effect in healthy volunteers, bleeding time was extended to the same extent as in healthy volunteers who received clopidogrel at a dose of 75 mg / day.
In patients with cirrhosis of the liver, the use of clopidogrel at a daily dose of 75 mg for 10 days was safe and well tolerated, C max clopidogrel, both after single dose administration and in the equilibrium state, was many times higher in patients with cirrhosis than in healthy persons.
INDICATIONS
- prophylaxis of thrombotic complications in patients with myocardial infarction, ischemic stroke or occlusion of peripheral arteries;
- in combination with acetylsalicylic acid for the prevention of thrombotic complications in acute coronary syndrome: with elevation of the ST segment with the possibility of carrying out thrombolytic therapy; without ST segment elevation (unstable angina, myocardial infarction without Q-wave formation), incl. in patients who underwent stenting.
DOSING MODE
Tablets are taken orally, regardless of food intake.
For the prevention of ischemic disorders in patients after a previous myocardial infarction, ischemic stroke, or against the background of diagnosed peripheral arterial diseases, adults (including elderly patients) are treated with PlagrilВ® 75 mg once a day. Treatment should be started within 35 days after a Q-forming myocardial infarction and from 7 days to 6 months after an ischemic stroke.
In acute coronary syndrome without ST segment elevation (unstable angina or myocardial infarction without Q wave formation) treatment should begin with the appointment of a single loading dose of 300 mg, then continue the use of the drug at a dose of 75 mg 1 time / day (with concurrent administration of acetylsalicylic acid in a dose 75-325 mg / day).
Since the use of acetylsalicylic acid in high doses is associated with a high risk of bleeding, the recommended dose should not be more than 100 mg. The course of treatment is up to 1 year.
In acute coronary syndrome with ST segment elevation (acute myocardial infarction), the drug is prescribed at a dose of 75 mg 1 time / day using the initial loading dose in combination with acetylsalicylic acid, in combination or without thrombolytic agents.
For patients over the age of 75, clopidogrel treatment should be administered without the use of a loading dose. Combination therapy is started as soon as possible after the onset of symptoms and is continued for a minimum of 4 weeks.
SIDE EFFECT
Determination of the frequency of side effects: often (> 1%), sometimes (0.1-1%), rarely (0.01-0.1%), very rarely (<001%).
From the coagulation system: often - gastrointestinal bleeding; sometimes - hemorrhagic stroke, prolonged bleeding time, nosebleeds; rarely - hematomas, hematuria, and conjunctival bleeding.
From the hemopoietic system: sometimes - thrombocytopenia, neutropenia, leukopenia, eosinophilia; very rarely - thrombocytopenic purpura, granulocytopenia, agranulocytosis, anemia and aplastic anemia.
From the central nervous system and peripheral nervous system: sometimes - headache, dizziness, paresthesia; rarely - vertigo; very rarely - confusion, hallucinations.
From the cardiovascular system: very rarely - vasculitis, lowering blood pressure.
From the respiratory system: very rarely - bronchospasm, interstitial pneumonitis.
On the part of the digestive system: often - indigestion, diarrhea, abdominal pain; sometimes - nausea, gastritis, flatulence, constipation, vomiting, ulceration of the gastrointestinal mucosa, exacerbation of peptic ulcer of the stomach and duodenum; very rarely - colitis (including ulcerative or lymphocytic colitis), pancreatitis, taste changes, stomatitis, hepatitis, acute liver failure, increased activity of hepatic enzymes.
From the musculoskeletal system: very rarely - arthralgia, arthritis, myalgia.
From the side of the urinary system: very rarely - glomerulonephritis.
Dermatological reactions: sometimes itching; very rarely - bullous rash (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), erythematous rash, eczema, flat lichen.
Allergic reactions: very rarely - angioedema, hives, anaphylactoid reactions, serum sickness.
Other: very rarely - an increase in body temperature, an increase in serum creatinine.
CONTRAINDICATIONS
severe hepatic impairment;
- hemorrhagic syndrome;
- Acute bleeding (including intracranial hemorrhage) and diseases predisposing to its development (peptic ulcer of the stomach and duodenum in the acute phase, NNC, tuberculosis, lung tumors, hyperfibrinolysis);
- Pregnancy,
- the period of lactation (breastfeeding);
- children's age till 18 years;
- Hypersensitivity to the components of the drug.
Caution should be applied to the drug with moderate hepatic and / or renal failure, trauma, conditions that increase the risk of bleeding (including trauma, surgery), while taking acetylsalicylic acid and other NSAIDs (including COX-2 inhibitors), heparin and glycoprotein IIb / IIIa inhibitors.
PREGNANCY AND LACTATION
Contraindicated use of the drug during pregnancy and lactation (breastfeeding).
APPLICATION FOR FUNCTIONS OF THE LIVER
Caution should be applied to the drug with moderate renal failure
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Caution should be applied to the drug with moderate hepatic insufficiency.
In case of severe violations of liver function, one should remember about the risk of hemorrhagic diathesis.
APPLICATION FOR CHILDREN
Contraindicated in children and adolescents under 18 years.
APPLICATION IN ELDERLY PATIENTS
For patients over the age of 75, clopidogrel treatment should be administered without the use of a loading dose. Combination therapy is started as soon as possible after the onset of symptoms and is continued for a minimum of 4 weeks.
SPECIAL INSTRUCTIONS
In the case of surgical interventions, if antiaggregant effect is undesirable, the course of treatment should be discontinued 7 days before the operation.
Patients should be warned that because the stoppage of the bleeding that occurs when the drug is used requires more time, they should inform the doctor about every case of unusual bleeding. Patients should also inform the doctor about taking the drug if they are undergoing surgery or if the doctor appoints a new medication for the patient.
During the treatment period, it is necessary to monitor the parameters of the hemostasis system (APTT, platelet count, platelet function tests), to regularly study the functional activity of the liver.
In case of severe violations of liver function, one should remember about the risk of hemorrhagic diathesis.
Use in Pediatrics
The drug is not prescribed for children under the age of 18 due to the fact that safety and effectiveness of its use in this age group are not established.
Impact on the ability to drive vehicles and manage mechanisms
Signs of deterioration in the ability to drive or reduce mental performance after taking Plagril was not found.
OVERDOSE
Symptoms: with a single oral intake of healthy people 600 mg of clopidogrel (8 tablets of 75 mg), no side effects were noted. The bleeding time was extended 1.7 times, which corresponds to the value registered after taking a therapeutic dose (75 mg / day).
Treatment: transfusion of platelet mass. There is no specific antidote.
DRUG INTERACTION
With the simultaneous use of Plagril В® enhances the antiplatelet effect of acetylsalicylic acid, heparin, indirect anticoagulants, NSAIDs, increases the risk of bleeding from the gastrointestinal tract.
By inhibiting the activity of CYP2C9, clopidogrel increases the concentration of drugs metabolized by this isoenzyme (phenytoin, tolbutamide).
There was no clinically significant pharmacodynamic interaction with clopidogrel in combination with atenolol, nifedipine, phenobarbital, cimetidine, estrogens, digoxin, theophylline, tolbutamide, antacid agents.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a dry, protected from light, out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 2 years.
