Composition, structure and packing
Tablets, film-coated pink and cream-colored, round, biconvex, transverse section of the two layers are visible.
1 tab. hydrosulfate clopidogrel 98 mg, which corresponds to the content of clopidogrel 75 mg.
Excipients: potato starch, lactose, microcrystalline cellulose, gipromelloza (hydroxypropylmethylcellulose), macrogol 6000 (polyethylene glycol 6000), stearic acid, magnesium stearate.
The composition of the shell: gipromelloza (hydroxypropylmethylcellulose), titanium dioxide, macrogol 6000 (polyethylene glycol 6000), iron oxide red.
Clinico-pharmacological group: antiagrigant.
Pharmacological action
Antiagrigant. Clopidogrel prevents platelet aggregation by selective blockade of binding of adenosine diphosphate (ADP) to its receptor on platelets and activation of the complex GPIIb / IIIa. Inhibits platelet aggregation induced by other agonists, by reducing the activity of platelets released ADP, does not affect the activity of PDE.
Changes in ADP-receptor inhibitors, due to clopidogrel are irreversible: Platelets are non-functional during the whole period of life, antiplatelet effect persisted throughout this period. Restoration of normal function occurs as updates platelets (approximately 7 days). In the presence of atherosclerosis, clopidogrel prevents the development of atherothrombosis regardless of the localization process of vascular (cerebrovascular, cardiovascular or peripheral lesions).
Pharmacokinetics
Absorption
After oral administration 75 mg clopidogrel medication quickly absorbed out of the digestive tract, but the concentration in plasma is low and 2 h after receiving less than measurement limit (0.025 ug / l), and inhibition of platelet aggregation reaches with 40%. The maximum effect (60% suppression of aggregation) develops after 4-7 days continuous use of the drug at a dose of 98 mg / day (in terms of clopidogrel -75 mg / day). Cmax metabolite after repeated receptions clopidogrel 75 mg, about 3 mg / L and observed after approximately 1 h after ingestion.
Distribution
Linking to plasma proteins clopidogrel and its main metabolite: 98-94%, respectively.
Metabolism
The drug is metabolized in the liver. The main metabolite - inactive derivative of a carboxylic acid.
Withdrawal
About 50% of the dose excreted in the urine and approximately 46% of the faeces (within 120 h after injection).
T1 / 2 main metabolite after single and repeated administration of the drug - 8 pm
Pharmacokinetics s special clinical situations
Concentration of the main metabolite in plasma after administration of clopidogrel 75 mg / day lower in patients with severe kidney disease (CC 5-15 ml / min) compared to patients with kidney disease moderate (QC from 30 to 60 ml / min) and healthy persons. Cmax of the drug in blood plasma was higher in patients with cirrhosis, as after receiving a single dose or in equilibrium. This safety and tolerability in these patients is not altered by the application of 75mg/sut clopidogrel for 10 days.
Statement
Prevention of ischemic disorders (myocardial infarction, stroke, peripheral artery thrombosis, sudden cardiovascular death) in patients with atherosclerosis, including:
after myocardial infarction;
after ischemic stroke;
with peripheral arterial disease;
patients with acute coronary syndrome without ST elevation ST (unstable angina, myocardial infarction without teeth Q), in combination with acetylsalicylic acid;
during the operation of percutaneous koronaroplastiki.
Dosage regimen
The drug, taken orally 1 tablet 1 time per day, regardless of the meal.
Treatment should begin within the time frame from days to 35 days in patients after myocardial infarction and from 7 days to 6 months in patients after ischemic stroke. In acute coronary syndrome without ST elevation ST (unstable angina, myocardial infarction without teeth Q) treatment should begin with the appointment of a single loading dose - 4 pi. Agregal drug (300 mg clopidogrel), then continue for 1 tab. / day (75 mg clopidogrel) with the simultaneous appointment of acetylsalicylic acid in a dose 75-375mg/sut. The maximum rate of joint use of the drug Agregal and acetylsalicylic acid - 1 year (with more prolonged use of safety has not been studied). Scheme selection and duration of treatment with Agregal during percutaneous koronaroplastiki determined by the physician depending on the type of stent and timing of the operation.
Side effect
On the part of the coagulating the blood system: gastrointestinal bleeding (2% required hospitalization in 0.7% of cases) and sometimes - hematomas, hematuria, hemorrhage in the conjunctiva.
On the part of the hemopoietic system: marked neutropenia (number of granulocytes <450/mkl; observed in 0.04%), severe thrombocytopenia (platelet count <80 000/mkl; was observed in 0.2%).
On the part of the digestive system: abdominal pain, indigestion (constipation, diarrhea, nausea), gastritis, rarely - changes hepatic samples.
From the central nervous system and peripheral nervous system: headache, dizziness, paresthesias. Dermatological reactions: skin rash, itching. Allergic reactions: seldom - bronchospasm, angioedema, anaphylactic reactions. Other: thrombocytopenic purpura (1 / 200, 000). Other clinically significant side effects noted in a number of major international research, with a frequency> 0.1%, as well as all serious side effects are presented below, according to the WHO classification. Their frequency is defined as follows: frequent (> 1 / 100, but <1> 1 / 1000 but <1> 1 / 10000, but <1 / 1000).
From the central nervous system and peripheral nervous systems: common - headache, dizziness, paresthesias, rare - vertigo.
On the part of the digestive system: often - diarrhea, abdominal pain, sometimes - nausea, gastritis, flatulence, constipation, vomiting, stomach ulcer and duodenal ulcer.
From the blood coagulation system: sometimes - lengthening the time of bleeding. On the part of the hemopoietic system: sometimes - leukopenia, fewer neutrophils, eosinophilia, decrease in the number of platelets. Dermatological reactions: sometimes - a rash and itching.
Contraindications
severe hepatic impairment;
severe bleeding (eg peptic ulcer or intracranial hemorrhage);
Pregnancy
breastfeeding;
childhood;
Hypersensitivity to the drug's components.
Precautions should be prescribed to patients with increased risk of bleeding (trauma, to surgical interventions), and moderate hepatic or renal failure (development of hemorrhagic diathesis).
Pregnancy and lactation
Use of the drug in beremnnosti and during breast-feeding is contraindicated due to the lack of safety data.
Application for violations of liver function
Do not use this drug for severe hepatic insufficiency. With care use in patients with moderate hepatic insufficiency.
Application for violations of renal function
With care use in patients with renal insufficiency. Cautions In the case of combining the drug Agregal with acetylsalicylic acid, other NSAIDs, heparin, inhibitors of glycoprotein IIb / IIIa or fibrinolytics, it is necessary to analyze the blood during the first week of treatment (APTT, the number and functional activity of platelets). The course of treatment by Agregal discontinue for 7 days before the planned surgery. Patients should be warned that there should be reported to your doctor about any case of bleeding.
Overdose
No cases of overdose were observed. Treatment: platelet transfusion. Specific antidote exists.
Drug Interactions
The simultaneous use of the drug Agregal with warfarin is not recommended, since it is possible intensification of bleeding. The simultaneous use of the drug Agregal with inhibitors of glycoprotein Ilb / IIIa requires caution.
Acetylsalicylic acid does not alter the inhibitory effect of the drug Agregal on ADP-induced platelet aggregation, but the drug Agregal intensifies the effect of aspirin on collagen-induced aggregation of platelets. The combined use of these drugs requires caution. According to clinical trial conducted in healthy individuals, clopidogrel does not alter any requirements of heparin, or the effect of heparin on blood coagulation.
The simultaneous use of heparin did not alter the inhibiting action of clopidogrel to platelet aggregation. However, the safety of such combinations has not been established and the simultaneous use of these drugs requires caution. Safety of simultaneous use of clopidogrel, recombinant tissue plasminogen activator (rt - PA) and heparin was investigated in patients with recent myocardial infarction. The frequency of clinically significant bleeding was similar to that observed in the case of simultaneous application of rt - PA and heparin. Safety joint for clopidogrel with other fibrinolytics not yet installed and the simultaneous use of these drugs require caution.
The simultaneous use of the drug Agregal with NSAIDs requires caution due to possible increased risk of bleeding. There was no clinically significant pharmacodynamic interactions with clopidogrel use in the simultaneous application with atenolol, nifedipine, phenobarbital, cimetidine, estrogens, digoxin, theophylline, phenytoin, tolbutamide and antacid, however, there is evidence that clopidogrel inhibits the activity of one isozyme SUR2S9 and may change the concentration of drugs metabolized by CYP2C9 (including phenytoin, tolbutamide).
Terms and Conditions of storage
List of B. The product should be stored out of reach of children, dry, dark place at temperatures not above 25 ° C.
Shelf life - 2 years.
Tablets, film-coated pink and cream-colored, round, biconvex, transverse section of the two layers are visible.
1 tab. hydrosulfate clopidogrel 98 mg, which corresponds to the content of clopidogrel 75 mg.
Excipients: potato starch, lactose, microcrystalline cellulose, gipromelloza (hydroxypropylmethylcellulose), macrogol 6000 (polyethylene glycol 6000), stearic acid, magnesium stearate.
The composition of the shell: gipromelloza (hydroxypropylmethylcellulose), titanium dioxide, macrogol 6000 (polyethylene glycol 6000), iron oxide red.
Clinico-pharmacological group: antiagrigant.
Pharmacological action
Antiagrigant. Clopidogrel prevents platelet aggregation by selective blockade of binding of adenosine diphosphate (ADP) to its receptor on platelets and activation of the complex GPIIb / IIIa. Inhibits platelet aggregation induced by other agonists, by reducing the activity of platelets released ADP, does not affect the activity of PDE.
Changes in ADP-receptor inhibitors, due to clopidogrel are irreversible: Platelets are non-functional during the whole period of life, antiplatelet effect persisted throughout this period. Restoration of normal function occurs as updates platelets (approximately 7 days). In the presence of atherosclerosis, clopidogrel prevents the development of atherothrombosis regardless of the localization process of vascular (cerebrovascular, cardiovascular or peripheral lesions).
Pharmacokinetics
Absorption
After oral administration 75 mg clopidogrel medication quickly absorbed out of the digestive tract, but the concentration in plasma is low and 2 h after receiving less than measurement limit (0.025 ug / l), and inhibition of platelet aggregation reaches with 40%. The maximum effect (60% suppression of aggregation) develops after 4-7 days continuous use of the drug at a dose of 98 mg / day (in terms of clopidogrel -75 mg / day). Cmax metabolite after repeated receptions clopidogrel 75 mg, about 3 mg / L and observed after approximately 1 h after ingestion.
Distribution
Linking to plasma proteins clopidogrel and its main metabolite: 98-94%, respectively.
Metabolism
The drug is metabolized in the liver. The main metabolite - inactive derivative of a carboxylic acid.
Withdrawal
About 50% of the dose excreted in the urine and approximately 46% of the faeces (within 120 h after injection).
T1 / 2 main metabolite after single and repeated administration of the drug - 8 pm
Pharmacokinetics s special clinical situations
Concentration of the main metabolite in plasma after administration of clopidogrel 75 mg / day lower in patients with severe kidney disease (CC 5-15 ml / min) compared to patients with kidney disease moderate (QC from 30 to 60 ml / min) and healthy persons. Cmax of the drug in blood plasma was higher in patients with cirrhosis, as after receiving a single dose or in equilibrium. This safety and tolerability in these patients is not altered by the application of 75mg/sut clopidogrel for 10 days.
Statement
Prevention of ischemic disorders (myocardial infarction, stroke, peripheral artery thrombosis, sudden cardiovascular death) in patients with atherosclerosis, including:
after myocardial infarction;
after ischemic stroke;
with peripheral arterial disease;
patients with acute coronary syndrome without ST elevation ST (unstable angina, myocardial infarction without teeth Q), in combination with acetylsalicylic acid;
during the operation of percutaneous koronaroplastiki.
Dosage regimen
The drug, taken orally 1 tablet 1 time per day, regardless of the meal.
Treatment should begin within the time frame from days to 35 days in patients after myocardial infarction and from 7 days to 6 months in patients after ischemic stroke. In acute coronary syndrome without ST elevation ST (unstable angina, myocardial infarction without teeth Q) treatment should begin with the appointment of a single loading dose - 4 pi. Agregal drug (300 mg clopidogrel), then continue for 1 tab. / day (75 mg clopidogrel) with the simultaneous appointment of acetylsalicylic acid in a dose 75-375mg/sut. The maximum rate of joint use of the drug Agregal and acetylsalicylic acid - 1 year (with more prolonged use of safety has not been studied). Scheme selection and duration of treatment with Agregal during percutaneous koronaroplastiki determined by the physician depending on the type of stent and timing of the operation.
Side effect
On the part of the coagulating the blood system: gastrointestinal bleeding (2% required hospitalization in 0.7% of cases) and sometimes - hematomas, hematuria, hemorrhage in the conjunctiva.
On the part of the hemopoietic system: marked neutropenia (number of granulocytes <450/mkl; observed in 0.04%), severe thrombocytopenia (platelet count <80 000/mkl; was observed in 0.2%).
On the part of the digestive system: abdominal pain, indigestion (constipation, diarrhea, nausea), gastritis, rarely - changes hepatic samples.
From the central nervous system and peripheral nervous system: headache, dizziness, paresthesias. Dermatological reactions: skin rash, itching. Allergic reactions: seldom - bronchospasm, angioedema, anaphylactic reactions. Other: thrombocytopenic purpura (1 / 200, 000). Other clinically significant side effects noted in a number of major international research, with a frequency> 0.1%, as well as all serious side effects are presented below, according to the WHO classification. Their frequency is defined as follows: frequent (> 1 / 100, but <1> 1 / 1000 but <1> 1 / 10000, but <1 / 1000).
From the central nervous system and peripheral nervous systems: common - headache, dizziness, paresthesias, rare - vertigo.
On the part of the digestive system: often - diarrhea, abdominal pain, sometimes - nausea, gastritis, flatulence, constipation, vomiting, stomach ulcer and duodenal ulcer.
From the blood coagulation system: sometimes - lengthening the time of bleeding. On the part of the hemopoietic system: sometimes - leukopenia, fewer neutrophils, eosinophilia, decrease in the number of platelets. Dermatological reactions: sometimes - a rash and itching.
Contraindications
severe hepatic impairment;
severe bleeding (eg peptic ulcer or intracranial hemorrhage);
Pregnancy
breastfeeding;
childhood;
Hypersensitivity to the drug's components.
Precautions should be prescribed to patients with increased risk of bleeding (trauma, to surgical interventions), and moderate hepatic or renal failure (development of hemorrhagic diathesis).
Pregnancy and lactation
Use of the drug in beremnnosti and during breast-feeding is contraindicated due to the lack of safety data.
Application for violations of liver function
Do not use this drug for severe hepatic insufficiency. With care use in patients with moderate hepatic insufficiency.
Application for violations of renal function
With care use in patients with renal insufficiency. Cautions In the case of combining the drug Agregal with acetylsalicylic acid, other NSAIDs, heparin, inhibitors of glycoprotein IIb / IIIa or fibrinolytics, it is necessary to analyze the blood during the first week of treatment (APTT, the number and functional activity of platelets). The course of treatment by Agregal discontinue for 7 days before the planned surgery. Patients should be warned that there should be reported to your doctor about any case of bleeding.
Overdose
No cases of overdose were observed. Treatment: platelet transfusion. Specific antidote exists.
Drug Interactions
The simultaneous use of the drug Agregal with warfarin is not recommended, since it is possible intensification of bleeding. The simultaneous use of the drug Agregal with inhibitors of glycoprotein Ilb / IIIa requires caution.
Acetylsalicylic acid does not alter the inhibitory effect of the drug Agregal on ADP-induced platelet aggregation, but the drug Agregal intensifies the effect of aspirin on collagen-induced aggregation of platelets. The combined use of these drugs requires caution. According to clinical trial conducted in healthy individuals, clopidogrel does not alter any requirements of heparin, or the effect of heparin on blood coagulation.
The simultaneous use of heparin did not alter the inhibiting action of clopidogrel to platelet aggregation. However, the safety of such combinations has not been established and the simultaneous use of these drugs requires caution. Safety of simultaneous use of clopidogrel, recombinant tissue plasminogen activator (rt - PA) and heparin was investigated in patients with recent myocardial infarction. The frequency of clinically significant bleeding was similar to that observed in the case of simultaneous application of rt - PA and heparin. Safety joint for clopidogrel with other fibrinolytics not yet installed and the simultaneous use of these drugs require caution.
The simultaneous use of the drug Agregal with NSAIDs requires caution due to possible increased risk of bleeding. There was no clinically significant pharmacodynamic interactions with clopidogrel use in the simultaneous application with atenolol, nifedipine, phenobarbital, cimetidine, estrogens, digoxin, theophylline, phenytoin, tolbutamide and antacid, however, there is evidence that clopidogrel inhibits the activity of one isozyme SUR2S9 and may change the concentration of drugs metabolized by CYP2C9 (including phenytoin, tolbutamide).
Terms and Conditions of storage
List of B. The product should be stored out of reach of children, dry, dark place at temperatures not above 25 ° C.
Shelf life - 2 years.
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