International nonproprietary name:
Dosage Form : parabolan side effects, film-coated
1 parabolan side effects contains
Clopidogrel hydrogen sulfate – 0.098 g (in terms of clopidogrel – 0,075 g) Excipients:
potato starch, lactose (milk sugar), microcrystalline cellulose. HIPRO-melloza (hydroxypropyl methylcellulose). Macrogol 6000 (polyethylene glycol 6000). stearic acid, magnesium stearate.
hypromellose (hydroxypropyl methylcellulose), titanium dioxide, macrogol 6000 (polietileng-glycol 6000), iron oxide red.
Description : film-coated parabolan side effectss pink – cream color, round, biconcave. The cross section shows two layers.
ATC code: V01AS04
It inhibits platelet aggregation by binding of the selective blockade of adenosine diphosphate (ADP) to its receptor on platelets and activation of the complex GPIIb / IIIa. Inhibits aggregation grombotsitov caused by other agonists by avoiding platelet adenosine diphosphate released, does not affect the activity of phosphodiesterase. Changes of platelet ADP receptors caused by clopidogrel is irreversible, methasterone and therefore non-functional platelets remain throughout the period of the life of platelets, antiplatelet agents, and the effect is maintained throughout this period. Restoration of normal function is as an update of platelets (approximately 7 days). In the presence of atherosclerotic vascular lesions, clopidogrel prevents the development of atherothrombosis regardless of the localization process of vascular (cerebrovascular, cardiovascular or peripheral lesions).
After ingestion of 75 mg clopidogrel drug it is quickly absorbed from the gastrointestinal
tract, however, the low plasma concentration after 2 h after administration does not reach the measurement limit (0.025 mg / l), and inhibition of platelet aggregation reached at
40%. The maximum effect (60% inhibition of aggregation) develops within 4-7 days of continuous use of the drug at a dose 98 mg / day (based on kdopidogrel -75 mg / day). The drug is metabolized in the liver. The major metabolite – inactive derivative of a carboxylic acid, the maximum concentration in plasma (TStah) which after repeated Clopidogrel 75 mg, about 3 mg / l and observed after about 1 hour after ingestion. Clopidogrel and its major metabolite are bound to plasma proteins (98-94%, respectively)
Excretion: after oral administration around 50% of the dose excreted in urine and approximately 46% through the intestine to feces (in section 120 hours after administration). The half-life (T 1/2) of the main metabolite after single and repeated administration – 8 hours.
Farmakokinetia in special clinical situations:
– The concentration of the main metabolite in plasma after administration of clopidogrel 75 mg / d lower in patients with severe renal disease (creatinine clearance of endogenous (CC) 5-15 ml / min) compared with patients with moderately severe renal disease (creatinine clearance from 30 endogenous 60 ml / min) and HEALTHCENTER persons;
– Maximum drug concentration in plasma (Cmax) was higher in patients with cirrhosis, after a single dose and at steady state. At the same time the safety and tolerability of the drug in such patients does not change when taking clopidogrel 75 mg / day for 10 days.
Indications for use:
Prophylaxis of ischemic disorders (myocardial infarction, stroke, peripheral arterial thrombosis, vascular sudden death) in patients with atherosclerosis, including:
– After myocardial infarction and ischemic stroke
– with peripheral artery disease;
– in acute coronary syndrome without ST segment elevation (unstable angina or myocardial infarction without tooth Q), in combination with acetylsalicylic acid;
– during the operation of percutaneous coronary angioplasty;
• hypersensitivity to the drug:
• severe hepatic insufficiency;
• acute bleeding (eg, peptic ulcer or intracranial hemorrhage),
• pregnancy, lactation;
• children’s age.
Pregnancy and lactation: Contraindicated due to the lack of safety data
The drug should be used with caution in patients with an increased risk of bleeding (injuries, before surgery) and with moderate hepatic and / or renal insufficiency (may develop hemorrhagic diathesis).Patients should be warned that they must tell your doctor about every case of bleeding.
Dosage and administration:
Inside – 1 parabolan side effects 1 time per day, regardless of the write.
Treatment should begin within the period of a few days up 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 the ST (unstable angina or myocardial infarction without tooth the Q ) treatment should be started with the appointment of a single loading dose of 4 parabolan side effectss of the drug Agregal (300 mg clopidogrel), and then continued at 1 parabolan side effects Agregal drug per day (75 mg clopidogrel) with simultaneous appointment of acetylsalicylic acid at a dose of 75-375mt / day) The maximum rate of co-use of the drug Agregal and acetylsalicylic acid – 1 year (for more prolonged use of safety has not been studied).
Selecting the scheme and the duration of treatment Agregal during percutaneous coronary angioplasty is determined by the doctor depending on the type of stent and the timing of the operation.
From the blood coagulation system : gastrointestinal bleeding (2% to 0.7% of the cases requiring hospitalization); less frequently – hematoma, hematuria and hemorrhage in the conjunctiva.
From hemopoiesis system: severe neutropenia (number of granulocytes <450 / l) was observed in 0.04%; severe thrombocytopenia (platelet counts <80,000 / ul) – 0.2%.
From the digestive system: abdominal pain, dyspepsia (constipation, diarrhea, nausea), gastritis; rarely – changes in liver samples.
On the part of the central nervous system and peripheral nervous system: headache, dizziness, paresthesia.
Dermatological reactions: skin rash, pruritus.
Allergic reactions: rarely – 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%, and any serious side effects are presented below in accordance with the WHO classification.Their frequency is defined as follows: common (> 1/100 but <1/10.); sometimes (> 1/1000, but <1/100); rare (> 1/10000. at <1/1000).
On the part of the central nervous system and peripheral nervous system: often – headache, dizziness, paresthesia; rare – vertigo.
From the digestive system: often – diarrhea, abdominal pain: sometimes – nausea, gastritis, flatulence, constipation, vomiting, gastric ulcer and duodenal ulcer.
From the blood coagulation system: sometimes – prolongation of bleeding time.
From hemopoiesis system: sometimes – leukopenia, a reduction in the number of neutrophils and eosinophils, decreased platelet count.
Dermatological reactions: sometimes, rash and pruritus.
No cases of overdose were observed.
A echenie: transfusion of platelets. There is no specific antidote.
Interaction with other drugs:
Warfarin : the topical application of the drug is not recommended Agregal with warfarin, as this combination can enhance the intensity of bleeding.
Inhibitors of glycoprotein IIb / IIIa :. Appointment of inhibitors of glycoprotein IIb / IIIa in conjunction with the preparation Agregal requires caution.
Acetylsalicylic acid: acetylsalicylic acid does not alter the formulation Agregal ingibiruyushego effect on ADP-induced platelet aggregation, but enhances Agregal drug acetylsalicylic acid on collagen-induced platelet aggregation. The combined use of these drugs requires caution.
Heparin: according to clinical trials conducted in healthy persons, not izenyaet clopidogrel or heparin requirements nor the action of heparin on blood clotting. The simultaneous use of heparin did not alter the inhibitory effect of clopidogrel on platelet aggregation. However, the safety of such combinations has not been established and the simultaneous use of these drugs requires caution.
Fibrinolitiki : safety of combined use of clopidogrel, recombinant tissue plasminogen activator (rt-PA) and heparin was studied in patients with a recent myocardial infarction. The incidence of clinically significant bleeding was similar to that
I observed in the case of joint use of rt-PA and heparin. Security co-application of clopidogrel with other fibrinolytics is not yet established, and the simultaneous use of these drugs requires caution.
Nonsteroidal anti-inflammatory agents : Assignment NSAIDs together with the drug Agregal requires caution (may increase the risk of bleeding).
The combined use with other medicinal products : there were no observed clinically significant pharmacodynamic interaction with clopidogrel in conjunction with atenolol, nifedipine, phenobarbital, cimetidine, estrogens, digoxin, theophylline, phenytoin, tolbutamide and antacid, however, there is evidence that clopidogrel inhibits the activity of one of cytochrome CYP2C9 enzyme and may alter the concentration of medicines metabolized by CYP2C9 (phenytoin, tolbutamide, and others).