Dosage form: tablet, film coated
Composition: 1 tablet, film-coated, contains:
active substance: clopidogrel hydrosulfate 97,875 mg, equivalent to clopidogrel – 75 mg
auxiliary substances: starch pregelatinization 27 mg, anhydrous lactose (milk sugar anhydrous) 63,125 mg, macrogol (polyethylene glycol 6000) 8 mg magnesium stearate 1 mg microcrystalline cellulose 40 mg hydrogenated castor oil 3 mg,
the composition of the film shell: Select AQ-01673 – 9 mg: hypromellose (hydroxypropyl methylcellulose) 3.6 mg, macrogol (polyethylene glycol 400) 0.9 mg, macrogol (polyethylene glycol 6000) of 0.9 mg titanium dioxide 2.7 mg, aluminum lacquer dye Ponceau 4 R of 0.9 mg.
Description: Tablets, film-coated pink, round, biconvex shape.
Pharmacotherapeutic group: antiplatelet drug.
Code ATX: В01АС04
Clopidogrel is a specific and active inhibitor of platelet aggregation, has koronrodilatirtee action. Selectively reduces the binding of ADP receptors on platelets and activation of the receptors of the GPI Ib/IIIa by the action of ADP, impairing platelet aggregation.
Reduces agregatia platelets, caused by other agonists, preventing activation of the released ADP, does not affect the activity of phosphodiesterase (PDE). Irreversibly binds to ADP-receptors platelets, which remain impervious to the stimulation of ADP throughout the life cycle (about 7 days).
Inhibition of platelet aggregation is observed 2 hours after administration (40% inhibition) initial dose of 400 mg. the Maximum effect (60% suppression of aggregation) develops in 4 to 7 days of admission at a dose of 50 – 100 mg/day. Antiplatelet effect lasts the entire lifetime of the platelet (7 – 10 days).
In the presence of atherosclerotic lesions of the vessel prevents the development of atherothrombosis regardless of the localization of vascular process (cerebrovascular, cardiovascular or peripheral lesions).
Clopidogrel is rapidly absorbed in exchange ingestion of 75 mg a day. Bioavailability of high. However, the concentration of the original substance in the plasma is low and in 2 hours after admission does not reach the measurement limit (0,025 µg/l). Relationship with blood plasma proteins – 98-94%.
Clopidogrel is rapidly metabolized in the liver. Its main metabolite – inactive derivative carboxylato acid, the time to maximum concentration (Dmah) which, after repeated oral doses of 75 mg achieved through 1 h (Cmax about 3 mg/l).
About 50% of the drug excreted by the kidney and approximately 46% in the feces within 120 hours after injection. The half-life of the main metabolite after single and repeated administration is 8 hours. The concentration of secreted metabolites by the kidneys – 50%.
The concentration of the main metabolite in plasma after administration of 75 mg/day lower in patients with severe renal disease (creatinine clearance (CC) – 5-15 ml/min) compared with patients with kidney disease of moderate severity (QC of 30 to 60 ml/min) and healthy subjects.
Indications for use:
Prevention of atherothrombotic events in patients with myocardial infarction, ischemic stroke or with diagnosed occlusive peripheral arterial disease.
Prevention of atherothrombotic events (in combination with acetylsalicylic acid) in patients with acute coronary syndrome:
-without ST-segment elevation (unstable angina or myocardial infarction without Q wave), including patients who was held stenting in percutaneous coronary intervention
-c a ST-segment elevation (acute myocardial infarction) treatment is medication and the possibility of thrombolysis.
-Hypersensitivity to any active or auxiliary component of the drug,
-Severe hepatic insufficiency,
-Active bleeding (including bleeding from peptic ulcer or intracranial hemorrhage),
-Pregnancy and lactation,
-The age 18 years (efficacy and safety not established),
-Lactose intolerance, lactase deficiency, syndrome of glucose-galactose malabsorption.
Moderate liver failure, chronic renal failure (CRF), pathological conditions that increase the risk of bleeding (including trauma, surgery), concomitant use of ASA, warfarin, nonsteroidal anti-inflammatory drugs (NSAIDs) (including COX-2 inhibitors), heparin, and inhibitors of glycoprotein IIb/IIIa, genetic reduction of function of the CYP2C19 isoenzyme.
Pregnancy and lactation
Due to lack of data, it is recommended not to take clopidogrel during pregnancy and lactation.
Method of application and dose:
Adults and elderly clopidogrel should be taken orally at 75 mg once a day, regardless of meals.
Treatment should begin with the first days on the 35th day after myocardial infarction, in terms from 7 days to 6 months after ischemic stroke.
For the prevention of thrombotic complications in acute coronary syndrome without ST-segment elevation (unstable angina or myocardial infarction without Q wave) treatment with clopidogrel should be started one-time loading dose of 300 mg and then continued with a dose of 75 mg once daily (ASA 75-325 mg daily). Because the use of high doses of ask associated with a higher risk of bleeding, the recommended dose should not exceed 100mg. Maximum beneficial effect after 3 months. The course of treatment up to 1 year.
To prevent thrombotic complications of acute coronary syndrome with ST-segment elevation (acute myocardial infarction with ST-segment elevation) – 75 mg/day with an initial one-time admission loading dose in combination with ASA and with thrombolytic drugs (or without thrombolytics).
For patients older than 75 years, treatment with clopidogrel should be undertaken without the use of a loading dose. Combination therapy should begin as soon as possible after symptoms develop and continue for at least four weeks.
In patients with a genetically determined reduced function of the CYP2C19 isoenzyme may reduce the effect of clopidogrel. The optimum dosage regimen in such patients is not installed.
Experience of use in patients with chronic renal failure or moderate hepatic insufficiency is limited.
Frequency of adverse reactions given below were determined according to the following:
-very often >,1/10,
often >,1/100, <,1 10=”” br=””>,-infrequently >,1/1000, <,1 100=”” br=””>,-rarely >,1/10 000, <,1 1000=”” br=””>, which very seldom <,1 10=”” 000=”” p=””>,
Of the cardiovascular system frequent: bruising very rare: severe bleeding, bleeding from the operative wound, vasculitis, decrease in blood pressure.
From the nervous system uncommon: headache, dizziness, paresthesia, intracranial hemorrhage rarely: systemic dizziness very rare: confusion, hallucinations, disorders of taste sensations.
From the gastrointestinal tract common: gastrointestinal bleeding, diarrhea, abdominal pain, dyspepsia rare: gastric ulcer, duodenal ulcer, gastritis, nausea, vomiting, constipation, flatulence rare: retroperitoneal hematoma is very rare: pancreatitis, colitis (including ulcerative or lymphocytic colitis), stomatitis acute liver failure, hepatitis, severe gastrointestinal bleeding with fatal outcome.
From the hematopoietic system uncommon: thrombocytopenia, leukopenia, eosinophilia rare: neutropenia, including severe, very rare: thrombotic thrombocytopenic purpura (TTP) (see section “Special instructions”), severe thrombocytopenia (platelet count <,30 109=”” br=””>,From the musculoskeletal system very rare: haemarthrosis, arthritis, arthralgia, myalgia.
Urogenital system infrequent: hematuria,very rare: glomerulonephritis.
With the skin frequently: bruising, uncommon: skin rash, pruritus, purpura very rare: angioneurotic edema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis,rash erythematous, urticaria, eczema and oral lichen planus.
From the respiratory organs very common: epistaxis very rare: bronchospasm, interstitial pneumonitis, pulmonary hemorrhage, hemoptysis.
From the senses uncommon: bleeding in the conjunctiva, retina, rare: dizziness.
Allergic reactions very rarely – anaphylactic reactions, serum sickness.
Laboratory parameters very rare: alterations in liver function tests, increased level of blood creatinine, prolonged bleeding time.
Other common: haemorrhage at the injection site very rare: fever.
An overdose of clopidogrel may lead to prolonged bleeding time and haemorrhagic complications. Upon detection of bleeding should be applied the appropriate treatment.
Not discovered antidotes pharmaceutical activity of clopidogrel.
If you need a fast correction of the lengthening of bleeding time, it is recommended that the platelet transfusion.
Interaction with other drugs
Warfarin: concomitant use with clopidogrel can increase the intensity of bleeding, therefore, the use of this combination is not recommended.
Blockers IIb/IIIa receptor: assigning blockers IIb/IIIa receptor in conjunction with clopidogrel requires caution in patients with an increased risk of bleeding (trauma and surgical interventions or other pathological conditions).
Acetylsalicylic acid: acetylsalicylic acid does not alter the effect of clopidogrel inhibition of ADP-induced platelet aggregation, but clopidogrel potentiates the effect of acetylsalicylic acid on collagen-induced platelet aggregation. However, simultaneous with clopidogrel acetylsalicylic acid on 500 mg 2 times a day for 1 day did not cause a significant increase in bleeding time caused by clopidogrel. Between clopidogrel and acetylsalicylic acid is possible pharmacodynamic interaction, which leads to increased risk of bleeding. Therefore, during their concomitant use should be with caution. Although clinical studies, patients received combination therapy with clopidogrel and acetylsalicylic acid up to one year.
Heparin: in clinical trials conducted with the participation of healthy individuals in the clopidogrel is not required change the dose of heparin and did not change its anticoagulant effects. Coadministration of heparin did not change the antiplatelet effect of clopidogrel. Medulloepithelioma and heparin is possible pharmacodynamic interaction, which may increase the risk of bleeding, so the simultaneous use of these drugs requires caution.
Thrombolytics: the safety of joint use of clopidogrel, fibrinoliticeski or fibrinolizina drugs and heparin was studied in patients with acute myocardial infarction. The frequency of clinically significant bleeding was similar to that observed in the case of a joint application means of the thrombolytic and heparin with acetylsalicylic acid.
Nonsteroidal anti-inflammatory drugs (NSAIDs): in a clinical study involving healthy volunteers, the combined use of clopidogrel and naproxen increased the hidden blood loss through the gastrointestinal tract. However, no studies have vzaimodeistviyami with other NSAIDs, nastojashee time it is not known whether there is increased risk of gastrointestinal bleeding when taking clopidogrel with other NSAIDs. Therefore, the appointment of NSAIDs, including COX-2 inhibitors in combination with clopidogrel should be undertaken with caution.
Another combination therapy: since clopidogrel is metabolised to the formation of its active metabolite partly by means of a system of CYP2C19, use of drugs inhibiting this system (eg, omeprazole), is not recommended.
Conducted a series of clinical trials with clopidogrel and other, at the same time prescribed drugs, to study the possible pharmacodynamic pharmacokinetic interactions, which showed that:
-the use of clopidogrel in conjunction with atenolol, nifedipine, or both drugs simultaneously clinically significant pharmacodynamic interactions were observed
-concurrent use of phenobarbital, cimetidine or estrogen had no significant effect on the pharmacodynamics of clopidogrel
-the pharmacokinetic parameters of digoxin or theophylline were not changed in their combined use with clopidogrel
-antacids did not reduce the absorption of clopidogrel
-phenytoin and tolbutamide can be safely used in conjunction with clopidogrel (CAPRIE study), despite the fact that data obtained in studies with human liver microsomes, indicate that the carboxyl metabolite of clopidogrel can inhibit the activity of isoenzyme 2C9 of cytochrome P450 family that can lead to increased plasma concentrations of certain drugs (phenytoin, tolbutamide, and some NSAIDs), which are metabolized with isoenzyme 2C9 of the cytochrome P450 family.
-ACE inhibitors, diuretics, ?-blockers, blockers slow calcium channels, lipid-lowering means, coronary vasodilators, lipid-lowering means (including insulin), antiepileptic remedies, hormone replacement therapy and blockers of GPIIb/IIIa receptor: in clinical studies, no clinically significant undesirable interactions.
During treatment necessary to monitor the indicators of hemostasis system (activated partial thromboplastin time (APTT), number of platelets, tests of functional activity of platelets), regularly examine the functional activity of the liver.
The patients should be carefully monitored to detect any signs of bleeding, including hidden, especially during the first weeks of the drug and/or after invasive procedures on the heart or surgery.
Clopidogrel should be used with caution in patients with increased risk of bleeding with trauma, surgery, other pathological conditions, diseases predisposing to the development of bleeding (especially gastrointestinal and ocular), and in patients receiving ASA, nonsteroidal anti-inflammatory drugs (including COX-2 inhibitors), heparin or inhibitors of glycoprotein IIb/IIIa.
The simultaneous use of clopidogrel and warfarin is not recommended, as it may intensify the bleeding (except for special rare clinical situations).
In the case of surgery if antiplatelet effect is undesirable, the treatment should be discontinued 7 days before surgery.
Clopidogrel prolongs bleeding time and should be used with caution in patients with diseases predisposing to the development of bleeding (particularly gastrointestinal and intraocular).
Patients should be warned that because the stop occurs on the background of the use of clopidogrel (in combination with ASA or no) bleeding requires more time, they should inform the doctor about each case of bleeding. Patients should also inform the doctor (including your dentist) about the drug, if they have surgery, dental procedures and before taking any new drug.
Very rarely after administration of clopidogrel (including short-term use) were observed thrombotic thrombocytopenic purpura (TTP). This condition is characterized by thrombocytopenia and microangiopathic hemolytic anemia in combination with neurological signs, impaired kidney function or fever. TTP is a potentially life-threatening disease requiring immediate treatment, including the use of plasmapheresis.
Experience with the use of clopidogrel in patients with impaired renal function is limited, therefore, these patients clopidogrel should be administered with caution.
In severe liver dysfunction should be aware of the risk of developing hemorrhagic diathesis, experience with the drug in patients with moderate hepatic impairment is limited, therefore, these patients clopidogrel should be administered with caution.
Clopidogrel should not be taken by patients with rare hereditary galactose intolerance, lactase deficiency and malabsorption syndrome of glucose-galactose.
Effects on ability to drive a vehicle, other mechanisms.
In connection with the possibility of dizziness when taking clopidogrel should be careful when driving and occupation of other potentially hazardous activities, requ re high concentration and psychomotor speed reactions.
Form of issue:
Tablets, film-coated, 75 mg. For 7, 10, 15 or 30 tablets in a contour cell package made of polyvinylchloride film and aluminum foil printed patent. 2, 4 contour packs of 7 tablets or 1, 3, 5, 6 contour sells packaging of 10 tablets or 1, 2, 4 contour packs of 15 tablets or 1, 2 contour cell packs of 30 tablets along with instructions for use in a cardboard package.
Storage conditions: Store in a dry, protected from light place at temperature not exceeding 25 0C.
Keep out of reach of children.
Shelf life: 2 years. Do not use after expiration date.
|The purpose of the medication||Anti-aggregants|