Clopidex
Clopidex: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Klopidex
ATX code: B01AC04
Active ingredient: clopidogrel (Clopidogrel)
Producer: Bilim Pharmaceuticals (Turkey)
Description and photo update: 2019-12-07
Prices in pharmacies: from 293 rubles.
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Clopidex is an antiplatelet drug.
Release form and composition
The drug is produced in the form of film-coated tablets, biconvex, round, pale pink (15 pcs. In a blister, 2 blisters in a cardboard box; 14 pcs. In a blister, in a cardboard box 1 or 4 blisters and instructions for use Clopidex).
1 film-coated tablet contains:
- active substance: clopidogrel hydrogen sulfate form-I - 97.875 mg, which corresponds to clopidogrel in the amount of 75 mg;
- additional components: mannitol, hyprolose, microcrystalline cellulose, hydrogenated castor oil, macrogol-6000;
- film shell: Opadry pink [hypromellose (15 CPS), lactose monohydrate, triacetin, titanium dioxide (E171), iron oxide red (E172)].
Pharmacological properties
Pharmacodynamics
Clopidogrel is a prodrug in which one of the active metabolites is an inhibitor of platelet aggregation. This metabolic product of clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) and its receptors on platelets, as well as further activation of the glycoprotein IIb / IIIa complex (GPIIb / IIIa) associated with ADP, which inhibits platelet aggregation.
Due to irreversible binding, platelets show resistance to ADP stimulation throughout the rest of their life (on average, 7-10 days). Normal platelet function is restored at a rate that matches the rate at which platelets are renewed.
Platelet aggregation, caused by agonists different from ADP, is also suppressed by blocking the intensive activation of platelets by the released ADP.
Since the formation of an active metabolite is carried out with the participation of enzymes of the P450 system, a number of which can be suppressed by other drugs or can differ in polymorphism, adequate suppression of platelets is possible not in all patients.
Clopidex has the ability to prevent the onset of atherothrombosis during the course of an atherosclerotic process in the cerebral, coronary or peripheral arteries, as well as in any other localization of atheromatous plaque deposition. In the case of daily intake of clopidogrel at a dose of 75 mg, from the first day of the course of treatment, a pronounced inhibition of ADP-induced platelet aggregation is recorded, which then increases for 3-7 days and demonstrates a constant level upon reaching an equilibrium state.
Platelet aggregation against the background of an equilibrium state is inhibited by about 40-60%. At the end of the use of the drug, platelet aggregation and bleeding time, on average, within 5 days, return to their original value.
Pharmacokinetics
After oral administration of Clopidex at a daily dose of 75 mg, it demonstrates high absorption and bioavailability. At the same time, the plasma level of the starting substance is rather low and does not reach 2 hours after the measurement limit is taken (0.025 μg / l). According to the renal secretion of the metabolic products of clopidogrel, absorption is approximately 50%.
The active substance and its main inactive metabolite circulating in the blood carry out a reversible connection with plasma proteins by 98 and 94%, respectively.
The biotransformation of clopidogrel proceeds intensively in the liver. The main metabolite, which is an inactive derivative of carboxylic acid, accounts for approximately 85% of the substance circulating in plasma. The period of reaching the highest concentration (T Cmax) of this metabolite (C max - approximately 3 mg / l after a course of oral use at a dose of 75 mg) is reached 1 hour after administration.
The active metabolite of the substance, which is a thiol derivative, is formed through the oxidation of clopidogrel to 2-oxoclopidogrel and further hydrolysis. This in vitro metabolic pathway is produced with the participation of isoenzymes P450, CYP1A2, CYP2C19 and CYP2B6. The thiol metabolite isolated in vitro binds irreversibly and quickly to platelet receptors and suppresses their aggregation.
On average, within 120 hours after oral administration of the drug, 50% of the active substance is excreted by the kidneys and 46% by the intestines. After a single oral administration of Clopidex at a dose of 75 mg, its half-life (T 1/2) is approximately 6 hours. T 1/2 of the main circulating inactive metabolite is 8 hours, both after a single dose and after repeated administration.
The isoenzyme CYP2C19 is involved in the formation of an active metabolite, as well as an intermediate metabolite - 2-oxoclopidogrel. The antiplatelet effect and pharmacokinetic parameters of the active metabolite, established by ex vivo platelet aggregation, differ in accordance with the genotype of the CYP2C19 isoenzyme inherent in the patient. The allele of the CYP2C19 * 1 gene ensures the normal functioning of the metabolism, and the alleles of the CYP2C19 * 2 and CYP2C19 * 3 gene are responsible for reducing its intensity. These alleles are responsible for the weakening of metabolic processes on average in 85% of representatives of the Caucasian race and in 99% of the Mongoloid race. Other alleles associated with reduced metabolism, such as CYP2C19 * 4, * 5, * 6, * 7 and * 8, are much less common in the general population.
In certain groups of patients, the pharmacokinetic parameters of the active metabolite have not been studied.
Indications for use
- prevention of atherothrombotic events in diagnosed peripheral arterial occlusive disease, ischemic stroke or myocardial infarction;
- prevention of atherothrombotic events in combination with acetylsalicylic acid (ASA), against the background of acute coronary syndrome: with ST segment elevation (acute myocardial infarction) during standard drug treatment and the possibility of thrombolytic therapy; without ST-segment elevation (myocardial infarction without Q wave or unstable angina pectoris), including in the case when stenting was performed during percutaneous coronary intervention.
Contraindications
Absolute:
- acute bleeding (including intracranial hemorrhage or peptic ulcer);
- severe liver failure;
- syndrome of glucose-galactose malabsorption, lactase deficiency, lactose intolerance (since Clopidex contains lactose);
- age up to 18 years;
- pregnancy and lactation;
- hypersensitivity to any of the constituents of the drug.
Relative (Clopidex is recommended to be taken with caution):
- chronic renal failure (CRF);
- moderate hepatic impairment;
- pathological conditions that aggravate the risk of bleeding (including surgical interventions, trauma), a predisposition to bleeding;
- hereditary decrease in CYP2C19 function;
- combination therapy with non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase 2 (COX-2); ASA, warfarin, heparin, GPIIb / IIIa inhibitors.
Clopidex, instructions for use: method and dosage
Clopidex 75 mg film-coated tablets are intended for oral administration. Meal time does not affect the effectiveness of the drug.
The recommended dosage regimen of Clopidex, taking into account the indications:
- prevention of atherothrombotic events in patients with diagnosed peripheral arterial occlusive disease, with an ischemic stroke or myocardial infarction: 1 time per day at a dose of 75 mg; in persons with myocardial infarction, it is necessary to start using Clopidex from the first days and continue taking it until the 35th day after a heart attack; in persons with ischemic stroke, it is recommended to take the drug in the period from 7 days to 6 months after suffering an acute violation of cerebral circulation;
- prevention of atherothrombotic events in persons with acute coronary syndrome without ST segment elevation (unstable angina pectoris or myocardial infarction without Q wave): at the beginning of the course, a single dose of 300 mg loading dose, then - 1 time per day at a dose of 75 mg (in combination with ASA in daily doses of 75–325 mg, the recommended optimal dose is 100 mg, since taking higher doses of ASA is associated with an increase in the threat of bleeding); the most favorable effect is noted 3 months after the start of admission, the course - up to 1 year;
- prevention of atherothrombotic events in persons with acute coronary syndrome with ST segment elevation (acute myocardial infarction): a single dose of 300 mg loading dose, then - in a daily dose of 75 mg in combination with ASA and thrombolytics, or without thrombolytics; combined treatment should be started as soon as possible after the onset of symptoms and continued for at least 4 weeks; the effectiveness of the combined administration of clopidogrel and ASA for more than 4 weeks for this indication has not been studied.
In patients with a genetically determined decrease in the function of the isoenzyme CYP2C19, a weakening of the effect of Clopidex may be observed. The mode of using higher doses (loading dose - 600 mg, daily therapeutic dose - 150 mg) with low activity of the isoenzyme CYP2C19 increases the antiplatelet effect of clopidogrel. At the moment, in the course of studies taking into account clinical outcomes, the optimal dosing regimen in these patients has not been determined.
If the patient has forgotten to take the next dose of Clopidex, in the case when less than 12 hours have passed since the pass, the tablets should be taken immediately, and the next ones should be used as usual. If, after missing the next dose, more than 12 hours have passed, you need to take the next one at the usual time. To compensate for the missed dose of clopidogrel, you should not use the missed and current doses at the same time.
Side effects
- sense organs: infrequently - hemorrhage in the retina and / or conjunctiva of the eye; rarely - vertigo;
- nervous system: infrequently - dizziness, headache, paresthesia, intracranial bleeding (including fatal cases); extremely rarely - a violation of taste, hallucinations, confusion;
- hematopoietic organs: infrequently - eosinophilia, thrombocytopenia, leukopenia; rarely - neutropenia, including severe; extremely rare - anemia, including aplastic; thrombotic thrombocytopenic purpura (TTP), agranulocytosis, pancytopenia, granulocytopenia, severe thrombocytopenia;
- respiratory system: very often - nosebleeds; extremely rare - bronchospasm, hemoptysis, pulmonary hemorrhage, interstitial pneumonitis;
- cardiovascular system: often - hematoma; extremely rarely - severe bleeding (cases of severe bleeding were recorded with a combination of clopidogrel with ASA or with ASA and heparin), lowering blood pressure (BP), bleeding from an operating wound, vasculitis;
- skin: often - subcutaneous hemorrhage; infrequently - itching, skin rash, purpura; extremely rare - urticaria, erythematous rash, eczema, angioedema, erythema multiforme, lichen planus, toxic epidermal necrolysis, Stevens-Johnson syndrome;
- digestive system: often - abdominal pain, dyspepsia, diarrhea, bleeding from the gastrointestinal tract (GIT); infrequently - flatulence, vomiting, constipation, nausea, gastritis, gastric and duodenal ulcers; rarely - retroperitoneal bleeding; extremely rarely - stomatitis, colitis, including ulcerative and lymphocytic; pancreatitis, impaired liver function tests, hepatitis, acute liver failure, bleeding from the gastrointestinal tract with a fatal outcome;
- allergic reactions: extremely rarely - serum sickness, anaphylactic reactions;
- genitourinary system: infrequently - hematuria; extremely rare - hypercreatininemia, glomerulonephritis;
- musculoskeletal system: extremely rare - myalgia, arthralgia, hemarthrosis, arthritis;
- laboratory parameters: infrequently - lengthening of bleeding time;
- others: extremely rare - fever.
Overdose
Symptoms of an overdose of clopidogrel may be prolonged bleeding time and subsequent complications in the form of bleeding. When these violations appear, measures are taken to stop bleeding and platelet transfusion is prescribed.
special instructions
In the course of treatment with Clopidex, the indicators of the hemostasis system, such as platelet count, activated partial thromboplastin time (APTT), should be monitored, and tests to assess liver function should be performed regularly.
During the period of drug therapy, especially during the first weeks of the course and / or after surgery or invasive procedures on the heart, patients must be closely monitored for the timely detection of any signs of bleeding (including latent).
If the patient requires surgery and the antiplatelet effect is undesirable, the course of therapy should be completed 7 days before the operation.
It should be remembered that in the case of using clopidogrel (alone or in combination with ASA), it may take a longer period of time to stop bleeding. If unusual (in terms of location / duration) bleeding occurs, the patient should seek the advice of a specialist.
Patients who are to undergo surgical interventions (including dental ones) should inform the doctor about the drug treatment.
Against the background of therapy with Clopidex, the development of Moshkovitz's syndrome (TTP) was extremely rarely recorded, sometimes even after a short-term admission. This complication is characterized by the occurrence of thrombocytopenia and microangiopathic hemolytic anemia in combination with neurological manifestations, fever and kidney damage. This syndrome is one of the potentially dangerous conditions requiring immediate treatment, including plasmapheresis.
Due to the lack of data, it is not recommended to prescribe Clopidex in the first 7 days after an acute ischemic stroke.
It has been established that taking medications containing hydrogenated castor oil can lead to dyspepsia and diarrhea.
Influence on the ability to drive vehicles and complex mechanisms
Clopidex does not adversely affect the ability to drive a car and other complex mechanisms.
Application during pregnancy and lactation
There are no clinical data on the use of Clopidex in pregnant women. The drug can be prescribed during pregnancy only if the expected benefit to the mother outweighs the possible threat to the health of the fetus.
According to the data of preclinical studies on animals, direct or indirect negative effects of Clopidex on pregnancy, embryo development, childbirth and postnatal development have not been recorded.
Whether clopidogrel is excreted in human milk has not been established. In animal tests, it was noted that Clopidex can pass into breast milk. If it is necessary to take clopidogrel during lactation, you need to transfer the child to artificial feeding.
Pediatric use
There is no experience with clopidogrel in children. Treatment of patients under 18 years of age with Clopidex is contraindicated.
With impaired renal function
After taking Clopidex in a daily dose of 75 mg, the plasma level of the main circulating metabolite of clopidogrel in patients with severe chronic renal failure, with creatinine clearance (CC) of 5-15 ml / min, was lower than that in patients with moderate CRF (CC - 30-60 ml / min) and in healthy volunteers. After repeated use of clopidogrel at the same daily dose in patients with severe chronic renal failure, suppression of ADP-induced platelet aggregation was recorded 25% lower than a similar effect in healthy volunteers. In this case, the lengthening of the bleeding period was the same as in the volunteers who received clopidogrel at a dose of 75 mg per day.
The experience of using Clopidex in patients with chronic renal failure is limited; therefore, patients from this group must be prescribed it with extreme caution.
For violations of liver function
In the presence of cirrhosis of the liver, oral administration of clopidogrel at a daily dose of 75 mg for 10 days was well tolerated and was quite safe. With single and repeated administration in patients with liver cirrhosis, the C max of the active substance was much higher than that in healthy volunteers. However, the plasma level of the main circulating metabolite and ADP-induced platelet aggregation, as well as the bleeding time were comparable in both groups.
In patients with severe hepatic impairment, therapy with Clopidex is contraindicated, with a moderate degree - it should be carried out with caution due to the limited experience of using the drug in this group of patients. In persons with moderate hepatic impairment, it is required to take into account the aggravation of the risk of developing hemorrhagic diathesis.
Use in the elderly
Between young volunteers and patients over the age of 75, there were no differences in the increase in bleeding time and indicators characterizing platelet aggregation. Elderly patients do not need a dose adjustment of the drug, however, persons over the age of 75 years should start using Clopidex without taking a loading dose.
Drug interactions
- warfarin: an increase in the intensity of bleeding is possible, as a result of this, in addition to special exceptional clinical situations, including stenting in patients with atrial fibrillation or the presence of a floating thrombus in the left ventricle, this combination is not recommended;
- NSAIDs; inhibitors of GPIIb / IIIa: the threat of bleeding is aggravated, caution is required with combination therapy;
- ASA: there is no change in the inhibitory effect of clopidogrel on ADP-induced platelet aggregation, but there is an increase in the effect of ASA on collagen-induced aggregation of the latter; the combined use of these funds requires caution, however, in the presence of acute coronary syndrome without ST segment elevation, long-term combination therapy of these drugs is recommended (up to 1 year);
- inhibitors of CYP2C19 (including omeprazole): concurrent use is not recommended;
- tolbutamide, phenytoin, NSAIDs: the plasma concentrations of these drugs in the blood increase, due to the suppression of the activity of the CYP2C9 isoenzyme by the active metabolite of clopidogrel;
- antacids: there is no change in the absorption of clopidogrel;
- angiotensin-converting enzyme (ACE) inhibitors; atenolol, phenobarbital, nifedipine, cimetidine, digoxin, theophylline, estrogens, drugs that lower blood cholesterol levels: no significant interaction was found in clinical studies with the simultaneous use of these drugs and clopidogrel.
Analogs
Analogs of Clopidex are Detromb, Zilt, Deplatt-75, Cardogrel, Cardutol, Pidogrel, Klapitax, Clopidogrel, Plavix, Tromborel, etc.
Terms and conditions of storage
Keep out of the reach of children at a temperature not exceeding 25 ° C.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Clopidex
According to a few reviews, Clopidex has worked well when used as part of a combination therapy after a myocardial infarction. The effect of the treatment was also noted by patients taking it against the background of cardiac arrhythmias.
It is extremely rare to indicate the occurrence of side effects. A single case is described when taking Clopidex at a dose of 75 mg for 3 days caused ruptures of small blood vessels on the lower extremities with the formation of hematomas, especially in the folds.
The price of Clopidex in pharmacies
The price of Clopidex 75 mg, film-coated tablets, can be 280–410 rubles. per package containing 30 pcs.
Clopidex: prices in online pharmacies
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Drug name Price Pharmacy |
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Clopidex 75 mg film-coated tablets 30 pcs. 293 r Buy |
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Clopidex tablets p.p. 75mg 30 Pcs. 482 r Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
