Pharmacological properties of the drug Atherocard
The drug has an antiplatelet effect. Selectively and irreversibly inhibits the binding of adenosine diphosphate (ADP) to its receptors on the surface of platelets, blocks platelet activation and thus inhibits their aggregation. Inhibition of platelet aggregation is observed 2 hours after oral administration of a single dose of the drug (40% inhibition). With repeated use, the effect increases, a stable state is achieved after 3–7 days of treatment (up to 60% inhibition). Platelet aggregation and bleeding time return to baseline levels as platelet turnover occurs, which is an average of 7 days after discontinuation of dosing. After oral administration in a dose of 75 mg, it is quickly absorbed into the gastrointestinal tract. Due to rapid biotransformation in the liver, the concentration of the drug in the blood plasma 2 hours after administration is insignificant (0.025 μg/l). The main metabolite (85% of the compound circulating in the blood plasma) is inactive. The active thiol metabolite quickly and irreversibly binds to platelet receptors. It is not detected in blood plasma. Clopidogrel and the main circulating metabolite are reversibly bound to plasma proteins. After taking the drug orally, about 50% of the dose taken is excreted in the urine and 46% in the feces. The half-life of the main metabolite is 8 hours.
special instructions
If bleeding is suspected, appropriate tests and/or a complete blood count should be performed immediately.
Atherocardium should be discontinued 7 days before the proposed surgery, as the drug increases the duration of bleeding.
Patients should be warned that during treatment with clopidogrel bleeding may be prolonged and stop later. Any case of unusual bleeding in duration or location should be reported to your doctor.
Atherocardium does not affect or has a minimal effect on the speed of psychomotor reaction and the ability to concentrate. If dizziness develops while taking the drug, you should stop driving and other potentially dangerous activities.
Use of the drug Atherocard
Orally, 1 tablet (75 mg) 1 time per day, regardless of meals. Treatment should begin within a period of several days to 35 days in patients after myocardial infarction and from 7 days to 6 months in patients after an ischemic stroke. In patients with acute coronary syndrome (ACS) without ST , treatment with Atherocard should be started with a single dose of 300 mg on the 1st day of treatment, and then continued with a dose of 75 mg/day in combination with acetylsalicylic acid at a dose of 75–325 mg/day .
Release form and composition
Atherocardium is produced in the form of film-coated tablets: round, biconvex, pink (10 pieces in a blister, 1 or 4 blisters in a cardboard pack).
Composition of 1 tablet:
- active ingredient: clopidogrel (in the form of clopidogrel hydrogen sulfate) – 75 mg;
- auxiliary components: magnesium stearate, povidone, lactose monohydrate, pregelatinized starch, polyethylene glycol 6000, microcrystalline cellulose;
- film shell: Opadry II Pink (hypromellose, triacetin, titanium dioxide, lactose monohydrate, polyethylene glycol, indigo carmine aluminum varnish, charming red aluminum varnish).
Side effects of the drug Aterocard
From the blood coagulation system: hematuria, purpura, nasal, gastrointestinal, conjunctival and intracranial bleeding. From the hematopoietic system: very rarely - neutropenia, thrombocytopenia. From the digestive system: abdominal pain, nausea, constipation, diarrhea, exacerbation of peptic ulcers of the stomach and duodenum. Disorders of the liver and biliary tract. From the side of the central nervous system: headache, dizziness. Dermatological reactions: skin rash. Hypersensitivity reactions have been noted; in some cases - bronchospasm, angioedema, anaphylactic reactions, fever.
Side effects
- digestive system: often - dyspepsia, abdominal pain, gastrointestinal bleeding, diarrhea; uncommon – nausea, vomiting, gastritis, duodenal and gastric ulcers, flatulence, constipation; rarely – retroperitoneal bleeding; very rarely - stomatitis, colitis (including lymphocytic or ulcerative), pancreatitis, retroperitoneal and gastrointestinal bleeding with a fatal outcome;
- hepatobiliary system: very rarely - hepatitis, acute liver failure, impaired liver function tests;
- cardiovascular system: often – hematoma; very rarely - vasculitis, severe hemorrhage, arterial hypotension, bleeding from the surgical wound;
- hematopoietic system: infrequently – leukopenia, thrombocytopenia, eosinophilia; rarely – neutropenia (including severe); very rarely - anemia, agranulocytosis, granulocytopenia, thrombotic thrombocytopenic purpura, pancytopenia, severe thrombocytopenia;
- respiratory system: often – nosebleeds; very rarely - bronchospasm, pulmonary hemorrhage, hemoptysis, interstitial pneumonitis;
- central nervous system: uncommon – dizziness, paresthesia, intracranial bleeding (sometimes fatal), headache; very rarely - taste disturbance, hallucinations, confusion;
- sensory organs: uncommon – ocular, conjunctival or retinal bleeding; rarely – dizziness due to pathology of the ear and labyrinth;
- musculoskeletal system: very rarely - arthritis, myalgia, hemarthrosis, arthralgia;
- urinary system: infrequently – hematuria; very rarely - increased plasma creatinine levels, glomerulonephritis;
- skin and subcutaneous tissue: often – subcutaneous hemorrhage; uncommon – itching, rash, purpura; very rarely - urticaria, lichen planus, erythematous rash, eczema, bullous dermatitis, angioedema;
- allergic reactions: very rarely - anaphylactic reactions, serum sickness;
- laboratory parameters: infrequently - prolongation of bleeding time;
- other: very rarely – fever.
Special instructions for the use of the drug Atherocard
Prescribe with caution to patients with an increased risk of bleeding (peptic ulcer, intracranial hemorrhage, trauma, surgery, coagulopathy, etc.). In the case of surgical interventions, if the antiplatelet effect is undesirable, the drug should be discontinued 7 days before surgery. If symptoms of excessive bleeding appear (bleeding gums, menorrhagia, hematuria), a study of the hemostasis system (bleeding time, platelet count, platelet functional activity tests) is indicated. When treating patients with severely impaired liver function, the possibility of developing hemorrhagic diathesis should be taken into account; Regular monitoring of laboratory parameters of liver function is recommended. No dose adjustment is required in elderly patients or patients with renal failure.
Contraindications
Absolute:
- severe liver failure;
- intracranial hemorrhage, peptic ulcer and other conditions with a risk of acute bleeding;
- lactase deficiency, galactose intolerance, glucose-galactose malabsorption syndrome;
- children and adolescents up to 18 years of age;
- pregnancy;
- breast-feeding;
- increased individual sensitivity to clopidogrel or any of the auxiliary components of the drug.
Relative (Atherocard is used with caution):
- moderate to mild liver failure;
- renal failure;
- hemorrhagic diathesis (history);
- surgical interventions, trauma and other pathological conditions with an increased risk of bleeding;
- simultaneous use with heparin, ASA, non-steroidal anti-inflammatory drugs and glycoprotein IIb/IIIa inhibitors.
Drug interactions Atherocard
The drug potentiates the effect of acetylsalicylic acid on platelet aggregation induced by collagen. Increases the risk of gastrointestinal bleeding while taking NSAIDs. The combined use of the drug with warfarin is not recommended, since this combination may increase bleeding. When used simultaneously with phenytoin and tolbutamide, their levels in the blood plasma may increase. However, their combined use with clopidogrel is safe. There was no clinically significant interaction of the drug with diuretics, beta-adrenergic blockers, ACE inhibitors, calcium channel blockers, drugs that dilate coronary vessels, antacids, hypoglycemic, hypocholesterolemic, antiepileptic drugs, phenobarbital, cimetidine, digoxin and theophylline.
Atherocard tablets for thrombosis 75 mg, 30 pcs.
Medicines, the use of which is accompanied by an increased risk of bleeding. Due to the potential additive effect, there is an increased risk of bleeding complications, therefore the simultaneous use of such drugs with clopidogrel requires caution.
Oral anticoagulants. Simultaneous use of the drug with oral anticoagulants is not recommended, since such a combination may increase the intensity of bleeding (see section “Peculiarities of use”). Although the use of clopidogrel at a dose of 75 mg per day does not change the pharmacokinetic profile of S-warfarin or the international normalized ratio (INR) in patients receiving long-term warfarin treatment, concomitant use of clopidogrel and warfarin increases the risk of bleeding due to the existence of independent effects on hemostasis.
Inhibitors of glycoprotein receptors IIb/IIIa. Atherocardium should be prescribed with caution to patients receiving inhibitors of glycoprotein IIb/IIIa receptors (see section "Peculiarities of use").
ASK. Acetylsalicylic acid does not change the inhibitory effect of clopidogrel on ADP-induced platelet aggregation, but clopidogrel enhances the effect of ASA on collagen-induced platelet aggregation. However, the simultaneous use of 500 mg ASA 2 times a day for one day did not cause a significant increase in bleeding time, which was prolonged due to the use of clopidogrel. Since a pharmacodynamic interaction between clopidogrel and ASA is possible with an increased risk of bleeding, the simultaneous use of these drugs requires caution (see section "Peculiarities of use"). Despite this, clopidogrel and ASA were used together for up to 1 year.
Heparin. According to the study, clopidogrel did not require adjustment of the heparin dose and did not change the effect of heparin on coagulation. Concomitant use of heparin did not change the inhibitory effect of clopidogrel on platelet aggregation. Since there is a possible pharmacodynamic interaction between clopidogrel and heparin with an increased risk of bleeding, the simultaneous use of these drugs requires caution.
Thrombolytic agents. The safety of concomitant use of clopidogrel, fibrin-specific or fibrin-nonspecific thrombolytic agents and heparins has been studied in patients with acute myocardial infarction. The incidence of clinically significant bleeding was similar to that observed with the simultaneous use of thrombolytic drugs and heparin with ASA.
Non-steroidal anti-inflammatory drugs (NSAIDs). Concomitant use of clopidogrel and naproxen increased the incidence of occult gastrointestinal bleeding. However, due to the lack of studies on the interaction of the drug with other NSAIDs, it has not yet been established whether the risk of gastrointestinal bleeding increases when used with all NSAIDs. Therefore, caution is required when simultaneous use of NSAIDs, in particular COX-2 inhibitors, with clopidogrel.
Selective serotonin reuptake inhibitors (SSRIs). Caution should be exercised when SSRIs are used concomitantly with clopidogrel, as SSRIs affect platelet activation and increase the risk of bleeding.
Concomitant use of other drugs. Since clopidogrel is converted to its active metabolite in part by the action of CYP2C19, the use of drugs that reduce the activity of this enzyme will most likely lead to a decrease in the concentration of the active metabolite of clopidogrel in the blood plasma. The clinical significance of this interaction is unclear. Therefore, as a precaution, concomitant use of strong and moderate CYP2C19 inhibitors should be avoided.
Drugs that inhibit CYP2C19 activity include omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, carbamazepine and efavirenz.
Proton pump inhibitors (PPIs). Omeprazole at a dose of 80 mg 1 time per day, when used simultaneously with clopidogrel or within 12 hours between doses of these drugs, reduced the concentration of the active metabolite in the blood by 45% (loading dose) and by 40% (maintenance dose). This reduction was accompanied by a decrease in platelet aggregation inhibition by 39% (loading dose) and 21% (maintenance dose). It is expected that esomeprazole will have a similar interaction with clopidogrel. Observational and clinical studies have provided conflicting data regarding the clinical consequences of these pharmacokinetic and pharmacodynamic interactions in terms of the development of major cardiovascular events. As a precaution, omeprazole or esomeprazole should not be used concomitantly with clopidogrel.
A less pronounced decrease in the concentration of the metabolite in the blood was observed with the use of pantoprazole or lansoprazole.
With simultaneous use of pantoprazole at a dose of 80 mg 1 time per day, plasma concentrations of the active metabolite decreased by 20% (loading dose) and by 14% (maintenance dose). This reduction was accompanied by a decrease in mean platelet aggregation inhibition of 15% and 11%, respectively. The results obtained indicate the possibility of simultaneous use of clopidogrel and pantoprazole.
There is no evidence that other drugs that reduce gastric acid production, such as H2 blockers or antacids, affect the antiplatelet activity of clopidogrel.
Combinations with other drugs. There is evidence that clinical studies have been conducted with clopidogrel and other drugs to study potential pharmacodynamic and pharmacokinetic interactions.
No clinically significant pharmacodynamic interactions were observed when clopidogrel was used concomitantly with atenolol, nifedipine, or both drugs. In addition, the pharmacodynamic activity of clopidogrel remained virtually unchanged when used simultaneously with phenobarbital and estrogen.
The pharmacokinetic properties of digoxin or theophylline did not change when administered concomitantly with clopidogrel.
Antacids do not affect the level of absorption of clopidogrel.
It is known that data obtained from studies of human liver microsomes indicate that the carboxyl metabolites of clopidogrel can inhibit the activity of cytochrome P4502C9. This may potentially increase plasma levels of drugs such as phenytoin and tolbutamide and NSAIDs, which are metabolized by cytochrome P4502C9. Despite this, research suggests that phenytoin and tolbutamide can be safely used concomitantly with clopidogrel.
Medicines that are substrates of the CYP2C8 enzyme. Clopidogrel has been shown to increase repaglinide exposure in healthy volunteers. In vitro studies have demonstrated that the increase in repaglinide exposure is due to inhibition of the CYP2C8 enzyme by the glucuronic metabolite of clopidogrel. Given the risk of increased plasma concentrations, the simultaneous use of clopidogrel and drugs that are eliminated from the body primarily through metabolism mediated by the CYP2C8 enzyme (such as repaglinide, paclitaxel) requires caution.
With the exception of the information regarding interactions with specific drugs provided above, no studies have been conducted on the interaction of clopidogrel with drugs that are commonly prescribed to patients with atherothrombosis. However, patients participating in clinical trials of clopidogrel were concomitantly treated with other drugs, including diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, calcium antagonists, cholesterol-lowering agents, coronary vasodilators, antidiabetic agents (including insulin), antiepileptic agents, and GPIIb antagonists. /IIIa, without signs of clinically significant adverse reactions.
Antiretroviral therapy (ART). Reduced exposure to the active metabolite of clopidogrel and decreased platelet inhibition in HIV-infected patients receiving ritonavir- or cobicistat-boosted antiretroviral therapy (ART). Although the clinical significance of these findings is uncertain, there have been spontaneous reports of HIV-infected patients receiving intensified ART who experienced recurrent occlusive events after deobstruction or thrombotic events while on clopidogrel. The effects of clopidogrel and the mean platelet inhibition effects may be reduced by concomitant use of ritonavir.
