Clopidogrel pills 75mg 28pcs

Composition

A film-coated tablet contains:

Composition of the tablet core:

Active ingredient:

clopidogrel hydrosulfate-97.87 mg (in terms of clopidogrel-75.00 mg);

Auxiliary substances:

lactose anhydrous-67.87 mg;

microcrystalline cellulose-54.60 mg;

crospovidone-12.50 mg;

glyceryl dibegenate-7.50 mg;

talc – 7.50 mg;

sodium starch glycolate-2.50 mg.

Composition of the tablet shell:  

opadray II pink (85G240008) – 8.00 mg (polyvinyl alcohol-44.00%, titanium dioxide-19.50%, macrogol 3350-12.35%, talc-20.00%, lecithin (soy) – 3.50%, iron oxide dye red-0.50%, iron oxide dye yellow-0.15%).

Indications

Prevention of atherothrombotic complications:

• in patients with a myocardial infarction (from a few days to 35 days ago), ischemic stroke (from 7 days to 6 months ago), or with a diagnosed occlusive disease of the peripheral arteries.
• in patients with acute coronary syndrome:
  • non-ST-segment elevation (unstable angina or non-Q-wave myocardial infarction), including patients who underwent stenting during percutaneous coronary intervention (in combination with acetylsalicylic acid);
  • with ST-segment elevation (acute myocardial infarction) during drug treatment and the possibility of thrombolysis (in combination with acetylsalicylic acid).

Prevention of atherothrombotic and thromboembolic complications, including stroke, in atrial fibrillation (atrial fibrillation)

In patients with atrial fibrillation (atrial fibrillation), who have at least one risk factor for vascular complications, cannot take indirect anticoagulants and have a low risk of bleeding (in combination with ASA).

Contraindications

• Hypersensitivity to clopidogrel and / or any other component of the drug;
• Severe liver failure;
• Acute bleeding, such as bleeding from a peptic ulcer or intracranial hemorrhage.
• Rare hereditary problems of galactose intolerance, lactase deficiency, and glucose-galactose malabsorption.
• Pregnancy and lactation period (see the section “Pregnancy and lactation period”);
• Children under 18 years of age (safety and efficacy have not been established).

With caution

• With moderate hepatic insufficiency, in which a predisposition to bleeding is possible (limited clinical experience).
• In patients with mild to moderate chronic renal failure (limited clinical experience).
• In diseases that are predisposed to bleeding (especially gastrointestinal and intraocular), and in patients taking concomitant medications that may cause damage to the gastrointestinal mucosa (such as ASA and nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors).
• Patients who have an increased risk of bleeding due to injury, surgery, or other medical conditions, as well as patients treated with ASA, heparin, oral anticoagulants, glycoprotein IIb/IIIa inhibitors, NSAIDs, including selective COX-2 inhibitors, or selective serotonin reuptake inhibitors (SSRIs) (see the section “Special instructions”).
• If a history of allergic and hematological reactions to other thienopyridines (such as ticlopidine, prasugrel)is indicated due to the possibility of cross-reactions (see the section “Special instructions”).
• In case of a recent transient cerebrovascular accident or ischemic stroke (when used concomitantly with ASA, see the section “Special instructions”).

Side effects

To assess the frequency of adverse events, the following WHO classification is used: :

Very often (≥ 1/10)

Often (≥ 1/100 and < 1/10)

Infrequently (≥ 1/1000 and

Rarely (≥ 1/10,000 and

Very rare (≥ 1/10,000)

The frequency is unknown (according to available data, it is not possible to determine the frequency of the development of an adverse event).

Blood and lymphatic system disorders:

infrequently-thrombocytopenia, leukopenia, eosinophilia;

rarely-neutropenia, including severe neutropenia;

very rarely-thrombotic thrombocytopenic purpura, aplastic anemia, pancytopenia, agranulocytosis, severe thrombocytopenia, granulocytopenia, anemia;

frequency unknown-acquired hemophilia A.

From the immune system:

very rarely – anaphylactic reactions, serum sickness;

frequency unknown-cross-hypersensitivity to other thienopyridines (for example, ticlopidine, prasugrel);

Nervous system disorders:

infrequently-intracranial hemorrhage (several fatal cases), headache, paresthesia, dizziness;

very rarely-impaired taste perception.

Mental disorders:

very rarely – confusion, hallucinations.

From the side of the visual organ:

infrequently-retinal hemorrhage, conjunctival hemorrhage, hemophthalmus.

Hearing disorders and labyrinth disorders:

rarely-vertigo.

Skin and subcutaneous tissue disorders:

often – “bruises” (local subcutaneous hemorrhage);

infrequently – skin rash and itching, thrombocytopenic purpura;

very rarely – angioedema, rash erythematous, urticaria, bullous dermatitis (toxic epidermal necrolysis, and Stevens-Johnson syndrome, erythema multiforme), eczema, oral lichen planus, the drug hypersensitivity syndrome, drug rash with eosinophilia and systemic manifestations (DRESS syndrome), exfoliative rash.

From the side of the kidneys and urinary tract:

infrequently–hematuria;

very rarely–glomerulopathy (including glomerulonephritis), hypercreatininemia.

Musculoskeletal and connective tissue disorders:

very rarely – hemorrhages in muscles and joints, arthritis, arthralgia, myalgia.

From the gastrointestinal tract:

very often, gastrointestinal bleeding, diarrhea, abdominal pain, dyspepsia;

uncommon – stomach ulcer and duodenal ulcer, gastritis, vomiting, nausea, constipation, flatulence;

rarely – retroperitoneal bleeding;

rarely – gastrointestinal bleeding and retroperitoneal hemorrhage with fatal outcome, pancreatitis, colitis (including ulcerative colitis or lymphocytic colitis), stomatitis.

Liver and biliary tract disorders:

very rarely-acute liver failure, hepatitis (non-infectious).

Respiratory, thoracic and mediastinal disorders:

often-nosebleeds;

very rarely-bleeding from the respiratory tract (hemoptysis, pulmonary hemorrhage), interstitial pneumonitis, bronchospasm, eosinophilic pneumonia.

From the cardiovascular system:

often-hematoma;

very rarely-severe bleeding, bleeding from an operating wound, vasculitis, low blood pressure.

Laboratory and instrumental data:

infrequently-prolongation of bleeding time, a decrease in the number of neutrophils and / or platelets in peripheral blood, violations of liver function tests, an increase in the concentration of creatinine in blood plasma.

General disorders and disorders at the injection site:

often-bleeding from the site of puncturing blood vessels;

very rarely-fever.

Interaction

Oral anticoagulants: concomitant use of clopidogrel and oral anticoagulants may increase the intensity of bleeding, and therefore the use of this combination is not recommended. Clopidogrel does not affect the pharmacokinetics of warfarin and does not change the value of the international normalized ratio (INR) in patients taking warfarin for a long time. However, co-use of warfarin with clopidogrel may increase the risk of bleeding due to the independent effect of these drugs on hemostasis.

The use of glycoprotein IIb/IIIa inhibitors in combination with clopidogrel requires caution in patients with an increased risk of bleeding (due to injuries and surgical interventions or other pathological conditions) (see the section “Special instructions”).

Acetylsalicylic Acid: ASA does not alter the effect of clopidogrel, which inhibits ADP-induced platelet aggregation, but clopidogrel enhances the effect of ASA on collagen-induced platelet aggregation. However, concomitant use of 500 mg ASA twice daily for 1 day with clopidogrel did not significantly increase the bleeding time caused by clopidogrel. There may be a pharmacodynamic interaction between clopidogrel and ASA, which leads to an increased risk of bleeding. Therefore, caution should be exercised when they are used simultaneously, although in clinical studies patients received combination therapy with clopidogrel and ASA for up to one year.

Heparin: according to a clinical study conducted in healthy volunteers, clopidogrel did not require a change in the dose of heparin and did not change its anticoagulant effect.Co-use of heparin did not alter the inhibitory effect of clopidogrel on platelet aggregation. There may be a pharmacodynamic interaction between clopidogrel and heparin, which may increase the risk of bleeding, so the simultaneous use of this combination requires caution.

Thrombolytics: The safety of co-use of clopidogrel, fibrin-specific or fibrin-specific thrombolytic drugs, and heparin has been studied in patients with acute myocardial infarction. The frequency of clinically significant bleeding was similar to that observed in the case of combined use of thrombolytics and heparin with ASA.

Nonsteroidal anti-inflammatory drugs (NSAIDs): in a clinical study conducted in healthy volunteers, the combined use of clopidogrel and naproxen increased hidden blood loss through the gastrointestinal tract. However, due to the lack of studies on the interaction of clopidogrel with other NSAIDs, it is currently unknown whether there is an increased risk of gastrointestinal bleeding when taking clopidogrel together with other NSAIDs. Therefore, the use of NSAIDs, including COX-2 inhibitors, in combination with clopidogrel should be carried out with caution.

Selective serotonin reuptake inhibitors (SSRIs): Since SSRIs interfere with platelet activation and increase the risk of bleeding, co – use of SSRIs with clopidogrel should be carried out with caution.

CYP2C19 inhibitors

Since clopidogrel is partially metabolized to form its active metabolite by the CYP2C19 isoenzyme, the use of drugs that inhibit this isoenzyme may lead to a decrease in the level of the active metabolite of clopidogrel and reduce its clinical effectiveness. The clinical significance of this interaction has not been established. As a precautionary measure, it is recommended to avoid co-use of clopidogrel with drugs that inhibit the CYP2C19 isoenzyme (omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine, chloramphenicol).

Proton Pump inhibitors

If it is necessary to prescribe proton pump inhibitors simultaneously with clopidogrel, the drug with the lowest inhibition of CYP2C19 (pantoprazole or lanzoprazole) should be used.

Other combination therapies

A number of clinical studies have been conducted with clopidogrel and other concomitant medications to investigate possible pharmacodynamic and pharmacokinetic interactions, which have shown 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 and estrogen had no significant effect on the pharmacodynamics of clopidogrel;

– the pharmacokinetic parameters of digoxin or theophylline was not altered in their joint application with clopidogrel;

– antacids did not reduce the absorption of clopidogrel;

– the results of the CAPRIE study, phenytoin and tolbutamide safety used in conjunction with clopidogrel. It is unlikely that clopidogrel may affect the metabolism of other drugs, such as phenytoin and tolbutamide and the NSAIDs, which are metabolized via CYP2C19 isoenzyme;

– clinical studies have not revealed clinically significant undesirable interaction of clopidogrel with angiotensin converting enzyme inhibitors, diuretics, beta-blockers, blockers of “slow” calcium channels, lipid means, coronary vasodilators, hypoglycemic agents (including insulin), antiepileptic drugs, drugs for hormone replacement therapy.

How to take, course of use and dosage

Inside, regardless of food intake.

  Patients with normal CYP2 isoenzyme activityC19

Myocardial infarction, ischemic stroke, or diagnosed occlusive disease of the peripheral arteries.

Take 1 film-coated tablet (75 mg) once a day.

In patients with myocardial infarction (MI), treatment can be started from the first days to the 35th day of MI, and in patients with ischemic stroke (IS) – from 7 days to 6 months after IS.

Non-ST-segment elevation acute coronary syndrome (unstable angina, non-Q-wave myocardial infarction)

Treatment with clopidogrel should begin with a single loading dose of 300 mg, and then continue with a dose of 75 mg once a day (in combination with ASA in doses of 75-325 mg per day). Since the use of higher doses of ASA is associated with an increased risk of bleeding, the recommended dose of ASA for this indication should not exceed 100 mg. The optimal duration of treatment for this indication is not officially determined. The results of clinical studies confirm the feasibility of taking the drug up to 12 months after the development of acute coronary syndrome without ST-segment elevation. The maximum beneficial effect is observed by the third month of treatment.

Acute ST-segment elevation coronary syndrome (acute ST-segment elevation myocardial infarction)

Clopidogrel is given as a single dose of 75 mg once a day with an initial single loading dose of clopidogrel 300 mg in combination with ASA and thrombolytics (or without thrombolytics). In patients over 75 years of age, treatment with clopidogrel should begin without taking its loading dose. Combination therapy should be initiated as early as possible after the onset of symptoms and continued for at least four weeks. The effectiveness of combined use of clopidogrel and acetylsalicylic acid for more than 4 weeks in this indication has not been studied.

Atrial fibrillation (atrial fibrillation)

Clopidogrel should be taken once a day at a dose of 75 mg. In combination with clopidogrel, you should start and then continue taking ASA(75-100 mg / day).

Skipping the next dose

• If less than 12 hours have passed since you missed the next dose, then you should immediately take the missed dose of the drug, and then take the next dose at the usual time.
• If more than 12 hours have passed since the next dose was missed, then the patient should take the next dose at the usual time (do not take a double dose).

Patients with genetically determined reduced activity of the CYP2C19 isoenzyme

The status of a slow CYP2C19 metabolizer is associated with a decrease in the antiplatelet effect of clopidogrel. A higher dose regimen (600 mg as a loading dose, followed by 150 mg once daily) increases the antiplatelet effect of clopidogrel in slow metabolizers (see section “Pharmacokinetics”). However, the optimal dosage regimen for patients with reduced CYP2C19 isoenzyme activity in clinical studies has not yet been established.

Special patient groups

Elderly patients

No dose adjustment is required.

Children’s patients

There is no experience of using the drug in children.

Patients with impaired renal function

After repeated use of clopidogrel 75 mg / day in patients with severe renal impairment (creatinine clearance from 5 to 15 ml / min), the inhibition of ADP-induced platelet aggregation (25%) was lower compared to that in healthy volunteers, however, the prolongation of bleeding time was similar to that in healthy volunteers receiving clopidogrel 75 mg / day. In addition, all patients had good drug tolerance.

Patients with impaired liver function

After taking clopidogrel daily for 10 days at a daily dose of 75 mg in patients with severe liver damage, the inhibition of ADP-induced platelet aggregation was similar to that in healthy volunteers. The mean bleeding time was also comparable in both groups.

Patients of different racial backgrounds

The prevalence of alleles of the CYP2C19 isoenzyme genes responsible for the intermediate and reduced metabolism of clopidogrel to its active metabolite varies among representatives of different ethnic groups (see the section “Pharmacogenetics”). There are only limited literature data for representatives of the Mongolian race to assess the clinical significance of genotyping of the CYP2C19 isoenzyme in predicting the development of ischemic complications.

Overdose

Symptoms: increased bleeding time with subsequent complications in the form of the development of bleeding.

Treatment: if bleeding occurs, appropriate treatment measures are required, as well as platelet mass transfusion. There is no specific antidote.

Special instructions

During treatment with clopidogrel, especially during the first weeks of treatment and/or after invasive cardiac procedures/surgery, patients should be carefully monitored for signs of bleeding, including latent bleeding.

Due to the risk of bleeding and hematological undesirable effects (see the section “Side effects”), if clinical symptoms appear during treatment that indicate the possibility of bleeding, it is urgently necessary to perform a clinical blood test, determine the activated partial thromboplastin time (APTT), platelet count, platelet functional activity indicators, and conduct other necessary studies.

Clopidogrel, as well as other antiplatelet drugs, should be used with caution in patients who have an increased risk of bleeding associated with injuries, surgery or other pathological conditions, as well as in patients receiving ASA, NSAIDs, including COX-2 inhibitors, heparin or glycoprotein IIb/IIIa inhibitors, SSRIs and thrombolytic drugs.

Concomitant use of clopidogrel with warfarin may increase the intensity of bleeding (see section “Interactions with other medications”), so caution should be exercised when using clopidogrel and warfarin together.

If the patient is going to undergo elective surgery, and there is no need for an antiplatelet effect, then 7 days before the operation, clopidogrel should be discontinued.

Clopidogrel prolongs the bleeding time and should be used with caution in patients with diseases predisposing to the development of bleeding (especially gastrointestinal and intraocular). Medications that can cause damage to the gastrointestinal mucosa (such as ASA, NSAIDs) Caution should be exercised in patients taking clopidogrel.

Patients should be warned that it may take longer to stop bleeding when taking clopidogrel (alone or in combination with ASA), and that if they experience unusual (by location or duration) bleeding, they should inform their doctor about this. Patients should inform their doctor (including their dentist) about taking clopidogrel before any upcoming surgery and before starting any new medication.

Thrombotic thrombocytopenic purpura, which is characterized by thrombocytopenia and microangiopathic hemolytic anemia, accompanied by neurological disorders, impaired renal function and fever, and is a potentially life-threatening condition that requires immediate treatment, including plasmapheresis, has been reported very rarely after the use of clopidogrel (sometimes even for a short time).

During the treatment period, it is necessary to monitor the functional activity of the liver. With severe liver damage, keep in mind the risk of developing hemorrhagic diathesis.

The drug should be used with caution in patients with impaired renal function.

Taking clopidogrel is not recommended for acute stroke with a duration of less than 7 days (since there are no data on its use in this condition).

In patients with a recent transient cerebral circulatory disorder or stroke who are at high risk of developing recurrent ischemic complications, the combination of ASA and clopidogrel increases the frequency of major bleeding. Therefore, such combination therapy should be carried out with caution and only in the case of proven clinical benefits from its use.

Cases of acquired hemophilia have been reported with clopidogrel. If there is a confirmed isolated increase in APTT, accompanied or not accompanied by the development of bleeding, the possibility of developing acquired hemophilia should be considered. Patients with a confirmed diagnosis of acquired hemophilia should be monitored and treated by specialists for this disease and stop taking clopidogrel.

In patients with low activity of the CYP2C19 isoenzyme, when using clopidogrel at the recommended doses, less of the active metabolite of clopidogrel is formed and its antiplatelet effect is less pronounced, and therefore, when taking the usually recommended doses of clopidogrel in acute coronary syndrome or percutaneous coronary intervention, a higher incidence of cardiovascular complications is possible than in patients with normal activity of the CYP2C19 isoenzyme. Tests are available to determine the CYP2C19 genotype. These tests can be used to help you choose a therapeutic strategy. The issue of using higher doses of clopidogrel in patients with low activity of the CYP2C19 isoenzyme is being considered (see the section “Pharmacogenetics” of the section “Pharmacological properties”, sections “With caution”, “Method of use and doses”).

Check the patient’s history of allergic and/or hematological reactions to other thienopyridine derivatives (ticlopidine, prasugrel), as cases of cross-allergic and / or hematological reactions between thienopyridines are described (see the section “Side effects”). Patients who have previously experienced allergic and / or hematological reactions to other thienopyridine derivatives should be closely monitored throughout the treatment period for signs of hypersensitivity to clopidogrel.

Clopidogrel should not be used in patients with rare hereditary problems of galactose intolerance, lactose deficiency, and glucose-galactose malabsorption syndrome.

Effect of the drug on the performance of potentially dangerous activities that require increased concentration and speed of psychomotor reactions

Clopidogrel does not significantly affect the ability to drive a car or engage in potentially dangerous activities.

Form of production

tablets of round, biconvex shape, covered with a film-coated pink color, with a risk on one side.

On the cross-section – the core is white to white with a yellowish tinge of color.

Active ingredient

Clopidogrel

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

Adults as prescribed by a doctor

Indications

Angina, Thrombosis prevention, Acute myocardial infarction Prevention, Stroke prevention, Thromboembolism prevention