Clopidogrel pills 75mg №60

Indications and usage

Prevention of atherothrombotic events in patients after myocardial infarction (with prescription from several days to 35 days), ischemic stroke (with prescription from 7 days to 6 months) or having 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 a Q wave), including patients who underwent stenting for percutaneous coronary intervention;

- With the rise of the ST segment (acute myocardial infarction) with drug treatment and the possibility of thrombolysis.

Adults and elderly patients with normal activity of the isoenzyme CYP2C19

Clopidogrel-SZ should be taken orally, regardless of the meal.

Myocardial infarction, ischemic stroke and diagnosed occlusive peripheral artery disease

The drug is taken 75 mg 1 time / day.

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

Acute coronary syndrome without ST segment elevation (unstable stenocardia, myocardial infarction without Q wave)

Treatment with Klopidogrel-SZ should be started with a single dose of a loading dose of 300 mg, and then continued at a dose of 75 mg 1 time / day (in combination with Acetylsalicylic acid as an antiplatelet agent at doses of 75-325 mg / day). Since the use of acetylsalicylic acid in higher doses is associated with an increased risk of bleeding, the dose of acetylsalicylic acid recommended for this indication should not exceed 100 mg. The maximum therapeutic effect is observed by the third month of treatment. The course of treatment is up to 1 year.

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

Clopidogrel is prescribed in a dose of 75 mg 1 time / day with an initial single dose of a loading dose in combination with acetylsalicylic acid as an antiplatelet agent and thrombolytic agents (or without thrombolytic agents). Combination therapy is started as soon as possible after the onset of symptoms and continues for at least 4 weeks. In patients over the age of 75, treatment with Klopidogrel-SZ should be started without taking a loading dose.

Patients with a genetically determined reduction in the function of the isoenzyme CYP2C19

The weakening of metabolism using CYP2C19 isoenzyme can lead to a decrease in the antiplatelet effect of clopidogrel. The optimal dosing regimen for patients with a weakened metabolism using the CYP2C19 isoenzyme has not yet been established.

After repeated administration of the drug Klopidogrel-SZ at a dose of 75 mg / day in patients with severe kidney damage (CC from 5 to 15 ml / min) inhibition of ADP-induced platelet aggregation (25%) was lower compared to that in healthy volunteers, however, the lengthening of bleeding time was similar to that in healthy volunteers who received Clopidogrel-SZ at a dose of 75 mg / day. In addition, all patients had good tolerability.

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

The prevalence of alleles of the CYP2C19 isoenzyme genes, which are responsible for the intermediate and reduced metabolism of clopidogrel to its active metabolite, differs among members of different ethnic groups. Only limited data are available for representatives of the Mongoloid race to assess the effect of the CYP2C19 isoenzyme genotype on the clinical outcomes.

Adverse reactions

Classification of the incidence of side effects (WHO): often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100), rarely (> 1/10 000 and <1/1000), very rarely (<1/10 000).

From the central and peripheral nervous system: infrequently - headache, dizziness and paresthesias; rarely - vertigo; very rarely - a violation of taste.

Psychological: very rarely - confusion, hallucinations.

Cardiovascular: very rarely - vasculitis, marked reduction in blood pressure, intracranial hemorrhage, ocular hemorrhages (conjunctival, in the tissue and retina), hematoma, nosebleeds, bleeding from the respiratory tract, Gastrointestinal bleeding, retroperitoneal hemorrhage, and hemorrhage into muscles and joints hematuria.

Respiratory: very rarely - bronchospasm, interstitial pneumonitis.

Gastrointestinal: often - diarrhea, abdominal pain, dyspepsia; infrequently - gastric and duodenal ulcers, gastritis, vomiting, nausea, constipation, flatulence; very rarely - pancreatitis, colitis (including ulcerative or lymphocytic colitis), stomatitis, acute liver failure, hepatitis.

Urogenital: very rarely - glomerulonephritis.

From the blood coagulation system: infrequently - lengthening bleeding time.

Hemic and lymphatic: infrequently - thrombocytopenia, leukopenia, neutropenia and eosinophilia; very rarely - thrombocytopenic thrombohemolytic purpura, severe thrombocytopenia (platelet count ≤ 30 × 10⁹/ l), agranulocytosis, granulocytopenia, aplastic anemia (pancytopenia), anemia.

Dermatological: infrequently - skin rash and itching; very rarely - angioedema, urticaria, erythematous rash (associated with clopidogrel or acetylsalicylic acid); very rarely - bullous dermatitis (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), eczema and lichen planus.

Musculoskeletal system: very rarely - arthralgia, arthritis, myalgia.

Immune system: very rarely - anaphylactoid reactions, serum sickness.

From the laboratory indicators: very rarely - a change in liver function tests, an increase in serum creatinine concentration.

Other: very rarely - fever.

Contraindications

- severe liver failure;

- acute bleeding (for example, bleeding from a peptic ulcer or intracranial hemorrhage);

- rare hereditary lactose intolerance, lactase deficiency and glucose-galactose malabsorption;

- pregnancy;

- lactation period;

- children and adolescents under 18 years of age (safety and efficacy have not been established);

- Hypersensitivity to clopidogrel or any of the excipients of the drug.

Carefully:

- moderate hepatic impairment, in which a predisposition to bleeding is possible (limited clinical experience of use);

- renal failure (limited clinical experience of use);

- trauma, surgery;

- Diseases in which there is a predisposition to the development of bleeding (especially gastrointestinal or intraocular);

- simultaneous administration of nonsteroidal anti-inflammatory drugs, incl. selective COX-2 inhibitors;

- simultaneous use of Warfarin, Heparin, glycoprotein IIb / IIIa inhibitors;

- in patients with a genetically determined decrease in the function of the isoenzyme CYP2C19 in recommended doses (there are literature data indicating that patients with a genetically determined decrease in the function of the isoenzyme CYP2C19 undergo a less systemic exposure to the active metabolite of clopidogrel and have a less pronounced effect of the drug, in addition they may there is a higher incidence of cardiovascular complications after myocardial infarction compared with patients with normal function of the isoenzyme CYP2C19).

As a precaution, it is not recommended to use clopidogrel during pregnancy due to the lack of clinical data on its use in pregnant women, although animal studies have not revealed any direct or indirect adverse effects on the course of pregnancy, fetal development, childbirth and postnatal development.

Breastfeeding in the case of treatment with clopidogrel should be discontinued, because studies on rats have shown that clopidogrel and / or its metabolites are excreted in breast milk. Whether clopidogrel penetrates human breast milk is unknown.

The use of the drug is contraindicated in severe liver failure.

Precautions should be prescribed when moderate hepatic insufficiency, in which a predisposition to bleeding is possible (limited clinical experience of use).

Precautions should be prescribed for renal failure (limited clinical experience).

The drug is contraindicated for use in children and adolescents under 18 years of age (safety and efficacy have not been established).

When treating Klopidogrel-SZ, especially during the first weeks of therapy and / or after invasive cardiac procedures / surgery, it is necessary to carefully monitor patients for signs of bleeding, including and hidden.

Due to the risk of bleeding and hematological undesirable effects, if clinical symptoms that are suspicious of bleeding occur during the treatment, a clinical blood test should be urgently performed, the APTT, platelet count, platelet functional activity indicators and other necessary studies should be determined.

Clopidogrel-SZ, as well as other antiplatelet drugs, should be used with caution in patients with an increased risk of bleeding associated with injuries, surgical interventions or other pathological conditions, as well as in patients receiving acetylsalicylic acid, NSAIDs, including COX-2 inhibitors, heparin or glycoprotein IIb / IIIa inhibitors.

The combined use of clopidogrel with warfarin can increase the intensity of bleeding, therefore,with the exception of rare clinical situations (such as the presence of a floating thrombus in the left ventricle, stenting in patients with atrial fibrillation), the combined use of clopidogrel and warfarin is not recommended.

If the patient has a planned surgical intervention, and there is no need for an antiplatelet effect, then 7 days before the operation, the use of the drug Klopidogrel-SZ should be stopped.

Clopidogrel prolongs bleeding time and should be used with caution in patients with diseases that predispose to the development of bleeding (especially gastrointestinal and intraocular).

Patients should be warned that when using the drug Klopidogrel-SZ (alone or in combination with acetylsalicylic acid), it may take longer to stop the bleeding, and also that if they have unusual (by localization or duration) bleeding should report this to your doctor. Before any forthcoming operation and before the start of taking any new drug, patients should be informed to the doctor (including the dentist) about taking the drug Klopidogrel-SZ.

Very rarely, after use of the drug Klopidogrel-SZ (sometimes even briefly), there have been cases of thrombocytopenic thrombohemolytic purpura (THP), which is characterized by thrombocytopenia and microangiopathic hemolytic anemia, accompanied by neurological disorders, impaired kidney function and fever.TBD is a potentially life-threatening condition that requires immediate treatment, including plasmapheresis.

During the period of treatment it is necessary to control the functional activity of the liver. For severe violations of liver function, you should remember the risk of hemorrhagic diathesis.

The use of the drug Klopidogrel-SZ is not recommended for acute stroke with a prescription of less than 7 days (since there are no data on its use in this state).

Clopidogrel-SZ should not be taken in patients with rare hereditary intolerance to galactose, lactase deficiency, and glucose-galactose malabsorption syndrome.

Influence on ability to drive motor transport and control mechanisms

Klopidogrel-SZ does not have a significant impact on the ability to drive vehicles or work with machinery.

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

Treatment: stop bleeding, platelet mass transfusion. The antidote is unknown.

Warfarin

Simultaneous use with clopidogrel can increase the intensity of bleeding, so the use of this combination is not recommended.

IIb / IIIa receptor blockers

The use of IIb / IIIa receptor blockers in conjunction with clopidogrel requires caution in patients who have an increased risk of bleeding (for injuries and surgical interventions or other pathological conditions).

Acetylsalicylic acid

Acetylsalicylic acid does not alter the effect of clopidogrel, which inhibits ADP-induced platelet aggregation, but clopidogrel potentiates the effect of acetylsalicylic acid on collagen-induced platelet aggregation. However, the simultaneous use of acetylsalicylic acid as an antipyretic with 500 mg of clopidogrel 2 times a day for 1 day did not cause a significant increase in the bleeding time caused by the use of clopidogrel. Between clopidogrel and acetylsalicylic acid pharmacodynamic interaction is possible, which leads to an increased risk of bleeding. Therefore, with their simultaneous use, care should be taken, although in clinical studies, patients received combination therapy with clopidogrel and acetylsalicylic acid for up to one year.

Heparin

According to a clinical study conducted with the participation of healthy volunteers, taking clopidogrel did not require a change in the dose of heparin and its anticoagulant effect did not change. The simultaneous use of heparin did not alter the antiplatelet effect of clopidogrel. Between clopidogrel and heparin, pharmacodynamic interaction is possible, which may increase the risk of bleeding, therefore the simultaneous use of these drugs requires caution.

Thrombolytic

The safety of the simultaneous use of clopidogrel, fibrin-specific or fibrin-specific thrombolytic agents 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 simultaneous use of thrombolytic agents and heparin with acetylsalicylic acid.

NSAIDs

In a clinical study conducted with healthy volunteers, the simultaneous use of clopidogrel and Naproxen increased latent blood loss through the gastrointestinal tract. However, due to the lack of research on the interaction of clopidogrel with other NSAIDs, it is currently unknown if there is an increased risk of gastrointestinal bleeding when taking clopidogrel along with other NSAIDs. Therefore, the appointment of NSAIDs, incl. selective inhibitors of COX-2, in combination with clopidogrel should be carried out with caution.

Other combination therapy

Since Clopidogrel is metabolized before the formation of its active metabolite using CYP2C19 isoenzyme, the use of drugs that inhibit this system can lead to a decrease in the concentration of the active metabolite of clopidogrel and a decrease in its clinical efficacy. Simultaneous administration of drugs inhibiting the isoenzyme CYP2C19 (for example, omeprazole) is not recommended.

A series of clinical studies were conducted with clopidogrel and other concomitantly prescribed drugs in order to study possible pharmacodynamic and pharmacokinetic interactions, which showed that:

- when using clopidogrel together with Atenolol, Nifedipine or with both drugs at the same time, no clinically significant pharmacodynamic interaction was observed;

- simultaneous use of phenobarbital, cimetidine and estrogen had no significant effect on clopidogrel pharmacodynamics;

- pharmacokinetic indices of Digoxin and theophylline did not change when they were applied simultaneously with clopidogrel;

- antiacid means did not reduce the absorption of clopidogrel;

- Phenytoin and tolbutamide can be safely applied simultaneously with clopidogrel, although data from human liver microsome studies suggest that the carboxyl metabolite of clopidogrel may inhibit the activity of the CYP2C9 isoenzyme, which can lead to an increase in plasma concentrations of some drugs (phenytoin, tolbutamide and some NSAIDs) that are metabolized by the isoenzyme CYP2C9;

- ACE inhibitors, diuretics, beta-blockers, slow Calcium channel blockers, hypoglycemic agents (including insulin), hypolipidemic agents, antiepileptic drugs, HRT and GP IIb / IIIa receptor blockers - have not been clinically diagnosed in clinical studies significant unwanted interactions.

The drug is available on prescription.

The drug should be stored out of the reach of children, dry, protected from light, at a temperature not exceeding 25 ° C.