Plavix - instructions for use, reviews, analogs and forms of release (75 mg and 300 mg tablets) drugs for the treatment and prevention of thrombosis and thromboembolism in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Plavix. Presented are reviews of visitors to the site - consumers of this medication, as well as opinions of specialists on the use of Plavix in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Plavix in the presence of existing structural analogues. Use for the treatment and prevention of thrombosis and thromboembolism in patients with infarction and angina in adults, children, as well as during pregnancy and lactation. Composition of the preparation.

Plavix antiaggregant.It is a prodrug, one of the active metabolites of which is an inhibitor of platelet aggregation. The active metabolite of Clopidogrel selectively inhibits the binding of ADP to the P2Y12 receptor of platelets and the subsequent ADP-mediated activation of the glycoprotein 2b / 3a complex, leading to suppression of platelet aggregation. Due to irreversible binding, platelets remain immune to stimulation of ADP for the rest of their life (about 7-10 days), and restoration of normal platelet function occurs at a rate corresponding to the rate of platelet renewal.

Aggregation of platelets caused by agonists other than ADP is also inhibited by blockade of enhanced platelet activation by the released ADP.

Because the formation of an active metabolite occurs with the participation of P450 isoenzymes, some of which are polymorphic or inhibited by other drugs, not all patients can adequately suppress platelets.

With a daily intake of clopidogrel at a dose of 75 mg from the first day of admission a significant inhibition of ADP-induced platelet aggregation,which gradually increases within 3-7 days and then goes to a constant level (upon reaching the equilibrium state). In the equilibrium state, platelet aggregation is suppressed by an average of 40-60%. After stopping the use of clopidogrel, platelet aggregation and bleeding time gradually return to the baseline level on average for 5 days.

Clopidogrel is able to prevent the development of atherothrombosis in any localization of atherosclerotic vascular lesions, in particular, in the lesions of cerebral, coronary or peripheral arteries.

A clinical study of ACTIVE-A showed that patients with atrial fibrillation who had at least one risk factor for vascular complications but were unable to take indirect anticoagulants, clopidogrel in combination with Acetylsalicylic acid (compared to taking only acetylsalicylic acid alone ) reduced the incidence of combined stroke, myocardial infarction, systemic thromboembolism outside the central nervous system (CNS), or vascular death, to a greater extent by reducing the risk of stroke.The effectiveness of clopidogrel in combination with acetylsalicylic acid was detected early and persisted to 5 years. The reduction in the risk of major vascular complications in the group of patients taking clopidogrel in combination with acetylsalicylic acid was mainly due to a greater reduction in the frequency of strokes. The risk of developing a stroke of any severity with clopidogrel in combination with acetylsalicylic acid was reduced, and there was a tendency to decrease the incidence of myocardial infarction in the group treated with clopidogrel in combination with acetylsalicylic acid, but there was no difference in the frequency of thromboembolism outside the CNS or vascular death. In addition, the use of clopidogrel in combination with acetylsalicylic acid reduced the total number of days of hospitalization for cardiovascular reasons.

Composition

Clopidogrel hydrogensulfate + auxiliary substances.

Pharmacokinetics

With a single and repeated intake of a dose of 75 mg per day Plavix quickly absorbed. According to excretion of metabolites of clopidogrel with urine, its absorption is approximately 50%.

Clopidogrel is extensively metabolized in the liver.Clopidogrel is metabolized in two ways: the first through esterases and subsequent hydrolysis with the formation of an inactive derivative of carboxylic acid (85% of the circulating metabolites), the second through the isoenzymes of the cytochrome P450 system.

Within 120 hours after ingestion of 14C-labeled clopidogrel in person, about 50% of the radioactivity is excreted in the urine and approximately 46% - with feces.

Indications

Prevention of atherothrombotic complications:

• in adults with myocardial infarction (with a duration of several days to 35 days), with ischemic stroke (with a duration of 7 days to 6 months), with diagnosed occlusive disease of peripheral arteries;
• in adult patients with acute coronary syndrome without ST segment elevation (unstable angina or Q-free myocardial infarction), including patients who underwent stenting with percutaneous coronary intervention (in combination with acetylsalicylic acid);
• in adults with acute coronary syndrome with ST segment elevation (acute myocardial infarction) with 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), which have at least one risk factor for vascular complications, can not take indirect anticoagulants and have a low risk of bleeding (in combination with acetylsalicylic acid).

Forms of release

Tablets coated with 75 mg and 300 mg.

Instructions for use and reception scheme

Tablets 75 mg

The drug is taken orally, regardless of food intake.

Adults and elderly patients with normal activity of the isoenzyme CYP2C19

Myocardial infarction, ischemic stroke and diagnosed peripheral arterial occlusive disease

The drug is prescribed in a dose of 75 mg once a day.

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

Treatment with Plavix should begin with a single dose of 300 mg loading dose, and then continue at a dose of 75 mg once a day (in combination with acetylsalicylic acid at doses of 75-325 mg per day).Since the use of acetylsalicylic acid in higher doses is associated with an increased risk of bleeding, the recommended dose of acetylsalicylic acid at this indication does not exceed 100 mg. The optimal duration of treatment is not officially defined. Clinical trials support the use of the drug for up to 12 months, and the maximum beneficial effect was observed by 3 months of treatment

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

Plavix is ​​prescribed once in a dose of 75 mg once a day with the initial single dose loading in combination with acetylsalicylic acid and thrombolytic agents or without combination with thrombolytics. In patients older than 75 years, treatment with Plavix should be started without taking a loading dose. Combination therapy starts as soon as possible after the onset of symptoms and lasts for at least 4 weeks. The effectiveness of the use of a combination of clopidogrel and acetylsalicylic acid with this indication over 4 weeks has not been studied.

Atrial fibrillation (atrial fibrillation)

Plavix is ​​prescribed once a day at a dose of 75 mg.In combination with clopidogrel, you should start and then continue taking acetylsalicylic acid (75-100 mg per day).

Skipping the next dose

If less than 12 hours have passed after missing the next dose, the missed dose of the drug should be taken immediately, and then taken at the usual time in the following doses.

If more than 12 hours have passed after missing the next dose, the patient should take the next dose at the usual time (do not take a double dose).

Special patient groups

In elderly volunteers (over 75 years old), when compared with young volunteers, there was no difference in platelet aggregation and bleeding time. Older patients do not need a dose adjustment.

After repeated use of clopidogrel at a dose of 75 mg per day in patients with severe renal disease (SC from 5 to 15 ml / min), inhibition of ADP-induced platelet aggregation (25%) was lower than that of healthy volunteers, but prolongation of bleeding time was similar to that of healthy volunteers who received clopidogrel at a dose of 75 mg per day. In addition, all patients had good tolerability of the drug.

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

Patients of different ethnicity. The prevalence of the alleles of the CYP2C19 isoenzyme genes responsible for the intermediate and decreased metabolism of clopidogrel to its active metabolite differs among representatives of different ethnic groups. There are only limited data for representatives of the Mongoloid race on the evaluation of the effect of the genotype of the isoenzyme CYP2C19 on clinical manifestations.

Patients are female and male. In a small comparative study of the pharmacodynamic properties of clopidogrel in men and women, there was less inhibition of ADP-induced platelet aggregation in women, but there was no difference in bleeding time elongation. In a large controlled study of CAPRIE (clopidogrel versus acetylsalicylic acid in patients at risk of developing ischemic complications), the incidence of clinical outcomes,other side effects and deviations from the norm of clinical and laboratory indicators were the same for both men and women.

Tablets 300 mg

Adults and elderly patients Plavix should be taken orally, regardless of food intake. The drug in a dose of 300 mg, is intended for use as a loading dose for patients with acute coronary syndrome.

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

Treatment with clopidogrel should begin with a single loading dose of 300 mg, and then continue taking 75 mg once a day (in combination with acetylsalicylic acid at doses of 75-325 mg per day). Since the use of acetylsalicylic acid in higher doses is associated with an increased risk of bleeding, the recommended dose of acetylsalicylic acid should not exceed 100 mg. The maximum favorable 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 administered once in a dose of 75 mg once a day with the initial single dosewith a loading dose of 300 mg in combination with acetylsalicylic acid and thrombolytic agents (or without thrombolytics). Combination therapy starts as soon as possible after the onset of symptoms and lasts for at least 4 weeks. In patients older than 75 years, treatment with clopidogrel should be started without taking its loading dose.

For a maintenance dose of clopidogrel (75 mg), Plavix 75 mg tablets are used.

Side effect

• thrombocytopenia, leukopenia, eosinophilia, neutropenia, thrombotic thrombocytopenic purpura, aplastic anemia, pancytopenia, agranulocytosis, granulocytopenia, anemia;
• serum sickness;
• anaphylactoid reactions;
• intracranial hemorrhage (several cases have been reported with a fatal outcome);
• headache;
• paresthesia;
• dizziness;
• violation of taste perception;
• hallucinations;
• confusion of consciousness;
• eye hemorrhage (conjunctival, in the tissue and retina of the eye);
• hematoma;
• severe bleeding from the operating wound;
• vasculitis;
• a decrease in blood pressure;
• nose bleed;
• bleeding from the respiratory tract (hemoptysis, pulmonary hemorrhage);
• bronchospasm;
• interstitial pneumonia;
• gastrointestinal bleeding;
• diarrhea;
• stomach ache;
• dyspepsia;
• stomach ulcer and duodenal ulcer;
• vomiting, nausea;
• constipation;
• bloating;
• retroperitoneal hemorrhage;
• gastrointestinal bleeding and retroperitoneal hemorrhage;
• Colitis (including nonspecific ulcerative colitis or lymphocytic colitis);
• stomatitis;
• acute liver failure;
• hepatitis;
• subcutaneous bruising;
• rash;
• itching;
• purpura (subcutaneous hemorrhage);
• bullous dermatitis (toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme);
• hives;
• eczema;
• flat lichen;
• bleeding in the muscles and joints;
• arthritis;
• arthralgia;
• myalgia;
• hematuria;
• glomerulonephritis;
• increase in the concentration of creatine in the blood;
• fever;
• bleeding from the point of vascular puncture;
• increased bleeding time;
• decrease in the number of neutrophils;
• decrease in the number of platelets in the peripheral blood.

Contraindications

• severe hepatic impairment;
• acute bleeding, eg bleeding from peptic ulcers or intracranial hemorrhage;
• rare hereditary intolerance to galactose, lactase deficiency and glucose-galactose malabsorption syndrome;
• pregnancy;
• lactation period (breastfeeding);
• children under 18 years of age (safety and efficacy not established);
• hypersensitivity to the components of the drug.

Application in pregnancy and lactation

Contraindicated the use of the drug Plavix during pregnancy and lactation (breastfeeding) because of the lack of data on the clinical use of the drug during pregnancy. In experimental studies, neither direct nor indirect adverse effects on the course of pregnancy, embryonic development, childbirth and postnatal development have been identified.

It is not known whether clopidogrel with human milk is excreted in humans. Breastfeeding in the treatment of clopidogrel should be discontinued; it has been shown that clopidogrel and / or its metabolites are excreted in breast milk in lactating rats.

Use in children

Contraindicated for children under the age of 18 years (safety and efficacy not established).

special instructions

When using Plavix, especially during the first weeks of treatment and / or after invasive cardiac procedures / surgery, patients should be closely monitored for the exclusion of signs of bleeding, incl. and hidden.

In connection with the risk of bleeding and hematological side effects in the event of clinical symptoms appearing during treatment, suspicious for the occurrence of bleeding, it is urgent to do a clinical blood test, determine APTT, the number of platelets, the indices of the functional activity of platelets and conduct other necessary studies.

Plavix, as well as other antiplatelet drugs, should be used with caution in patients with an increased risk of bleeding associated with trauma, surgery or other pathological conditions, as well as with combined therapy with acetylsalicylic acid, NSAIDs (including inhibitors COX-2), Heparin or glycoprotein 2b / 3a inhibitors.

Joint use of clopidogrel with Warfarin may increase the risk of bleeding, therefore, caution should be exercised when using clopidogrel and warfarin together.

With planned surgical interventions and in the absence of the need for an antiplatelet effect, treatment with Plavix should be discontinued 7 days before surgery.

Clopidogrel prolongs bleeding time, so the drug should be used with caution in patients with diseases predisposing to the development of bleeding (especially, gastrointestinal and intraocular).

Preparations that can cause damage to the gastrointestinal mucosa (such as acetylsalicylic acid, NSAIDs) in patients receiving clopidogrel should be used with caution. Patients should be warned that when taking clopidogrel (alone or in combination with acetylsalicylic acid), it may take longer to stop bleeding, and that if they have unusual (localized or prolonged) bleeding, they should be informed about this to your doctor. Before any future operation and before starting any new drug, patients should inform the doctor (including the dentist) about taking clopidogrel.

Very rarely, after taking clopidogrel (sometimes even briefly), there have been cases of thrombotic thrombocytopenic purpura (TTP), which is characterized by thrombocytopenia and microangiopathic hemolytic anemia in combination with either neurologic symptoms, impaired renal function, or fever. The development of TTP can pose a threat to life and require the adoption of urgent measures, including plasmapheresis.

The use of clopidogrel is not recommended for acute stroke with a prescription of less than 7 days, because There is no data on the use of the drug in this state.

During the treatment it is necessary to monitor the functional activity of the liver. With severe liver damage, the risk of developing hemorrhagic diathesis should be considered.

Plavix should not be given to patients with a rare hereditary intolerance to galactose, a deficiency of lactase and a glucose-galactose malabsorption syndrome.

Impact on the ability to drive vehicles and manage mechanisms

Plavix does not significantly affect the ability to drive vehicles or engage in other potentially hazardous activities.

Drug Interactions

Although the use of clopidogrel at a dose of 75 mg per day did not alter the pharmacokinetics of warfarin (substrate of the isoenzyme CYP2C9) or MHO in patients receiving long-term treatment with warfarin, concurrent administration of clopidogrel increases the risk of bleeding due to its independent additional effect on clotting. Therefore, care should be taken while taking warfarin and clopidogrel.

The appointment of glycoprotein 2b / 3a receptor blockers together with clopidogrel requires caution, especially in patients with an increased risk of bleeding (with trauma and surgical interventions or other pathological conditions).

Acetylsalicylic acid does not change the inhibitory effect of clopidogrel on ADP-induced platelet aggregation, but clopidogrel potentiates the effect of acetylsalicylic acid on collagen-induced platelet aggregation. However, simultaneous with clopidogrel, the intake of acetylsalicylic acid 500 mg twice a day for 1 day did not cause a significant increase in 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 trials patients received combined therapy with clopidogrel and acetylsalicylic acid for up to 1 year.

With simultaneous application with heparin, according to a clinical study conducted on healthy volunteers, when taking clopidogrel, there was no need to change 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 Plavix and heparin, pharmacodynamic interaction is possible, which may increase the risk of bleeding (this combination requires caution).

The safety of the combined use of Plavix, fibrin-specific or fibrin-nonspecific thrombolytic drugs and heparin was investigated in patients with acute myocardial infarction. The frequency of clinically significant bleeding was similar to that observed in the joint use of thrombolytic agents and heparin with acetylsalicylic acid.

In a clinical study conducted with the participation of healthy volunteers, the combined use of clopidogrel and Naproxen increased latent blood loss through the gastrointestinal tract. However, due to the lack of studies on the interaction of clopidogrel with other nonsteroidal anti-inflammatory drugs (NSAIDs), it is currently unknown whether there is an increased risk of gastrointestinal bleeding with the use of clopidogrel together with other NSAIDs (NSAIDs, including COX-2 inhibitors , together with Plavix requires caution).

Because Clopidogrel is metabolized to form an active metabolite partially with the participation of the CYP2C19 isoenzyme, the use of drugs that inhibit this isoenzyme can lead to a decrease in the concentration of the active metabolite of clopidogrel. The clinical significance of this interaction is not established. Simultaneous use of strong or moderate inhibitors of the CYP2C19 isoenzyme (eg, omeprazole) should be avoided with clopidogrel. If simultaneous use of a proton pump inhibitor and clopidrelrel is necessary, a proton pump inhibitor with the least inhibition of the CYP2C19 isoenzyme, such as pantoprazole, should be given.

A number of clinical studies with clopidogrel and other concomitantly prescribed drugs were conducted to study the possible pharmacodynamic and pharmacokinetic interactions, which were shown the following.

When clopidogrel was used together with atenolol, nifedipine, or both, clinically significant pharmacodynamic interaction was not observed.

Simultaneous use of phenobarbital, cimetidine and estrogens had no significant effect on the pharmacodynamics of clopidogrel.

Pharmacokinetic indices of Digoxin and theophylline did not change when they were combined with clopidogrel.

Antacids did not reduce the absorption of Plavix.

Phenytoin and tolbutamide can be safely used simultaneously with clopidogrel (CAPRIE study). It is unlikely that clopidogrel may affect the metabolism of other drugs, such as phenytoin and tolbutamide, as well as NSAIDs that are metabolized with the participation of the CYP2C9 isoenzyme.

In clinical studies, there was no clinically significant undesirable interaction of clopidogrel with ACE inhibitors, diuretics, beta-blockers, slow calcium channel blockers,lipid-lowering agents, coronary vasodilators, hypoglycemic agents (including insulin), antiepileptic drugs, hormone replacement drugs, with glycoprotein 2b / 3a receptor blockers.

Analogues of the drug Plavix

Structural analogs for the active substance:

• Agregal;
• Payplat 75;
• Detromb;
• Zilt;
• Cardutol;
• Clopigrant;
• Clopidex;
• Clopidogrel;
• Clopidogrel hydrogen sulfate;
• Clopidogrel bisulfate;
• Clopilet;
• Listab;
• Lopyrel;
• Plagril;
• Plyglare;
• Target;
• Troken;
• Egitromb.

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