Clopidogrel - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 181.175 mg, prosalt [microcrystalline cellulose 98%,silicon dioxide colloid 2%] 92,250 mg, croscarmellose sodium (impellose) 16,400 mg, silicon dioxide colloid (aerosil) 4,100 mg, sodium stearyl fumarate 8,200 mg;

shell composition: Opadrai II pink (lactose monohydrate 36.0%, hypromellose (E464) 28.0%, titanium dioxide (E171) 25.7%, macrogol (polyethylene glycol) (E1521) 10.0%, carmine (E120) 0.2 %, iron dye oxide yellow (E172) 0.1%) 9.930 mg, silicone emulsion 0.070 mg.

Description:

Round biconvex tablets, covered with a film membrane, pink. Insignificant roughness of the surface is permissible. Color of tablets on a break - white or white with a yellowish shade.

Pharmacotherapeutic group:antiplatelet agent

ATX: & nbsp

B.01.A. C.04 Clopidogrel

Pharmacodynamics:

Clopidogrel is a prodrug, one of its metabolites is active and inhibits the aggregation of platelets. The active metabolite of clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to P2Y12 receptor of platelets and subsequent ADP-mediated activation of the glycoprotein complex IIb/IIIa, leading to suppression of platelet aggregation. Due to irreversible binding, platelets remain immune to stimulation of ADP for the rest of their life(approximately 7-10 days), and the 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.

Since the formation of the active metabolite occurs with the isoenzymes of the P450 system, some of which may be polymorphic or may be inhibited by other drugs, not all patients may adequately inhibit platelet aggregation (see Pharmacokinetics, Pharmacogenetics).

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

When comparing pharmacodynamic properties of clopidogrel in men and women, a smaller inhibition of ADP-induced platelet aggregation is observed in women, but no sex differences in lengthening of bleeding time are revealed.

Pharmacokinetics:

Suction

After a single dose and with oral administration at a dose of 75 mg per day clopidogrel quickly absorbed.

The mean maximum concentration of unchanged clopidogrel in the blood plasma (approximately 2.2-2.5 ng / ml after ingestion of a single dose of 75 mg) is reached approximately 45 minutes after administration. According to the data on excretion of metabolites of clopidogrel with urine, its absorption is approximately 50%.

Distribution

In vitro Clopidogrel and its main circulating non-active metabolite in the blood reversibly bind to plasma proteins (98% and 94%, respectively), and this bond is unsaturated in a wide range of concentrations.

Metabolism

Clopidogrel is extensively metabolized in the liver. In vitro and in vivo 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 in the systemic bloodstream), and the second pathway through the cytochrome P450 system. Originally clopidogrel is metabolized to 2-oxoklopidogrel, which is an intermediate metabolite. Subsequent metabolism of 2-oxoclopidogrel leads to the formation of an active metabolite of clopidogrel-thiol clopidogrel derivative. In vitro this pathway of metabolism occurs by means of isoenzymes CYP3A4, CYP2C19, CYP1A2 and CYP2B6.

The active thiol metabolite of clopidogrel, which was isolated in studies in vitro, quickly and irreversibly binds to platelet receptors, thus inhibiting their aggregation.

The maximum concentration (C_mOh) of the active metabolite with a simultaneous reception of a loading dose of 300 mg is 2 times greater than that of a maintenance dose of 75 mg for 4 days. FROM_max The active metabolite is reached in 30-60 minutes after the drug intake Clopidogrel.

Excretion

Within 120 hours after ingestion by a human ¹⁴C-labeled clopidogrel about 50% of radioactivity is excreted by the kidneys and approximately 46% of the radioactivity - through the intestine. After a single oral dose of 75 mg, the half-life of clopidogrel (T_1/2) is approximately 6 hours. After a single dose and repeated doses of T_1/2The main circulating inactive blood metabolite is 8 hours.

Pharmacogenetics

Using isoenzyme CYP2C19 are formed as an active metabolite, and an intermediate metabolite - 2-oxoklopidogrel. Pharmacokinetics and antiplatelet effect of the active metabolite clopidogrel, in the study of platelet aggregation ex vivo, varies depending on the genotype of the isoenzyme CYP2C19. Gene allele CYP2C19 * 1 corresponds to fully functional metabolism, whereas gene alleles CYP2C19 * 2 and CYP2C19 * 3 are non-functional. Alleles of genes CYP2C19 * 2 and CYP2C19 * 3 cause a decrease in metabolism in the majority of representatives of the Caucasoid (85%) and Mongoloid races (99%). Other alleles that are associated with a lack or decrease in metabolism are less common and include, but are not limited to, gene alleles CYP2C19 * 4, * 5, * 6, * 7 and * 8. Patients, which are weak metabolizers, should have the two alleles of the gene with loss of function indicated above. Published frequency of occurrence of phenotypes of weak metabolizers CYP2C19 are 2% in the Caucasoid race, 4% in the Negroid race, and 14% in the Mongoloid race.

Individual patient groups

The pharmacokinetics of the active metabolite of clopidogrel in these patient groups have not been studied.

Elderly people

In elderly volunteers (over 75 years), when compared with young volunteers, there was no difference in platelet aggregation and bleeding time. Do not require dose adjustment in the elderly.

Children

No data available.

Impaired renal function

After repeated use of clopidogrel at a dose of 75 mg / day in patients with severe renal disease (creatinine clearance from 5 to 15 ml / min), inhibition of ADP-induced platelet aggregation was below 25% compared to that of healthy volunteers, but the prolongation of bleeding time was similar to that of healthy volunteers who received clopidogrel in a dose of 75 mg per day.

Impaired liver function

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

Race

Prevalence of alleles of isoenzyme genes CYP2C19, responsible for the intermediate and reduced metabolism, is different in representatives of different racial groups.There are very small literature data on their prevalence in representatives of the Mongoloid race, which does not allow us to assess their values of genotyping isoenzyme CYP2C19 for the development of ischemic complications.

Indications:

Prevention of atherothrombotic complications

In adults with myocardial infarction (from a few days to 35 days old), ischemic stroke (with a prescription from 7 days to 6 months) or with a diagnosed occlusive disease of peripheral arteries.

In adults with acute coronary syndrome:

- without lifting the segment ST (unstable angina or myocardial infarction without a tooth Q), including patients who underwent stenting with percutaneous coronary intervention (in combination with acetylsalicylic acid);

- with segment lift ST (acute myocardial infarction) with drug treatment and the possibility of carrying out 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).

Contraindications:

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

- severe hepatic impairment;

- acute bleeding, eg bleeding from peptic ulcers or intracranial hemorrhage;

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

- pregnancy and lactation period (see Section "Application during pregnancy and lactation");

- Children under 18 years of age (safety and efficacy not established).

Carefully:

- With moderate hepatic insufficiency, which may predispose to bleeding (limited clinical experience of use);

- with renal failure (limited clinical experience of use);

- with injuries, surgical interventions (risk of increased bleeding, see section "Special instructions");

- in diseases in which there is a predisposition to the development of bleeding (especially gastrointestinal or intraocular,Section "Special instructions");

- with the simultaneous administration of non-steroidal anti-inflammatory drugs, including selective inhibitors of cyclooxygenase-2 (COX-2) (see section "Special instructions");

- while concurrent administration of oral anticoagulants, heparin, blockers of glycoprotein receptors IIb/IIIa;

- hypersensitivity to other thienopyridines (eg, ticlopidine, prasugrel);

- in patients with a genetically determined decrease in the isoenzyme function CYP2C19 (in patients who are weak CYP2C19- metabolizers when using clopidogrel in recommended doses, less active metabolite of clopidogrel is formed and its antiplatelet effect is less pronounced; weak metabolizers who received clopidogrel in recommended doses, with acute coronary syndrome or percutaneous coronary intervention, may have a higher incidence of cardiovascular complications than patients with normal isoenzyme activity CYP2C19) (see Sections "Pharmacokinetics", "Pharmacogenetics", "Method of administration and dose").

Pregnancy and lactation:

As a precautionary measure, the use of clopidogrel during pregnancy is not recommended due to the lack of clinical data on its intake by pregnant women,although animal studies did not reveal any direct or indirect adverse effects on the course of pregnancy, embryonic development, childbirth and postnatal development.

Breastfeeding in case of clopidogrel treatment should be discontinued, as it has been shown that clopidogrel and / or its metabolites are excreted in breast milk in laboratory animals.

Dosing and Administration:

Adults and elderly people with normal isoenzyme activity 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 segment elevation ST (unstable angina, myocardial infarction without a tooth Q)

Treatment with clopidogrel should be started with a single loading dose of 300 mg (4 tablets of the drug Clopidogrel), and then continued with a 75 mg dose once a day (in combination with acetylsalicylic acid at doses of 75-325 mg per day). Since the use of higher doses of acetylsalicylic acid 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. The optimal duration of treatment is not officially defined.

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

Clopidogrel is given once in a dose of 75 mg once a day with the initial single dose 300 mg loading dose (4 tablets of the drug Clopidogrel) in combination with acetylsalicylic acid and thrombolytics (or without thrombolytics). Combination therapy is started as soon as possible after the onset of symptoms and continues for at least four weeks. In patients older than 75 years, treatment with clopidogrel should begin without taking a loading dose. 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)

Clopidogrel should be taken once a day at a dose of 75 mg. In combination with clopidogrel, you must start and then continue taking acetylsalicylic acid (75-100 mg / 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 pass after missed the next dose, the patient should take the next dose at the usual time (do not take a double dose).

Patients with a genetically determined decrease in the isoenzyme function CYP2C19

Low isoenzyme activity CYP2C19 is associated with a decrease in the antiplatelet effect of clopidogrel. The mode of application of high doses (600 mg - loading dose, then 150 mg once a day daily) in weak metabolizers increases the antiaggregant effect of clopidogrel (see Sections "Pharmacokinetics", "Pharmacogenetics"). However, the optimal dosing regimen for patients with low isoenzyme activity CYP2C19 in clinical studies on clinical outcomes has not yet been established (see Sections "Pharmacokinetics", "Pharmacogenetics").

Special patient groups

Elderly people

In elderly volunteers (over 75 years old), when compared with young volunteers, there was no difference in platelet aggregation and bleeding time. Do not require dose adjustment for the elderly.

Children

There is no experience of using the drug in children.

Patients with impaired renal function

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

Patients with impaired hepatic function

Patients of different race

Prevalence of alleles of isoenzyme genes CYP2C19, responsible for the intermediate and decreased metabolism of clopidogrel to its active metabolite, is different in representatives of different ethnic groups (see Section "Pharmacogenetics"). There are only limited data for members of the Mongoloid race to assess the effect of the isoenzyme genotype CYP2C19 on the clinical outcome events.

Female and male patients

In a small study comparing the pharmacodynamic properties of clopidogrel in men and women, women had less inhibition of ADP-induced platelet aggregation, but there was no difference in bleeding time elongation. In a large controlled study comparing clopidogrel with acetylsalicylic acid in patients with the risk of developing ischemic complications, the frequency of clinical outcomes, other side effects and deviations from the norm of clinical and laboratory indicators was the same for both men and women.

Side effects:

The frequency of adverse reactions that were observed either during clinical trials of the original drug, or were obtained from spontaneous reports on the development of adverse reactions, is determined as follows: often (≥1/100 - <1/10); infrequently (≥1/1000 - <1/100); rarely (≥1/10000 - <1/1000); very rarely (<1/10000). In each system-organ class, undesirable reactions are presented in order of decreasing severity.

Violations of the blood and lymphatic system

Infrequent: thrombocytopenia, leukopenia, eosinophilia.

Rarely: neutropenia, including severe neutropenia.

Very rarely: thrombotic thrombocytopenic purpura (see Section "Special instructions"), aplastic anemia, pancytopenia, agranulocytosis, severe thrombocytopenia, granulocytopenia, anemia.

Immune system disorders

Very rarely: serum sickness, anaphylactoid reactions.

The frequency is unknown: cross-over hypersensitivity to other thienopyridine (eg, ticlopidine, prasugrel).

Disorders of the psyche

Very rarely: hallucinations, confusion.

Disturbances from the nervous system

Infrequently: intracranial hemorrhage (several cases of fatal cases have been reported), headache, paresthesia, dizziness.

Very rarely: a violation of taste perception.

Disturbances on the part of the organ of sight

Infrequent: eye hemorrhage (conjunctival, in the tissue and retina of the eye).

Hearing disorders and labyrinthine disorders

Rarely: vertigo.

Disorders from the cardiovascular system

Often: hematoma.

Very rarely: serious bleeding from the operating wound, vasculitis, lowering blood pressure.

Disturbances from the respiratory system

Often: nosebleeds.

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

Disorders from the digestive system

Very often: gastrointestinal bleeding, diarrhea, abdominal pain, indigestion.

Infrequently: stomach and duodenal ulcer, vomiting, nausea, constipation, bloating.

Rarely: retroperitoneal hemorrhage.

Very rarely: gastrointestinal bleeding and retroperitoneal hemorrhage with fatal outcome, pancreatitis, colitis (including ulcerative colitis and lymphocytic colitis), stomatitis, acute hepatic insufficiency, hepatitis, abnormal liver function.

Disturbances from the skin and subcutaneous tissues

Often: subcutaneous bruising.

Infrequent: rash, itching, purpura (subcutaneous hemorrhage).

Very rarely: bullous dermatitis (toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme) angioedema, erythematous rash, urticaria, eczema, flat lichen.

Disturbances from musculoskeletal and connective tissue

Very rarely: hemorrhages in the muscles and joints, arthritis, arthralgia, myalgia.

Disorders from the kidneys and urinary tract

Infrequently: hematuria.

Very rarely: glomerulonephritis, an increase in the concentration of creatinine in the blood.

General disorders

Often: bleeding from the point of vascular puncture.

Very rarely: fever.

Laboratory and instrumental data

Infrequent: increased bleeding time, fewer neutrophils, a decrease in the number of platelets in the peripheral blood.

Overdose:

Symptoms

An overdose of clopidogrel may lead to an increase in bleeding time with subsequent complications in the form of bleeding.

Treatment

When bleeding occurs, appropriate treatment is required. The antidote of clopidogrel is not established. If rapid recovery of prolonged bleeding time is necessary, transfusion of platelet mass is recommended.

Interaction:

Oral anticoagulants

Simultaneous use of clopidogrel and oral anticoagulants may increase the intensity of bleeding, and therefore, the use of this combination is not recommended.

Although taking clopidogrel 75 mg / day did not change the pharmacokinetics of warfarin (substrate isoenzyme CYP2C9), or an international normalized ratio (INR) in patients with long-term warfarin treatment, concomitant administration with clopidogrel may increase the intensity of bleeding, so caution should be exercised while taking warfarin and clopidogrel.

Blockers of glycoprotein receptors IIb/IIIa

PThe use of glycoprotein receptor blockers IIb/IIIa with clopidogrel requires caution in patients who have an increased risk of bleeding (with trauma and surgical interventions or other pathological conditions) (see section "Special instructions").

Acetylsalicylic acid

Acetylsalicylic acid does not alter the effect of clopidogrel, an inhibitor of 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, when they are used simultaneously, care should be taken, although in clinical trials patients received combined therapy with clopidogrel and acetylsalicylic acid for up to one year.

Heparin

According to the clinical trial conducted with the participation of healthy individuals, 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 clopidogrel and heparin, pharmacodynamic interaction is possible, which may increase the risk of bleeding, so the simultaneous use of these drugs requires caution.

Thrombolytics

The safety of the joint use of clopidogrel, fibrin-specific or fibrin-specific 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.

Non-steroidal anti-inflammatory drugs (NSAIDs)

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 research on the interaction of clopidogrel with other NSAIDs, it is currently unknown whether there is an increased risk of gastrointestinal bleeding when taking clopidogrel along with other NSAIDs. Therefore, the appointment of NSAIDs, including COX-2 inhibitors, in combination with clopidogrel should be done with caution (see section "Special instructions").

Other combination therapy

As clopidogrel metabolized to the formation of its active metabolite in part by means of isoenzyme CYP2C19, the use of drugs that inhibit this system can lead to a decrease in the concentration of the active metabolite clopidogrel. The clinical significance of this interaction is not established. The simultaneous use of strong or moderate inhibitors with clopidogrel should be avoided CYP2C19 such as omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine, chloramphenicol (see Sections "Pharmacokinetics", "Pharmacogenetics", "Special instructions"). If proton pump inhibitors are to be taken concomitantly with clopidogrel, proton pump inhibitors with the lowest isoenzyme inhibition activity CYP2C19, such as pantoprazole or lansoprazole.

A number of clinical studies with clopidogrel and other concomitantly prescribed drugs were conducted to study possible pharmacodynamic and pharmacokinetic interactions that showed that:

- when clopidogrel was used together with atenolol, nifedipine, or with both drugs, 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 combined with clopidogrel;

- antacids did not reduce the absorption of clopidogrel;

- phenytoin and tolbutamide can be safely used simultaneously with clopidogrel. It is unlikely that clopidogrel can influence the metabolism of other medicines, such as phenytoin and tolbutamide, as well as non-steroidal anti-inflammatory drugs that are metabolized by isoenzymeCYP2C9 families of cytochrome P450;

- ACE inhibitors, diuretics, beta-blockers, "slow" calcium channel blockers, lipid-lowering agents, coronary vasodilators, lipid-lowering agents (including insulin), antiepileptics, hormone replacement therapy and glycoprotein receptor blockers IIb/IIIa: Clinical studies did not reveal clinically significant adverse interactions.

Special instructions:

In the treatment of clopidogrel, especially during the first weeks of treatment and / or after invasive cardiac procedures / surgery, careful monitoring of patients for bleeding, including concealed bleeding, should be performed.

In connection with the risk of bleeding and hematological side effects (see Fig.Section "Side effect") in case of appearance during treatment of clinical symptoms, suspicious for the occurrence of bleeding, it is urgent to do a clinical blood test, determine activated partial thromboplastin time (APTT), platelet count, platelet function and conduct other necessary studies.

Clopidogrel, as well as other antiplatelet agents, should be used with caution in patients with trauma, surgical interventions or other pathological conditions, due to the risk of increased bleeding, as well as in patients receiving acetylsalicylic acid, nonsteroidal anti-inflammatory drugs, including inhibitors COX-2, heparin or blockers of glycoprotein receptors IIb/IIIbut because of the increased risk of bleeding.

Joint use of clopidogrel with warfarin may increase the intensity of bleeding (see Section "Interaction with other medicinal products"), therefore caution should be exercised when using clopidogrel and warfarin together except in special clinical situations (such as,as the presence of a floating thrombus in the left ventricle or stenting of the coronary arteries in patients with atrial fibrillation).

In patients with recent ischemic stroke or transient ischemic attack and a high risk of recurrent atherothrombotic events, combination therapy with clopidogrel and acetylsalicylic acid has not demonstrated greater efficacy in comparison with clopidogrel monotherapy, but may increase the risk of major bleeding.

It should be clarified the presence in the patient's history of hypersensitivity to other derivatives of thienopyridine (ticlopidine, prasugrel), t. cases of cross-allergic reactions between thienopyridines are described. Patients who have previously experienced hypersensitivity to other thienopyridine require careful follow-up throughout the treatment period to identify signs of hypersensitivity to clopidogrel.

The experience of using clopidogrel in patients with chronic renal failure is limited, in connection with which, clopidogrel in this category of patients should be used with caution.

With severe violations of liver function, the use of clopidogrel is contraindicated, due to the high risk of hemorrhagic diathesis. The experience of using the drug in patients with moderate violations of the liver is limited, so these patients clopidogrel should be administered with caution.

If the patient is to have a planned surgical operation, and thus there is no need for an antiaggregant effect, then for 5-7 days before the operation, the use of clopidogrel should be discontinued.

Clopidogrel prolongs bleeding time and should be used with caution in patients with diseases predisposing to the development of bleeding (especially, gastrointestinal and intraocular). Drugs that can cause damage to the mucous membrane of the gastrointestinal tract (such as acetylsalicylic acid, NSAIDs) in patients receiving clopidogrel, should be used with caution.

Patients should be warned that taking clopidogrel (alone or in combination with acetylsalicylic acid) may require more time to stop bleeding, and that if they have an unusual bleeding (localization or duration), they should 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 the use of clopidogrel (sometimes even briefly), there have been cases of thrombotic thrombocytopenic purpura (TTP), which is characterized by thrombocytopenia and microangiopathic hemolytic anemia, accompanied by neurological disorders, impaired renal function and fever. TTP is a potentially life-threatening condition requiring immediate treatment, including plasmapheresis.

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

Taking clopidogrel is not recommended for an acute stroke less than 7 days old (as there is no data on its use in this condition).

Clopidogrel should not be taken to patients with a rare hereditary lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome (see Section "Composition").

Effect on the ability to drive transp. cf. and fur:

Clopidogrel does not significantly affect the abilities necessary for driving or working with machinery.

Form release / dosage:

Tablets coated with a film coating, 75 mg.

Packaging:

For 7 or 10 tablets in a contour mesh package.

For 1, 2, 3 or 4 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002442

Date of registration:28.04.2014

The owner of the registration certificate:NANOLEC, LTD. NANOLEC, LTD. Russia

Manufacturer: & nbsp

BIOKOM, CJSC Russia

Information update date: & nbsp02.08.2015

Illustrated instructions

Instructions

Clopidogrel (Clopidogrel)