Clopidogrel, coated tablets 75 mg - Product - ATC Classification

Rx Prescription information

CLOPIDOGREL

(User’s information)

Trade name: Clopidogrel.

International nonproprietary name: Clopidogrel.

Description: biconvex, pink film-coated tablets. White or almost white nucleus is visible when tablet is broken. Tablet surface may have a rough film coating.

Composition: each tablet contains active substance: clopidogrel (as clopidogrel bisulfate) – 75 mg; excipients: mannitol, croscarmellose sodium, macrogol 4000, crospovidone, calcium stearate, silica, colloidal anhydrous, microcrystalline cellulose, hypromellose 2910, propylene glycol, titanium dioxide, carmoisine E-122, talc.

Pharmaceutical form: film - coated tablets.

Pharmaceutical group: Anti-aggregation agents.

ATC code: B01AC04

Pharmacological action

It is an anti-aggregation agent. The thrombocyte aggregation is being hindered evidently since the first day of the preparation administration. The inhibiting effect on the thrombocytes aggregation is enhanced and a stable condition is achieved in 3 – 7 days. The thrombocytes aggregation and the bleeding time return to the initial level on the average after 5 days after the treatment discontinuation.

It dilates the coronary artery. When a vessel is atherosclerotic the substance prevents thrombosis development independent on the vascular process localization (cerebrovascular, cardiovascular or peripheral disorders).

Indications

Prevention of thrombotic events in:

1. Patients having survived myocardial infarction, ischemic stroke or having been diagnosed peripheral arteries diseases.

2. Patients suffering from acute coronary syndrome:

- without ST segment rise (unstable stenocardia or myocardial infarction without Q wave)

in combination with acetyl salicylic acid;

- with ST segment rise (acute myocardial infarction) in combination with acetyl salicylic

acid in patients who take medicamentous therapy with possible thrombolytic therapy.

Dosage and mode of administration

Adults and elderly persons

75 mg orally once a day disregarding the food taking for prevention of ischemic disorders in patients having survived myocardial infarction, ischemic stroke or having been diagnosed peripheral arteries diseases. The treatment should be commenced within several days to 35 days after survival of a Q-forming myocardial infarction and within 7 days to 6 months after survival of ischemic stroke.

The clopidogrel treatment in patients suffering from acute coronary syndrome without ST segment rise (unstable stenocardia or myocardial infarction without Q wave) should be commenced with administration of 300 mg as a single loading dose followed by 75 mg dose once a day (in combination with 75 – 325 mg of acetyl salicylic acid per day). As high dose administration of acetyl salicylic acid is associated with a high risk of bleedings the recommended dose should be not more than 100 mg. The treatment duration is up to a year.

75 mg dose of clopidogrel once a day is prescribed in patients with acute myocardial infarction with the ST segment rise using the initial loading dose combined with acetyl salicylic acid and with or without thrombolytic agents. Patients older 75 should be treated with clopidogrel without use the initial loading dose.

Combined therapy should be commenced as soon as possible after occurrence of symptoms and continued for at least four weeks.

Side effects

Gastrointestinal bleedings; hemorrhagic stroke; neutropenia (rarely), thrombocytopenia; bellyache, dyspepsia, gastritis, constipations; GIT mucous membrane ulceration; diarrhea; allergic reactions (skin rash).

Contraindications

- individual hypersensitivity to the drug product or its components;

- severe hepatic insufficiency;

- acute bleeding, for example in case of a peptic ulcer or intracranial hemorrhage;

- pregnancy and lactation (See section Pregnancy and Lactation);

- pediatric use up to 18 years (the drug safety and efficiency have not been confirmed).

Use with caution in case of:

- liver and kidneys disease (moderate hepatic and/or renal insufficiency);

- traumas;

- preoperative conditions.

Overdose

Symptoms: the clopidogrel overdose can result in bleeding time prolongation followed by complications. When bleeding has been found an adequate treatment should be applied.

Treatment: no clopidogrel antidote is known. When the prolonged bleeding time requires a rapid correction transfuse of thrombocyte concentrate is recommended.

Interaction with other drug products

Warfarin: concomitant administration of clopidogrel and warfarin is not recommended as the drug combination can intensify the bleeding.

IIb/IIIa glycoprotein inhibitors: IIb/IIIa glycoprotein inhibitors may be prescribed in combination with clopidogrel with a particular caution.

Acetyl salicylic acid: acetyl salicylic acid does not effect on the clopidogrel inhibiting action on the ADP induced thrombocytes aggregation, however clopidogrel enhances impact of acetyl salicylic acid on the collagen induced thrombocytes aggregation. Those drugs combined administration requires caution (See section Precautions). However, patients suffering from acute coronary syndrome without ST segment rise are recommended to be administered clopidogrel and acetyl salicylic acid in combination for a long time (up to a year).

Heparin: as follows from a clinical trial in healthy participants, clopidogrel impacts neither on the heparin need nor on the heparin effect on the blood coagulation. Concomitant administration of heparin and clopidogrel has not changed the thrombocytes aggregation. However, safety of such combination has not been confirmed yet and concomitant administration of these preparations combination may be prescribed with caution (See section Precautions).

Thrombolytics: the safety of the combined administration of clopidogrel, fibrin-specific or fibrin-unspecific thrombolytic preparations and heparin was studied in patients with acute myocardial infarction. Frequency of clinically significant bleedings was similar to that observed when thrombolytic preparations and heparin were administered in combination with acetyl salicylic acid.

Non-steroid anti-inflammatory drugs (NSAIDs): NSAIDs and clopidogrel combined prescription requires particular caution (risk of bleeding increases).

Concomitant administration of clopidogrel and inhibitors of the proton pump (omeprazole, etc.) should be avoided as the clopidogrel active metabolite concentration reduces, and therefore its clinical efficiency reduces.

When clopidogrel and omeprazole are administrated separately the risk of their interaction development does not reduce.

One should refrain from clopidogrel administration simultaneously with other drug productscapable to inhibit the CYP2C19 activity. The drug products suppressing the CYP2C19 activity include cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, felbamate, fluoxetine, fluvoxamine, ticlopidine.

The antacids and most of H2-histamine receptors blockers impact on the clopidogrel anti-thrombocyte activity has not been proven sufficiently.

Combined administration with other drug products: no clinically significant pharmacodynamic interaction has been reported with concomitant administration of clopidogrel and atenolol, nifedipine, phenobarbital, estrogens, digoxin, theophylline, phenytoin, tolbutamide, and antacid agents.

Precautions for use

Blood test should be performed during the first week of treatment when clopidogrel is prescribed in combination with acetyl salicylic acid, non-steroid anti-inflammatory drugs, heparin, IIb/IIIa glycoprotein inhibitors or fibrinolytis agents as well as when patient is at high risk of bleeding due a trauma, surgical interventions or another pathological conditions.

In case of occurrence of symptoms indicating risk of development of bleeding and hematological side effects in course of treatment the blood test (APTT, thrombocyte number, tests for thrombocytes functional activity) and liver functional activity test should be immediately performed.

In case of surgical intervention the clopidogrel therapy should be ceased 7 days before the surgery.

Clopidogrel should be administered with caution in patients at risk of bleeding (gastrointestinal and intraocular bleedings in particular).

Patients should be warned to inform a doctor on each bleeding event.

Some cases of thrombotic thrombocytopenic purpura (TTP) developing after the clopidogrel ingestion have been reported. This condition was characterized by thrombocytopenia and microangiopathic hemolytic anemia combined either with neurological symptoms and renal function impairment or with fever. Development of TTP can threaten to life and require urgent actions including plasmapheresis.

Do not prescribe clopidogrel in acute period of ischemic stroke (the first 7 days) due to insufficient data.

The preparation should be prescribed with caution in patients with the renal function impairment. Clopidogrel should be prescribed with caution in patients with moderate liver function impairment as hemorrhagic diathesis is possible.

Patients with congenital galactose intolerance, syndrome of glucose – galactose malabsorption and lactase deficit should not administrate clopidogrel.

The risk of cardiac events such as acute myocardial infarction increases with concomitant administration of clopidogrel and inhibitors of the proton pump. When a patient needs inhibitors of the proton pump administration with underlying clopidogrel administration the preparations of that group with less expressed ability to interact should be prescribed. Pantoprazole is one of such drug products.

Administration during pregnancy and lactation

Due to absence of adequate clinical data on safety, clopidogrel administration is not recommended during pregnancy and lactation.

Effect on ability to drive and use other mechanisms

Clopidogrel administration has not been confirmed to deteriorate ability to drive or psychic ability to work. It does not effect on ability to drive and use other mechanisms.

Storage conditions

Store in protected from light place at temperature below 25°C.

Keep out of the rich of children.

Shelf life

2 years.

Package

10 tablets in a blister. One or three blisters together with leaflet are packed in a cardboard pack.

Pharmacy purchasing terms

On prescription.

Manufacturer:

Belmedpreparaty RUE

Republic of Belarus, 220007 Minsk, 30, Fabritsius st.,