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

Excipients: lactose monohydrate 0.186275 g, povidone K 17 (low molecular weight polyvinylpyrrolidone) 0.001850 g,cellulose microcrystalline - 0,044400 g, talc - 0,011100 g, croscarmellose sodium (impellose) - 0.014800 g, magnesium stearate - 0.003700 g;

film sheath auxiliaries: Opadrai II Pink - 0.0097 g (polyvinyl alcohol, titanium dioxide, talc, macrogol (polyethylene glycol), carmine red dye (E120), aluminum dye based on sunset yellow sunset (E110), aluminum varnish based on the dye red charming E129), an aluminum lacquer based on the dye quinoline yellow (E104)), silicone emulsion - 0.0003 g.

Description:Round biconvex tablets, covered with a film membrane, pink. On a cross-section the color of the core of the tablet is white or white with a yellow tinge.

Pharmacotherapeutic group:Antiaggregant agent

ATX: & nbsp

B.01.A. C.04 Clopidogrel

Pharmacodynamics:

Clopidogrel is a specific and active inhibitor of platelet aggregation. Selectively reduces the binding of adenosine diphosphate (ADP) to receptors on platelets and activation of receptors of glycoprotein IIb/IIIbut under the action of ADP, weakening the aggregation of platelets.

Reduces platelet aggregation, caused by other agonists, preventing their activation by released ADP, does not affect the activity of phosphodiesterase (PDE).Irreversibly binds to the platelet ADP receptors that remain impervious to ADP stimulation throughout the life cycle (about 7 days).

The inhibition of platelet aggregation is observed 2 hours after admission (40% inhibition) of the initial dose of 400 mg. The maximum effect (60% suppression of aggregation) develops after 4-7 days of constant admission in a dose of 50-100 mg / day. Antiaggregant effect persists throughout the life span of platelets (7-10 days).

In the presence of an atherosclerotic lesion, the vessel interferes with the development of atherothrombosis regardless of the localization of the vascular process (cerebrovascular, cardiovascular or peripheral lesions).

Pharmacokinetics:

Clopidogrel is rapidly absorbed after repeated administration of 75 mg per day.

Bioavailability is high. However, the concentration of the starting material in the plasma is low and already within 2 hours after administration it does not reach the measurement limit (0.025 μg / l). The connection with plasma proteins is 98-94%.

Clopidogrel is rapidly metabolized in the liver. The active metabolite is an inactive carboxylic acid derivative, the time to reach the maximum concentration (TC_mOh) which after repeated oral doses of 75 mg is achieved after 1 hour (the average maximum concentration of C_mOh - about 3 mg / l).

About 50% of the drug is excreted by the kidneys and approximately 46% by the intestine within 120 hours after administration. The half-life (T_1/2) of the main metabolite after a single and repeated administration is 8 hours. The concentration of kidney metabolites is 50%.

The concentration of the main metabolite in the plasma after taking 75 mg / day is lower in patients with severe kidney disease (creatinine clearance of 5-15 ml / min) compared with patients with moderate kidney disease (QC 30 to 60 ml / min) and healthy persons.

Indications:

Prevention of thrombotic complications in patients with myocardial infarction, ischemic stroke or peripheral arterial occlusion.

In combination with acetylsalicylic acid for the prevention of thrombotic complications in acute coronary syndrome:

- with segment lift ST if possible, thrombolytic therapy;

- without lifting the segment ST (unstable angina or myocardial infarction without Q-wave), incl. in patients undergoing stenting.

Contraindications:

Hypersensitivity to the active or any auxiliary component of the drug.

Deficiency of lactase, lactose intolerance, glucosogalactose malabsorption.

Age to 18 years (efficacy and safety of use not established).

Severe hepatic insufficiency.

Active pathological bleeding (peptic ulcer or intracranial hemorrhage).

Pregnancy and lactation.

Carefully:

Moderate hepatic impairment.

Chronic liver failure (CRF).

Pathological conditions that increase the risk of bleeding (including trauma, surgery).

Simultaneous administration of ASA, warfarin, non-steroidal anti-inflammatory drugs (NSAIDs) (including COX-2 inhibitors), heparin, glycoprotein inhibitors IIb/IIIa.

Hereditary decrease of the isoenzyme function CYP2C19.

Pregnancy and lactation:

In the absence of data, it is not recommended to take clopidogrel during pregnancy and lactation.

Dosing and Administration:

Inside, regardless of food intake.

For the prevention of thrombotic complications in patients with myocardial infarction, ischemic stroke or peripheral arterial occlusion - 75 mg once a day.

In patients with myocardial infarction, treatment can begin from the first days to the 35th day

myocardial infarction, and in patients with ischemic stroke - in the period from 7 days to 6 months after ischemic stroke.

For prophylaxis of thrombotic complications in acute coronary syndrome without ST segment elevation (unstable angina, myocardial infarction without Q wave) - begin with a single dose 300 mg loading, and then take 75 mg / day (in combination with ASK in doses of 75-325 mg / day, the recommended dose is 100 mg / day) . The maximum favorable effect occurs after 3 months. The course of treatment is up to 1 year.

For prophylaxis of thrombotic complications in acute coronary syndrome with ST segment elevation (acute myocardial infarction with ST segment elevation) - 75 mg / day with the initial single dose loading in combination with ASA and thrombolytic agents (or without thrombolytics).

Combination therapy begins 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 begin without taking its loading dose.

In patients with a genetically determined decrease in the isoenzyme function of CYP2C19 possibly reducing the effect of clopidogrel.The optimal dosage regimen in these patients is not established.

Experience of application in patients with CRF or moderate degree of hepatic insufficiency is limited.

Side effects:

Bleeding is the most frequent reaction that occurs during the first month of taking the drug. Cases of severe bleeding have been reported in patients taking clopidogrel simultaneously with ASA or clopidogrel with ASA and heparin (see section "Special instructions").

The frequency of side effects is determined according to the following definitions: very often - more 1/10, often - more 1/100 and less 1/10, infrequently - more 1/1000 and less 1/100, rarely - more 1/10000 and less 1/1000, very rarely - less than 1/10000, including isolated cases.

Within each class of frequencies, undesirable effects are presented in order of decreasing severity.

On the part of the organs of hematopoiesis: infrequently - thrombocytopenia, leukopenia, eosinophilia; rarely - neutropenia, incl. expressed; very rarely - thrombotic thrombocytopenic purpura, anemia, incl. aplastic, pancytopenia, agranulocytosis, severe thrombocytopenia, granulocytopenia.

Allergic reactions: very rarely - anaphylactic reactions, serum sickness.

From the nervous system: infrequently - headache, dizziness, paresthesia, intracranial hemorrhage, incl. with lethal outcome; very rarely - confusion, hallucinations, a taste disorder.

From the sense organs: infrequently - hemorrhage in the conjunctiva, eyes, retina; rarely - vertigo.

From the side of the cardiovascular system: often - hematoma; very rarely - heavy bleeding, bleeding from the operating wound, vasculitis, lowering blood pressure.

From the respiratory system: very often - nosebleeds; very rarely - bronchospasm, interstitial pneumonitis, pulmonary hemorrhage, hemoptysis.

From the digestive system: often - diarrhea, abdominal pain, indigestion, bleeding from the gastrointestinal tract; infrequently - stomach ulcer and duodenal ulcer, gastritis, vomiting, nausea, constipation, flatulence; rarely - retroperitoneal bleeding; very rarely - pancreatitis, colitis, incl. ulcerative or lymphocytic, stomatitis, acute hepatic insufficiency, hepatitis, a violation of functional liver tests, bleeding from the gastrointestinal tract with lethal outcome.

From the skin: often - subcutaneous hemorrhage; infrequently - skin rash, itching, purpura; very rarely - angioedema, urticaria, erythematous rash, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, eczema, lichen planus.

Co the side of the musculoskeletal system: very rarely - hemarthrosis, arthritis, arthralgia, myalgia.

From the genitourinary system: infrequently - hematuria; very rarely - glomerulonephritis, hypercreatininaemia.

Laboratory indicators: infrequent - prolongation of bleeding time.

Other: very rarely: arthralgia, arthritis, myalgia, anaphylactoid reactions, serum sickness, fever, impaired functional liver tests, increased blood creatinine concentration, glomerulonephritis, fever, hemarthrosis, hematuria.

Overdose:

An overdose of clopidogrel may lead to prolonged bleeding time and subsequent complications. If a bleeding is detected, appropriate treatment should be applied.

Antidotes of the pharmaceutical activity of clopidogrel have not been found.

If rapid correction of prolonged bleeding time is necessary, transfusion of platelet mass is recommended.

Interaction:

The simultaneous administration of warfarin with clopidogrel may increase the intensity of bleeding, so the use of this combination is not recommended.

The appointment of inhibitors of glycoprotein IIb / IIIa, ASA, heparin together with clopidogrel increases the risk of bleeding.

When used simultaneously with NSAIDs, the risk of bleeding may increase.

Simultaneous administration with inhibitors of CYP2C19 (eg, omeprazole) Not recommended.

The active metabolite of clopidogrel inhibits the activity of the isoenzyme CYP2C9, resulting in increased concentrations of phenytoin, tolbutamide and NSAIDs in plasma.

Special instructions:

During the treatment period it is necessary to monitor the parameters of the hemostasis system (activated partial thromboplastin time (APTTV)), the number of platelets, tests of the functional activity of thrombocytes), to regularly investigate the functional activity of the liver.

Clopidogrel should be used with caution in patients with a risk of severe bleeding in trauma, surgery, in patients with injuries prone to bleeding (especially gastrointestinal and intraocular), as well as in patients receiving ASA, nonsteroidal anti-inflammatory drugs (including inhibitors of COX-2), heparin or glycoprotein inhibitors IIb/IIIa. Patients should be carefully monitored to detect any signs of bleeding, including latent, especially during the first weeks of the drug and / or after invasive procedures on the heart or surgical procedures. The simultaneous use of clopidogrel and warfarin is not recommended, since it can intensify bleeding;

In the case of surgical interventions, if antiaggregant effect is undesirable, the course of treatment should be discontinued 7 days before the operation.

Patients should be warned that since stopping the bleeding due to the use of clopidogrel (in combination with or without ASA) requires more time, they should inform the doctor about every case of bleeding. Patients should also inform the doctor about taking the drug if they are to be promptly operated.

After taking clopidogrel, thrombotic thrombocytopenic purpura (TTP) was detected very rarely, sometimes after short-term use. This condition is characterized by thrombocytopenia and microangiopathic hemolytic anemia in combination with neurological signs of impaired renal function or fever.TTP is potentially fatal, a condition requiring immediate treatment, including with the use of plasmapheresis.

Due to lack of data clopidogrel It can not be recommended for acute (less than 7 days) ischemic stroke.

The experience of using clopidogrel in patients with impaired renal function is limited, so these patients clopidogrel should be administered with caution.

In case of serious violations of liver function, one should remember about the risk of hemorrhagic diathesis development, the experience of using the drug in patients with moderate violations of the liver function is limited, therefore, these patients clopidogrel should be administered with caution.

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

Clopidogrel may cause side effects from the nervous system (headache, dizziness, systemic dizziness, confusion, hallucinations, which can affect the ability to drive vehicles and to engage in other potentially dangerous activities requiring increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets coated with a film coating, 75 mg.

Packaging:

For 7 and 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 a dry, 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-000076

Date of registration:10.12.2010 / 11.12.2015

Expiration Date:Unlimited

The owner of the registration certificate:BIOKOM, CJSC BIOKOM, CJSC Russia

Manufacturer: & nbsp

BIOKOM, CJSC Russia

Information update date: & nbsp29.01.2018

Illustrated instructions

Instructions

Clopidogrel (Clopidogrel)