Klopidogrel

General characteristics. Structure:

Active ingredient: 75 mg of a klopidogrel in 1 tablet.

Drug with the expressed anti-aggregation action.

Pharmacological properties:

Pharmacodynamics. Selectively it is also irreversible blocks linkng of ADF with receptors of thrombocytes, suppresses their activation, reduces the number of the functioning ADF-receptors (without damage), interferes with sorption of fibrinogen and inhibits aggregation of thrombocytes.

Pharmacokinetics. At intake it is quickly soaked up, characterized by high bioavailability. Time of achievement of Cmax  makes about 1 h. Is pro-medicine, it biotransformirutsya in a liver with formation of an active metabolite. T1/2  makes about 8 h. It is removed with urine and excrements.

The inhibition of aggregation begins later 2 h after reception (40% of inhibition), is registered at an initial dose of 400 mg. The maximum effect (60% of suppression of aggregation) is observed in 4–7 days of constant reception in a dose of 50-100 mg/days. The anti-aggregation effect remains the entire period of life of thrombocytes (7–10 days). In the presence of atherosclerotic defeat of a vessel interferes with development of an aterotromboz, irrespective of the nature of vascular process (cerebrovascular, cardiovascular or peripheral defeats).

At treatment klopidogrely in comparison with aspirin the relative total risk of an ischemic stroke, myocardial infarction and vascular death decreases by 8,7%.

Indications to use:

Prevention of aterotrombotichesky complications at the patients who had a myocardial infarction, an ischemic stroke or with the diagnosed occlusal disease of peripheral arteries.

Prevention of aterotrombotichesky events (in a combination with acetylsalicylic acid) at patients with an acute coronary syndrome:

- without raising of a segment of ST (unstable stenocardia or a myocardial infarction without Q tooth), including patients to whom stenting at transdermal coronary intervention was carried out;

- with raising of a segment of ST (an acute myocardial infarction) at drug treatment and a possibility of carrying out a thrombolysis.

Route of administration and doses:

Inside. At a myocardial infarction, an ischemic stroke or occlusion of peripheral arteries — on 75 mg of 1 times a day, regardless of meal. Treatment should be begun in terms from several days to 35 days at patients after a myocardial infarction and from 7 days to 6 months at patients after an ischemic stroke.

At an acute coronary syndrome without raising of a segment of ST (unstable stenocardia, a myocardial infarction without Q tooth) — begin with a single dose of a load dose (300 mg), then 75 mg of 1 times a day (in combination with acetylsalicylic acid). The maximum favorable effect occurs in 3 months of treatment. A course of treatment — till 1 year.

At an acute coronary syndrome with raising of a segment of ST (an acute myocardial infarction) — on 75 mg once a day with an initial single dose of a load dose in a combination with acetylsalicylic acid and trombolitikam (or without trombolitik). The combination therapy is begun as soon as possible after emergence of symptoms and continued during, at least, 4 weeks.

At patients it has to is more senior 75 years treatment klopidogrely to begin without load dose.

Features of use:

Use at pregnancy and feeding by a breast. It is not recommended during pregnancy due to the lack of clinical data on use by pregnant women though researches on animals did not reveal either direct, nor indirect adverse effects on the course of pregnancy, embryonic development, childbirth and post-natal development.

Category of action on a fruit on FDA — B. For the period of treatment it is necessary to stop breastfeeding since in researches on rats, it was shown that klopidogret and/or its metabolites are excreted in breast milk. Gets or not klopidogret into breast milk of the person — it is unknown.

At treatment klopidogrely, especially within the first weeks of treatment and/or after the invasive cardiological procedures / surgical intervention, it is necessary to conduct careful observation of patients regarding an exception of symptoms of bleeding, including hidden.

Due to the risk of development of bleeding and hematologic undesirable effects in case of emergence during treatment of clinical symptoms, suspicious concerning developing of bleeding, it is necessary to make urgently clinical blood test, to define AChTV, quantity of thrombocytes, indicators of functional activity of thrombocytes and to conduct other necessary researches.

Klopidogrel, also as well as other antithrombocytic drugs, it is necessary to apply with care at the patients having the increased risk of development of bleeding connected with injuries, surgical interventions or other morbid conditions and also at patients receiving acetylsalicylic acid, other NPVS, including TsOG-2 inhibitors, heparin or inhibitors of receptors of a glycoprotein IIb/IIIa.

Combined use of a klopidogrel with warfarin can increase intensity of bleeding therefore, except for special rare clinical situations (such as existence of the floating blood clot in a left ventricle, stenting at patients with a ciliary arrhythmia), combined use with warfarin is not recommended.

If planned surgery is necessary to the patient and at the same time there is no need for antithrombocytic effect, then in 7 days prior to operation reception of a klopidogrel should be stopped.

Klopidogrel extends a bleeding time and has to be applied with care at patients with the diseases contributing to development of bleedings (especially gastrointestinal and intraocular).

Patients have to be warned that at reception of a klopidogrel (one or in a combination with acetylsalicylic acid) for a stop of bleeding more time can be required, and also that in case of emergence at them unusual (on localization or duration) they should report bleedings about it to the attending physician. Before any forthcoming operation and before reception of any new patients have to report HP to the doctor (including the stomatologist) about reception of a klopidogrel.

Very seldom after use of a klopidogrel (sometimes even short) cases of development of the Werlhof's trombogemolitichesky disease (WTD) which is characterized by the thrombocytopenia and mikroangiopatichesky hemolitic anemia which are followed by neurologic frustration, a renal failure and fever were noted. TTP is potentially life-threatening state demanding immediate treatment including a plasma exchange.

During treatment it is necessary to control functional activity of a liver. At severe damages of a liver it is necessary to remember risk of development of hemorrhagic diathesis.

Reception of a klopidogrel is not recommended at an acute stroke with prescription less than 7 days (since there are no data on its use at this state).

Side effects:

From a nervous system and sense bodys: fatigue, adynamy, headache, dizziness, paresthesia, spasms of legs, hyperesthesia, neuralgia, cataract, conjunctivitis.

From cardiovascular system and blood (a hemopoiesis, a hemostasis): peripheral hypostases, arterial hypertension, heart failure, generalized hypostases, syncope, heartbeat, thrombocytopenia, anemia (aplastic or hypochromia), agranulocytosis, leukopenia, neutropenia.

Coagulative frustration and bleedings: a purpura, extravasates, эпистаксис, gastrointestinal bleeding, hemorrhage in joints, bleeding from urinary tract, a pneumorrhagia, intracraneal hemorrhage, a retroperitoneal hemorrhage, bleeding from an operational wound, intraocular hemorrhage, a hemothorax, pulmonary bleeding, an allergic purpura, a Werlhof's trombogemolitichesky disease.

From bodies of a GIT: abdominal pain, dyspepsia, diarrhea, nausea, vomiting, lock, taste disturbance, perforation of stomach ulcer, hemorrhagic gastritis, helcomenia of upper parts of a GIT, increase in activity of liver enzymes, hyperbilirubinemia, hepatitis, liver steatosis.

From a musculoskeletal system: arthralgia, dorsodynia, arthritis, arthrosis.

From respiratory system: inflammation of upper respiratory tracts, short wind, rhinitis, bronchitis, cough, pneumonia, sinusitis.

From urinogenital system: infections of urinary tract, cystitis, menorrhagia.

From integuments: rash, itch, eczema, skin ulcerations, violent dermatitis, erythematic rash, makulopapulyarny rash, small tortoiseshell.

Others: stethalgia, injuries, grippopodobny symptoms, pain. It was reported about isolated cases of a hemolitic uraemic syndrome, hymenoid nephropathy and reactions of hypersensitivity (ангиоотек, a bronchospasm, anaphylactic reactions).

Interaction with other medicines:

Co-administration of a klopidogrel and warfarin in connection with the increased risk of bleeding is not recommended.

Acetylsalicylic acid does not change ADF-indutsirovannuyu the aggregation of thrombocytes caused klopidogrely. Periodic purpose of acetylsalicylic acid, 500 mg 2 times a day, did not cause lengthening of a bleeding time. Klopidogrel can exponentiate effect of acetylsalicylic acid on the aggregation of thrombocytes induced by collagen. Possible pharmakodinamichesky interaction of a klopidogrel and acetylsalicylic acid increases risk of bleeding therefore their combined use is possible no more than one year. The question of combined use of these drugs has to be comprehensively estimated.

Due to the increased risk of bleeding it is recommended to be careful at co-administration of a klopidogrel and heparin or thrombolytic drugs.

Co-administration of a klopidogrel and NPVS increases risk of development of ulcers of a GIT and ulcer bleedings. Therefore it is necessary to be careful at their simultaneous appointment.

Significant clinical interaction at co-administration of a klopidogrel and such drugs as атенолол, the APF inhibitors, means reducing the content of cholesterol in blood, nifedipine, digoxin, phenobarbital, Cimetidinum, estrogen, theophylline is not revealed.

Klopidogrel inhibits activity of CYP2C19 enzyme of system of P450 cytochrome and at simultaneous use with the drugs which are metabolized with the participation of this enzyme (Phenytoinum, толбутамин), increase in their concentration in a blood plasma is possible.

Antacids do not influence absorption of a klopidogrel.

Contraindications:

The hypersensitivity, hemorrhagic syndrome, acute bleeding, intracraneal hemorrhage and diseases contributing to their development (a peptic ulcer of a stomach and duodenum in aggravation stages, nonspecific ulcer colitis, tuberculosis, tumors of lungs, a hyper fibrinolysis), the expressed liver failure; for the dosage forms containing lactose (in addition): hereditary intolerance of a galactose, deficit of lactase and sprue of glucose galactose.

Restrictions to use. A moderate liver failure at which predisposition to bleeding (limited clinical experience of use), a renal failure (limited clinical experience of use) is possible; patients with the increased risk of bleeding after injuries, surgical interventions or as a result of other morbid conditions, and also patients with tendency to bleedings (especially gastrointestinal and intraocular); concomitant use of NPVS (including the selection TsOG-2 inhibitors); co-administration of warfarin, heparin, inhibitors of receptors of a glycoprotein IIb/IIIa, age up to 18 years (safety and efficiency of use are not defined).

Overdose:

Symptoms: increase in a bleeding time, hemorrhagic complications is possible.

Treatment: bleeding stop, transfusion of a platelet concentrate.

Storage conditions:

To store at a temperature of 15-25 °C, in dry, protected from light and the place, unavailable to children. Period of validity 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of 75 mg, on 20 tablets in each blister, on one, two or three blisters together with the application instruction in cardboard packaging.