Clopidogrel-Akrihin - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate 75.0 mg, microcrystalline cellulose 76.0 mg, pregelatinized starch 46.75 mg, hydrogenated castor oil 6.0 mg, macrogol-6000 2.5 mg, silicon dioxide colloid 2.0 mg, talc 10.0 mg, crospovidone 7.0 mg;

film coating: hypromellose-15 5.688 mg, titanium dioxide 3.0 mg, propylene glycol 1.1 mg, iron-oxide red oxide (E 172) 0.132 mg.

Description:

Round tablets covered with a film shell of pink color.

Pharmacotherapeutic group:Antiaggregant agent

ATX: & nbsp

B.01.A. C.04 Clopidogrel

Pharmacodynamics:

One of the active metabolites of clopidogrel is an inhibitor of platelet aggregation. The active metabolite of clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to the platelet receptor 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 (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.

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.

With a daily intake of clopidogrel at a dose of 75 mg from the first day of admission, there is a significant suppression of ADP-induced platelet aggregation, which

Gradually increases within 3-7 days and then goes to a constant level (when the equilibrium state is reached). 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.

Pharmacokinetics:

Suction

When taking oral administration at a dose of 75 mg per day clopidogrel quickly absorbed. Mean maximum concentrations of unchanged clopidogrel in the blood plasma (approximately 2.2-2.5 ng / ml after ingestion of a single dose of 75 mg) are reached approximately 45 minutes after admission.According to 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).

Metabolism

Clopidogrel is extensively metabolized in the liver. In vitro and in vivo Clopidogrel is metabolized in two ways: first through esterases and subsequent hydrolysis to form an inactive derivative of carboxylic acid (85% of the circulating metabolites), and the second pathway through the cytochrome P450 system.

Excretion

About 50% is excreted in the urine and approximately 46% - with mildew. After a single oral dose of 75 mg, the half-life of clopidogrel is approximately 6 hours. After a single reception and taking repeated doses, the half-life of the inactive metabolite circulating in the blood is 8 hours.

Individual patient groups

The pharmacokinetics of the active metabolite of clopidogrel in certain groups of patients has not been studied.

In the elderly the pharmacokinetics are the same as in individuals <75 years old. Do not need dose adjustment for the elderly.

Children of the age: no data.

Impaired renal function: after repeated use of clopidogrel at a dose of 75 mg / day, inhibition of ADP-induced platelet aggregation in patients with severe renal disease (creatinine clearance from 5 to 15 ml / min) was lower (25%) than in healthy volunteers, 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.

Indications:

Prevention of thrombotic complications in patients after myocardial infarction, stroke, peripheral arterial thrombosis, sudden vascular death) in patients with atherosclerosis (including after a previous myocardial infarction, ischemic stroke or on the background of diagnosed peripheral arterial diseases, as well as acute coronary syndrome without lifting segment ST - unstable angina or myocardial infarction without tooth formation Q - in combination with acetylsalicylic acid (ASA) and acute myocardial infarction with an increase in the interval ST in combination with ASA y patients who received medication with possible use of thrombolytic therapy).

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;

- pregnancy and lactation (see "Pregnancy and lactation");

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

Carefully:

When:

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

- renal failure (limited clinical experience of use);

- injuries, surgical interventions (see "Special instructions");

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

- simultaneous administration of non-steroidal anti-inflammatory drugs, including selective inhibitors of cyclooxygenase-2 (COX-2);

- simultaneous administration of ASA, warfarin, heparin, glycoprotein inhibitors IIb/IIIa;

- hereditary decrease in the isoenzyme function CYP2C19.

Pregnancy and lactation:

The drug is contraindicated in pregnancy and lactation (breastfeeding).

Dosing and Administration:

Adults and Seniors

Clopidogrel should be taken orally, regardless of food intake.

Myocardial infarction, ischemic stroke and diagnosed peripheral arterial occlusive disease

The drug is taken 75 mg once a day.

In patients with myocardial infarction (MI) treatment can start from the first days to 35 days of MI, and in patients with ischemic stroke (AI) - in the period from 7 days to 6 months after the AI.

Acute coronary syndrome without segment elevation ST (unstable angina, myocardial infarction without a tooth Q)

Treatment with clopidogrel should be started with a single dose of loading dose,which is 300 mg, and then continued with a 75 mg dose once a day (in combination with acetylsalicylic acid in 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.

Acute myocardial infarction with segment elevation ST

Clopidogrel 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 drugs (or without thrombolytic drugs).

Combination therapy is started as soon as possible after the onset of symptoms and continues for at least four weeks.

Patients older than 75 years treatment Clopidogrel should begin without taking its loading dose.

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 acetylsalicylic acid or clopidogrel with acetylsalicylic acid and heparin (see section "Special instructions").

The frequency of side effects is determined according to the following definitions: very often more than 1/10, often more than 1/100 and less than 1/10, infrequently more than 1/1000 and less than 1/100, rarely more than 1/10000 and less than 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 bleeding, 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 (GIT): infrequently - stomach and duodenal ulcer, gastritis, vomiting, nausea, constipation, flatulence; rarely - retroperitoneal bleeding; very rarely - pancreatitis, colitis (including ulcerative or lymphocytic colitis), stomatitis, acute hepatic insufficiency, hepatitis, a violation of functional liver tests, bleeding from the gastrointestinal tract with a lethal outcome.

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

From the musculoskeletal system: very rarely - hemarthrosis, arthritis, arthralgia, myalgia.

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

Local Reactions: often - bleeding at the injection site.

Laboratory indicators: infrequent - prolongation of bleeding time.

Other: very rarely - fever.

Overdose:

Symptoms: prolonged bleeding time, hemorrhagic complications.

Treatment: stop bleeding, transfusion of platelet mass.

Interaction:

Warfarin: simultaneous reception together with clopidogrel may increase the intensity of bleeding, so the use of this combination is not recommended.

Inhibitors of glycoprotein IIb/IIIa receptors: administration of glycoprotein inhibitors IIb/IIIa receptors in conjunction with clopidogrel requires caution in patients who have an increased risk of bleeding (with trauma and surgical interventions or other pathological conditions) (see "Special instructions").

Acetylsalicylic acid: acetylsalicylic acid does not alter the effect of clopidogrel, which inhibits ADP-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.

Fibrin-specific or fibrin-specific thrombolytic drugs and heparin: the safety of their combined use with clopidogrel 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.

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.Simultaneous use of heparin did not change the antiplatelet effect of clopidogrel. Between clopidogrel and heparin, pharmacological interaction is possible, which may increase the risk of bleeding, so the simultaneous use of these drugs requires caution.

Non-steroidal anti-inflammatory drugs (NSAIDs): in the clinical a study conducted with the participation of healthy volunteers, the combined use of clopidogrel and naproxen increased hidden blood loss through the gastrointestinal tract. However, due to the lack of research on the interaction of clopidogrel with other NSAIDs, it is not currently known whether there is an increased risk of gastrointestinal bleeding when taking clopidogrel together with other NSAIDs. Therefore, the appointment of NSAIDs, including COX-2 inhibitors, in combination with clopidogrel should be carried out with caution (see "Special instructions").

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

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

Special instructions:

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 because the stoppage of the bleeding that occurs when the drug is used requires more time, they should inform the doctor about every case of unusual bleeding. Patients should also inform the doctor about taking the medication if they are undergoing surgery (including dental surgery) or if the doctor prescribes a new medication for the patient. During the treatment period, it is necessary to monitor the parameters of the hemostatic system (activated partial thromboplasty new time (APTT), the number of platelets, tests of the functional activity of thrombocytes); regularly investigate the functional activity of the liver.

In case of severe violations of liver function, one should remember about the risk of hemorrhagic diathesis.

It is not recommended to prescribe to patients with ischemic stroke less than 7 days.

Dosage forms containing hydrogenated castor oil can induce dyspepsia and diarrhea.

Very rarely, when taking clopidogrel, thrombotic thrombocytopenic purpura developed, sometimes after short-term use. The condition is characterized by thrombocytopenia and microangiopathic hemolytic anemia, associated with neurologic disorders, kidney damage and fever. Thrombotic thrombocytopenic purpura is a potentially life-threatening condition requiring immediate treatment, including plasmapheresis.

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

Clopidogrel does not influence or slightly affect the ability to drive vehicles and work with machinery.

Form release / dosage:

Tablets coated with a film coat of 75 mg.

Packaging:

10 tablets per blister Aluminum / Aluminum.

3 or 9 blisters together with instructions for use in a pack of cardboard.

15 tablets per blister Aluminum / Aluminum.

1 or 2 blisters together with instructions for use in a cardboard pack.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008856/10

Date of registration:30.08.2010 / 12.04.2017

Expiration Date:Unlimited

The owner of the registration certificate:Micro Labs LimitedMicro Labs Limited India

Manufacturer: & nbsp

MICRO LABS, Limited India

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp29.01.2018

Illustrated instructions

Instructions

Clopidogrel-Akrihin (Clopidogrel-Akrichin)