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

Prevents the aggregation of platelets due to selective blockade of adenosine diphosphate (ADP) binding with its receptors on platelets and activation of receptors of glycoprotein IIb/IIIa. Reduces platelet aggregation caused by other agonists, by eliminating the activity of platelets liberated by ADP, does not affect the activity of phosphodiesterase. Changes in ADP-receptor platelets caused by clopidogrel are irreversible, and therefore platelets remain dysfunctional throughout their life, and the antiplatelet effect persists throughout this period. Recovery of normal function occurs as platelets are refreshed (approximately 7 days later).

Pharmacokinetics:

After ingestion of 75 mg clopidogrel, the drug is rapidly absorbed from the gastrointestinal tract,however, the concentration in the blood plasma is low and after 2 hours after administration it does not reach the measurement limit (0.025 μg / l), and the inhibition of platelet aggregation reaches 40% at the same time. The maximum effect (60% suppression of aggregation) develops after 4-7 days of constant drug intake at a dose of 98 mg / day (in terms of clopidogrel - 75 mg / day).

Clopidogrel is a prodrug that requires activation by isoenzymes of microsomal liver enzymes CYP3A4 and 2B6 and to a lesser extent 1A1, 1A2 and 2C19. Metabolised in the liver. An active metabolite in plasma is not detected. The main metabolite is the inactive derivative of carboxylic acid, the maximum concentration in the blood plasma (TS_mOh) which after repeated clopidogrel administration in a dose of 75 mg is about 3 mg / l and is observed approximately 1 hour after the drug administration. Clopidogrel and its main metabolite bind to plasma proteins (98-94%, respectively).

Excretion: after oral administration, about 50% of the dose is excreted by the kidneys and approximately 46% through the intestine (within 120 hours after administration). The half-life (T_1/2) of the main metabolite after a single and repeated administration of the drug - 8 hours.

Pharmacokinetics in special clinical cases

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

The maximum concentration of the drug in the blood plasma (C_mOh) is higher in patients with cirrhosis, both after taking a single dose, and in an equilibrium state. At the same time, the safety and tolerability of the drug in such patients does not change when taking clopidogrel 75 mg / day for 10 days.

Indications:

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

Prophylaxis of thrombotic complications (in combination with acetylsalicylic acid (ASA)) in acute coronary syndrome without segment elevation ST (unstable angina, myocardial infarction without a tooth Q), incl. In patients undergoing stenting with percutaneous intervention.

Contraindications:

- Hypersensitivity to the components of the drug;

severe hepatic impairment;

- Acute bleeding (eg, peptic ulcer or intracranial hemorrhage);

- pregnancy, lactation period;

- Children's age up to 18 lay down;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Carefully:The drug should be administered with caution to patients with an increased risk of bleeding (trauma, before surgery) and with moderate hepatic and / or renal failure (possibly the development of hemorrhagic diathesis); with simultaneous administration of warfarin, non-steroidal anti-inflammatory drugs (NSAIDs), including inhibitors of COX-2, heparin and glycoprotein inhibitors IIb/IIIa; with a hereditary decrease in the isoenzyme function CYP2C19.

Pregnancy and lactation:

Contraindicated because there is no safety data.

Dosing and Administration:

Clopiletto should be taken orally, 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 of the 35th day of 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 segment elevation ST (unstable angina, myocardial infarction without a tooth Q) - start with a single dose of 300 mg, 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.

Side effects:

Frequency: 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.

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 - angioedema, 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 of the eye, 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 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.

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

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

Local Reactions: often - bleeding at the injection site.

Laboratory indicators: infrequent - prolongation of bleeding time.

Other: very rarely - a fever.

Overdose:

Symptoms: prolongation of bleeding time, hemorrhagic complications.

Treatment: stop bleeding, transfusion of platelet mass.

Interaction:

Warfarin: the combined use of Klopilet with warfarin is not recommended, since such a combination may increase the intensity of bleeding.

Inhibitors of glycoprotein IIb/IIIa: administration of glycoprotein inhibitors IIb/IIIa together with the Clopilet preparation requires caution.

ASA does not alter the inhibitory effect of the Clopilet preparation on ADP-induced platelet aggregation, but Clopilet enhances the effect of acetylsalicylic acid on collagen-induced platelet aggregation. Joint use of these drugs requires caution.

Heparin: according to a clinical trial conducted on healthy individuals, clopidogrel does not change either the need for heparin, nor the action of heparin on blood coagulation. The simultaneous use of heparin did not alter the inhibitory effect of clopidogrel on platelet aggregation. However, the safety of this combination has not yet been established, and the simultaneous use of these drugs requires caution.

Fibrinolytics: The safety of the combined use of clopidogrel, the recombinant tissue plasminogen activator (rt-PA), and heparin was investigated in patients with recent myocardial infarction. The frequency of clinically significant bleeding was similar to that observed with the combined use of rt-PA and heparin. The safety of the joint use of clopidogrel with other fibrinolytics has not yet been established and the simultaneous use of these drugs requires caution.

NSAIDs: The appointment of NSAIDs in conjunction with the Clopyleth preparation requires caution (possibly an increased risk of bleeding).

Combined use with other drugs: no clinically significant pharmacodynamic interaction was observed when appliedclopidogrel together with atenolol, nifedipine, phenobarbital, cimetidine, estrogens, digoxin, theophylline, phenytoin, tolbutamide and antacid agents, however, there is evidence that clopidogrel inhibits the activity of one of the cytochrome CYP2C9 enzymes and can alter the concentration of drugs metabolized by CYP2C9 (phenytoin, tolbutamide and others).

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 hemostasis system (APTT, platelet count, platelet functional activity tests); 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.

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.

The drug is not recommended for patients with ischemic stroke less than 7 days old.

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

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

Form release / dosage:

Tablets coated with a film coating, 75 mg.

Packaging:

10 tablets per strip of aluminum foil.

3 strips, together with instructions for use, are placed in a cardboard box.

Storage conditions:

In a dry, protected from light, place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-000632/10

Date of registration:03.02.2010

Expiration Date:Unlimited

The owner of the registration certificate:San Pharmaceutical Industries Co., Ltd.San Pharmaceutical Industries Co., Ltd. India

Manufacturer: & nbsp

Sun Pharmaceutical Industries, Ltd. India

Representation: & nbspSAN PHARMACEUTICAL INDUSTRIES LTD. SAN PHARMACEUTICAL INDUSTRIES LTD. India

Information update date: & nbsp29.01.2018

Illustrated instructions

Instructions

Clopilet (Clopilet)