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

Excipients: lactose monohydrate (200 mesh) 60.0 mg, microcrystalline cellulose (Avicel PH 101) 40.125 mg, giprolose 3.0 mg,microcrystalline cellulose (Avicel PH 112) 26.0 mg, crospovidone 6.0 mg, vegetable hydrogenated water type I (Sterotex-Dryx) 10.0 mg, sodium lauryl sulfate 7.0 mg;

film shell "Opadrai II OY-L-34836 pink"lactose monohydrate 2,16 mg, hypromellose 15 cP (E464) 1.68 mg, titanium dioxide (E171) 1.53 mg, macrogol-4000 0.60 mg, iron dye red oxide (E172) 0.024 mg, indigocarmine 0, 0030 mg, iron oxide dye yellow (E172) 0.0006 mg.

Description:

Tablets of capsular form, covered with a film membrane, light pink or pink with engraving "93" on one side and "7314" on the other.

Pharmacotherapeutic group:Antiaggregant agent

ATX: & nbsp

B.01.A. C.04 Clopidogrel

Pharmacodynamics:

Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to platelet receptors and the activation of glycoprotein receptors IIb/IIIbut under the action of ADP, thereby inhibiting platelet aggregation.

Clopidogrel inhibits platelet aggregation caused by other agonists, preventing their activation by liberated ADP, does not affect the activity of phosphodiesterase (PDE).

Clopidogrel binds irreversibly to platelet ADP receptors, which remain immune to ADP stimulation during the life cycle (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 of platelets (7-10 days).

Pharmacokinetics:

Suction and distribution

After a single dose and with oral administration at a dose of 75 mg per day clopidogrel quickly absorbed. Absorption and bioavailability are high. However, the concentration of the starting substance in the blood plasma is insignificant and after 2 hours after the intake it does not reach the measurement limit (0.25 μg / l). Clopidogrel and the main metabolite reversibly bind to plasma proteins (98% and 94%, respectively).

Metabolism

Clopidogrel is rapidly biotransformed in the liver. Clopidogrel is a prodrug. An active metabolite, a thiol derivative, is not detected in the plasma. The main metabolite, a carboxylic acid derivative, is inactive, constituting about 85% of the compound circulating in the plasma. The maximum concentration (C_mOh) of this metabolite in blood plasma after repeated use of clopidogrel at a dose of 75 mg is about 3 mg / l and is reached approximately 1 hour after administration.

Excretion

About 50% of the dose taken is excreted by the kidneys and approximately 46% is secreted by the intestine within 120 hours after administration. Half-life (T_1/2) of the main metabolite after a single and repeated administration is 8 hours.

Pharmacokinetics in special clinical cases

Concentrations of the main metabolite in the blood plasma after taking 75 mg / day were lower in patients with severe renal insufficiency (creatinine clearance 5-15 ml / min) compared with patients with chronic, renal insufficiency of moderate severity (QC 30 -60 ml / min) and healthy individuals.

In patients with cirrhosis of the liver, the use of clopidogrel at a daily dose of 75 mg for 10 days was safe and well tolerated. FROM_mOh Clopidogrel, both after taking a single dose, and in an equilibrium state was many times higher in patients with cirrhosis than in healthy individuals.

Indications:

Prevention of thrombotic complications:

- after a myocardial infarction (from several days to 35 days), ischemic stroke (from 6 days to 6 months) or with diagnosed peripheral arterial disease;

- with acute coronary syndrome without ST segment elevation (unstable angina or myocardial infarction without pathological Q wave), including patients undergoing percutaneous coronary artery bypass surgery, a in combination with acetylsalicylic acid;

- with acute coronary syndrome with segment elevation ST (acute myocardial infarction) in combination with acetylsalicylic acid, in patients receiving medication with the possible use of thrombolytic therapy.

Contraindications:

- Hepatic insufficiency severe;

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

- pregnancy;

- the period of breastfeeding;

- age under 18 years (safety and efficacy not established);

- hypersensitivity to the components of the drug.

Carefully:

In diseases of the liver and kidneys (including with moderate hepatic and / or renal failure), injuries, preoperative conditions.

Dosing and Administration:

Inside, regardless of food intake.

For prevention of ischemic disorders in patients after a previous myocardial infarction, ischemic stroke, and diagnosed peripheral arterial disease - 75 mg once a day.Treatment should begin within a few days to 35 days after myocardial infarction and from 7 days to 6 months after an ischemic stroke.

When acute coronary syndrome without segment elevation ST (unstable angina or myocardial infarction without a tooth Q) treatment should begin, with the appointment of a single loading dose of 300 mg, and then continue to use the drug at a dose of 75 mg 1 time / day (with simultaneous administration of acetylsalicylic acid at a dose of 75-325 mg / day). Since the use of acetylsalicylic acid in high doses is associated with a high risk of bleeding, the recommended dose should not be more than 100 mg. The course of treatment is up to 1 year.

When acute myocardial infarction with segment elevation ST the drug is prescribed in a dose of 75 mg 1 time / day using the initial loading dose in combination with acetylsalicylic acid in combination or without thrombolytics.

For patients over the age of 75, clopidogrel treatment should be administered without the use of a loading dose. Combination therapy is started as soon as possible after the onset of symptoms and is continued for a minimum of 4 weeks.

Side effects:

The frequency of side effects is determined according to the following criteria: 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.

From the coagulation system of the blood: often - bleeding (in most cases - during the first month of treatment), purpura, hematoma; infrequently - conjunctive bleeding; rarely - intracranial hemorrhages; prolonged bleeding time, leukopenia, a decrease in the number of neutrophils and eosinophilia, a decrease in the number of platelets.

On the part of the hematopoiesis system: very rarely - thrombocytopenic thrombohemolytic purpura, severe thrombocytopenia (platelet count <30000 / μl), granulocytopenia, agranulocytosis, anemia, incl. aplastic anemia, pancytopenia.

From the nervous system: infrequently - headache, dizziness, paresthesia; rarely - vertigo; very rarely - confusion, hallucinations.

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 - an ulcer of the stomach and duodenum, gastritis, vomiting, nausea, flatulence, constipation; rarely - retroperitoneal bleeding; very rarely - colitis (including ulcer or lymphocytic), pancreatitis, taste changes, stomatitis, hepatitis, acute liver failure, increased activity of liver enzymes.

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

From the side of the urinary system: infrequently - hematuria; very rarely - glomerulonephritis, hypercreatininaemia.

Dermatological reactions: very rarely - bullous rash (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), erythematous rash, eczema, flat lichen.

Allergic reactions: very rarely angioedema, urticaria, anaphylactoid reactions, serum sickness.

Other: very rarely - fever.

Overdose:

Symptoms: prolonged bleeding time and subsequent complications.

Treatment: When bleeding occurs, appropriate therapy should be performed. If rapid correction of prolonged bleeding time is necessary, transfusion of platelet mass is recommended. There is no specific antidote.

Interaction:

Joint use of clopidogrel with warfarin It is not recommended, since such a combination may increase the intensity of bleeding.

Appointment inhibitors glycoprotein IIb/IIIa together with clopidogrel increases the risk of bleeding.

Application non-steroidal anti-inflammatory drugs together with clopidogrel increases the risk of bleeding.

It is not recommended to take clopidogrel simultaneously with inhibitors CYP2C19 (eg, omeprazole).

There was no clinically significant pharmacodynamic interaction with clopidogrel combined with atenolol, nifedipine, phenobarbital, cimetidine, estrogens, digoxin, theophylline, tolbutamide, antacid agents.

Special instructions:

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

Clopidogrel should be used with caution in patients at risk of severe bleeding in trauma, surgery; patients receiving acetylsalicylic acid, non-steroidal anti-inflammatory drugs (including COX-2 inhibitors), heparin or glycoprotein inhibitors IIb/IIIa. Careful monitoring of patients to identifyv any signs of bleeding, including latent, especially during the first weeks of application of the drug and / or after invasive procedures on the heart or surgical operations.

With planned surgical interventions, the course of treatment with clopidogrel should be discontinued 7 days before surgery.

Patients should be warned that stopping bleeding will take longer than normal, so they should inform the doctor about every case of bleeding.

There were rare cases of thrombotic thrombocytopenic purpura (TTP) after taking clopidogrel.This condition was characterized by thrombocytopenia and microangiopathic hemolytic anemia in combination with neurologic symptoms, impaired renal function, or fever. The development of TTPs poses a threat to life and requires urgent measures, including plasmapheresis.

Due to insufficient data volume clopidogrel It should not be prescribed in an acute period of ischemic stroke (in the first 7 days).

The drug should be administered with caution in patients with impaired renal function.

Clopidogrel should be administered with caution to patients with moderate impairment of liver function, which may cause hemorrhagic diathesis.

In patients with congenital intolerance to galactose, glucose-galactose malabsorption syndrome and lactase deficiency, one should not take clopidogrel.

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

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

Form release / dosage:

Tablets coated with a film coating, 75 mg.

Packaging:

7 tablets per blister of orientated polyamide / aluminum foil / PVC / aluminum foil.

By 2, 4, 8 or 12 blisters together with instructions for use in a cardboard bundle.

10 tablets per blister of orientated polyamide / aluminum foil / PVC / aluminum foil. For 9 blisters together with instructions for use in a cardboard pack.

When produced at OOO Teva, Russia

7 tablets per blister of orientated polyamide / aluminum foil / PVC / aluminum foil. By 2, 4, 8 or 12 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000374

Date of registration:24.02.2011 / 18.01.2017

Expiration Date:Unlimited

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Industries, Ltd. Israel

Teva, Open Company Russia

Representation: & nbspTeva Teva Israel

Information update date: & nbsp29.01.2018

Illustrated instructions

Instructions

Clopidogrel-Teva (Clopidogrel-Teva)