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

TObisected biconvex tablets covered with a film coat, white or almost white with a yellowish hue, with a risk, odorless or almost odorless; On the cross-section, the core is white or almost white.

Pharmacotherapeutic group:antiplatelet agent

ATX: & nbsp

B.01.A. C.04 Clopidogrel

Pharmacodynamics:

Clopidogrel is an antiplatelet agent. Selectively reduces the binding of adenosine diphosphate (ADP) to receptors on platelets and activation of receptors of glycoprotein IIb/IIIa 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).

Pharmacokinetics:

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 material in the plasma is low and after 2 hours after the intake it does not reach the measurement limit (0.025 μg / l). The connection with plasma proteins is 98-94%. Is a prodrug.

Clopidogrel is rapidly metabolized in the liver. An active metabolite is not found in the blood. The main detectable metabolite is the inactive derivative of carboxylic acid, the time to reach the maximum concentration (TC_mOh) which after repeated oral doses of 75 mg is achieved after 1 hour, the maximum concentration (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 chronic renal failure (creatinine clearance 5-15 ml / min) compared with patients with chronic renal insufficiency of moderate severity (QC from 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 (ASA) 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 a tooth Q), incl. in patients undergoing stenting.

Contraindications:

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

Lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome.

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

Severe hepatic insufficiency.

Acute bleeding (including peptic ulcer or intracranial hemorrhage). Pregnancy and lactation.

Carefully:

Moderate hepatic impairmentnosetь, chronic Pehblack shortnesstatonicity), pathological conditions that increase the risk of bleeding (including trauma, surgery), propensity to bleed, simultaneous administration of ASA,warfarin, non-steroidal anti-inflammatory drugs (NSAIDs) (including COX-2 inhibitors), heparin, glycoprotein inhibitors IIb/IIIa, the hereditary decrease in 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 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 loading dose of 300 mg, and then take 75 mg / day (in combination with ASA 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 the prevention of thrombotic complications in acute coronary syndrome with segment elevation ST (acute myocardial infarction with segment elevation ST) - 75 mg / day with the initial single dose loading in combination with ASA and thrombolytic (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 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 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.

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

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

Allergic reactions: very rarely - anaphylactic reactions, serum sickness. Laboratory indicators: infrequently - lengthening the bleeding time, disturbing functional liver samples, increasing the concentration of the creatinine of the blood.

Other: very rarely: fever.

Overdose:

An overdose of clopidogrel may lead to prolonged bleeding time and subsequent hemorrhagic 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:

Simultaneous reception warfarin with clopidogrel may increase the intensity of bleeding, so the use of this combination is not recommended.

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

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

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:

During the treatment period, it is necessary to monitor the parameters of the hemostasis system (activated partial thromboplastin time (APTT), platelet count, functional platelet function tests); regularly investigate the functional activity of the liver.

Clopidogrel should be used with caution in patients with riceexpressed bleeding in trauma, surgery, patients with injuries prone to bleeding (especially gastrointestinal and intraocular), as well as in patients receiving ASA, non-steroidal anti-inflammatory drugs (including COX-2 inhibitors), 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, as it can increase 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, impaired renal function or fever. TTP is a potentially fatal condition requiring immediate treatment, including with the use of plasmapheresis.

Because of the absence of qInformation 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 severe violations of liver function, one should remember about the risk of developing hemorrhagic diathesis,experience in the use of the drug in patients with moderate violations of the liver, is limited, so these patients clopidogrel should be administered with caution.

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

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

Form release / dosage:

Tablets coated with a film coating, 75 mg.

Packaging:

For 7, 10 or 14 tablets are placed in a contoured cell pack of a polyvinylchloride film and aluminum foil.

2, 4, 8 or 12 contour cell packs (7 tablets each) along with the instructions for use are placed in a cardboard box.

3 or 9 contour cell packs (10 tablets each) along with the instructions for use are placed in a cardboard box.

1 or 2 contourcell packs (14 tablets each), along with instructions for use, are placed in a cardboard box.

Storage conditions:

Store in a 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 after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-009043/10

Date of registration:31.08.2010

The owner of the registration certificate:Oxford Laboratories Pvt. Ltd.Oxford Laboratories Pvt. Ltd. India

Manufacturer: & nbsp

OXFORD Laboratories, Pvt. Ltd. India

Representation: & nbspOXFORD LABORATORY Pvt. Ltd. OXFORD LABORATORY Pvt. Ltd. India

Information update date: & nbsp07.08.2015

Illustrated instructions

Instructions

Piltrel (Plogrel)