PLAGRIL

Active material: Clopidogrel
When ATH: B01AC04
CCF: Antiplatelet
ICD-10 codes (testimony): I20.0, I21, I63, I73.0, I73.1, I73.9, I74, I79.2, I82
When CSF: 01.12.11.06.01
Manufacturer: DR. REDDY`S LABORATORIES LTD. (India)

Pharmaceutical form, composition and packaging

Pills, Film-coated Pink colour, round, lenticular, Embossed “With 127” on one side.

Excipients: microcrystalline cellulose (Avicel PH 112), mannitol, Croscarmellose sodium, colloidal silicon dioxide, magnesium stearate.

The composition of the shell: dye opadraj pink 03B 54202 (gipromelloza, Titanium dioxide, macrogol 400, iron oxide red).

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.

Pharmacological action

A specific inhibitor of platelet aggregation, provides koronarorasshiratee effect. Selectively reduces the binding of ADP receptors on platelets and activation of GPIIb/IIIa receptors under the influence of ADP, weakening, thus, platelet aggregation.

It reduces platelet aggregation, induced by other agonists, preventing them from activating released ADP, does not affect the activity of Phosphodiesterase (PDE). It binds irreversibly to platelet ADP receptors, which remain impervious to ADP stimulation lifecycle (about 7 days).

Inhibition of platelet aggregation is a 2 h after dosing (40% inhibition of) at an initial dose 400 mg. Maximum effect (60% Suppression of aggregation) develops through 4-7 days of admission to the dose of 50-100 mg / day. Antiagregantnyj effect is the entire period of the life of platelets (7-10 days). Platelet aggregation and bleeding time returned to the original level, average, through 5 days after cessation of treatment.

In the presence of atherosclerotic vessel prevents the development of aterotromboza irrespective of the localization of vascular process (cerebrovascular, cardiovascular or peripheral lesions).

Pharmacokinetics

Absorption and distribution

Absorption and high bioavailability; The plasma concentration is low and by 2 h after administration reaches the measurement limit (0.025 ug / l). Clopidogrel and the main metabolite bind reversibly to plasma proteins (98% and 94% respectively).

Metabolism

It is metabolized in the liver. The main metabolite is inactive derivative karboksilovoj acid, amounting to about 85% circulating plasma connection. C_max metabolite, After repeated oral dose of klopidogrela techniques 75 mg, achieved through 1 and h is about 3 mg / l. Clopidogrel is a precursor of the active substance. Its active metabolite, thiol derivative, formed by oxidation of clopidogrel in 2-oxo-clopidogrel and subsequent hydrolysis. Oxidation process is governed by the, Firstly, izofermentami cytochrome p 450 2 B6 and 3A4, and, less, – 1A1, 1A2 and 1S19. Tiolnyj active metabolite quickly and irreversibly binds to the trombocitarnymi receptor, suppressing, thus, platelet aggregation. This metabolite in plasma is not detected.

Deduction

Report the news – 50%, kishechnika – 46% (during 120 hours after injection). T_1/2 the main metabolite after single and repeated administration – 8 no. The concentration of metabolites kidneys allocated — 50%.

Pharmacokinetics in special clinical situations

After taking klopidogrela dose 75 mg/day in patients with severe kidney disease (CC 5-15 ml / min) the concentration of plasma metabolita lower, than in patients with moderate kidney disease (KK from 30 to 60 ml / min) and healthy persons. Although ingibiruty effect on the ADF-inducyrovannuu agregatia platelets turned out to be reduced (25%), compared to the same effect in healthy volunteers, bleeding time was lengthened to the same extent, as in healthy volunteers, treated with Clopidogrel in the dose 75 mg / day.

In patients with cirrhosis of the liver reception klopidogrela in daily dose 75 mg for 10 day was safe and well tolerated, C_max klopidogrela, After taking a single dose, and equilibrium, was many times higher in patients with liver cirrhosis, than in healthy individuals.

Testimony

Prevention of ischemic disorders (myocardial infarction, stroke, peripheral arterial thrombosis, sudden vascular death) in patients with atherosclerosis, including:

— post-myocardial infarction, ischemic stroke or on the background of diagnosed diseases of peripheral arteries;

— acute coronary syndrome without ST segment recovery (unstable angina or myocardial infarction without zubza Q) in combination with acetylsalicylic
acid);

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

Dosage regimen

The tablets are taken orally, regardless of the meal.

To Prevention of ischemic disorders in patients with post-myocardial infarction, ischemic stroke or on the background of diagnosed diseases of peripheral arteries adult (incl. elderly patients) Plagril^® administered at a dose of 75 mg 1 time / day. Treatment should be started in time to 35 days after suffering the Q-forming myocardial infarction and from 7 days before 6 Months – After ischemic stroke.

At acute coronary syndrome without ST-segment elevation (unstable angina or myocardial infarction without zubza Q ) treatment should start with the appointment of a single loading dose 300 mg, then continue to use the drug in a dose 75 mg 1 time / day (While taking acetylsalicylic acid dose 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 exceed 100 mg. A course of treatment – to 1 year.

At acute coronary syndrome with ST segment elevation (acute myocardial infarction) the drug is prescribed in a dose 75 mg 1 times per day using the initial loading dose in combination with acetylsalicylic acid, in combination with or without trombolitikov. To patients aged 75 years klopidogrelom treatment should be carried out without the use of a loading dose. Combination therapy beginning as soon as possible after the onset of symptoms and continued for at least 4 weeks.

Side effect

Depending on the frequency of occurrence of the following group of side effects: frequent – > 1%, infrequent – 0.1-1%, few – 0.01-0.1%, very rare – < 001%.

From the blood coagulation system: often-gastrointestinal bleeding; infrequently – hemorrhagic stroke, prolonged bleeding, nosebleeds; rarely – hematoma, hematuria, and kongunguale haemorrhage.

From the hematopoietic system: infrequently – thrombocytopenia, neutropenia, leukopenia, eozinofilija; rarely – trombotsitopenicheskaya purpura, granulocytopenia, agranulocytosis, anemia and anemia aplasticheskaya.

From the central and peripheral nervous system: rarely is the headache, dizziness, paraesthesia; rarely – vertigo; rarely – confusion, hallucinations.

Cardio-vascular system: rarely – vasculitis, decrease in blood pressure.

The respiratory system: rarely – bronchospasm, interstitial pneumonitis.

From the digestive system: often – dyspepsia, diarrhea, abdominal pain; infrequently – nausea, gastritis, flatulence, constipation, vomiting, ulceration of the gastrointestinal mucosa, aggravation of gastric ulcer and duodenal ulcer; rarely – colitis (incl. yazvennыy or limfotsitarnыy colitis), pancreatitis, change in taste, stomatitis, hepatitis, acute liver failure, increase in liver enzymes.

On the part of the musculoskeletal system: rarely – arthralgia, arthritis, myalgia.

From the urinary system: rarely – glomerulonefrnt.

Dermatological reactions: infrequently – itch; rarely – bullous rash (erythema multiforme, Stevens syndrome- Johnson, toxic epidermal necrolysis), erythematous rash, eczema, lichen planus.

Allergic reactions: rarely – angioedema, hives, anaphylactoid reactions, serum sickness.

Other: rarely – fever, increase in blood creatinine.

Contraindications

- Severe hepatic impairment;

- Hemorrhagic syndrome;

- Severe bleeding (incl. intracranial hemorrhage) and disease, predispose to its development (gastric ulcer and duodenal ulcer in the acute stage, nespetsificheskiy yazvennыy colitis, tuberculosis, lung tumor, giperfiʙrinoliz);

- Pregnancy,

- Lactation (breast-feeding);

- Children up to age 18 years;

- Hypersensitivity to the drug.

FROM caution You should use the drug at a moderate hepatic and/or renal failure, injuries, states, increase the risk of bleeding (incl. trauma, operations), While admission of acetylsalicylic acid or other NSAIDS (including COX-2 inhibitors), heparin and glycoprotein IIb/IIIa inhibitors.

Pregnancy and lactation

Do not use this drug during pregnancy and lactation (breast-feeding).

Cautions

In the case of surgical procedures, If antiplatelet effect is not desirable, the course of treatment should stop for 7 days before the operation.

Patients should be warned about, because stop appearing on the background of the preparation use bleeding requires more time, they should inform the doctor about each case, unusual bleeding. Patients should also inform the doctor about the admission of drug, If they face surgical procedures or if the doctor prescribes a new drug for the patient.

During the period of treatment is necessary to monitor the performance of the hemostatic system (APTT, the number of platelets, Platelet function tests), regularly examine the functional activity of the liver.

In case of severe violations of the liver should be aware of the risk of hemorrhagic Diathesis.

Use in Pediatrics

The drug is not prescribed children under the age of 18 years because, what safety and efficacy of their use in this age group are not installed.

Effects on ability to drive vehicles and management mechanisms

Signs of deterioration in the ability to control the car or reducing mental health after taking Plagrila^® It was found.

Overdose

Symptoms: When one-off oral healthy people 600 mg of clopidogrel (8 tab. by 75 mg) side effects have been reported. Bleeding time was lengthened in 1.7 times, which corresponds to the largest, registered after taking therapeutic doses (75 mg / day).

Treatment: transfusion of thrombocyte mass. The specific antidote is absent.

Drug Interactions

If you are applying to Plagril^® increases antiagregantnyj effect of acetylsalicylic acid, geparina, anticoagulants, NSAIDs, It increases the risk of bleeding from the gastrointestinal tract.

Inhibiting CYP2C9 activity, Clopidogrel increases the concentration of medicines, metaboliziruthan by this izofermenta (phenytoin, tolbutamid).

No clinically meaningful interaction farmakodinamicheskogo when applying klopidogrela in conjunction with atenolol, nifedipine, fenoʙarʙitalom, cimetidine, Estrogen, digoksinom, theophylline, tolʙutamidom, the funds may.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored in a dry, dark place at a temperature no higher than 25 ° C. Shelf life – 2 year.