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

Excipients: microcrystalline cellulose (Avicel PH 112) 211,125 mg, mannitol 58.0 mg, croscarmellose sodium 12.0 mg, silicon dioxide colloidal2.0 mg, magnesium stearate 4.0 mg;

sheath: opadrai pink 03V54202 (hypromellose 62.5%, titanium dioxide 30.6%, macrogol-400 6.25%, iron dye oxide red 0.65%) 13.475 mg.

Description:

Round, biconvex tablets, covered with a film shell of pink color, with an embossed "C 127" on one side.

Pharmacotherapeutic group:antiplatelet agent

ATX: & nbsp

B.01.A. C.04 Clopidogrel

Pharmacodynamics:

Specific and active inhibitor of platelet aggregation; has coronary rash effect. Selectively reduces the binding of adenosine diphosphate (ADP) to receptors on platelets and activation of receptors GPIIb/IIIa under the action of ADP, thereby 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 after 2 hours after administration (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). Aggregation of platelets and bleeding time return to the baseline level on average 5 days after discontinuation of treatment.

In the presence of an atherosclerotic lesion, the vessel interferes with the development of atherothrombosis regardless of the localization of the vascular process (cerebrovascular, cardiovascular or peripheral lesions).

Pharmacokinetics:

Suction and distribution

Absorption and bioavailability are high; the concentration in the plasma is low and after 2 hours after administration it does not reach the measurement limit (0.025 μg / l). Clopidogrel and the main metabolite reversibly bind to plasma proteins (98% and 94%, respectively).

Metabolism

Metabolised in the liver. The main metabolite is an inactive derivative of carboxylic acid, which accounts for about 85% of the compound circulating in the plasma. Time to reach the peak concentration (TFROM_mOh) metabolite, after repeated oral doses of clopidogrel 75 mg, is achieved in an hour (peak concentration (C_mOh) - about 3 mg / l). Clopidogrel is the precursor of the active substance.Its active metabolite, a thiol derivative, is formed by oxidizing clopidogrel to 2-oxo-clopidogrel and subsequent hydrolysis. Oxidative process is regulated, first of all, by cytochrome P450 2B6 and 3A4 isoenzymes and, to a lesser extent, 1A1, 1A2 and 1C19. The active thiol metabolite quickly and irreversibly binds to platelet receptors, thereby suppressing platelet aggregation. This metabolite is not detected in plasma.

Excretion

Excretion: kidneys - 50%, intestines - 46% (within 120 hours after administration). The half-life (T_1/2) of the main metabolite, after a single and repeated intake, 8 hours. Concentrations of kidney metabolites - 50%.

Pharmacokinetics in special clinical cases

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

Although the inhibitory effect on ADP-induced platelet aggregation was reduced (25%) compared to the same effect in healthy volunteers, bleeding time was extended to the same extent as in healthy volunteers who received clopidogrel in a dose of 75 mg / day.

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 in patients with myocardial infarction, ischemic stroke or peripheral arterial occlusion.

In combination with acetylsalicylic acid for the prevention of thrombotic complications in acute coronary syndrome:

- with the rise of the ST segment with the possibility of carrying out thrombolytic therapy;

- without ST segment elevation (unstable angina, myocardial infarction without Q wave), including in patients undergoing stenting.

Contraindications:

- Hypersensitivity to the components of the drug;

severe hepatic impairment;

- hemorrhagic syndrome, acute bleeding (including intracranial hemorrhage) and diseases predisposing to its development (gastric ulcer and duodenal ulcer in the acute stage, ulcerative colitis, tuberculosis, lung tumors, hyperfibrinolysis);

- pregnancy, lactation (breastfeeding);

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

Carefully:

- Moderate hepatic and / or renal insufficiency;

- traumas, conditions that increase the risk of bleeding (including trauma, surgery);

- simultaneous administration of acetylsalicylic acid, non-steroidal anti-inflammatory drugs (including COX-2 inhibitors), heparin and glycoprotein inhibitors IIb/IIIa.

Dosing and Administration:

Inside, regardless of food intake.

For prevention of ischemic disorders in patients after a previous myocardial infarction, ischemic stroke or on the background of diagnosed diseases of peripheral arteries adults (including elderly patients) prescribe 75 mg 1 time / day. Treatment should be started within a period of up to 35 days after the transfer Q-bearing 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 tooth formation Q) treatment should begin with the appointment of a single loading dose of 300 mg, then continue to use the drug at a dose of 75 mg 1 time / day (with simultaneous reception of acetylsalicylic acid at a dose of 75-325 mg / day).Since the use of acetylsalicylic acid in large doses is associated with a greater risk of bleeding, the recommended dose should not be more than 100 mg. The course of treatment is up to 1 year.

When acute coronary syndrome with segment elevation ST (acute myocardial infarction) 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 thrombolytic agents. 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:

Depending on the frequency of occurrence, the following groups of side effects are distinguished: frequent - more than 1%, infrequent - 0,1-1%, rare - 0,01-0,1%, very rare - less than 0,01%.

From the coagulation system of the blood: often - gastrointestinal bleeding; infrequently - hemorrhagic stroke, prolonged bleeding time, nosebleeds; rarely - hematomas, hematuria, and conjunctive bleeding.

On the part of the hematopoiesis system: infrequently - thrombocytopenia; infrequently - neutropenia,leukopenia, eosinophilia; very rarely - thrombocytopenic purpura; granulocytopenia, agranulocytosis, anemia and aplastic anemia.

From the side of the central nervous system and peripheral nervous system: infrequently - headache, dizziness, paresthesia; rarely - vertigo; very rarely - confusion, hallucinations.

From the cardiovascular system: very rarely - vasculitis, lowering blood pressure.

From the respiratory system: very rarely - bronchospasm, interstitial pneumonitis.

From the digestive system: often - indigestion, diarrhea, abdominal pain; infrequently - nausea, gastritis, flatulence, constipation, vomiting, ulceration of the mucous membrane of the gastrointestinal tract; exacerbation of peptic ulcer of the stomach and duodenum; very rarely - colitis (including ulcerative or lymphocytic colitis), 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: very rarely glomerulonephritis.

Dermatological reactions: infrequently - itching; 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, increased blood creatinine.

Overdose:

Symptoms: with a single oral administration of 600 mg of clopidogrel (an amount equivalent to 8 standard tablets of 75 mg), no healthy side effects were observed. The bleeding time was extended 1.7 times, which corresponds to the value recorded after taking a therapeutic dose (75 mg per day).

Treatment: transfusion of platelet mass. There is no specific antidote.

Interaction:

Strengthens the antiplatelet effect Acetylsalicylic acid, heparin, indirect anticoagulants, non-steroidal anti-inflammatory drugs, when combined, increases the risk of developing bleeding from the gastrointestinal tract.

Inhibiting the activity of one of the enzymes of cytochrome CYP2C9, increases the concentration of drugs metabolized by CYP2C9 (phenytoin, tolbutamide).

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

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 drug if they are undergoing surgery or if the doctor prescribes new medicines 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.

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

Signs of impairment of the ability to drive or reduce mental performance after the reception was found.

Form release / dosage:

Tablets coated with a film coating, 75 mg.

Packaging:

For 10 tablets in PVC / PVDC / aluminum blister.

By 3, 10 blisters together with instructions for use in a pack of cardboard.

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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005821/09

Date of registration:17.07.2009

The owner of the registration certificate:Dr. Reddy's Laboratories Ltd.Dr. Reddy's Laboratories Ltd. India

Manufacturer: & nbsp

DR. REDDY`S LABORATORIES, LTD. India

Representation: & nbspDR REDDY'S LABORATORIS LTD. DR REDDY'S LABORATORIS LTD. India

Information update date: & nbsp07.08.2015

Illustrated instructions

Instructions

Plagril® (Plagril® )