Agregal

General characteristics. Structure:

Active substance: Klopidogrela of hydrosulphate - 0,098 g (in terms of klopidogret - 0,075 g)
Excipients: potato starch, lactose (sugar milk), cellulose microcrystallic, hypro-melloza (gidroksipropilmetiltsellyuloza). macrogoal 6000 (polyethyleneglycols 6000), stearic acid, magnesium stearate.
Structure of a cover
Gipromelloz (gidroksipropilmetiltsellyuloz), titanium dioxide, macrogoal 6000 (polyethyleneglycol 6000), iron oxide red.
Description
Tablets, coated one-time - cream color, round, biconvex. On cross section two layers are visible.

Pharmacological properties:

Pharmacodynamics. Interferes with aggregation of thrombocytes due to the selection blockade of linkng of adenosinediphosphate (ADF) with his receptor on thrombocytes and activation of the GPIIb/IIIa complex. Inhibits the aggregation of grombotsit caused by other agonists, way elimination of activity of thrombocytes the released adenosinediphosphate, does not influence a phosphodiesterase kativnost. The changes of ADF-receptors of thrombocytes caused klopidogrely are irreversible in this connection thrombocytes remain nonfunctional throughout the entire period of life of thrombocytes, and the antiagreganty effect remains all this period. Recovery of normal function happens in process of updating of thrombocytes (approximately in 7 days). In the presence of atherosclerotic defeat of a vessel, klopidogret interferes with development of an aterotromboz irrespective of localization of vascular process (cerebrovascular, cardiovascular or peripheral defeats).

Pharmacokinetics. After intake of 75 mg of a klopidogrel drug is quickly adsorbed from digestive tract, however concentration in a blood plasma low and in 2 h after reception does not reach a measurement limit (0,025 mkg/l), and braking of aggregation of thrombocytes reaches at the same time 40%. The maximum effect (60% aggregation suppression) develops in 4-7 days of constant administration of drug in a dose of 98 mg/days (in terms of kdopidogret - 75 mg/days). Drug is metabolized in a liver. The main metabolite - inactive derivative carboxyl acid, the maximum concentration in a blood plasma (Tstakh) of which after repeated receptions of a klopidogrel in a dose of 75 mg, makes about 3 mg/l and is observed approximately in 1 hour after administration of drug. Klopidogrel and his main metabolite contact proteins of a blood plasma (98-94%, respectively).

Removal: after intake about 50% of a dose are allocated with urine and about 46% through intestines with a fecal masses (within 120 hours after introduction). An elimination half-life (T 1/2) the main metabolite after one-time and repeated reception - 8 hours.

Indications to use:

Prevention of ischemic disturbances (a myocardial infarction, a stroke, thrombosis of peripheral arteries, sudden vascular death) at patients with atherosclerosis, including:
- after the had myocardial infarction and an ischemic stroke;
- at the diagnosed diseases of peripheral arteries;
- at an acute coronary syndrome without raising of a segment of ST (unstable stenocardia or a myocardial infarction without Q tooth), in a combination with acetylsalicylic acid;
- when carrying out operation of a transdermal koronaroplastika.

Route of administration and doses:

Inside - on 1 tablet of 1 times a day, irrespective of reception write.

Treatment should be begun in terms from several days to 35 days at patients after a myocardial infarction and from 7 days to 6 months - at patients after an ischemic stroke.

At an acute coronary syndrome without raising of a segment of ST (unstable stenocardia or a myocardial infarction without Q tooth) treatment has to be begun with purpose of a single load dose 4 tablets of drug Agregal (300 mg of a klopidogrel), and then is continued on 1 tablet of drug Agregal in days (75 mg of a klopidogrel) with co-administration of acetylsalicylic acid in a dose 75-375mt/days).

The maximum course of combined use of drug Agregal and acetylsalicylic acid – 1 year (at more prolonged use safety was not studied).

The choice of the scheme and duration of treatment by drug Agregal when carrying out a transdermal koronaroplastika is defined by the doctor depending on a type of a stent and terms of carrying out operation.

Features of use:

In case of a drug combination Agregal with acetylsalicylic acid, other non-steroidal anti-inflammatory drugs (NPVS), heparin, inhibitors of a glycoprotein IIb/IIIa or a fibrinolitikama, it is necessary to make blood test within the first week of treatment (the activated partial tromboplastinovy time (APTT), quantity of thrombocytes, tests of functional activity of thrombocytes and functional activity). At the planned surgical interventions the course of treatment drug Agregal should be stopped for 7 days before operation.

Side effects:

From coagulant system of blood: gastrointestinal bleedings (2% in 0,7% of cases are required hospitalization); less often – hematomas, a hamaturia and hemorrhage in a conjunctiva.
From system of a hemopoiesis: the expressed neutropenia (number of granulocytes <450/mkl) was observed in 0,04%; heavy thrombocytopenia (number of thrombocytes <80 000/mkl) - in 0,2%.
From the alimentary system: abdominal pains, dyspepsia (lock, diarrhea, nausea), gastritis; seldom - changes of hepatic tests.
From the central nervous system and peripheral nervous system: headache, dizziness, paresthesias.
Dermatological reactions: skin rash, itch.
Allergic reactions: extremely seldom - a bronchospasm, a Quincke's disease, anaphylactic reactions.
Others: Werlhof's disease (1/200 000).
The other clinically significant side effects noted in a number of large international researches with a frequency> 0.1%, and also all heavy side effects are given below, according to the WHO classification. Their frequency is determined as follows: often (> 1/100. but <1/10); sometimes (> 1/1000, but <1/100); seldom (> 1/10000. in <1/1000).
From the central nervous system and peripheral nervous system: often - a headache, dizziness, paresthesias; seldom – вертиго.
From the alimentary system: often - diarrhea, abdominal pains: sometimes - nausea, gastritis, a meteorism, a lock, vomiting, a peptic ulcer of a stomach and duodenum.
From coagulant system of blood: sometimes - lengthening of a bleeding time.
From system of a hemopoiesis: sometimes - a leukopenia, decrease in number of neutrophils and eosinophils, decrease in number of thrombocytes. Dermatological reactions: sometimes - rash and an itch.

Interaction with other medicines:

Warfarin: topical administration of drug Agregal with warfarin is not recommended as such combination can increase intensity of bleedings.
IIb/IIIa glycoprotein inhibitors: purpose of inhibitors of a glycoprotein of IIb/IIIa together with drug Agregal demands care.
Acetylsalicylic acid: acetylsalicylic acid does not change the inhibiting effect of drug Agregal on ADF-indutsirovannuyu aggregation of thrombocytes, but drug Agregal strengthens effect of acetylsalicylic acid on collagen - the induced aggregation of thrombocytes. Combined use of these drugs demands care.
Heparin: according to the clinical testing which is carried out on healthy faces klopidogret does not izenyat either the need for heparin, or effect of heparin on a blood coagulation. Simultaneous use of heparin did not change an inhibiting effect of a klopidogrel to aggregation of thrombocytes. However safety of such combination is not established yet and simultaneous use of these drugs demands care.
Fibrinolitiki: safety of combined use of a klopidogrel, the recombinant activator of fabric plasminogen (rt-PA) and heparin was investigated at patients with a recent myocardial infarction. Frequency of clinically considerable bleeding was similar to that that it was observed in case of combined use of rt-PA and heparin. Safety joint use of a klopidogrel with other fibrinolitika is not established yet, and simultaneous use of these drugs demands care.
Non-steroidal anti-inflammatory drugs: purpose of non-steroidal anti-inflammatory drugs together with drug Agregal demands care (possibly increase in risk of bleeding).
The combined use with other medicines: clinically significant pharmakodinamichesky interaction at use of a klopidogrel together with atenololy, nifedipine, phenobarbital, Cimetidinum, estrogen, digoxin, theophylline, Phenytoinum, Tolbutamidum and antiacid means was not revealed, however, there are data that klopidogret inhibits activity of one of enzymes of CYP2C9 cytochrome and can change concentration of the medicines which are metabolized by means of CYP2C9 (Phenytoinum, Tolbutamidum and others).

Contraindications:

Hypersensitivity to drug components;
heavy liver failure;
acute bleeding (for example, round ulcer or intracraneal hemorrhage);
pregnancy, lactation period;
children's age.

Overdose:

Cases of overdose are noted.
Treatment: transfusion of a platelet concentrate. The specific antidote does not exist.

Storage conditions:

List B. In the dry place protected from light at a temperature not above 25 °C. To store in the places unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 75 mg.
On 14 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.
On 1 or 2 blister strip packagings with the application instruction in a pack from a cardboard.