Ï¿ßÔáí® 75

General characteristics. Structure:

Active agent of a klopidogrel hydrosulphate of 98 mg it is equivalent to a klopidogrel of 75 mg.

Excipients: Mannitolum, cellulose microcrystallic, hypro rod, croscarmellose sodium, silicon dioxide, talc, stearic acid.
Structure of a film cover: gipromelloza, macrogoal-6000, titanium dioxide (E171), talc, dye ferrous oxide red (E172), диметикон, water очищенная*.
* - does not contain in ready drug.

Description: round, biconvex tablets, film coated, light pink color.

Pharmacological properties:

Pharmacodynamics. Antiagregantny means, specific and active inhibitor of aggregation of thrombocytes. Klopidogrel selectively suppresses linkng of adenosinediphosphate (ADF) with a platelet glycoprotein (GP) of IIb/IIIa which is carrying out a role of a receptor capable (in the activated state) to form complementary bonds with the proteins and factors participating in aggregation of thrombocytes. Klopidogrel it is irreversible contacts thrombocyte ADF-receptors, depriving of them a susceptibility to stimulation of ADF throughout all life cycle (7-10 days). Klopidogrel also suppresses the aggregation caused by other inductors, preventing their activation by the released ADF, at the same time, he does not influence activity of phosphodiesterase. Decrease in intensity of aggregation of thrombocytes is observed in 2 hours after a single dose of a klopidogrel in a dose of 400 mg. The Antiagregantny effect gradually amplifies, reaching a maximum for the 3-7th days of constant administration of drug, at the same time the level of suppression of aggregation makes 40-60% (at a daily dose of 75 mg). After drug withdrawal, indicators of aggregation and a bleeding time are recovered with a speed, the corresponding speed of receipt in a blood stream of new thrombocytes (approximately within 5 days).

Klopidogrel has high antitrombotichesky activity, interferes with development of an aterotromboz of the vessels having atherosclerotic defeats irrespective of localization of vascular process (cerebrovascular, cardiovascular or peripheral defeats).

Pharmacokinetics. Klopidogrel is quickly soaked up after repeated oral administration of drug in a dose of 75 mg. Concentration in a blood plasma low and in 2 hours after reception does not reach a measurement limit (0,025 mkg/l). Klopidogrel is pro-medicine, he gains antiagregantny properties thanks to transformation in a liver in active tiolny derivative which quickly and is irreversible contacts platelet receptors, suppressing thus aggregation of thrombocytes. This metabolite in plasma is not found. The main metabolite circulating in blood - carboxyl derivative klopidogret, does not influence aggregation of thrombocytes. Its peak concentration in plasma are reached approximately in 1 hour after intake, the maximum concentration in a blood plasma - about 3 mg/l, and an elimination half-life makes about 8 hours. The kinetics of the main metabolite has linear character within doses of drug from 50 to 150 mg. Klopidogrel and his main metabolite reversibly contact proteins of a blood plasma (98% and 94% respectively).

Food significantly does not influence bioavailability of drug. About 50% of drug are removed by kidneys, 46% - with a stake (within 5 days after reception). Both in plasma, and in urine it is found glyukuronidny derivative the main inactive metabolite of a klopidogrel.

Concentration of the main metabolite in plasma after reception of 75 mg/days is lower at patients with a serious illness of kidneys (clearance of creatinine of 5-15 ml/min.) in comparison with patients with diseases of moderately severe kidneys (clearance of creatinine from 30 to 60 ml/min.) and healthy faces.

Indications to use:

Prevention of aterotrombotichesky complications at patients with a myocardial infarction, an ischemic stroke or with the diagnosed occlusal diseases of peripheral arteries.
Prevention of aterotrombotichesky complications (in a combination with acetylsalicylic acid) at patients with an acute coronary syndrome:
without raising of a segment of ST (unstable stenocardia or a myocardial infarction without Q tooth), including patients to whom stenting at transdermal coronary intervention was carried out;
with raising of a segment of ST (an acute myocardial infarction) at medikametozny treatment and a possibility of performing thrombolytic therapy.

Route of administration and doses:

Adults, including elderly people

Ï¿ßÔáí® 75 it is necessary to accept inside, irrespective of meal.

Myocardial infarction, ischemic stroke and the diagnosed occlusal diseases of peripheral arteries

Ï¿ßÔáí® 75 about 75 mg are accepted once a day.

At patients with the myocardial infarction (MI) treatment can be begun from the first days, and at patients with the ischemic stroke (IS) - in terms not earlier than 7 days from development of AI.

Acute coronary syndrome without raising of a segment of ST (unstable stenocardia or a myocardial infarction without Q tooth)

Treatment by drug has to be begun with a single dose of the load dose making 300 mg and then is continued by reception of a dose of 75 mg once a day (in combination with acetylsalicylic acid in doses of 75-325 mg a day). As use of higher doses of acetylsalicylic acid is connected with uvelichesniy risk of bleedings, the dose of acetylsalicylic acid recommended at this indication does not exceed 100 mg. The maximum favorable effect is observed to the third treatments. A course of treatment till 1 year.

Acute coronary syndrome with raising of a segment of ST (an acute myocardial infarction with raising of a segment of ST)

Ï¿ßÔáí® 75 it is appointed once in a dose of 75 mg with an initial single dose of a load dose in a combination with acetylsalicylic acid and trombolitikam once a day (or without trombolitik). The combination therapy is begun as soon as possible after emergence of symptoms and continued within, at least, four weeks. At patients it has to is more senior 75 years treatment drug to begin without reception of its load dose.

At patients with genetically caused depression of function of an isoenzyme of CYP2C19 reduction of effect of a klopidogrel is possible. The optimum mode of dosing at such patients is not set.

Experience of use for patients with HPN or moderate degree of a liver failure is limited.

Features of use:

Drug extends time necessary for a bleeding stop. It should be considered for patients to whom operation is necessary (including, in stomatology).

In case of surgical interventions if antiagregantny action is undesirable, treatment should be stopped in 7 days prior to operation.

Patients should be warned that as the stop of the drug of bleeding arising against the background of use demands bigger time, they have to report to the doctor about each case of unusual bleeding. Patients have to inform also the doctor on administration of drug if operative measures are coming them or if the doctor appoints medicine, new to the patient.

With care appoint the patient with heavy disturbances of functions of a liver because of risk of development of hemorrhagic diathesis, and also the patient receiving drugs which can induce bleedings (heparin, indirect anticoagulants, acetylsalicylic acid and other nonsteroid protivospalitelny means).

Because of the insufficient volume of data it is not necessary to appoint klopidogret in the acute period of an ischemic stroke (the first 7 days).

 During treatment it is necessary to control indicators of system of a hemostasis (the activated partial tromboplastinovy time, number of thrombocytes, tests of functional activity of thrombocytes), to regularly investigate functional activity of a liver.

Very seldom against the background of reception of a klopidogrel the trombotichesky Werlhof's disease, sometimes after short-term use developed. The state is characterized trombotsitopeniyey by the mikroangeopatichesky hemolitic anemia associated with neurologic disturbances, damage of kidneys and fever. The Trombotichesky Werlhof's disease - potentially zhizneugrozhayushchy state demanding immediate treatment including a plasma exchange.

 Influence on ability to control of motor transport and mechanisms.

Signs of influence of a klopidogrel on intellectual and psychomotor functions, abilities to control of motor transport and mechanisms are not revealed.

Side effects:

At reception of therapeutic doses, drug, as a rule, is well transferred.

The main side effects klopidogret the following:

Hemostasis: gastrointestinal bleedings, hematomas, a hamaturia, hemorrhages in a conjunctiva. Intracraneal hemorrhage, a hemarthrosis, a pneumorrhagia, a hamaturia, retroperitoneal, intraocular or pulmonary hemorrhages / bleedings were extremely seldom noted.

From system of a hemopoiesis: at clinical trials the expressed neutropenia, anemia, thrombocytopenia, a granulocytopenia, an agranulocytosis, a leukopenia was extremely seldom noted.

From system of digestive organs: abdominal pains, dyspepsia (a lock, diarrhea, nausea), gastritis, in rare instances - vomiting, a peptic ulcer of a stomach and duodenum can sometimes be noted, it is very rare - colitis, pancreatitis.

From a liver: very seldom - hepatitis, a steatosis.

Kidneys and urinary system: very seldom - a glomerulonephritis, cystitis.

From cardiovascular system: in rare instances hypostases, heart failure, arterial hypertension can be observed.

Dermatological reactions: skin rash and itch. Were very seldom noted emergence of a small tortoiseshell, eczema, erythematic rash, violent rash, makulopapullezny rash.

Allergic reactions: very seldom - a Quincke's disease, anaphylactoid reactions.

From a musculoskeletal system: very seldom - arthralgias, arthritises.

From respiratory system: very seldom - a bronchospasm.

From the central and peripheral nervous system: the headache, dizziness, neuralgia, вертиго, a hyperesthesia, paresthesia are in rare instances possible.

Laboratory analyses: very seldom - change of activity of hepatic transaminases, increase in creatinine of blood.

Others: very seldom - a vasculitis, fervescence.

Interaction with other medicines:

Acetylsalicylic acid does not change significantly action of a klopidogrel for thrombocytes. Klopidogrel exponentiates influence of acetylsalicylic acid on the aggregation of thrombocytes induced by collagen. The question of combined use of these drugs has to be comprehensively estimated.

Combined use of a klopidogrel with warfarin is not recommended as such combination can increase intensity of bleeding.

Purpose of inhibitors of a glycoprotein of IIb/IIIa together with klopidogrely demands care.

At simultaneous use with heparin, according to the clinical testing which is carried out on healthy volunteers klopidogret does not change either the general need for heparin, or effect of heparin to 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 so far, and simultaneous use of these drugs demands care.

Safety of combined use klopidogret, fibrin - specific or fibrin - nonspecific thrombolytic drugs and heparin was investigated at patients with an acute myocardial infarction. Frequency of clinically significant bleedings was similar to that that it was observed in case of combined use of thrombolytic means and heparin with acetylsalicylic acid.

Purpose of non-steroidal anti-inflammatory drugs together with klopidogrely demands care.

Inhibiting activity of one of enzymes of CYP2C9 cytochrome increases concentration of the medicines which are metabolized by means of this enzyme (Phenytoinum, Tolbutamidum).

Clinically significant pharmakodinamichesky interaction at use of a klopidogrel together with atenololy, nifedipine, phenobarbital, Cimetidinum, estrogen, digoxin, theophylline, antiacid means is noted.

Contraindications:

Hypersensitivity to any component of drug, a heavy liver failure, acute bleeding (for example, at a round ulcer or intracraneal hemorrhage), pregnancy, the lactation period, age up to 18 years (safety of use is not established).

With care

Klopidogrel, as well as other antiagregantny drugs, it is necessary to apply with care at patients at:
diseases of a liver and kidneys (moderate liver and/or renal failure);
the morbid conditions increasing risk of development of bleeding including at injuries and operations;
concomitant use of acetylsalicylic acid, non-steroidal anti-inflammatory drugs (including cyclooxygenase 2 inhibitors), heparin and inhibitors of a glycoprotein IIb/IIIa.

Use at pregnancy and feeding by a breast

In animal experiments it is shown that klopidogret and its metabolites get into breast milk, do not influence fertility and have no toxic effect on a fruit. However, in view of lack of sufficient data about safety, it is not recommended to use drug at pregnant women and the feeding women.

Overdose:

At a single dose in a dose of 1050 mg of a klopidogrel (14 tablets on 75 mg) no undesirable phenomena and need for use of special therapeutic measures were noted.

At a single dose in a dose of 600 mg of a klopidogrel (8 tablets on 75 mg) healthy volunteers, by-effects are noted. Increase in a bleeding time corresponded to the size registered after reception of a therapeutic dose (75 mg/days).

In need of bystry correction of the increased bleeding time transfusion of a platelet concentrate is recommended.

The specific antidote is not known.

Storage conditions:

Period of validity: 2 years. Not to apply after the termination of the period of validity specified on packaging. To store in the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 75 mg.

On 10 tablets in a blister strip packaging. On 1, 2, 3, 6 or 9 blister strip packagings together with the application instruction in a pack from a cardboard.

On 14 tablets in a blister strip packaging. On 1 or 2 blister strip packagings together with the application instruction in a pack from a cardboard.