Klopidogrel

Klopidogrel – antiagregantny drug.

Form of release and structure

Klopidogrel release in the form of tablets, film coated: round, biconvex, pink color (in blister strip packagings on 7, 10, 14, 15, 30 pieces, on 1-4, 6, 8, 10 packagings in a cardboard pack; in banks on 7, 10, 14, 20, 28, 30, 50, 56, 60, 100 pieces, after 1 bank in a cardboard pack).

Is a part of 1 tablet:

• Active agent: klopidogret – 75 mg (in the form of a klopidogrel of hydrosulphite – 97,875 mg);
• Auxiliary components: prezhelatinizirovanny starch – 27 mg, anhydrous lactose (anhydrous milk sugar) – 63,125 mg, magnesium stearate – 1 mg, polyethyleneglycol 6000 (macrogoal) – 8 mg, microcrystallic cellulose – 40 mg, the hydrogenated castor oil – 3 mg;
• Cover: Opadry II pink – 9 mg (a gidroksipropilmetiltsellyuloz (gipromelloz) – 2,52 mg, monohydrate of lactose – 3,6 mg, triacetin – 0,72 mg, titanium dioxide – 2,0484 mg, dye indigo carmine – 0,0036 mg, dye red charming – 0,108 mg).

Indications to use

• Prevention of development of aterotrombotichesky events (in combination with acetylsalicylic acid) at patients with an acute coronary syndrome: with raising of a segment of ST (an acute myocardial infarction) at a possibility of carrying out a thrombolysis and drug treatment; without raising of a segment of ST (a myocardial infarction without tooth Q or unstable stenocardia), including patients to whom carried out stenting at transdermal coronary intervention;
• Prevention of aterotrombotichesky events at patients with an ischemic stroke, a myocardial infarction or with the diagnosed occlusal disease of peripheral arteries.

Contraindications

• Liver failure (heavy degree);
• Active bleeding (including intracraneal hemorrhage or bleeding from a round ulcer);
• Deficit of lactase, lactose intolerance, galactose/glucose sprue;
• Pregnancy and the period of breastfeeding (safety and efficiency of use of Klopidogrel for this group of patients are not established);
• Age up to 18 years (safety and efficiency of administration of drug for this age group of patients were not established);
• Hypersensitivity to drug components.

Klopidogrel it is necessary to take with caution at the following diseases / states:

• Chronic renal failure;
• Liver failure of average degree;
• The morbid conditions increasing risk of development of bleeding including injuries and surgical interventions;
• Hereditary decrease of the activity of an isoenzyme of CYP2C19;
• Simultaneous use with warfarin, acetylsalicylic acid, heparin, non-steroidal anti-inflammatory drugs (including TsOG-2 inhibitors), IIb/IIIa glycoprotein inhibitors.

Route of administration and dosage

Klopidogrel accept inside, regardless of meal.

The adult and elderly patient drug appoint in a daily dose 75 mg in 1 reception.

Therapy needs to be begun: after a myocardial infarction – from 1 to 35 day; after an ischemic stroke – during the period from 7 days to 6 months.

The mode of dosing is defined by indications:

• Acute coronary syndrome without raising of a segment of ST (unstable stenocardia or a myocardial infarction without Q tooth): therapy begin 300 mg with a single load dose, further apply 75 mg a day along with reception of acetylsalicylic acid (75-325 mg a day). The recommended dose of acetylsalicylic acid – to 100 mg a day as higher doses increase risk of development of bleedings. The maximum favorable effect develops in 3 months. Duration of a medical course – till 1 year;
• Acute coronary syndrome with raising of a segment of ST (an acute myocardial infarction with raising of a segment of ST): 75 mg a day with initial reception of a load dose (once) along with acetylsalicylic acid and trombolitika (or without them).

At patients with genetically caused reduction of activity of an isoenzyme of CYP2C19 Klopidogrel's effect can be lowered. For such patients the optimum mode of dosing is not set.

To patients Klopidogrel is more senior than 75 years appoint without use of a load dose. The combined treatment needs to be begun as soon as possible after development of symptoms and to continue not less than 1 month.

Experience of use for patients with a liver failure of average degree or a chronic renal failure is limited.

Side effects

During Klopidogrel's use the following side effects can develop (≥1/10 – very often; from ≥1/100 to <1/10 – it is frequent; from ≥1/1000 to <1/100 – infrequently; from ≥1/10 000 to <1/1000 – it is rare; <1/10 000 (including separate messages) – it is very rare):

• Nervous system: infrequently – a headache, paresthesias and dizziness, intracraneal hemorrhage; seldom – a rotatory vertigo; very seldom – hallucinations, confusion of consciousness, frustration of flavoring feelings;
• Alimentary system: often – dyspepsia, diarrhea, gastrointestinal bleedings, an abdominal pain; infrequently – gastritis, nausea, stomach ulcer and a duodenum, a lock, vomiting, a meteorism; seldom – a retroperitoneal hematoma; very seldom – pancreatitis, stomatitis, colitis (including ulcer or lymphocytic), hepatitis, an acute liver failure, heavy gastrointestinal bleeding with a lethal outcome;
• Cardiovascular system: often – a hematoma; very seldom – a vasculitis, bleedings from an operational wound, heavy bleedings, a lowering of arterial pressure;
• Urinary system: infrequently – a hamaturia; very seldom – a glomerulonephritis;
• Musculoskeletal system: very seldom – a hemarthrosis, an arthralgia, arthritis, a mialgiya;
• System of a hemopoiesis: infrequently – a leukopenia, thrombocytopenia, an eosinophilia; seldom – a neutropenia, including expressed; very seldom – a trombotichesky Werlhof's disease, an agranulocytosis, heavy thrombocytopenia (with number of thrombocytes ^{≤30×109/л}), a granulocytopenia, a pancytopenia, anemia, including aplastic;
• Respiratory organs: very often – nasal bleeding; very seldom – an intersticial pneumonitis, a bronchospasm, a pneumorrhagia, pulmonary bleeding;
• Sense bodys: infrequently – retinal apoplexies, a conjunctiva;
• Skin and hypodermic fabrics: often – hypodermic hemorrhages; infrequently – a purpura;
• Laboratory indicators: very seldom – increase in concentration of creatinine in blood, disturbances of functional trials of a liver, lengthening of a bleeding time;
• Allergic reactions: infrequently – a skin itch, rash; very seldom – a mnogoformny erythema, a Quincke's disease, Stephens-Johnson's syndrome, a small tortoiseshell, erythematic rash, a toxic epidermal necrolysis, anaphylactic reactions, a serum disease;
• Others: often – bleeding in the place of an injection; very seldom – increase in temperature.

Special instructions

During therapy it is necessary to control indicators of system of a hemostasis, including number of thrombocytes, the activated partial tromboplastinovy time, tests of functional activity of thrombocytes, and also to regularly investigate functional activity of a liver.

For identification of any symptoms of bleeding, including hidden, it is necessary to watch carefully a condition of patients, in particular for the first weeks of use of Klopidogrel and/or after carrying out surgeries or invasive procedures on heart.

Drug needs to be used with care at patients with the increased risk of bleeding at surgical intervention, injuries, other morbid conditions, in the presence of the diseases contributing to development of bleedings (especially eye and gastrointestinal), and also at the patients receiving acetylsalicylic acid, non-steroidal anti-inflammatory drugs (including TsOG-2 inhibitors), inhibitors of a glycoprotein IIb/IIIa or heparin.

Simultaneous use with warfarin is not recommended as it can increase intensity of bleedings (except special rare clinical situations).

At surgical interventions if antiagregantny action is undesirable, Klopidogrel's reception needs to be interrupted in 7 days prior to carrying out operation.

Drug extends a bleeding time therefore it is appointed with care to patients with the diseases contributing to development of bleedings (especially, intraocular and gastrointestinal).

Seldom or never after reception Klopidogrela (including its short-term use) arose the trombotichesky Werlhof's disease which is characterized by mikroangiopatichesky hemolitic anemia and thrombocytopenia in combination with neurologic symptoms, functional disturbance of kidneys or fever. The Trombotichesky Werlhof's disease is potentially life-threatening disease demanding immediate therapy including using a plasma exchange.

In the presence of heavy functional disturbances of a liver it is necessary to consider risk of developing of hemorrhagic diathesis. Experience of use of Klopidogrel for patients with moderate functional disturbance of a liver is limited owing to what such patient drug is appointed with care.

Because of the existing possibility of development of dizziness, during therapy it is recommended to be careful at control of motor transport and performance of other potentially dangerous works demanding high concentration of attention and bystry psychomotor reactions.

Medicinal interaction

(At surgical interventions, injuries or at other morbid conditions) co-administration of Klopidogrel with blockers of IIb/IIIa-receptors demands care from the patients having the increased risk of development of bleeding.

At simultaneous use of Klopidogrel with some medicines there can be undesirable effects:

• Acetylsalicylic acid: potentiation of its influence on collagen - the induced aggregation of thrombocytes (it is necessary to be careful);
• Warfarin: increase in intensity of bleedings (use of this combination is not recommended);
• Heparin: increase in risk of development of bleedings (it is necessary to be careful).

Terms and storage conditions

To store in protected from light, the place, dry, unavailable to children, at a temperature up to 25 °C.

Period of validity – 2 years.