Таргетек®

General characteristics. Structure:

Active agent: Klopidogrela bisulphate of 97,875 mg equivalent to a klopidogrel of 75 mg. Excipients: lactoses monohydrate - 94,425 mg, cellulose microcrystallic - 26,20 mg, a hypro rod of L - 22,50 mg, a macrogoal of 6000 - 3,00 mg, the castor oil hydrogenated - 6,00 mg. Film cover: опадрай pink 03B54564 - 6,50 mg (a gipromelloza 6 Wednesday (HPMC 2910) - 62,5%, titanium dioxide of-31,02%, a macrogoal of 400 - 6,25%, dye ferrous oxide of red-0,23%.)

Description: Tablets from light pink till pink color, biconvex, round, film coated with an engraving of "C4" on one party and smooth with another.

Type of a tablet on a break: the homogeneous pressed weight from white till almost white color.

Pharmacological properties:

Pharmacodynamics. Klopidogrel (to be exact his active metabolite) it is irreversible contacts platelet ADF-receptors (adenosinediphosphate receptors) and selectively inhibits linkng of ADF with ADF-receptors of thrombocytes and the subsequent activation of the GPIIb/IIIa complex under the influence of ADF thanks to what aggregation of thrombocytes is suppressed ADF-indutsiruyemaya. The C of opium dogret as well the N ги би rut the aggregation of thrombocytes caused by other agonists because blocks activation of thrombocytes the released ADF. Due to the irreversibility of communication of a klopidogrel with ADF-receptors and try bots of t, thrombocytes remain unreceptive to stimulation of ADF during all remaining period of the life, and recovery of normal function of thrombocytes happens to speed, the corresponding speed of updating of thrombocytes.

Klopidogrel is capable to prevent development of an aterotromboz at any localizations of atherosclerotic defeat of vessels, in particular at defeats of cerebral, coronary arteries or peripheral.

At daily reception of a klopidogrel in a dose of 75 mg from the first day of reception considerable suppression ADF-indutsiruyemoy of aggregation of thrombocytes which gradually increases within 3-7 days is noted and then reaches constant level (at achievement and an equilibrium state). In an equilibrium state aggregation of thrombocytes is suppressed on average for 4 0 - 6 0%. After the termination of reception aggregation of thrombocytes and a bleeding time gradually klopidogret are returned to initial level on average within 5 days.

Pharmacokinetics. At course intake in a dose of 75 mg a day klopidogret quickly it is soaked up. However concentration of not changed drug in plasma are very low, and in 2 hours after reception they are below a limit колич the estvenny definition making 0,00025 mg/l. Proceeding from data on excretion with urine of a metabolitovklopidogrel, its absorption makes not less than 50%. Being pro-medicine, klopidogret intensively it is metabolized in a liver with formation of the active metabolite, tiolny derivative, by oxidation to 2-oxo-klopidogrela and its subsequent hydrolysis. Oxidation of a klopidogrel happens generally to the help of isoenzymes 2B6 and 3A4, and to a lesser extent - isoenzymes 1A1, 1A2 and 2C19 of family of P450 cytochrome. An active tiolny metabolite of a klopidogrel which was allocated in the researches in vitro quickly and it is irreversible contacts platelet receptors, blocking, thus, aggregation of thrombocytes. In plasma this metabolite is not found. The main metabolite of a klopidogrel (its carboxyl derivative) to which share about 85% of the m circulating in plasma етабол and t of C оп fall and dogret and, the N е has pharmacological activity, however it is capable in vitro to inhibit activity of an isoenzyme 2C9 of family of P450 cytochrome. Against the background of a course p ри I eat and 75 m of of a klopidogrel a day maximum пл азм unlimited concentration I this metabolite (about 3 mg/l) are reached approximately in 1 hour п осл е очередн oho пр and I eat and drug. In the range of doses of a klopidogrel from 50 to 1 50 m of the pharmacokinetics of this metabolite is linear (plasma concentration in zrastat in proportion to a dose). In vitro klopidogret and its main metabolite circulating in blood reversibly contact proteins of human plasma (for 98% and 94%, respectively) and this communication is not saturable with the broad range of concentration. Within 120 hours after intake by the person 1 4 With - a marked klopidogrel about 50% of radioactivity are allocated with urine and about 46% of radioactivity - with a fecal masses. After single at I eat and and reception and repeated doses the elimination half-life of the main metabolite circulating in blood makes 8 hours. After repeated receptions of a klopidogrel in a dose of 75 mg/days plasma the end of a ntration of the basic of the metabolite circulating in blood at patients with severe damage of kidneys (clearance of creatinine from 5 to 15 ml/min.) below, than at patients with damage of kidneys of moderate severity (clearance of creatinine from 30 to 60 ml/min.) and at healthy faces. Though ngib ruyushchy вл the iyaniye on ADF-indutsirovannuyu aggregation of thrombocytes at patients with a renal failure was weaker (suppression of aggregation for 25%) in comparison with that at healthy faces, lengthening of a bleeding time was similar to that at the healthy faces receiving klopidogret in a dose 75 mg a day. Clinical portability of a klopidogrel at patients with a renal failure practically did not differ from that at healthy faces.

Indications to use:

Prevention of trombotichesky complications at patients with a myocardial infarction, an ischemic stroke or occlusion of peripheral arteries. In a combination with ASK (acetylsalicylic acid) for prevention of trombotichesky complications at an acute coronary syndrome: with raising of a segment of ST (are acute й a myocardial infarction) at a possibility of performing thrombolytic therapy; without raising of a segment of ST (unstable stenocardia, a myocardial infarction without Q tooth), including at the patients who are exposed to stenting.

Route of administration and doses:

Inside, irrespective of meal. For prevention of trombotichesky complications at patients with a myocardial infarction, an ischemic stroke or occlusion of peripheral arteries - on 75 mg of 1 times a day. At patients with a myocardial infarction treatment can be begun from the first days to the 35th day of a myocardial infarction, and at patients with an ischemic stroke - in terms from 7 days up to 6 months after an ischemic stroke. For prevention of trombotichesky complications at an acute coronary syndrome without raising of a segment of ST (unstable stenocardia, a myocardial infarction without Q tooth) - begin with a single dose of a load dose - 300 mg, and then accept 75 mg/days (in combination with ASK in doses of 75-325 mg/days, the recommended dose - 100 mg/days). The maximum favorable effect occurs in 3 months. A course of treatment till 1 year.

For prevention of trombotichesky complications at an acute coronary syndrome with raising of a segment of ST (an acute myocardial infarction with rise сегм an enta of ST) - on 75 mg/days with an initial single dose of a load dose in a combination with ASK and trombolitikam (or without trombolitik). The combination therapy is begun as soon as possible after emergence of symptoms and continued within, at least, 4 weeks. At patients it has to is more senior 75 years treatment klopidogrely to begin without reception of its load dose. At patients with genetically Ob the caught 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 (chronic on chechny insufficiency) or moderate degree of a liver failure is limited.

Features of use:

In case of surgical interventions if antiagregantny action is undesirable, the course of treatment should be stopped in 7 days prior to operation. Patients should be warned that as a stop of the bleeding drug arising against the background of use I demand больш its time, they have to report to the doctor about each case of unusual bleeding. Patients have to inform also the doctor about reception е drug if operative measures are coming them (including dental) or if the doctor appoints new to the patient of HP (medicine). In a feather of odes of l of an echena I bypass m about to control indicators of system of a hemostasis (APTT (the activated partial tromboplastinovy time), number of thrombocytes, tests функц ionalny activity of thrombocytes); it is regular to investigate functional activity of a liver. At heavy abnormal liver functions it is necessary to remember risk of development of hemorrhagic diathesis. It is not recommended to appoint to patients with an ischemic stroke prescription less than 7 days. As the tablets Targetek® contain as excipient the hydrogenated kastory oil they can cause dyspepsia and diarrhea.

Very seldom against the background of reception of a klopidogrel having developed the trombotichesky Werlhof's disease, sometimes after short-term use atsya. The state is characterized by thrombocytopenia and mikroangiopatichesky hemolitic anemia, an assotsiirova ache with neurologic break to eniye and, damage of kidneys and fever. The Trombotichesky Werlhof's disease - потен ци alno the zhizneugrozhayushchy state demanding immediate treatment including a plasma exchange.

Influence on ability to drive the car and to work with mechanisms. Таргетек® has no significant effect on the abilities necessary for driving or work with mechanisms.

Side effects:

Frequency: very often - more than 1/10, often
- more than 1/100 and less than 1/10, infrequently - more than 1/1000 and less than 1/100, it is rare - more than 1/10000 and less than 1/1000, is very rare - less than 1/10000, including isolated cases.

From bodies кроветворения:нечасто - тромбоцитоп an eniya, a leukopenia, an eosinophilia; seldom - a neytropepiya, including expressed; very seldom - a trombotichesky topenichesky purpura of a trombotsa, anemia including aplastic, a pancytopenia, an agranulocytosis, heavy thrombocytopenia, a granulocytopenia. Allergic reactions: very seldom - anaphylactic ре actions, a serum disease. From a nervous system: infrequently - a headache, dizziness, paresthesias, intracranial bleeding, including with a lethal outcome; very seldom - confusion of consciousness, a hallucination, taste disturbance.

From sense bodys: infrequently - hemorrhage in a conjunctiva, eyes, a retina; seldom - вертиго. From CCC (cardiovascular system): often - a hematoma; very seldom
- heavy bleedings, bleeding from an operational wound, a vasculitis, decrease AP (arterial pressure). From respiratory system: very often - nasal bleeding; very seldom - bro нхоспазм, an intersticial pneumonitis, pulmonary bleeding, a pneumorrhagia. From the alimentary system: often - diarrhea, an abdominal pain, dyspepsia, bleeding from a GIT (digestive tract);

infrequently
- stomach ulcer and a 12-perstny gut, gastritis, vomiting, is lean a note, a lock, a meteorism; seldom - retroperitoneal bleeding; very seldom - pancreatitis, colitis, including ulcer or lymphocytic, stomatitis, an acute liver failure, hepatitis, disturbance of functional trials of a liver, bleeding from a GIT with a lethal outcome.

From integuments: often - hypodermic hemorrhages; infrequently - skin rash, an itch, a purpura; very seldom
- a Quincke's disease, a small tortoiseshell, erythematic rash, a mnogoformny erythema, Stephens-Johnson's syndrome, a toxic epidermal necrolysis, eczema, red flat deprive.

From a musculoskeletal system: very seldom - a hemarthrosis, arthritis, an arthralgia, a mialgiya.

From urinogenital system: infrequently - a hamaturia; very seldom - a glomerulonephritis, a giperkreatininemiya.

Local reactions: often - bleedings in the place of an injection at the accompanying therapy.

Laboratory indicators: infrequently - lengthening of a bleeding time. Other: very seldom - fever.

Interaction with other medicines:

The concomitant use of warfarin with klopidogrely m ozht to increase intensity of bleedings therefore use of this combination is not recommended.
Purpose of inhibitors of a glycoprotein of IIb/IIIa, ASK, heparin together with klopidogrely increases risk of development of bleedings. At simultaneous use with NPVP (non-steroidal anti-inflammatory drugs) the risk of bleedings can increase.

The concomitant use with CYP2C19 inhibitors (for example, омепразол) is not recommended. The active metabolite of a klopidorgel inhibits activity of an isoenzyme of CYP2C9 therefore concentration of Phenytoinum, Tolbutamidum and NPVP in plasma can increase.

Contraindications:

Hypersensitivity, heavy liver failure, acute bleeding (including bleeding from a round ulcer or intracraneal hemorrhage), pregnancy and the period of a lactation, children's age up to 18 years.

As the tablets Targetek® contain in quality of excipient of lactose of m оногидрат, patients cannot accept them with a lactose intolerance, deficit of lactase and a syndrome of glyukozo-galaktozny malabsorption.

Overdose:

Symptoms: lengthening of time кровотечен and I, gems of an orraga of a cheska е complications.
Treatment: bleeding stop, transfusion of a platelet concentrate.

Storage conditions:

In the dry place at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after expiry date.

Issue conditions:

According to the recipe

Packaging:

Tablets film coated 75 mg.
7 tablets in the blister from aluminum foil, PVC of a film and polyamide, 2 or 4 blisters with the application instruction in a cardboard pack.
10 tablets in the blister from aluminum foil, PVC of a film and polyamide, 1, 2 or 3 blisters with the application instruction in a cardboard pack.