Кворекс

General characteristics. Structure:

Active agent - клопидогреля bisulphate (in terms of klopidogret) 75,0 mg.

Excipients: cellulose microcrystallic, lactoses monohydrate, коповидон (Kollidon VA 64), кросповидон XL-10, talc, silicon dioxide colloid (aerosil), magnesium stearate.

Structure of a cover: gipromelloz (gidroksipropilmetiltsellyuloz), titanium dioxide (Е 171), triacetin, liquid paraffin.

Pharmacological properties:

Pharmacokinetics. At reception single and repeated peroral doses on 75 mg a day klopidogret quickly it is soaked up. Average maximum plasma concentration not changed клопидогреля (about 2,2-2,5 ng/ml after one 75 mg of a peroral dose) were noted in 45 minutes after dosing.

Klopidogrel and his main circulating metabolite form reversible communication with proteins of plasma (98 and 94%, respectively). This communication is not saturable with the broad range of concentration.

Klopidogrel is exposed to intensive metabolism in a liver. Klopidogrel is metabolized in two based ways: one is mediated by esterases and leads to hydrolysis to inactive derivative carboxylic acid (85% of the metabolites which are in a blood-groove), another is mediated by numerous tsitokhroma of P450. At first klopidogret it is metabolized to an intermediate metabolite, 2-oxo-klopidogrelya. The subsequent metabolism of an intermediate metabolite 2-oxo-klopidogrelya leads to formation of an active metabolite, thiol derivative клопидогреля. This way of metabolism is mediated by CYP3A4, CYP2C19, CYP1A2 and CYP2B6. An active thiol metabolite quickly it is also irreversible takes up with receptors of thrombocytes, suppressing thereby aggregation of thrombocytes.

After reception клопидогреля, about, 50% also, about, 46% - with a fecal masses within 120 hours are allocated with urine.

After reception of one tablet of 75 mg the elimination half-life клопидогреля makes 6 hours. The elimination half-life of the main circulating (inactive) metabolite makes 8 hours after single and repeated receptions.

Renal failure. After repeated doses клопидогреля on 75 mg a day at patients with a serious illness of kidneys (clearance of creatinine from 5 to 15 ml/min.) suppression of the aggregation of thrombocytes provoked by adenosinediphosphate (ADF) was weaker (25%), however, lengthening of a bleeding time was analogous to that which it was observed at the healthy subjects receiving 75 mg клопидогреля in day. All patients had a good clinical portability.

Abnormal liver function. After repeated doses клопидогреля on 75 mg a day within 10 days at patients with heavy dysfunction baking suppression of the aggregation of thrombocytes provoked by ADF was analogous to the suppression observed at healthy subjects. Average lengthening of a bleeding time in both groups was analogous.

Pharmacodynamics. Кворекс - inhibitor of aggregation of thrombocytes. Selectively inhibits linkng of adenosinediphosphate (ADF) with his receptors located on surfaces of thrombocytes and the subsequent activation of a complex IIb/IIIa glycoprotein, inhibiting thus, aggregation of thrombocytes. Biotransformation клопидогреля is necessary for inhibition of thrombocytes. Кворекс also interferes with the aggregation of thrombocytes caused by other agonists, way of blockade of increase in activity of thrombocytes the released ADF. The effect клопидогреля lasts during all life of a thrombocyte, platelet function is recovered in 7-10 days after cancellation клопидогреля.

At long purpose of therapeutic doses of Kvoreks (75 mg a day) the noticeable inhibition of aggregation of thrombocytes is noted in the first day of treatment, then the antiagregantny effect gradually increases and reaches a maximum for 3-7 day of regular administration of drug. At long reception of therapeutic doses the average level of inhibition is between 40 and 60%. After the end of treatment Kvoreks's effect on aggregation of thrombocytes and a bleeding time usually decreases within 5 days. Drug leads to statistically reliable decrease in frequency of new ischemic disturbances (a myocardial infarction, an ischemic stroke and sudden death).

Indications to use:

It is shown to adults for prevention of aterotrombotichesky changes at:

- a myocardial infarction (from several days to less than 35 days);

- an ischemic stroke (from 7 days to less than 6 months);

- the diagnosed disease of peripheral arteries;

- syndrome of acute coronary insufficiency;

- a syndrome of acute coronary insufficiency without increase in a segment of ST (unstable stenocardia or a myocardial infarction without Q tooth), including the patient who is exposed to placement of a coronary stent during chrezkozhny coronary intervention in a combination with acetylsalicylic acid (ASK);

- an acute myocardial infarction with increase in a segment of ST, in a combination with ASK at patients on drug treatment, suitable for performing thrombolytic therapy.

Route of administration and doses:

Adult and elderly:

Кворекс it is necessary to accept 75 mg regardless of meal once a day.

At the patients suffering from a syndrome of acute coronary insufficiency:

- a syndrome of acute coronary insufficiency without increase in a segment of ST (unstable stenocardia or a myocardial infarction without Q tooth): treatment has to be begun with a single load dose of 300 mg, and then is continued by a dose of 75 mg once a day (with acetylsalicylic acid in a dose of 75 - 325 mg a day). As higher doses of acetylsalicylic acid are accompanied by the increased risk of bleeding, it is not recommended to exceed a dose of acetylsalicylic acid of 100 mg. Duration of treatment the attending physician, on average defines the от3rd - x up to 12 months.

Acute myocardial infarction with increase in a segment of ST:

- Кворекс it is necessary to apply in the single daily dose equal 75 mg, since a load dose in 300 mg in a combination with acetylsalicylic acid and with other trombolitika or without them. At patients 75 years are more senior treatment by Kvoreks should be begun without load dose. The combination therapy should be begun as soon as possible after emergence of symptoms and to continue, at least, within four weeks.

Safety and efficiency of use of Kvoreks for children and teenagers up to 18 years are not established.

Disturbance of renal function. Patients with a renal failure of Kvoreks should apply with care.

Abnormal liver function. Patients with an abnormal liver function of Kvoreks should apply with care.

Features of use:

Due to the risk of bleeding and hematologic undesirable effects, in case of emergence during treatment of the clinical symptoms indicating bleeding it is necessary to control a pattern of peripheral blood and/or to carry out other corresponding analyses. Also as well as other antithrombocytic drugs, Kvoreks it is necessary to apply with care in case of the patients subject to the increased risk of bleeding connected with an injury, surgical or other morbid conditions and also in case of the patients who are on treatment of ASK, heparin, inhibitors of a glycoprotein IIb/IIIa or non-steroidal anti-inflammatory drugs, including TsOG-2 inhibitors. It is necessary to control carefully existence at sick symptoms of bleeding, including the concealed hemorrhage, especially, in the first weeks of treatment and/or after the invasive procedures on heart or surgical intervention.

If elective surgical intervention is necessary to the patient, and the protivotrombotichesky effect is temporarily undesirable, in 7 days prior to operation Kvoreks's reception should be stopped. Before any operation and reception of any new medicine patients have to warn doctors and dentists that accept Kvoreks. Кворекс prolongs a bleeding time and it has to be applied with care in case of patients with the pathological changes contributing to bleeding (especially, gastrointestinal and intraocular).

Patients should be warned that at Kvoreks's reception (one or in a combination with ASK) for a stop of bleeding more time can be required, and also about what they should tell the attending physician if they have unusual (on localization or duration) a bleeding.

Very seldom, after Kvoreks's use, and sometimes after short exposure, chances of the trombotichesky Werlhof's disease (TWD) which is characterized by thrombocytopenia and mikroangiopatichesky hemolitic anemia, followed by neurologic changes, dysfunction of kidneys or fever. TTP is potentially deadly state demanding immediate treatment including a plasma exchange.

In view of lack of data, Kvoreks it is impossible to recommend in the first 7 days after an acute ischemic stroke.

Кворекс contains lactose. Patients with rare inherited disorders of portability of a galactose, with deficit of lactase of Lapp and a syndrome of malabsorption of glucose and a galactose, cannot accept this drug.

Considering side effects of medicine, it is necessary to be careful when driving and work with potentially dangerous mechanisms.

Side effects:

Often:

- hematoma;

- nasal bleeding;

- gastrointestinal bleeding, diarrhea, abdominal pains, dyspepsia;

- bruises;

- bleeding on site punctures.

Sometimes:

- thrombocytopenia, leukopenia, eosinophilia;

- intracraneal hemorrhage (it is possible with a lethal outcome), a headache, paresthesias, dizziness;

- hematopsia (conjunctival, ocular, retinal);

- vomiting, nausea, lock, meteorism, stomach ulcer and duodenum, gastritis;

- rash, itch, purpura;

- hamaturia;

- lengthening of a bleeding time, neutropenia, thrombocytopenia.

Seldom:

- retroperitoneal bleeding.

Very seldom:

- trombotichesky Werlhof's disease (TWD), aplastic anemia, pancytopenia, agranulocytosis, heavy thrombocytopenia, granulocytopenia, anemia;

- serum disease, anaphylactoid reactions;

- hallucinations, confusion of consciousness;

- disturbances of flavoring feelings;

- heavy bleeding from an operational wound, a vasculitis, arterial hypotension;

- bronchospasm, intersticial pneumonitis, pneumorrhagia, pulmonary bleeding;

- stomatitis, pancreatitis, colitis, including ulcer, gastrointestinal and retroperitoneal bleeding with a lethal outcome;

- pathological indicators of functional tests of a liver, hepatitis, acute liver failure;

- violent dermatitis (a toxic epidermal necrolysis, a syndrome Stephens-Johnson, a mnogoformny erythema), a Quincke's disease, erythematic rash, a small tortoiseshell, eczema and flat deprive;

- mialgiya, arthralgias, arthritises, hemarthrosis;

- a glomerulonephritis, increase in level of creatinine in blood;

- feverish syndrome.

Interaction with other medicines:

Oral anticoagulants. Simultaneous use of Kvoreks with oral anticoagulants is not recommended as it can strengthen bleeding.

IIb/IIIa glycoprotein inhibitors. Кворекс it is necessary to apply with care in case of patients who can be subject to the increased risk of bleeding connected with an injury, surgical or other morbid conditions and receive IIb/IIIa glycoprotein inhibitors.

Acetylsalicylic acid (ASK). Between Kvoreks and acetylsalicylic acid perhaps pharmakodinamichesky interaction, it leads to increase in risk of bleeding. Therefore, simultaneous use of these drugs should be carried out with care.

Heparin. Simultaneous use of heparin did not influence the suppression of aggregation of thrombocytes caused by Kvoreks. Between Kvoreks and heparin perhaps pharmakodinamichesky interaction, it leads to the increased risk of bleeding. Therefore, simultaneous use of these drugs demands care.

Thrombolytic means. Frequency of clinically significant bleedings is similar to that that is observed at use of thrombolytic means and heparin together with ASK.

Non-steroidal anti-inflammatory drugs (NPVS). Due to the lack of clinical trials of interactions with NPVS, it is not clear now whether the increased risk of gastrointestinal bleedings is characteristic of all NPVS. Thus, purpose of NPVS, including TsOG-2 inhibitors, and клопидогреля demands care.

Omeprazol, esomeprazole, флувоксамин, fluoxetine, моклобемид, вориконазол, флуконазол, тиклопидин, ciprofloxacin, Cimetidinum, carbamazepine, окскарбамазепин and chloramphenicol. Combined use with Kvoreks leads to decrease in medicinal concentration of an active metabolite of Kvoreks and reduction of its clinical performance in connection with suppression CYP2C19 enzyme by means of which Kvoreks is metabolized to the active metabolite. It is necessary to refuse simultaneous use of Kvoreks with these drugs.

Inhibitors of a protonew pomp. It is necessary to avoid simultaneous use of inhibitors of a protonew pomp if it is not absolutely necessary. Proofs that other medicines lowering acidity in a stomach such as blockers of H2 and antacids influence antithrombocytic activity of Kvoreks no.

Atenolol, nifedipine. Clinically significant pharmakodinamichesky interaction with Kvoreks was not observed.

Phenobarbital, Cimetidinum and estrogen. Combined use has no significant effect on pharmakodinamichesky activity of Kvoreks.

Digoxin, theophylline. Simultaneous use of Kvoreks does not influence pharmacokinetics of these drugs.

Antiacid means. Do not change extent of absorption of Kvoreks.

Phenytoinum, Tolbutamidum and NPVS which are metabolized by means of P4502C9 cytochrome. The combined reception with Kvoreks can lead to increase in plasma levels of the specified medicines as a metabolite клопидогреля, carboxylic acid, can suppress activity of P4502C9 cytochrome. However Phenytoinum and Tolbutamidum can be applied with safety along with Kvoreks.

Diuretic, β-blockers, APE inhibitors, antagonists of calcium, drugs, holesterinponizhayushchy means, coronary vazodilatator, anti-diabetic means (including insulin), antiepileptic means and antagonists of GPIIb/IIIa. The combined reception with Kvoreks does not cause essential undesirable interactions in the clinical relation. 

Contraindications:

- hypersensitivity to active ingredient or to any of medicine components;

- heavy abnormal liver functions;

- acute pathological bleeding, including, bleeding at a peptic ulcer of a stomach and a 12-perstny gut, ulcers of a gullet or intracraneal hemorrhage;

- pregnancy and period of a lactation.

Overdose:

Symptoms - lengthening of a bleeding time with the subsequent complications of bleeding.

Treatment: the antidote of pharmacological activity клопидогреля is not found. If bystry correction of the extended bleeding time is necessary, the transfusion of thrombocytes can stop Kvoreks's effects.

Storage conditions:

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:

On 10 tablets in a blister strip packaging from a film of polyvinyl chloride and aluminum foil.

On the 2nd blister strip packagings together with the approved instruction on a medical use in the state and Russian languages place in a pack from a cardboard.