Detromb - instructions for use, dose, side effects, contraindications

Excipients: sodium carboxymethyl starch 6,000 mg, silicon dioxide colloid 1,665 mg, croscarmellose sodium 3,665 mg, magnesium stearate 3,000 mg, macrogol-6000 1.665 mg, mannitol 15,000 mg, microcrystalline cellulose 132.085 mg;

film sheath: Hypromellose 8100 mg, colorant red ferric oxide (E 172) 0.025 mg talc 0.270 mg titanium dioxide (E 171) 0.650 mg.

Description:

Round, biconcave tablets covered with a film membrane, pink with a brownish tinge.

Pharmacotherapeutic group:Antiaggregant agent

ATX: & nbsp

B.01.A. C.04 Clopidogrel

Pharmacodynamics:

Clopidogrel selectively reduces the binding of adenosine diphosphate (ADP) receptor on platelets and activation of glycoprotein receptors IIb / IIIa under the action of ADP, thereby weakening platelet aggregation.

Reduces platelet aggregation, caused by other agonists, preventing their activation by released ADP. Irreversibly binds to the platelet ADP receptors that remain impervious to ADP stimulation throughout the life cycle (about 7 days).

Since the first day of the drug, there has been a significant inhibition of platelet aggregation. The inhibitory effect of platelet aggregation is enhanced, and a stable condition is achieved after 3-7 days. At the same time, on the average, the level of suppression of aggregation under the action of a daily dose of 75 mg was from 40 to 60%.Aggregation of platelets and bleeding time return to the baseline level on average 5 days after discontinuation of treatment.

Pharmacokinetics:

Absorption - high; bioavailability is high; the concentration in the plasma is low and after 2 hours after administration it does not reach the measurement limit (0.025 μg / l). Clopidogrel and the main circulating metabolite reversibly bind to plasma proteins (98% and 94%, respectively).

Metabolized in the liver. The main metabolite is an inactive derivative of carboxylic acid, the time of its maximum concentration after repeated oral doses of 75 mg is achieved after 1 hour (maximum concentration is about 3 mg / l).

Clopidogrel is a precursor of the active substance. Its active metabolite, a thiol derivative, is formed by oxidizing clopidogrel to 2-oxo-clopidogrel and subsequent hydrolysis. The oxidative process is regulated primarily by cytochrome P450 3A4 and 2B6 isoenzymes, and to a lesser extent - 1A1, 1A2 and 2C19. An active metabolite in plasma is not detected.

Excretion: kidneys - 50%, intestines - 46% (within 120 hours after administration). The half-life of the main metabolite after a single and repeated administration is 8 hours.

The concentration of the main metabolite in the plasma after taking 75 mg / day is lower in patients with severe kidney disease (creatinine clearance 5-15 ml / min) compared with patients with moderate kidney disease (creatinine clearance from 30 to 60 ml / min) and healthy persons.

In patients with cirrhosis of the liver, taking a daily dose of 75 mg for 10 days was safe and well tolerated. The maximum concentration of clopidogrel both after taking a single dose, and in an equilibrium state was significantly higher in patients with cirrhosis than in healthy individuals. However, the level of the main metabolite in the plasma, as well as the inhibiting effect of platelet aggregation, were comparable in both groups.

Indications:

Prevention of atherothrombotic complications in patients who underwent myocardial infarction, ischemic stroke or with diagnosed occlusive disease of peripheral arteries.

Prevention of atherothrombotic events (in combination with acetylsalicylic acid) in patients with acute coronary syndrome:

- without segment elevation ST (unstable angina or myocardial infarction without a tooth Q), including patients who underwent stenting with percutaneous coronary intervention;

- with segment lift ST (acute myocardial infarction) with drug treatment and the possibility of carrying out thrombolysis.

Contraindications:

- Hypersensitivity;

severe hepatic impairment;

- Acute bleeding, such as: peptic ulcer or intracranial hemorrhage;

- pregnancy, lactation period;

- Children under 18 years.

Carefully:

Moderate hepatic and / or renal failure, trauma, preoperative condition.

Dosing and Administration:

Inside, adults 75 mg once a day, regardless of food intake. Treatment should be started within a few days to 35 days - in patients after myocardial infarctionand from 7 days to 6 months - in patients after ischemic stroke.

In acute coronary syndrome without segment elevation ST (unstable angina, myocardial infarction without a tooth Q) treatment should be started with a single dose of 300 mg, and then continued with a 75 mg dose once daily (in combination with acetylsalicylic acid at doses of 75-325 mg per day). Since the use of higher doses of acetylsalicylic acid is associated with a greater risk of bleeding, the recommended dose of acetylsalicylic acid does not exceed 100 mg.The maximum favorable effect is observed by the third month of treatment. The course of treatment is up to 1 year.

In acute coronary syndrome with segment elevation ST (acute myocardial infarction with segment elevation ST) the drug is given once in a dose of 75 mg once a day with the initial single dose loading in combination with acetylsalicylic acid and thrombolytic agents (or without thrombolytics). Combination therapy is started as soon as possible after the onset of symptoms and continues for at least four weeks. In patients older than 75 years, treatment with clopidogrel should begin without taking its stress test.

Side effects:

On the part of the hematopoiesis system: sometimes - leukopenia, a decrease in the number of neutrophils and eosinophilia, a decrease in the number of platelets; very rarely thrombotic thrombocytopenic purpura (1 in 200 000 patients), severe thrombocytopenia (platelet count <30 000 / μl), granulocytopenia, agranulocytosis, anemia and aplastic anemia, pancytopenia.

From the side of the central nervous system and peripheral nervous system: sometimes - headache, dizziness, paresthesia; rarely - vertigo; very rarely - confusion, hallucinations.

From the digestive system: often - indigestion, diarrhea, abdominal pain; sometimes - nausea, gastritis, flatulence, constipation, vomiting, peptic ulcer of the stomach and duodenum; very rarely - colitis (including ulcerative or lymphocytic colitis), pancreatitis, changes in taste, stomatitis; hepatitis, acute liver failure, increased activity of hepatic enzymes.

From the coagulation system of the blood: most often - bleeding (in most cases - during the first month of treatment). There are several cases with a fatal outcome (intracranial, gastrointestinal and retroperitoneal bleeding); there are reports of severe cases of cutaneous hemorrhages (purpura), musculoskeletal bleeding (hemarthrosis, hematoma), ocular hemorrhage (conjunctival, ocular, retinal), nasal bleeding, hemoptysis, pulmonary hemorrhage, hematuria and bleeding from the operating wound; in patients taking clopidogrel simultaneously with acetylsalicylic acid or with acetylsalicylic acid and heparin, cases of severe bleeding were also noted.

Dermatological reactions: often - bruising; sometimes - a rash and itching; very rarely - bullous rash (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), erythematous rash, eczema, flat lichen.

From the side of the cardiovascular system: very rarely - vasculitis, arterial hypotension.

From the respiratory system: very rarely - bronchospasm, interstitial pneumonitis.

From the musculoskeletal system: very rarely - arthralgia, arthritis, myalgia.

From the side of the urinary system: very rarely - glomerulonephritis, an increase in the creatinine of the blood.

Allergic reactions: very rarely - angioedema, urticaria, anaphylactoid reactions, serum sickness.

Other: very rarely - a rise in temperature.

Overdose:

An overdose of clopidogrel may lead to lengthening of bleeding time and subsequent complications. If a bleeding is detected, appropriate treatment should be applied.

The antidote of clopidogrel was not detected. If rapid correction of prolonged bleeding time is necessary, transfusion of platelet mass is recommended.

Interaction:

Strengthens the antiplatelet effect Acetylsalicylic acid, heparin, indirect anticoagulants, non-steroidal anti-inflammatory drugs, increases the risk of developing bleeding from the gastrointestinal tract. However, in patients with acute coronary syndrome without segment elevation ST, long-term combined use of clopidogrel and acetylsalicylic acid (up to 1 year) is recommended.

Appointment inhibitors of glycoprotein IIb / IIIa together with clopidogrel requires caution in patients who have an increased risk of bleeding (with trauma and surgical interventions or other pathological conditions).

There was no clinically significant pharmacodynamic interaction with clopidogrel combined with atenolol, nifedipine, phenobarbital, cimetidine, estrogens, digoxin, theophylline, phenytoin, tolbutamide, and antacid agents.

Special instructions:

In the treatment of clopidogrel, especially during the first weeks of treatment, and / or after invasive cardiac procedures / surgery, patients should be closely monitored for the exclusion of bleeding symptoms,including the hidden one. In connection with the risk of bleeding and hematologic adverse effects (see "Side Effects"), if clinical symptoms that are suspect for bleeding occur during treatment, it is urgent to do a clinical blood test, determine activated partial thromboplastin time, platelet count, activity of platelets and conduct other necessary studies.

Clopidogrel, as well as other antiplatelet drugs, should be used with caution in patients with an increased risk of bleeding associated with trauma, surgery or other pathological conditions, as well as in patients receiving acetylsalicylic acid, non-steroidal anti-inflammatory drugs, including inhibitors cyclooxygenase-2, heparin or glycoprotein inhibitors Ilb/IIIa. Joint use of clopidogrel with warfarin may increase the intensity of bleeding (see "Interaction with other drugs"), therefore, with the exception of special rare clinical situations (such as the presence of a floating thrombus in the left ventricle, stenting in patients with atrial fibrillation)the combined use of clopidogrel and warfarin is not recommended.

Clopidogrel prolongs bleeding time and should be used with caution in patients with diseases predisposing to the development of bleeding (especially, gastrointestinal and intraocular). Very rarely, after the use of clopidogrel (sometimes even a short one), there have been cases of thrombotic thrombocytopenic purpura (TTP), which is characterized by thrombocytopenia and microangiopathic hemolytic anemia, accompanied by neurological disorders, impaired renal function and fever. TTP is a potentially life-threatening condition requiring immediate treatment, including plasmapheresis. During the treatment it is necessary to monitor the functional activity of the liver. With severe liver damage should be remembered about the risk of hemorrhagic diathesis. Taking clopidogrel is not recommended for an acute stroke less than 7 days old (as there is no data on its use in this condition).

Form release / dosage:

Tablets coated with a film coating, 75 mg.

Packaging:

For 7 or 10 tablets in a contour acrylic package from a film of oriented polyamide and aluminum foil printed lacquered.

2 contour packs of 7 tablets or 3 contour packs of 10 tablets together with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-007058/09

Date of registration:07.09.2009 / 18.10.2012

Expiration Date:Unlimited

The owner of the registration certificate:Anvilab, OOO Anvilab, OOO Russia

Manufacturer: & nbsp

Anvilab, OOO Russia

Representation: & nbspAnviLab Ltd AnviLab Ltd Russia

Information update date: & nbsp25.03.2017

Illustrated instructions

Instructions

Detromb® (Detromb®)