DETROMB

Active material: Clopidogrel
When ATH: B01AC04
CCF: Antiplatelet
ICD-10 codes (testimony): I20.0, I21, I63
When CSF: 01.12.11.06.01
Manufacturer: Antiviral NPO ZAO (Russia)

DOSAGE FORM, COMPOSITION AND PACKAGING

Pills, Film-coated pink color with a brownish tinge, round, lenticular.

Excipients: sodium carboxymethyl starch, colloidal silicon dioxide, Croscarmellose sodium, magnesium stearate, macrogol 6000, mannitol, microcrystalline cellulose.

The composition of the coating film: gipromelloza, iron oxide red dye (E172), talc, Titanium dioxide (E171), water (is removed in the manufacturing process).

7 PC. – packings Valium planimetric (2) – packs cardboard.
10 PC. – packings Valium planimetric (3) – packs cardboard.

Pharmacological action

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

It reduces platelet aggregation, induced by other agonists, preventing them from activating released ADP. It binds irreversibly to platelet ADP receptors, which remain impervious to ADP stimulation lifecycle (about 7 days).

From the first day of the drug showed a significant inhibition of platelet aggregation. Inhibitory effect of platelet aggregation is enhanced, and steady state is achieved through 3-7 days. Wherein, average, level suppression of aggregation by the action of the drug in a daily dose of 75 mg was from 40 to 60%. Platelet aggregation and bleeding times return to baseline at a mean 5 days after cessation of treatment.

Pharmacokinetics

Absorption and distribution

Absorption – high; bioavailability – high; The plasma concentration is low and by 2 h after administration reaches the measurement limit (0.025 ug / l). Clopidogrel and the main circulating metabolite bind reversibly to plasma proteins (98% and 94% respectively).

Metabolism

It is metabolized in the liver. The major metabolite – inactive derivative of a carboxylic acid, C_max which after repeated oral dose 75 mg achieved through 1 and h is about 3 mg / l.

Clopidogrel is a precursor of the active substance. Its active metabolite, thiol derivative, formed by oxidation of clopidogrel in 2-oxo-clopidogrel and subsequent hydrolysis. The oxidation process is governed primarily isozymes of cytochrome P4503A4 and 2B6, and to a lesser extent – 1A1, 1A2 and 2S19. Active metabolite in plasma not detectable.

Deduction

Excreted in the urine – 50%, with feces – 46% (during 120 hours after injection). T_1/2 the main metabolite after single and repeated administration – 8 no.

Pharmacokinetics in special clinical situations

Concentration of the major metabolite in plasma after ingestion dose 75 mg / d lower in patients with severe kidney disease (CC 5-15 ml / min) compared to patients with kidney disease of moderate severity (KK from 30 to 60 ml / min) and healthy individuals.

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

Testimony

Prevention of atherothrombotic events in patients, myocardial infarction, ischemic stroke or diagnosed with peripheral arterial occlusive disease.

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

- ST segment elevation(unstable angina or myocardial infarction without Q wave), including patients, which was held stenting for percutaneous coronary intervention;

- C ST-segment elevation (acute myocardial infarction) with drug treatment and the possibility of thrombolysis.

Dosage regimen

The drug is prescribed adult by 75 mg 1 time / day, regardless of the meal. Treatment can begin within the period of a few days before 35 days after myocardial infarction and in terms of 7 days before 6 months – after ischemic stroke.

At acute coronary syndrome without ST-segment elevation (unstable angina, myocardial infarction, non-Q wave) Treatment should be initiated with a single dose of a loading dose 300 mg, and then continue at a dose 75 mg 1 time / day (in combination with acetylsalicylic acid at doses 75-325 mg / day). Since the use of acetylsalicylic acid in higher doses associated with an increased risk of bleeding, The recommended dose in this indication acetylsalicylic acid does not exceed 100 mg. The maximum beneficial effect observed in 3 month of treatment. A course of treatment – to 1 year.

At acute coronary syndrome with ST segment elevation (acute myocardial infarction with ST-segment elevation) preparation prescribe a single dose 75 mg 1 times / day with an initial loading dose once-daily in combination with acetylsalicylic acid, thrombolytics (or without thrombolytics). Combination therapy is started as early as possible after the onset of symptoms and continued for, at least, 4 weeks.

In older patients 75 years Treatment should start without receiving a loading dose.

Side effect

From the hematopoietic system: sometimes – leukopenia, reduce the number of neutrophils and eosinophils, reduction in the number of platelets; very rarely - thrombotic thrombocytopenic purpura (1 on 200 000 patients), tyazhelaya thrombocytopenia (platelet count ≤ 30 000/l), granulocytopenia, agranulocytosis, anemia and anemia aplasticheskaya, pancytopenia.

From the central and peripheral nervous system: sometimes – headache, dizziness, paresthesia; rarely – vertigo; rarely – confusion, hallucinations.

From the digestive system: often – dyspepsia, diarrhea, abdominal pain; sometimes – nausea, gastritis, flatulence, constipation, vomiting, gastric ulcer and duodenal ulcer; rarely – colitis (incl. yazvennыy or limfotsitarnыy colitis), pancreatitis, change in taste, stomatitis; hepatitis, acute liver failure, increase in liver enzymes.

From the blood coagulation system: common – bleeding (In most cases – during the first month of treatment). Several fatalities (Intracranial, gastrointestinal and retroperitoneal haemorrhage); there are reports of serious cases of skin bleeding (purpura), musculoskeletal bleeding (gemartroz, hematoma), eye haemorrhage (conjunctival, ocular, retinal), nosebleeds, hemoptysis, pulmonary hemorrhage, hematuria and bleeding from the surgical wound; patients, clopidogrel together with acetyl salicylic acid or acetylsalicylic acid and heparin, as there have been cases of severe bleeding.

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

Cardio-vascular system: rarely – vasculitis, hypotension.

The respiratory system: rarely – bronchospasm, interstitial pneumonitis.

On the part of the musculoskeletal system: rarely – arthralgia, arthritis, myalgia.

From the urinary system: rarely – glomerulonephritis, increase in blood creatinine.

Allergic reactions: rarely – angioedema, hives, anaphylactoid reactions, serum sickness.

Other: rarely – fever.

Contraindications

- Severe hepatic impairment;

- Severe bleeding, eg, bleeding from a peptic ulcer or intracranial hemorrhage;

- Pregnancy;

- Lactation (breast-feeding);

- Children up to age 18 years;

- Hypersensitivity to the drug.

FROM caution should be prescribed with moderate hepatic and / or renal insufficiency, injuries, preoperative conditions.

Pregnancy and lactation

The drug is contraindicated during pregnancy and lactation.

Cautions

When treating Detrombom^®, especially during the first weeks of treatment and / or after invasive cardiological procedures / surgery, necessary to conduct a thorough monitoring of patients for signs of bleeding exceptions, incl. hidden. Due to the risk of bleeding and hematological adverse effects in case of occurrence of clinical symptoms during the treatment, suspected of bleeding, should urgently make the CBC, determine the activated partial thromboplastin time, platelet count, functional activity of platelets and conduct other necessary investigations.

Clopidogrel, as well as other anti-platelet drugs, should be used with caution in patients, with an increased risk of bleeding, related injuries, surgery or other pathological conditions, and in patients receiving aspirin, NSAIDs, incl. COX-2 inhibitors, heparin or inhibitors of glycoprotein IIb / IIIa.

The combined use of clopidogrel with warfarin may increase the intensity of bleedings, so, except in specific rare clinical situations (such as the presence of floating thrombus in the left ventricle, stenting in patients with atrial fibrillation) concomitant use of clopidogrel and warfarin is not recommended.

Clopidogrel prolongs bleeding time and should be used with caution in patients with diseases, predisposes to the development of bleeding (especially, gastrointestinal and intraocular).

Rarely, after clopidogrel (sometimes even a short) there have been cases of thrombotic thrombocytopenic purpura (TTP), which is characterized by thrombocytopenia and microangiopathic hemolytic anemia, accompanied nevrologicheskmi disorders, impaired renal function, and fever. Thrombotic thrombocytopenic purpura is a potentially life-threatening condition, requiring immediate treatment, including plasmapheresis.

In the period of treatment is necessary to control the functional activity of the liver. In severe liver problems should be aware of the risk of hemorrhagic diathesis.

Clopidogrel is not recommended for acute stroke with less prescription 7 days (since there is no data on its use in this condition).

Overdose

Symptoms: prolonged bleeding and subsequent complications in the form of bleeding.

Treatment: in case of bleeding should be held appropriate therapy. If you need a quick correction to lengthen bleeding time, It recommended a transfusion of platelets. No specific antidote.

Drug Interactions

It enhances the antiplatelet effect of aspirin, geparina, anticoagulants, non-steroidal anti-inflammatory drugs, It increases the risk of bleeding from the gastrointestinal tract. However, in patients with acute coronary syndrome without ST segment elevation recommend the combined use of clopidogrel long and acetylsalicylic acid (to 1 year).

Appointment of glycoprotein IIb / IIIa in conjunction with clopidogrel in patients requires caution, with an increased risk of bleeding (trauma and surgery or other pathological conditions).

There was no clinically significant pharmacodynamic interaction with clopidogrel together with atenolol, nifedipine, fenoʙarʙitalom, cimetidine, Estrogen, digoksinom, theophylline, phenytoin, tolbutamide and antacids.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored in a dry, protected from light, inaccessible to children at temperature not exceeding 25 ° C. Shelf life – 3 year.