VIXCAR 75mg BRV prevents thrombosis due to atherosclerosis (3 blisters x 10 tablets)

In patients with adults with atrial fibrillation, there is at least one risk factor for blood vessel events, not suitable for treatment with anti -vitamin K drugs, which are at risk of low bleeding, used in combination with aspirin to prevent thrombosis due to atherosclerosis and clogged thrombosis, including stroke.

Pharmacokology

ATC code: B01A C04

Medication group: Platelet inhibitors

Clopidogrel is a precursor to which one of its metabolites is platelet aggregation inhibitors. Clopidogrel after being metabolized by CYP450 enzymes produces metabolites that inhibit platelet aggregation. This metabolic substance selectively inhibits the cohesion of adenosin diphosphate (ADP) into the P2Y12 receptor on the platelet surface and thereby inhibit the activation of the Glycoprotein GPIIB/LLA complex (via ADP as an intermediate) so the platelet training is inhibited.

Due to the negative cohesion, platelets exposed to drugs are affected to the end of their lifespan (about 7-10 days) and the normal function of platelet function occurs at a constant rate. The platelet aggregation caused by other agonized substances is also inhibited by preventing platelet activation by releasing ADP. Because the active metabolites are formed by CYP450 enzymes, some of which are polymorphic or inhibited by other drugs, not all patients will have appropriate platelet inhibition.

The effect can be clearly seen after 2 hours of taking the daily dose of 75mg daily, significantly inhibiting platelet training due to the ADP on the first day and reaching a stability on the 3rd and 7th day. Stopping platelets and bleeding time gradually returning to the basic value, for about 5 days after stopping treatment. Clopidogrel's safety and effectiveness in preventing ischemic disasters in the blood vessels have been defined. In clinical trials that compare blindness with aspirin shows that Clopidogrel significantly reduces the incidence of new ischemic complications, no difference in mortality and benefits in patients over 75 years older than the patient group under 75 years old.

pharmacokinetics

Absorption

Clopidogrel is quickly absorbed after single dose and repeated dose 75mg daily. Clopidogrel's peak plasma peak concentration (about 2.2 - 2.5 mg/ml after taking a single dose of 75mg) reached about 45 minutes after taking the drug. The absorption is at least 50%, based on the excretion of clopidogrel metabolites in urine.

Distribution

Clopidogrel and main metabolites (inactive) in vitro is inversely cohesive with human plasma proteins (98% and 94% respectively). These In vitro cohesion are not saturated in a wide range.

Metabolism

Clopidogrel is greatly metabolized by the liver. In Vitro and In Vivo, Clopidogrel is metabolized in two main metabolic paths: one is the intermediary of the esterase and hydrolyzed into the derivative of carboxylic acid inactive (accounting for 85% of circulating metabolites) and the other is intermediaries with multiple cytochrom P450. Clopidogrel is first converted into a 2-oxo-clopidogrel conversion. Then 2-olo-clopidogrel is converted into an active metabolite, which is a clopidogrel's conductor.

In In vitro, this metabolic path is intermediate by CYP3A4, CYP2C19, CYP1A2 and CYP2B6. Active thiol metabolites have been isolated in this in vitro quickly and is not reversible with platelet platelet receptors, thus inhibiting platelets. The maximum concentration of metabolites is twice as activated after using a single dose of clopidogrel 300mg like after four days of maintenance dose of 75mg. The maximum concentration is about 30-60 minutes after taking the drug.

Elimination

After a dose of Clopidogrel, a 14C radioactive mark in humans, about 50% is excreted in the urine and about 46% excreted in the feces after about 120 hours after taking the drug. The sale time is about 6 hours after taking a single dose of 75mg Clopidogrel. The sale time of the main circulation metabolites (inactive) is 8 hours after the single dose and the dose repeated.

Genetic pharmacy

Due to CYP2C19 participating in the formation of both active metabolites and intermediate metabolites 2-oxo-clopidogre and Ex vivo tests showing the pharmacokinetic and inhibiting the platelet aggregation of the active metabolites also varies depending on the CYP2C19 genotype. People carrying genes of CYP2C19*1 have perfect metabolic function while those who carry the genes of CYP2C19*2 and CYP2C19*3 have a metabolic defect, while the genes of CYP2C 19*4*5*6*7 and*8 have poor metabolic function. The proportion of people with a poor metabolic CYP2C19 genotype is about 2% in white people, 4% in black and 14% in Chinese people. There have been tests to determine the CYP2C19 genotype for patients.

Renal failure

After the dose repeats Clopidogrel 75mg daily in people with severe renal failure (with creatinine clearance from 5 - 15 ml/minute), the inhibition of platelet aggregation is due to ADP as lower (25%) compared to healthy people. However, the prolongation of blood flow is similar to healthy people using Clopidogrel 75mg daily. In addition, clinical tolerance is good for all patients.

People with liver failure

After taking the dose of clopidogrel 75mg daily for 10 days in patients with severe hepatic failure, the inhibition of platelet aggregation due to ADP is similar to in healthy people. The average blood flow time is similar in two groups.

Be cautious when using

Bleeding and hematological disorders

Due to the risk of bleeding and adverse hematological reactions, during treatment, if any clinical symptoms suggest hemorrhage, it is necessary to test the number of bloody and other appropriate tests in time.

Due to the drug that prolongs bleeding time, caution must be used for patients to increase the risk of bleeding due to trauma, surgery or other diseases.

Be cautious when used in combination with aspirin, heparin, glycoprotein inhibitors ILB/LLA, nonsteroidal anti -inflammatory drugs (including COX 2 inhibitors), Serotonin recovery inhibitors. Patients need to be carefully monitored for special hemorrhage signs in the first week of treatment.

Do not be used with other oral anticoagulants because of increased bleeding level.

In case the patient is preparing for surgery, if you do not want to have a platelet resistance, it is necessary to stop the drug 7 days in advance.

Patients need to notify the doctor or dentist that they are taking this medicine before the surgery appointment or starting a new medicine.

It is necessary to inform the patient while taking the medication that the bleeding time is often longer than usual, so the drug should be stopped and notify the doctor when there is abnormal bleeding.

Object of thrombocytopenia (TTP)

A few rare cases of thrombocytopenia (TTP) have been reported after using clopidogrel, sometimes only for a short time. The characteristics of the disease are thrombocytopenia and microchemical anemia with nervous manifestations, kidney dysfunction or fever. This disease has a fatal potential that needs to be treated early, including plasma filter.

Bleeding disease is suffering from

Unedicated bleeding disease has been reported after using clopidogrel. In the event that the test results are long -lasting thromboplastin, partially activated (APTT), with or without bleeding, it is necessary to think of an acquired bleeding disease, then the need to stop the drug and the patient needs to be managed and treated by a specialist.

New heart attack

Due to lack of data, new patients with myocardial infarction, Clopidogrel should not be used for the first 7 days.

Cytochrom P4502C19 (CYP2C19)

In patients with weak metabolic CYP2C19 enzyme system when using clopidogrel at the offer dose will produce less active metabolites and less platelet effect effect. Testing to distinguish the CYP2C19 genotype is currently available.

Because the drug is partially metabolized through the CYP2C19 enzyme, it is necessary to avoid it at the same time with strong and moderate CYP2C19 enzyme inhibitors so as not to reduce the metabolites created and do not reduce the effects of the drug.

Cross reactions with thienopyridine

Patients need to be assessed for hypersensitivity to thienopyridin (such as clopidogrel, ticlopidin, prasugrel) due to the cross -reaction between the Thienopyricin. Thienopyridine can cause mild to severe allergic reactions such as rash, angioedema, or hematological reactions such as thrombocytopenia and neutropenia. Patients who have had allergic reactions or hemorrhagic reactions with a Thienopyricin may increase the risk of an allergic to another Thienopyricin. Need to monitor hypersensitive signs in patients who have been allergic to thienopyrin.

kidney failure, liver failure

Be cautious when taking medication for patients with renal impairment, average liver failure because it may be bleeding.

lactose

Because this product contains Lactose Monohydrate excipients, it is not advisable to use for patients with rare genetic problems in galactose, lactase deficiency, or under absorption of glucose-galactose.

The effect of the drug on the ability to drive and operate machinery

use the drug cautious for drivers or machinery operating because the drug can be more or less dizzy.

Using drugs for women during pregnancy and lactation

Clinical data is limited, animal studies do not see direct or indirect effects on pregnancy, the development of embryo and postpartum after birth.

Due to lack of data on exposure to drugs during pregnancy, for caution, it is best not to use this drug for pregnant women.

Do not know if the drug is not known to get into breast milk or not, animal research shows that Clopidogrel is excreted through milk, for caution reasons to stop breastfeeding during medication.

Interactive drug

should not be used at the same time with other oral anticoagulants because it can increase the level of bleeding.

Be careful when used with glycoprotein inhibitors of ILB/LLA group, selective inhibitors to recover serotonin.

Aspirin does not change the ability to inhibit platelet training via adp of clopidogrel, but clopidogrel increases Aspirin's efficiency on platelet aggregation through collagen. However, the combination of 500 mg of aspirin 2 times a day with clopidogrel once a day has not increased the meaning of bleeding time.

Using heparin, although there may be pharmacological interaction, increases blood flow time, but in a clinical study, it does not need to adjust the heparin and heparin dose nor does it affect the platelogram's plateloon condensation.

Safety when using clopidogrel, fibrin or non -fibrin and heparin non -fertilizers are evaluated in patients with acute myocardial infarction. The clinical significant bleeding rate is equivalent to thrombolytic and heparin drugs used in combination with aspirin.

With Naproxen nonsteroidal anti -inflammatory, when used with clopidogrel, it causes an increase in hidden stomach bleeding. As for other non -steroid anti -inflammatory drugs, there is no research, so it is necessary to be careful when using it.

There is no clinical interaction with pharmacological significance when used in combination with Atenolol or Nifedipin.

Clopidogrel is not much affected by phenobarbital, estrogen, stomach antacids.

Digoxin, Theophyllin is not affected by pharmacokinetics when combined with clopidogrel.

Research data shows that Phenytoin and Tolbutamid can be combined safely with clopidogrel.

Studies show that diuretics, beta inhibitors, enzyme inhibitors, calcium inhibitors, cholesterol -reducing drugs, coronary expansion drugs, anti -diabetic drugs (excluding insulin) anti -epileptic drugs, GPILB/LLA antagonists do not cause drug interaction.

Proton pump inhibitors:

Use omeprazol 80 mg, 1 time daily use at the same time or use 12 hours with clopidogrel reduces exposure to metabolites with 45% activity (loaded dose) and 40% (maintenance dose). This decrease is associated with reducing the inhibitory effect of plateletic dosage 39% (loaded dose) and 21% (maintenance dose). Esomeprazol is also said to have the same interaction with Clopidogrel.

The inconsistent data on clinical influences of pharmacokinetic/pharmacokinetic interaction on the main cardiovascular events has been reported from both observation and clinical studies. For caution reasons, use at the same time as omeprazol or esomeprazol is not recommended.

For Pantoprazol or Lansoprazol, the exposure rate with less metabolites is also noticeably observed.

Use pantoprazol 80 mg, 1 time daily. The plasma concentration of metabolites has a 20% decrease in activity (loaded dose) and a 14% decrease (maintenance dose) during treatment at the same time. This is related to the average reduction in platelet aggregation inhibitors of 15% and 11%, respectively. These results show that Clopidogrel can be used with Pantoprazol.

There is no evidence that other gastric acid -reducing drugs such as H2 or antacids inhibit the platelograph inhibitors of Clopidogrel.