Univixin Clopidogrel 75mg Korea United reduces events caused by atherosclerosis (3 blisters x 10 tablets)

Clopidogrel is a thienopyridin derivative structure and pharmacological effect similar to ticlopidin, which is a platelet aggregation inhibitor. Clopidogrel is a precursor (Prodrug) with the effect of inhibiting platelets depending on the metabolism in the liver into active thiol metabolites.

Biological metabolism occurs through 2 steps: Clopidogrel is initially oxidized into intermediate metabolites, 2-oxo-clopidogrel, then converted into active thiol metabolites. The metabolic path associated with some isenzyme cytochrom P450 (such as CYP3A4, CYP2C19, CYP1A2, CYP2B6).

Clopidogrel is an adenosin diphosphate receptor inhibitor (ADP Receptor), clopidogrel's active metabolites selectively and not competing with low affinity to the P2Y12 position of ADP receptor on platelet surface, thus inhibiting ADP attachment to receptors and leading to Glycoprotein GPIIB/III -III complex inhibitors It is necessary to attach platelet fibrinogen to inhibit platelet aggregation. Clopidogrel also inhibits concentrated seed release (containing ADP, calcium and serotonin) platelets through ADP intermediaries and Alfa beads (containing fibrinogen and thrombospondin), which contain substances that enhance platelet aggregation. Platases are in contact with Clopidogrel to maintain the end of the life of platelets (7 - 10 days). Unlike Aspirin, clopidogrel and ticlopidin inhibit the inactivated platelet training cyclooxygenase to prevent the synthesis of prostaglandin and thromboxan A. When taking daily dose clopidogrel 75 mg, the inhibitory effect of plateletal training appears on the first day of treatment and reaches 40-60% inhibition at a stable level of about 3-7 days. After stopping the drug, the stopping of platelets and the bleeding time return to the original level within 5 days.

Dynamic pharmacokinetics

Clopidogrel absorbed quickly and incomplete oral, absorbing at least 50%. When taking the dose of 75 mg clopidogrel, the clopidogrel concentration in plasma at 2 hours after taken very low, usually under the quantitative limit (0.00025 mg/liter). The highest concentration of the main metabolites in the plasma of clopidogrel (conductor of carboxylic acid is not active for platelet aggregation) is 3 mg/liter at 1 hour after drinking.

Clopidogrel is a precursor and is metabolized through the liver, mostly into carboxylic acid derivatives that are inactive metabolites. Metabolized by liver by isenzyme cytochrom P450 including CYP3A4, CYP2C19, CYP1A2, CYP2B6. The active metabolite is a thiol derivative, but it is very unstable if separated from the plasma. Clopidogrel and main metabolites associated with high -ratio plasma proteins (98% and 94%).

Clopidogrel and metabolites are eliminated through urine and feces. About 50% of oral doses are eliminated through urine and 46% excreted in feces. Half of the excretion of the metabolites is 8 hours after taking the single dose and the dose is repeated.

The pharmacokinetics research of the main metabolites shows that Clopidogrel's bioavailability is not affected by food.

The immune system disorders: The cross -sectional reaction between the thienopyridin (such as ticlopidin, prasugrel).

Notice the doctor unwanted effects when using the drug.

Be cautious when using

need to be very careful when taking the drug for patients in the following cases:

Blood and hematological disorders

Due to the risk of bleeding and unwanted effects on hematology, the determination of blood formula and/or other appropriate tests should be conducted immediately if clinical symptoms suggest increased hemorrhage during treatment. Like other anti-platelets, Clopidogrel should be used cautiously in patients at risk of increased bleeding due to trauma, surgery or other diseases and in patients treated with acetylsalicylic acid (ASA), heparin, Glycoprotein IIB/IIIA or non-steroid anti-inflammatory drugs including COX-2 inhibitors, reconcilitation drugs with Serotonin inhibits Selection (SSRIs) or other drugs related to the risk of bleeding like pentoxifylin. Patients should be carefully monitored any signs of bleeding including hidden bleeding, especially in the first weeks of treatment and/or after performing heart -invasive procedures or surgery. Clopidogrel should not be used simultaneously with oral anticoagulant drugs because it can enhance bleeding.

If the patient has to undergo surgery and temporarily does not need anti -platelet aggregation effect, Clopidogrel should stop using Clopidogrel 7 days before surgery. Patients should notify the doctor and dentist if they are taking clopidogrel before any surgery is planned and before using any new medicine. Clopidogrel prolongs bleeding time and should be cautious when used in patients with wounds that tend to bleed (especially in the stomach and internal eye).

Patients should be known that it may take more time than usual to stop bleeding when using clopidogrel (alone or in combination with ASA) and should notify any abnormal bleeding (location or time) to the doctor.

Object of thrombocytopenia (TTP)

Hemorrhage hemorrhage (TTP) has been recorded but very rare after using Clopidogrel, sometimes only after a short time of medication. This phenomenon is manifested by thrombocytopenia and microchemical anemia accompanied by or nervous manifestations, kidney dysfunction or fever. The thrombocytopenic hemorrhage is a fatal condition that requires timely treatment including plasma separation methods.

Bloody disorders are suffering from

Bloody disorders have been recorded when using clopidogrel. The coagulation disorder should be considered in cases where the extension of thromboplastin is partially active (APTT) attached or not accompanied by bleeding. Patients who have been diagnosed with coagulopathy disorders must be controlled and treated by experienced doctors and should stop using clopidogrel.

Excavading ischemic stroke

Due to lack of data, recommendations should not be used Clopidogrel in the first 7 days after the stroke due to acute ischemia.

Cytochrome P4502C19 (CYP2C19)

Pharmacokinetics: In patients with CYP2C19 enzyme deficiency, Clopidogrel with the recommended dose to produce less active metabolites of clopidogrel and are less effective on platelet function. Testing should be tested to determine CYP2C19 in each patient.

Because Clopidogrel is partially metabolized into an active metabolite by CYP2C19, the use of enzyme inhibitors will reduce the concentration of metabolic metabolites of clopidogrel. The clinical involvement of this interaction is not sure. Therefore, it should not be used simultaneously with strong or medium CYP2C19 inhibitors.

CYP2C8 substrate

Be cautious when using clopidogrel with drugs metabolized by CYP2C8.

Cross reactions between thienopyridin

Patients need to be assessed for hypersensitivity to Thienopyridin (such as clopidogrel, ticlopidin, prasugrel) for noting the cross -allergic reactions between Thienopyridin. Thienopyricin can cause mild to severe allergic reactions such as rash, angioedema, or cross -blood reactions such as thrombocytopenia and neutropenia. Patients who have had previously allergic and/or hematological reactions to a Thienopyridin may increase the risk of similar reactions or other reactions with another Thienopyricin. It is recommended to monitor the hypersensitivity signs in patients who already know allergies to the thienopyrin.

kidney failure

Experience is limited in patients with renal failure. Therefore should be cautious when using clopidogrel in these patients.

Hepatic failure

Experience is limited in patients with average liver failure, which is both a risk of organs bleeding. Therefore should be cautious when using clopidogrel in these patients.

The effect of the drug on driving and operating machinery

Clopidogrel does not affect or negligible on the ability to drive and operate machinery.

Using drugs for women during pregnancy and lactation

Using drugs for pregnant women:

Studies on reproduction are conducted on rats and rabbits with a dose of up to 500 and 300 mg/kg/day (65 and 78 times the recommended daily dose for adults by mg/m2 of body skin area), not detect evidence of fertility decreased or pregnancy poisoning due to clopidogrel. However, there are no complete and strictly controlled studies in pregnant women. Because animal reproduction studies are often not forecast to be met in humans, Clopidogrel is only used for pregnant women when they are really necessary.

Use medicine for breastfeeding women:

Rats studies show Clopidogrel and/or its metabolites are excreted into mother mouse milk. It is not known whether Clopidogrel will excrete on the mother's milk. Because many drugs are excreted in breast milk and because of the ability to cause serious harmful reactions for breastfeeding, need to decide or stop breastfeeding or stop taking the drug, taking into account the importance of the drug for the mother.

Interactive drug

drugs at risk of bleeding: Increasing the risk of bleeding due to the effect of synergies may occur. Caution should be careful when used simultaneously drugs at risk of bleeding.

Oral anticoagulant: should not be used simultaneously clopidogrel with oral anticoagulants because it can increase blood flow. Although Clopidogrel is a dose of 75 mg/day does not change the pharmacokinetics of s-warfarin or the Inr (International Normaleded Ratio) in patients with long-term treatment with warfarin, the use of clopidogrel with warfarin increases the risk of bleeding due to independent impact on hemostasis. Glycoprotein IIB/IIIA inhibitors: Clopidogrel should be used carefully in patients using Glycoprotein IIB/IIIA inhibitors.

Acetylsalicylic acid (ASA): ASA does not change the ability to inhibit platelet gathering due to the ADP of Clopidogrel. However, simultaneously used with 500 mg ASA 2 times/ day for 1 day does not significantly increase the extension of the bleeding time caused by clopidogrel. Pharmacological interaction between clopidogrel and acetylsalisylic acid may occur and increase the risk of bleeding. Therefore, it is necessary to be cautious when used in combination. However, coordination of clopidogrel and ASA has been designated to use simultaneously for up to 1 year.

Heparin: In a clinical study conducted in healthy people, the use in combination with clopidogrel shows no need to change heparin's doses or change the effects of heparin on blood clotting. Simultaneous use with heparin does not affect the inhibition of platelet gathering due to clopidogrel. Pharmacological interaction between clopidogrel and heparin may occur and increase the risk of bleeding. Therefore, it is necessary to be cautious when used in combination.

Blood solubility: Safety when using clopidogrel, specific or non -specific fibrin and heparin drugs that have been evaluated in patients with acute myocardial infarction. The clinical bleeding rate is similar to when the medications of thrombosis and heparin are used simultaneously with ASA.

Non -steroid anti -inflammatory drugs (NSAID): In a clinical study conducted in healthy people, the use of clopidogrel with naproxen increases hidden stomach loss. However, due to the lack of interactive studies with other NSAIDs, it is unclear whether this combination will increase the risk of stomach bleeding in all NSAIDs. Therefore should be careful when used in combination with clopidogrel with NSAIDs including COX-2 inhibitors.

Selective Serotonin Rehabilitation Inhibitors (SSRIs): Because SSRIs affect platelet activation and increase the risk of bleeding, should be cautious when using SSRIs with clopidogrel.

Other simultaneous treatment: Clopidogrel is partially metabolized into active metabolites by CYP2C19, so the use of active inhibitors of this enzyme will reduce the concentration of metabolic substances that are active of clopidogrel. The clinical involvement of this interaction is not sure. Therefore, it should not be used simultaneously with strong or medium CYP2C19 inhibitors.

Strong or medium CYP2C19 inhibitors, such as omeprazol and Esomeprazol, Fluvoxamin, Fluoxetin, Moclobemid, Voriconazole, Fluconazol, Ticlopidine, Carbamazepin and Efavirenz.

Proton pump inhibitors (PPI): Omeprazol 80 mg once daily or at the same time with clopidogrel or 12 hours between the use of two drugs that reduce the concentration of metabolites 45% (loaded dose) and 40% (maintenance dose). This decrease is associated with a 39% reduction (loaded dose) and 21% (maintenance dose) of platelet aggregation inhibitors. Esomeprazol is said to have the same interaction with Clopidogrel.

According to studies both observed and clinically, the data has not agreed on the clinical effects of pharmacokinetic/pharmacokinetic interactions for the main effects on the heart. Therefore should not be used simultaneously with omeprazol or esomeprazol.

The significant reduction of metabolic concentration has been recorded with Pantoprazol or Lansoprazol. The concentration of plasma of metabolites has a 20% decrease in (loaded dose) and a decrease of 14% (maintenance dose) during the treatment period along with pantoprazol 80 mg x 1 time/day. This is related to the reduction of the average platelet aggregation inhibitor, respectively, 15% and 11% respectively. This result shows that Clopidogrel can be used with Pantoprazol.

There is no evidence that other drugs reduce stomach acid such as drugs that prevent lowering receptors or antacids related to clopidogrel's anti -dumping effect.

Other drugs: A number of other clinical studies have been conducted with clopidogrel and other medications used to survey pharmacokinetical and pharmacokinetic interaction capabilities. There is no clinical pharmacological interaction when clopidogrel is used simultaneously with Atenolol, Nifedipin, or both Atenolol and Nifedipine. Moreover, Clopidogrel's pharmacological activity is not significantly affected when used simultaneously with phenobarbital, cimetidine or estrogen.

Digor pharmacokinetics of Digoxin or Theophyllin is not changed when used in combination with clopidogrel. The antacids do not change the absorption level of clopidogrel.

Data from Caprie studies shows that Phenytoin and Tolbutamid are metabolized by CYP2C9 that can be used safely with Clopidogrel.

Metabolic drugs by CYP2C8: Clopidogrel increases the level of repaglinid in healthy volunteers. In vitro studies show that increased repaglinid concentration is due to clopidogrel's glucuronid metabolism inhibits CYP2C8. Due to the risk of increased plasma concentrations, it is careful to simultaneously use clopidogrel with drugs metabolized mainly by CYP2C8 (eg repaglinid, paclitaxel).