Noklot 75mg Zydus prevents atherosclerosis (3 blisters x 10 tablets)

In adult patients with atrial fibrillation, there is at least one risk factor for vascular events, not suitable for treatment with vitamin K (VKA) antagonists and those at risk of low bleeding, clopidogrel is indicated in combination with ASA to prevent thrombosis and blockage due to thrombosis, including stroke.

Pharmacokology

Pharmacological group: Platelet inhibitors, except Heparin.

ATC code: b01ac04.

Mechanism of action

Clopidogrel is a precursor, one of the metabolites of the drug is platelet assistant inhibitors. Clopidogrel must be metabolized by CYP450 enzymes to create metabolites with platelet aggregation inhibitors. Clopidogrel's active metabolites selectively inhibit the cohesion of adenosin diphosphate (ADP) and P2Y12 receptor of platelets and then activate Glycoprotein GPIIB/IIIA complex through ADP intermediaries, which inhibits platelet aggregation. Due to the irreversible cohesion, the exposed platelets affected to the rest of the life cycle (about 7-10 days) and the normal rehabilitation of platelets that occur at a speed in accordance with platelet production. The inhibition of platelets caused by other vehicles is not ADP is also inhibited due to platelet activation lock due to ADP release.

Due to the active metabolites formed by CYP450 enzymes, some of which are polymorphic or inhibited by other drugs, not all patients will have adequate platelet inhibition.

Pharmacological effects

The daily dose of 75 mg per day creates a significant inhibition of platelet collection due to ADP from the first day; This inhibition increases and reaches a stable state between day 3 and 7. In a stable state, the average inhibitory concentration is recorded at a dose of 75 mg daily between 40% and 60%. Platelet collection and bleeding time gradually returning to the basis, generally within 5 days after the treatment.

Dynamic pharmacokinetics

absorption

After the single doses and the dose of 75 mg per day, Clopidogrel is quickly absorbed. The average serum peak concentration of Clopidogrel is constant (about 2.2-2.5 ng/ml after a single dose of oral 75 mg) occurs about 45 minutes after use. The absorption is at least 50%, based on the elimination of urine of the metabolites of clopidogrel.

distribution

Clopidogrel and the main metabolite in the circulation (inactive) can be reversed with the In vitro plasma potein (98% and 94% respectively). The cohesion is not saturated on an in vitro wide range.

transformation

Clopidogrel is strongly metabolized by the liver. In vitro and in vivo, clopidogrel are metabolized based on two main metabolic paths: one through the esterase intermediaries and leads to hydrolyzed into carboxylic acid derivatives (85% of metabolic substances in the circulation), and a multi -cytochrom P450 intermediary. Clopidogrel is first converted into 2-oxo-clopidogrel conversion. The metabolism of the intermediate substance is then 2-oxo-clopidogrel, which creates the formation of active metabolites, a derivative of clopidogrel. The active metabolites are formed mainly by CYP2C19 with the contribution from many other CYP enzymes, including CYP1A2, CYP2B6 and CYP3A4. Active thiol metabolites have been isolated in vitro, fast and unable to reverse the platelet platelet receptor, thus inhibiting platelet aggregation.

CMAX of metabolites is active, twice as high as a single dose of 300 mg of clopidogrel compared to the maintenance dose of 75 mg after 4 days. CMAX is achieved after about 30 to 60 minutes of use.

Elimination

After a dose of Clopidogrel is marked 4C in the South, about 50% are eliminated in the urine and about 46% in the stool for 120 hours after taking the drug. After a single dose of 75 mg oral, Clopidogrel has a sale time of about 6 hours. The sale time of the main metabolites in the circulation (inactive) is 8 hours after a single dose and repeated use.

Be cautious when using

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

bleeding and blood disorders

Due to the risk of bleeding and unwanted effects on hematology, determining the number of blood cells and/or other appropriate tests, it should be considered in time when clinical symptoms suggest increased bleeding during treatment. Like other anti-platelet drugs, cautious use Clopidogrel in patients may be at risk of increased bleeding due to trauma, surgery or other diseases and in patients treated with ASA, Heparin, Glycoprotein IIB/IIIA inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors, or SSRRRO (SSRIS), SSRIS) Other drugs are related to the risk of bleeding like pentoxyfyllin. Patients should be carefully monitored on any signs of bleeding including closed bleeding, especially in the first weeks of treatment and/or after invasive heart surgery or surgery. Concomitant use of clopidogrel with oral anticoagulant drugs is not recommended because it can increase the severity of bleeding.

If the patient needs surgery and temporary platelet resistance is inappropriate, Clopidogrel should be stopped 7 days before surgery. Patients should notify the doctor or dentist that they are using clopidogrel before planning any surgery and before using any new drug. Clopidogrel prolongs bleeding time and should be used cautiously in damaged patients tending to bleed (especially in the stomach and intraocular eyes).

Patients should be notified that bleeding time may last longer than usual when using clopidogrel (single or combined with ASA), and should report any case of abnormal bleeding (location or time) to the doctor.

Object of thrombocytopenia (TTP)

Blood thrombocytopenia (TTP) has been reported very rare after using clopidogrel, sometimes after a short contact. Characterized by thrombocytopenia and hemolytic anemia, capillary disease associated with signs of neurological disorders, kidney dysfunction or fever. TTP is a fatal condition that needs to be treated promptly including plasma separation.

Difficult hematoma

Hard -free hematoma has been reported after using clopidogrel. In cases where the extension of thromboplastin has been exposed to the isolated or no bleeding part, the hemorrhage is difficult to be considered. Patients who have been diagnosed with difficulty clotting should be evaluated and treated by a specialist and should stop clopidogrel.

Recent ischemic stroke

From data is not enough, Clopidogrel should not be used in the first 7 days after a stroke due to acute anemia.

cytochrom P450 2C19 (CYP2C19)

Genetic pharmacy: In patients with poor metabolism CYP2C19, Clopidogrel at recommended doses to form a small and small activity metabolitus on platelet function. The tests are available to determine the type of CYP2C19 gene in patients.

Because Clopidogrel is converted into partly active substances by CYP2C19, the use of enzyme inhibitors inhibits this enzyme is thought to lead to a reduction in the concentration of clopidogrel metabolites. The clinical involvement of this interaction is uncertain. As a precaution, simultaneous use of strong or average inhibitors CYP2C19 is not recommended.

CYP2C8

Be cautious in patients treated simultaneously with clopidogrel and drugs are CYP2C8.

Cross -reactions in thienopyridin groups

Rings should be evaluated in a history of hypersensitivity to Thienopyridin (such as Clopidogrel, Ticlopidin, Prasugrel) due to a report on cross -reactions in the Thienopyridin group. Thienopyridine can cause severe to severe allergic reactions such as rash, angioedema or hematological reactions such as thrombocytopenia and leukopenia. The patient has appeared an allergic reaction and/or previous hematological reaction with a Thienopyricin that may increase the risk of developing similar reactions or a different reaction to other Thienopyricin. Recommendation to monitor signs of hypersensitivity reactions in patients who have known allergies to Thienopyrin.

kidney failure

Clopidogrel treatment experience is limited to patients with renal failure. Therefore Clopidogrel should be used cautiously in these patients.

liver failure

Experience is limited in medium patients with liver disease that may have organ bleeding. Clopidogrel should therefore be used carefully in this population group.

excipients

This drug contains lactose. Patients with rare genetic problems are galactose intolerance, lactase deficiency, or glucose-galactose, which should not be used.

The effect of the drug on driving and operating machinery

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

Using drugs for women during pregnancy and lactation

Using drugs for pregnant women

Due to the lack of clinical data available for Clopidogrel's exposure during pregnancy, as a preventive measure should not use clopidogrel during pregnancy.

Animal studies do not indicate directly or indirect effects during pregnancy, embryo/fetal development, reproduction or postpartum development.

Using medicine for breastfeeding women

fertility

Clopidogrel does not change fertility in animal studies.

Drug interaction

drugs associated with the risk of bleeding: There is an increase in the risk of bleeding due to potential side effects. Caution should be careful when using the drugs related to the risk of bleeding.

Oral anticoagulants: Concomitant use of clopidogrel with oral anticoagulants are not recommended because it can increase the severity of bleeding. Although the use of Clopidogrel 75 mg/day does not change the pharmacokinetics of s-warfarin or the international normalization rate (INR) in patients using warfarin for a long time, the simultaneous use of clopidogrel with warfarin increases the risk of bleeding due to independent effects on hemostasis. Glycoprotein IIB/IIIA inhibitors: Clopidogrel should be used cautiously in patients using simultaneously with Glycoprotein IIB/IIIA inhibitors.

Acetylsalicylic acid (ASA): Asa does not change the inhibition of clopidogrel of platelet collection caused by ADP, but clopidogrel increases the influence of Asa on plateletic collection caused by collagen. However, simultaneous use of 500 mg ASA 2 times/day for 1 day does not significantly increase the prolongation of bleeding time caused by clopidogrel. There is a possibility of pharmacological interaction between clopidogrel and acetylsalicylic acid, resulting in an increased risk of bleeding. Therefore, be careful when using simultaneously. However, Clopidogrel and ASA have been used together for up to 1 year.

Heparin: In a clinical study conducted in healthy objects, clopidogrel did not change the dose of heparin or change the effects of heparin on blood clotting. Simultaneous use of heparin does not affect the inhibition of heparin platelet gathering. A pharmacological interaction between clopidogrel and heparin is possible, resulting in an increased risk of bleeding. Therefore, be careful when using simultaneously.

Blood solubility drugs: Safety of simultaneous use of clopidogrel, specific thrombolytic drugs such as fibrin or non -fibrin and heparin have been evaluated in acute myocardial infarction patients. The clinical bleeding rate is similar to those that are accepted when thrombolytic and heparin drugs are used with ASA.

NSAIDs: In a study conducted in healthy volunteers, simultaneously used clopidogrel and Naproxen increases gastrointestinal blood loss. However, due to the lack of interactive studies with other NSAID drugs, the risk of gastrointestinal bleeding occurs with all NSAIDs. Therefore, NSAIDs include Cox-2 and Clopidogrel inhibitors should be used cautiously.

SSRIs: Because SSRIs affect platelet activation and increase the risk of bleeding, should be cautious when using SSRIs with Clopidogrel simultaneously.

Other combination regimens: Because Clopidogrel is converted into a partially active metabolic substance by CYP2C19, the use of active inhibitors of this enzyme is thought to lead to a reduction in the concentration of clopidogreled metabolites. The clinical involvement of this interaction is unknown. As a measure to prevent the use of strong or average inhibitors CYP2C19.

Strong or medium inhibitors CYP2C19 include such as omeprazol and ecomeprazol, fluvoxamin, fluoxetin, moclobemid, voriconazole, fluconazole, ticlopidine, carbamazepine and efavirenz.

Proton pump inhibitors (PPI): Omeprazol 80 mg once a day are used at the same time as clopidogrel or within 12 hours between 2 drugs that reduce the concentration of metabolites with 45% active (load dose) and 40% (maintenance dose). This decrease is associated with a reduction in platelet aggregation inhibition of 39% (load dose) and 21% (maintenance dose). Esomeprazol is said to have the same interaction with clopidogrel.

The uniform data on the clinical significance of pharmacological interactions (PK)/Pharmaceutical (PD) in terms of cardiovascular events have been reported from both records and clinical studies. As a preventive measure, it is not recommended to use simultaneously with omeprazol or esomeprazol.

Pantoprazol and Lanzoprazol less reduce the concentration of metabolites more active.

Plasma concentrations of metabolites have a 20% reduction (load dose) and 14% (maintenance dose) while treating simultaneously with pantoprazol 80 mg once a day. This involves reducing the inhibition of platelets on average about 15% and 11%, respectively. These results indicate that clopidogrel can be used with pantoprazol. There is no evidence that other drugs reduce stomach acid such as H2 resistance or antacids that affect the platelet activity of clopidogrel.

Other drugs: A number of other clinical studies are conducted with clopidogrel and other drugs used to assess the possibility of pharmacokinetic and pharmacokinetic interactions. There is no clinical significant pharmacological interaction that is recorded when clopidogrel is used simultaneously with Atenolol, Nifedipin or both Atenolol and Nifedipin. In addition, Clopidogrel's pharmacological activity is not significantly affected by simultaneous use of phenobarbital or estrogen.

Digodic pharmacokinetics of Digoxin or theophyllin are not changed by the simultaneous use of clopidogrel. Antacids do not change the level of clopidogrel absorption.

Data from Caprie research shows that Phenytoin and Tobutamid are metabolized by CYP2C9 that can be used simultaneously with Clopidogrel.

Medicines are CYP2C8: Clopidogrel has been shown to increase the contact of repaglinid in healthy volunteers. In vitro studies have shown that the increase in the exposure of repaglinid is due to the inhibition of CYP2C8 due to Clopidogrel's glucuronide metabolism. Due to the increased risk of plasma concentrations, simultaneous use of clopidogrel and drugs mainly eliminated by CYP2C8 metabolism (such as repaglinid, paclitaxel) should be done cautiously.

taboo

Due to the absence of studies on the correlation of the drug, not mixing this drug with other drugs.