Clopidogrel

Molecular weight: C16H16ClNO2S·H2SO4

Warfarin: Because it can increase the intensity of bleeding, the combination of clopidogrel and warfarin is not recommended. Glycoprotein IIb/IIIa antagonists: Use clopidogrel with caution in patients with trauma, surgery or other bleeding tendencies and who use glycoprotein IIb/IIIa antagonists. Acetylsalicylic acid (aspirin): Aspirin does not change the inhibitory effect of clopidogrel on ADP-induced platelet aggregation, but clopidogrel enhances the inhibitory effect of aspirin on collagen-induced platelet aggregation. There may be pharmacodynamic interactions between clopidogrel and aspirin, which increases the risk of bleeding, so care should be taken when the two drugs are used together. However, there have been patients who have used clopidogrel and aspirin together for more than one year. Heparin: Studies conducted in healthy volunteers have shown that clopidogrel does not change the effect of heparin on coagulation. Co-use of heparin

This product is a compound preparation, each tablet contains 75 mg of clopidogrel bisulfate (calculated as clopidogrel) and 100 mg of aspirin. Clopidogrel hydrogen sulfate Chemical name: S()-2-(2-chlorophenyl)-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl) methyl acetate sulfate Molecular formula: C16H16ClNO2S•H2SO4 Molecular weight: 419.90 Aspirin Chemical name: 2-(Acetoxy)benzoic acid Molecular formula: C9H8O4 Molecular weight: 180.16 Excipients: stearic acid, anhydrous silicic acid, microcrystalline cellulose, hydroxypropyl methylcellulose, polyethylene glycol, methacrylic acid copolymer, talc, triethyl citrate, anhydrous lactose, low-substituted hydroxypropyl cellulose, tocopherol, pregelatinized starch, hydrogenated castor oil, sucrose stearate, titanium dioxide, polydimethylsiloxane silica mixture, carnauba wax, ink.

Chemical name: Methyl ()-(S)-α-o-chlorophenyl-6,7-dichlorothiophene [3,2-C] piperidine-5 (4H)-ethyl acetate hydrogen sulfate Chemical structure: Molecular formula: C16H16ClNO2S·H2SO4 Molecular weight: 419.9

Oral anticoagulants: Because they can increase the intensity of bleeding, the combination of Plavix and oral anticoagulants is not recommended (see Precautions). Although taking 75 mg of clopidogrel daily does not change the pharmacokinetics or international normalized ratio of S-warfarin in patients receiving long-term warfarin therapy, the combined use of warfarin and clopidogrel increases the risk of bleeding due to their independent inhibition of the hemostatic process. Glycoprotein IIb/IIIa antagonists: Clopidogrel and glycoprotein Ib/IIIa antagonists should be used with caution. Acetylsalicylic acid (aspirin): Aspirin does not change the inhibitory effect of clopidogrel on ADP-induced platelet aggregation, but clopidogrel enhances the inhibitory effect of aspirin on collagen-induced platelet aggregation. However, the combined use of aspirin 500 mg, taken twice a day, for one day, does not significantly increase the prolonged bleeding time caused by clopidogrel. There may be a pharmacodynamic interaction between clopidogrel and aspirin, which increases the risk of bleeding, so care should be taken when the two drugs are used together (see Precautions). However, there have been cases where clopidogrel has been used in combination with aspirin for more than 1 year (see Pharmacological Properties). Heparin: Studies conducted in healthy volunteers have shown that clopidogrel does not change the effect of heparin on coagulation, and there is no need to change the dose of heparin. The co-administration of heparin does not affect the inhibitory effect of clopidogrel on platelet aggregation. There may be a pharmacodynamic interaction between clopidogrel and heparin, which increases the risk of bleeding, so care should be taken when the two drugs are used together (see Precautions). Thrombolytic drugs: The safety of the combined use of clopidogrel, rt-PA and heparin has been evaluated in patients with recent myocardial infarction. The incidence of clinical bleeding is similar to that of patients who use rt-PA, heparin and aspirin together. (See [Adverse Reactions]) Nonsteroidal anti-inflammatory drugs (NSAIDs): In clinical trials conducted in healthy volunteers, the combination of clopidogrel and naproxen increased gastrointestinal occult bleeding. Due to the lack of studies on the interaction between clopidogrel and other nonsteroidal anti-inflammatory drugs, it is not clear whether the combination of clopidogrel and all nonsteroidal anti-inflammatory drugs will increase the risk of gastrointestinal bleeding. Therefore, caution should be exercised when NSAIDs, including Cox-2 inhibitors, are used with clopidogrel (see Precautions). Other combined therapies: Since clopidogrel is partially metabolized to active metabolites by CYP2C19, the use of drugs that inhibit the activity of this enzyme will result in reduced levels of active metabolites of clopidogrel and reduced clinical effectiveness. Co-administration with drugs that inhibit CYP2C19 (such as omeprazole) is not recommended. (See [Precautions] and [Pharmacokinetics]). Drugs that inhibit CYP2C19 include omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, clopidogrel, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine, and chloramphenicol. Proton pump inhibitors (PPIs): Omeprazole 80 mg once daily, taken with clopidogrel or 12 hours apart, reduces the plasma concentration of clopidogrel's active metabolite by 45% (loading dose) and 40% (maintenance dose). This blood concentration can lead to a 39% (loading dose) and 21% (maintenance dose) reduction in platelet aggregation inhibition, respectively. Esomeprazole and clopidogrel may have similar interactions. There are inconsistencies in the results of observational and clinical studies regarding the effects of pharmacokinetic (PK)/pharmacodynamic (PD) interactions on clinical outcomes such as major cardiovascular events. The combined use of clopidogrel with omeprazole or esomeprazole is not recommended (see [Precautions]). No significant decrease in the blood concentration of clopidogrel metabolites was observed after the combination of pantoprazole, lansoprazole and clopidogrel. When pantoprazole 80 mg was used once daily, the plasma concentration of clopidogrel's active metabolites decreased by 20% (loading dose) and 14% (maintenance dose), respectively, and was accompanied by a decrease in the average platelet aggregation inhibition rate of 15% and 11%, respectively. These results suggest that clopidogrel can be co-administered with pantoprazole. There is no evidence that other drugs that inhibit gastric acid secretion, such as H2 blockers (excluding the CYP2C19 inhibitor cimetidine) or antacids interfere with the antiplatelet activity of clopidogrel. Other drugs: Through a large number of other clinical studies, the pharmacodynamic and pharmacokinetic interactions between clopidogrel and other co-administered drugs have been studied. No clinically significant pharmacodynamic interactions occurred when clopidogrel was used alone or simultaneously with atenolol and nifedipine. In addition, the co-administration of clopidogrel with phenobarbital, cimetidine, and estradiol had no significant effect on the pharmacodynamic activity of clopidogrel. Clopidogrel does not change the pharmacokinetics of digoxin or theophylline. Antacids do not change the absorption of clopidogrel. The CAPRIE study data show that phenytoin and tolbutamide can be safely used in combination with clopidogrel. In addition to the above clear drug interaction information, the interaction between clopidogrel and commonly used drugs in patients with atherothrombotic diseases has been studied. However, in clinical trials, patients received a variety of concomitant medications while taking clopidogrel, including diuretics, beta-blockers, ACEIs, calcium antagonists, lipid-lowering drugs, coronary vasodilators, antidiabetic drugs (including insulin), antiepileptic drugs, hormone replacement therapy, and GPIIb/IIIa receptor antagonists, and no clinically significant adverse interactions were found.