Clopidogrel Bisulfate Tablets

Pharmacodynamic properties Drug therapy classification: Platelet aggregation inhibitors, excluding heparin, ATC number; BO1AC-04 Clopidogrel is a prodrug, one of whose metabolites is a platelet aggregation inhibitor. Clopidogrel must be metabolized by the CPY450 enzyme to produce an active metabolite that inhibits platelet aggregation. The active metabolite of clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet P2Y12 receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Since the binding is irreversible, the remaining life span of platelets exposed to clopidogrel (approximately 7-10 days) is affected, and the rate of recovery of normal platelet function is consistent with the turnover of platelets. Platelet aggregation induced by agonists other than ADP can also be inhibited by blocking the platelet activation aggregation pathway induced by released ADP. Because active metabolites are formed by CYP450 enzymes, some of which are polymorphic or inhibited by other drugs, not all patients will achieve adequate platelet inhibition. Clopidogrel 75 mg, repeated once daily, significantly inhibits ADP-induced platelet aggregation from day one, with inhibition increasing gradually and reaching steady state in 3-7 days. At steady state, the average inhibition level is 40%-60% with daily clopidogrel 75 mg, and platelet aggregation and bleeding time generally return to baseline levels within 5 days after discontinuation of treatment. Toxicology Studies: In preclinical studies in rats and baboons, the most common reaction was liver changes. These liver changes were the result of the drug's effects on hepatic metabolizing enzymes, administered at doses 25 times the exposure obtained in humans with 75 mg/day of clopidogrel. Clopidogrel has no effect on hepatic metabolizing enzymes at therapeutic doses in humans. Rat and baboon administration of very high doses of clopidogrel has an effect on gastric tolerance (gastritis, gastric ulcers and/or vomiting). No evidence of carcinogenicity was found in mice given clopidogrel at doses up to 77 mg/kg per day for 78 weeks and rats given clopidogrel for 104 weeks. The blood concentration at this dose is 25 times greater than the recommended human dose (75 mg per day). A series of in vivo and in vitro tests have confirmed that clopidogrel has no genotoxic effects. Clopidogrel has no effect on the fertility of female and male rats, and is not teratogenic in rats or rabbits. Clopidogrel slightly delays the development of pups in lactating rats. Pharmacokinetic studies have shown that clopidogrel and/or its metabolites are excreted in breast milk. Therefore, direct (mild toxicity) or indirect (bad taste) effects of clopidogrel cannot be ruled out.

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

Plavix 75 mg film-coated tablets are pink, round, biconvex, film-coated, engraved with "75" on one side and "1171" on the other side.

Clopidogrel is used to prevent atherothrombotic events in the following patients: · Patients with recent myocardial infarction (from a few days to less than 35 days), recent ischemic stroke (from 7 days to less than 6 months) or patients with established peripheral arterial disease. · Patients with acute coronary syndrome - non-ST-segment elevation acute coronary syndrome (including unstable angina or non-Q-wave myocardial infarction), including patients with stent implantation after percutaneous coronary intervention, in combination with aspirin. - For patients with ST-segment elevation acute coronary syndrome, in combination with aspirin, it can be used in combination with thrombolytic therapy. For more information, see [Clinical Trials] View full text

· The recommended dose of Plavix for adults and the elderly is 75 mg once daily. For patients with acute coronary syndrome: - Patients with non-ST-segment elevation acute coronary syndrome (unstable angina or non-Q-wave myocardial infarction) should start with a single loading dose of clopidogrel 300 mg, then continue to take 75 mg once a day (combined with aspirin 75-325 mg/day). Because taking higher doses of aspirin has a higher risk of bleeding, the recommended dose of aspirin should not exceed 100 mg. The optimal course of treatment has not yet been formally determined. Clinical trial data support 12 months of medication, and the maximum effect is shown after 3 months of medication. (See [Clinical Trials]) - ST-segment elevation acute myocardial infarction: should start with a loading dose of clopidogrel, then 75 mg once a day, combined with aspirin, with or without thrombolytics. For patients over 75 years of age, do not use a clopidogrel loading dose. Combination therapy should be started as soon as possible after the onset of symptoms and should be used for at least 4 weeks. No studies have confirmed the benefit of combined use of clopidogrel and aspirin for more than 4 weeks (see [Clinical Trials]). · The recommended dose for patients with recent myocardial infarction (from a few days to less than 35 days), recent ischemic stroke (from 7 days to less than 6 months) or patients with established peripheral arterial disease is 75 mg per day. · If a dose is missed: - Within 12 hours of the regular medication time: the patient should immediately take a standard dose and take the next dose at the regular medication time; - More than 12 hours after the regular medication time, the patient should take the standard dose at the next regular medication time, without doubling the dose. · Children and minors: Safety and effectiveness in patients under 18 years of age have not been established. · Renal impairment: There is limited experience in the treatment of patients with renal impairment. (See [Precautions]) · Hepatic impairment: There is limited experience in the treatment of patients with moderate hepatic impairment with bleeding tendency. (See [Precautions]) · Dosage: Oral, with or without food.

The safety of clopidogrel has been evaluated in more than 42,000 patients, of whom 9000 were treated for at least 1 year. Clinically relevant adverse reactions observed in CAPRIE, CURE, CLARITY, and COMMIT are discussed below. In the CAPRIE study, clopidogrel 75 mg/day was better tolerated than aspirin 325 mg/day. In this study, the overall tolerability of clopidogrel was similar to that of aspirin and was not associated with age, sex, or race. In addition to clinical study experience, there are spontaneous reports of adverse reactions. Bleeding is the most common adverse reaction in clinical studies and post-marketing reports and is often reported in the first month of treatment. In the CAPRIE study, the overall incidence of bleeding events was 9.3% for patients treated with clopidogrel or aspirin. The incidence of serious events with clopidogrel was similar to that with aspirin. In the CURE study, patients who stopped clopidogrel for more than 5 days before surgery had fewer major bleeding episodes within 7 days after coronary artery bypass grafting. In patients who continued treatment within 5 days of bypass surgery, the event rates were 9.6% for clopidogrel-aspirin and 6.3% for placebo-aspirin. In CLARITY, clopidogrel plus aspirin resulted in an increase in overall bleeding compared with placebo plus aspirin. The incidence of major bleeding was similar in the two groups. This was consistent across subgroups divided by baseline characteristics, fibrinolytic type, or the presence or absence of heparin treatment. In COMMIT, the overall rates of non-intracranial major bleeding and intracranial bleeding were low and similar in the two groups. Clinical studies and spontaneous adverse reactions reported are shown in the table below. The incidence of adverse reactions is defined as: common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000). Within each organ group, adverse drug reactions are ranked in descending order of severity.

1. Allergic to the active substance or any component of this product. 2. Severe liver damage. 3. Active pathological bleeding, such as peptic ulcer or intracranial hemorrhage.

Precautions for children: There is no experience of use in children. Precautions for pregnancy and lactation: · During pregnancy, there is no clinical data on its use in pregnancy. For the sake of caution, it should be avoided for use in pregnant women. There is no direct or indirect evidence from animal experiments that this drug has harmful effects on pregnancy, embryo/fetal development, delivery or postnatal growth. (See [Pharmacology and Toxicology]) · Studies on rats during lactation have shown that clopidogrel and/or its metabolites are excreted in breast milk, but it is unclear whether this drug is excreted in human breast milk. For the sake of caution, breastfeeding should be stopped while taking Plavix. · Reproduction: Clopidogrel has not been found to alter reproductive function in animal experiments. View complete precautions for the elderly: See [Usage and Dosage].

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.

No special storage requirements.

75mg

36 months