Ticagrelor Tablets

Ticagrelor is a cyclopentatriazole pyrimidine (CPTP) class compound. Ticagrelor and its major metabolite reversibly interact with the platelet P2Y12 ADP receptor, blocking signaling and platelet activation. Ticagrelor and its active metabolite are comparable in activity. In a 6-week study, the inhibition of platelet aggregation (IPA) by ticagrelor and clopidogrel was compared, and the acute and chronic platelet inhibition effects of 20uMADP as a platelet aggregation agonist were investigated. The onset of IPA was evaluated on study day 1 after a loading dose of ticagrelor 180 mg or clopidogrel 600 mg. IPA was higher at all time points with ticagrelor. The maximum IPA effect of ticagrelor was reached at approximately 2 hours and lasted for at least 8 hours. After 6 weeks of dosing, the resolution of IPA was evaluated after dosing with ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily, also in response to 20uMADP. The mean maximum IPA after the last dose of ticagrelor was 88% and 62% for clopidogrel. After 24 hours, the IPA in the ticagrelor group (58%) was similar to the IPA in the clopidogrel group (52%), indicating that the IPA of patients who missed a dose of ticagrelor can maintain a trough IPA similar to that of patients treated with clopidogrel. After 5 days, the IPA in the ticagrelor group was similar to that in the placebo group. For either ticagrelor or clopidogrel, it is not known whether the risk of bleeding or thrombosis is related to IPA. Switching from clopidogrel to ticagrelor resulted in an absolute increase in IPA of 26.4%, while switching from ticagrelor to clopidogrel resulted in an absolute decrease in IPA of 24.5%. Patients can switch from clopidogrel to ticagrelor without interruption of antiplatelet effect (see Dosage and Administration).

Ticagrelor

The active ingredient of this product is ticagrelor, and its chemical name is: (1S,2S,3R,5S)-3-[7-{[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]amino}-5-(propylthiouracil)-3H-[1,2,3]-triazolphos[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethyl)cyclopentane-1,2-diol. Molecular formula: C23H28F2N6O4S, molecular weight: 522.57. Properties: This product is a yellow film-coated tablet, which appears white or off-white after removing the coating.

This product is used to reduce the incidence of thrombotic cardiovascular events in patients with acute coronary syndrome (unstable angina, non-ST-segment elevation myocardial infarction or ST-segment elevation myocardial infarction), including patients receiving drug therapy and percutaneous coronary intervention (PCI). Compared with clopidogrel, this product can reduce the incidence of the composite endpoint of cardiovascular death, myocardial infarction or stroke. The difference between the two treatment groups comes from cardiovascular death and myocardial infarction, but there is no difference in stroke. In patients with ACS, the combination of this product and aspirin has been studied. The results showed that a maintenance dose of aspirin greater than 100 mg would reduce the clinical efficacy of ticagrelor in reducing composite endpoint events. Therefore, the maintenance dose of aspirin should not exceed 100 mg per day.

Oral administration. This product can be taken before or after meals. The starting dose of this product is a single loading dose of 180 mg (90 mg × 2 tablets), followed by 1 tablet (90 mg) twice a day. Unless there are clear contraindications, this product should be used in combination with aspirin. After taking the first dose of loading aspirin, the maintenance dose of aspirin is 75-100 mg once a day. Patients with ACS who have received a loading dose of clopidogrel can start using ticagrelor. Avoid missing doses during treatment. If the patient misses a dose, take 1 tablet of 90 mg (the patient's next dose) at the scheduled next dose time. The treatment duration of this product can be up to 12 months unless there is a clinical indication to discontinue treatment with this product (see Pharmacology and Toxicology). There is currently limited experience with medication for more than 12 months. Premature discontinuation of any antiplatelet drug (including this product) in patients with acute coronary syndrome may increase the risk of cardiovascular death or myocardial infarction caused by the underlying disease, so premature discontinuation of treatment should be avoided.

The safety of ticagrelor in patients with acute coronary syndromes (unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI)) was evaluated in a large Phase 3 study (PLATO study), comparing patients treated with ticagrelor (starting dose of 180 mg, maintenance dose of 90 mg twice daily) with patients treated with clopidogrel (starting dose of 300-600 mg, maintenance dose of 75 mg once daily), both in combination with aspirin (ASA) and other standard therapies. The safety of ticagrelor tablets was evaluated in 10,000 patients, including more than 3,000 patients treated for more than 1 year. The most commonly reported adverse reactions in patients treated with ticagrelor were dyspnea, contusion, and epistaxis, and the incidence of these events was higher than that in patients treated with clopidogrel.

Patients who are allergic to ticagrelor or any of the excipients of this product. Patients with active pathological bleeding (such as peptic ulcer or intracranial hemorrhage). Patients with a history of intracranial hemorrhage. Patients with moderate to severe liver damage. Because combined use can lead to a significant increase in the exposure of ticagrelor, it is prohibited to use ticagrelor tablets in combination with strong CYP3A4 inhibitors (such as ketoconazole, clarithromycin, nefazodone, ritonavir and atazanavir).

Precautions for children: The safety and effectiveness of this product for children under 18 years of age have not been established. Precautions for pregnancy and lactation: Pregnancy: There are no controlled studies on the use of ticagrelor in pregnant women. Animal studies have shown that ticagrelor can cause fetal malformations when the mother receives approximately 5-7 times the maximum recommended human dose (MRHD, based on body surface area). Ticagrelor can be used during pregnancy only if the potential benefit outweighs the risk to the fetus. Lactation: It is still unknown whether ticagrelor or its active metabolites are secreted into human milk. Ticagrelor can be secreted through rat milk. Because many drugs can be secreted into human milk and ticagrelor has the potential for serious adverse reactions to breastfeeding infants, the decision to stop breastfeeding or discontinue the drug should be made after considering the importance of ticagrelor to the mother. Precautions for the elderly: No dose adjustment is required for elderly patients. See Dosage and Administration. In the PLATO study, 43% of patients were ≥65 years old and 15% of patients were ≥75 years old. The relative risk of bleeding was similar across treatment groups and age groups. There is no overall difference in safety or effectiveness between elderly and younger patients. However, clinical experience does not confirm that the difference in efficacy between elderly and younger patients is consistent, and the possibility that some elderly patients are more sensitive to drugs cannot be ruled out.

Ticagrelor is mainly metabolized by CYP3A4, and a small part is metabolized by CYP3A5. Effects of other drugs on ticagrelor CYP3A inhibitors: The combined use of ketoconazole can increase the Cmax and AUC of ticagrelor by 2.4 times and 7.3 times, respectively, and the Cmax and AUC of the active metabolite can be reduced by 89% and 56%, respectively; other strong inhibitors of CYP3A4 will also have similar effects. This product should be avoided in combination with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromycin, etc.) (see contraindications and pharmacokinetics). CYP3A inducers: The combined use of rifampicin can reduce the Cmax and AUC of ticagrelor by 73% and 86%, respectively, the Cmax of the active metabolite is unchanged, and the AUC is reduced by 46%. Other CYP3A4 inducers (such as dexamethasone, phenytoin, carbamazepine and phenobarbital) are also expected to reduce the exposure of ticagrelor. This product should be avoided in combination with strong CYP3A inducers. Aspirin: When used in combination with a maintenance dose of aspirin greater than 100 mg, the clinical efficacy of ticagrelor in reducing composite endpoint events will be reduced. Others: Clinical pharmacology interaction studies have shown that when ticagrelor is used in combination with heparin, enoxaparin and aspirin or desmopressin, there is no effect on the PK of ticagrelor or its active metabolites, ADP-induced platelet aggregation compared to ticagrelor alone.

Store below 30°C.

90mg*14 tablets

Valid for 24 months.

AstraZeneca Pharmaceutical Co., Ltd.

• Founded in:

  1993-10-26

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  No. 2 Huangshan Road, New District, Wuxi

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