美国食品药品管理局2011年7月20日批准血液稀释药Brilinta（替卡格雷）用于减少急性冠脉综合症(ACS)患者的心血管死亡或心脏病发作。
ACS包括因心脏回流血减少引发的系列症状，例如不稳定型心绞痛或心脏病发作。Brilinta通过阻止新血栓的形成发挥作用，以通过保持体内血液流动帮助降低其他心血管事件的风险。
Brilinta与阿司匹林联合用药进行了研究。在向专业医护人员及患者发布的黑框警告表明，阿司匹林日剂量高于100毫克会降低药物的有效性。
同时，黑框警告表明像其他血液稀释剂一样，Brilinta会增加出血概率且可能引起显著的、有时致命的出血。临床试验中服用Brilinta患者报告的最常见不良反应是出血和呼吸困难（喘证）。
Brilinta获准上市时附有帮助确保药品收益大于风险的风险评估与降低计划。作为计划的一部分，制造商必须向医生进行教育推广，说明联合使用高剂量阿司匹林带来的风险。
此外，Brilinta还将分发告知患者药品重要信息的用药指南。
Manufacturer:
AstraZeneca Pharmaceuticals
Pharmacological Class:
P2Y12 platelet inhibitor (cyclopentyltriazolopyrimidine).
Active Ingredient(s):
Ticagrelor 90mg; tablets.
Indication(s):
To reduce the rate of thrombotic cardiovascular (CV) events in patients with acute coronary syndrome (ACS) (unstable angina or non-ST-elevation myocardial infarction [MI] or ST-elevation MI).
Pharmacology:
Ticagrelor is a platelet activation and aggregation inhibitor mediated by the P2Y12 class of ADP receptors. Ticagrelor and its major metabolite reversibly interact with the platelet P2Y12 ADP-receptor to prevent signal transduction and platelet activation. Both ticagrelor and its active metabolite are approximately equipotent.
Clinical Trials:
In a randomized, double-blind study, the use of ticagrelor was compared to a regimen of clopidogrel, both given in combination with aspirin and other standard therapy in patients with acute coronary syndromes. Patients were treated for at least 6 months and for up to 12 months.
The primary endpoint was the composite of first occurrence of cardiovascular death, non-fatal MI (excluding silent MI), or non-fatal stroke. The components were assessed as secondary endpoints.
At study completion, ticagrelor has been shown to significantly reduce the rate of a combined endpoint of cardiovascular death, MI or stroke compared to clopidogrel (9.8% vs. 11.7%, respectively, hazard ratio [HR] 0.84). The difference between treatments on the composite resulted from effects on CV death (HR 0.79) and MI (HR 0.84); each was statistically significant when considered as a secondary endpoint and there was no difference on strokes. There was also a decrease in all-cause mortality.
Among 11,298 patients with PCI receiving any stent during this study, there was a lower risk of stent thrombosis (1.3% for adjudicated “definite”) than with clopidogrel (1.9%).
Legal Classification:
Rx
Adults:
Initiate loading dose: 180mg once, then continue with 90mg twice daily. After the initial loading dose of aspirin (usually 325mg), take ticagrelor with maintenance dose of aspirin 75–100mg daily. ACS patients: may start ticagrelor after receiving a loading dose of clopidogrel.
Children:
Not established.
Contraindication(s):
History of intracranial hemorrhage. Active pathological bleeding (eg, peptic ulcer, intracranial hemorrhage). Severe hepatic impairment.
Warnings/Precautions:
Do not start in patients planned to undergo urgent CABG. When possible, discontinue at least 5 days before any surgery. Suspect bleeding in hypotensive patients who have recently undergone coronary angiography, PCI, CABG, or other surgery. Older age, history of bleeding disorders, undergoing percutaneous invasive procedures, concomitant anticoagulants, fibrinolytics, higher doses of aspirin, and chronic NSAID use: increased risk of bleeding. Avoid interruption of treatment; if temporarily discontinued, restart as soon as possible. Premature discontinuation increases risk for CV events (eg, MI, stent thrombosis, death). Effectiveness reduced with aspirin maintenance dose >100mg; avoid. Moderate hepatic impairment. Pregnancy (Cat. C). Nursing mothers: not recommended.
Interaction(s):
Concomitant strong CYP3A inhibitors (eg, ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, telithromycin,) or potent CYP3A inducers (eg, rifampin, dexamethasone, phenytoin, carbamazepine, phenobarbital): not recommended. Potentiates simvastatin, lovastatin; avoid >40mg/day doses. Monitor digoxin during ticagrelor initiation and dose adjustments.
Adverse Reaction(s):
Bleeding (may be fatal), dyspnea, headache, cough, dizziness, GI upset, atrial fibrillation, hyper- or hypotension, back pain, fatigue, chest pain.
How Supplied:
Tabs—60, 180
Last Updated:
8/25/2011