FDA批准氯吡格雷仿制药

随着本月赛诺菲-安万特公司丧失对其重磅炸弹药物Plaxis(氯吡格雷)的专有权，美国食品药品管理局(FDA)5月17日宣布了对一些氯吡格雷非专利制剂的批准决定。

氯吡格雷为P2Y12血小板抑制剂，每天口服1次，获准用于治疗急性冠状动脉综合征及近期心肌梗死(MI)、近期卒中或明确患有外周动脉疾病的患者。此外，氯吡格雷还可减少新发缺血性卒中(致死性或非致死性)、新发MI(致死性或非致死性)和其他血管死亡的复合终点事件，这也是其获准的适应证之一。氯吡格雷的黑框警告包含以下内容：对于CYP2C19弱代谢者，如果在急性冠状动脉综合征或经皮冠状动脉介入术后使用推荐剂量治疗，氯吡格雷对血小板功能的影响较小，并且心血管事件发生率较高。FDA指出，氯吡格雷可与奥美拉唑和埃索美拉唑发生相互作用，后两者可降低氯吡格雷的抗血小板活性，因此服用氯吡格雷的患者应避免合用这些药物。

1997年FDA批准赛诺菲-安万特公司生产的Plaxis(氯吡格雷)上市。仅2010年，该药的销售额就达50亿美元。FDA此次批准的两种氯吡格雷仿制药分别为75 mg(1次/d)制剂和300 mg负荷剂量制剂。300 mg剂型的生产商为Dr. Reddy’s Laboratories、Gate Pharmaceuticals、Mylan Pharmaceuticals和Teva Pharmaceuticals，75 mg剂型的生产商为Mylan、Teva、Apotex Corporation、Aurobindo Pharma、Roxane Laboratories、Sun Pharma和Torrent Pharmaceuticals。

FDA药品评价研究中心制药学办公室副主任Keith Webber表示，本次批准的非专利产品将为慢性疾病患者提供经济有效的药物选择，具有重要意义。

Just as Sanofi-Aventis loses its exclusivity for its blockbuster drug Plavix (clopidogrel) this month, several generic formulations of the antiplatelet agent have been approved, the U.S. Food and Drug Administration announced on May 17.

Clopidogrel, a P2Y12 platelet inhibitor taken orally once a day, is approved for the treatment of acute coronary syndrome and for patients who have had a recent myocardial infarction, recent stroke, or established peripheral artery disease. The approved indication includes the statement that clopidogrel “has been shown to reduce the combined endpoint of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death.”

Clopidogrel was initially approved by the Food and Drug Administration in 1997, and has been marketed as Plavix by Sanofi-Aventis. The agent generated $5 billion in sales in 2010 alone.

In the FDA statement announcing the approval, Keith Webber, Ph.D., deputy director of the Office of Pharmaceutical Science in the FDA’s Center for Drug Evaluation and Research, referred to the importance of having effective and affordable medications available for people with chronic health conditions. “The generic products approved today will expand those options for patients,” he said.

Generic formulations of both the 75-mg daily dose and the 300-mg loading dose have been approved, according to the FDA.

The manufacturers of the approved 300-mg generic formulations are Dr. Reddy’s Laboratories, Gate Pharmaceuticals, Mylan Pharmaceuticals, and Teva Pharmaceuticals. The manufacturers of the approved 75-mg doses are Mylan, Teva, Apotex Corporation, Aurobindo Pharma, Roxane Laboratories, Sun Pharma, and Torrent Pharmaceuticals.

The clopidogrel prescribing information includes a boxed warning about the smaller effect of clopidogrel on platelet function in people who are poor metabolizers of CYP2C19, and the higher rate of cardiovascular events in this population, when treated with recommended doses after acute coronary syndrome or percutaneous coronary intervention.

The FDA statement also points out the interactions with omeprazole and esomeprazole, which reduce the antiplatelet activity of clopidogrel, and says that these drugs should be avoided in people taking clopidogrel.