作者：Kate Johnson
出處：WebMD醫學新聞
May 13, 2010 — 美國食品藥物管理局（FDA）最近宣布，Eltrombopag（Promacta，葛蘭素史克藥廠）被證實與慢性肝臟疾病且血小板低下患者肝門靜脈高壓風險增加有關，該公司已經中止評估這個藥物使用於該族群的研究。
根據FDA安全性資訊與不良反應通報系統MedWatch日前發出的警訊，在ELEVATE研究中，這是一項隨機分派、雙盲、安慰劑控制多中心研究，6位病患（4%）接受eltrombopag，1位（1%）病患接受安慰劑發生肝門靜脈系統的栓塞事件。
FDA提醒健康照護專業人員，eltrombopag，一種血小板生成素受體致效劑，適用於治療罹患慢性免疫性（先天性）血小板低下紫斑症（ITP）成人患者的血小板低下，並未核准用於治療慢性肝臟疾病患者的血小板低下。
FDA指出，當臨床醫師向肝臟疾病患者投予這個藥物時，應該特別提高警覺。給藥劑量從25 mg每天一次開始，臨床醫師們應嚴密追蹤病患，特別是那些中重度疾病患者。
對有已知發生栓塞風險的患者投予eltrombopag應格外小心。
FDA表示，以Promacta治療的目標應針對增加血小板數目至一個降低出血風險的標準。Promacta不應該用於矯正病患血小板數目。
【ELEVATE研究】
這項警訊是在葛蘭素史克藥廠於5月4日給健康照護人員們的一封信之後發佈，在該公司決定中止ELEVATE研究之後。
ELEVATE研究被設計來檢驗eltrombopag用於降低血小板低下患者接受選擇性侵入措施的輸注血小板需求。
罹患輕度、中度與嚴重肝功能障礙且病因不同的患者，接受75 mg的eltrombopag或安慰劑，在接受侵入性措施前14天投予。
6位接受eltrombopag後發生栓塞的患者，5位病患在血小板數目高於200,000/μL以上時發生這些併發症。
這些發現於上個月發表在歐洲肝臟研究協會第45屆年會上。該公司已經將結果與試驗研究者們聯繫，並與有關當局合作將這潛在不良反應加入藥品仿單中。
更多資訊請洽FDA的MedWatch網站。
任何與diclofenac相關不良反應都應該通報到FDA的MedWatch通報系統，以電話1-800-FDA-1088或傳真至1-800-FDA-0178，線上通報
http://www.fda.gov/medwatch或郵寄到5600 Fishers Lane, Rockville, Maryland 20852-9787。
Promacta Study Halted Due to Increased Risk for Portal Venous Thrombosis in Patients With Liver Disease
By Kate Johnson
Medscape Medical News
May 13, 2010 — Eltrombopag (Promacta; GlaxoSmithKline) has been linked to an increased risk for portal venous thrombosis in patients with thrombocytopenia due to chronic liver disease, and the company has halted a study evaluating the drug in this population, the US Food and Drug Administration (FDA) recently announced.
In ELEVATE, a randomized, double-blind, placebo-controlled, multinational study, 6 patients (4%) receiving eltrombopag and 1 patient (1%) receiving placebo "experienced a thrombotic event of the portal venous system," according to an alert sent yesterday from MedWatch, the FDA's safety information and adverse event reporting program.
The FDA reminds healthcare professionals that eltrombopag, a thrombopoietin receptor agonist, "is indicated for the treatment of thrombocytopenia in adult patients with chronic immune (idiopathic) thrombocytopenia purpura (ITP) and is not indicated for the treatment of thrombocytopenia in patients with chronic liver disease."
Clinicians should exercise caution when administering the drug to patients with hepatic disease, the FDA says. Dosing should start at 25 mg once daily, and clinicians should monitor patients closely, particularly those with moderate to severe disease.
The FDA noted that additional caution should be taken when administering eltrombopag to patients with known risk factors for thromboembolism.
"Treatment with Promacta should be aimed at increasing the platelet count to a level that reduces the risk of bleeding; Promacta should not be used in an attempt to normalize the platelet count," the FDA says.
The ELEVATE Study
The alert was preceded by a letter to healthcare professionals from GlaxoSmithKline on May 4, after the company's decision to terminate the ELEVATE study.
ELEVATE was designed to examine the safety and efficacy of eltrombopag in reducing the need for platelet transfusion in thrombocytopenic patients undergoing elective invasive procedures.
Patients with mild, moderate, and severe hepatic impairment of diverse etiology received 75 mg of eltrombopag, or placebo, for 14 days before their procedure.
Of the 6 thrombosis patients who had received eltrombopag, 5 patients experienced the complication at platelet counts above 200,000/μL.
The finding was presented last month at the European Association for the Study of the Liver 45th Annual Meeting. The company has communicated the finding to the trial's investigators and is working with regulatory agencies to include this potential adverse effect in the drug's label.
More information is available on the FDA's MedWatch Web site.
Adverse events related to eltrombopag should be communicated to MedWatch by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at
http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.
