抗HIV药Prezista会引发肝炎

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New HIV Drug Linked to Risk for Hepatitis
March 13, 2008 — Use of ritonavir-boosted darunavir (Prezista, Tibotec Therapeutics) has been linked to cases of hepatitis in clinical trials and postmarketing experience, the US Food and Drug Administration (FDA) warned healthcare professionals yesterday.
2008年3月13日，昨天美国食品药品管理局警告医疗保健医生，通过临床试验和上市后经验表明，darunavir（(Prezista，Tibotec治疗部）可能和诱发肝炎有关
According to the revised labeling, drug-induced hepatitis (eg, acute hepatitis and cytolytic hepatitis) was reported in 0.5% of patients receiving darunavir/ritonavir during clinical trials. Patients with preexisting liver dysfunction, including active hepatitis B or C, are at increased risk for liver function abnormalities and severe hepatic adverse events.
根据修改后的标签，在临床试验中，有0.5％的接受darunavir/ritonavir治疗的病人报告发现药物诱发的肝炎（例如急性肝炎和溶细胞性肝炎）。对于已有肝功能损害包括乙型或丙型肝炎的病人，产生肝功能异常和严重的不可逆肝脏损害事件的风险更大。
Postmarketing cases of liver injury have generally occurred in patients with advanced HIV-1 infection taking multiple concomitant medications, having comorbidities such as hepatitis B or C coinfection, and/or developing immune reconstitution syndrome. The FDA notes that a causal role for darunavir/ritonavir has not been established.
上市后的肝脏损伤病例普遍发生于有先期HIV-1感染并服用多种联合药物的病人，并且都有合并症例如乙型或丙型肝炎，和/或出现免疫重建综合征。FDA也意识到darunavir/ritonavir是否是导致肝脏损伤的原因并未确定。
Appropriate laboratory testing should be conducted before initiating darunavir/ritonavir therapy, and patients should be monitored during treatment, according to an alert issued by MedWatch, the FDA's safety information and adverse event reporting program. More frequent monitoring of liver enzymes may be indicated for patients with underlying chronic hepatitis, cirrhosis, or baseline transaminase elevations.
病人在开始darunavir/ritonavir治疗前需要进行适当的实验室检测，在治疗过程中也需要被监控，根据药品监督网页FDA安全信息和有害事件报告系统发布的警告。对于那些有潜在慢性肝炎、肝硬化或基线转氨酶升高的患者，则需要更加频繁的检测其肝酶情况。
Interruption or discontinuation of therapy should be considered in patients with evidence of new or worsening liver dysfunction, as characterized by clinically significant increases in liver enzyme and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, and hepatomegaly.
当有证据表明患者出现新的肝功能损害或损害加重，例如明显的肝酶升高和/或出现疲劳、厌食、恶心、黄疸、尿颜色加深及肝脏肿大等症状，则需暂停或停止治疗
Darunavir is indicated for the treatment of HIV infection in antiretroviral treatment–experienced patients, such as those with HIV-1 strains resistant to more than 1 protease inhibitor. The drug's efficacy has not been determined in pediatric or treatment-naive patients.
Darunavir被推荐给那些曾经接受过抗逆转录病毒治疗的HIV感染患者，例如那些对HIV-1蛋白酶抑制剂耐药的HIV-1感染者。但是它的效用在儿科患者或初次接受治疗的患者中并未得到证实。
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FDA官方警告

http://www.fda.gov/cder/drug/InfoSheets/HCP/darunavirHCP.htm

Information for Healthcare Professionals
Darunavir Ethalolate (marketed as Prezista)
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FDA ALERT [3/21/2008]: FDA is highlighting the addition of information about hepatotoxicity to the WARNINGS section of the Prezista prescribing information.

FDA and Tibotec Therapeutics have reviewed information from clinical trials in which Prezista was administered and from postmarketing adverse event reports of hepatotoxicity in patients taking Prezista. While causality is not firmly established, an association between Prezista and hepatotoxicity is suspected.

Prezista, a protease inhibitor indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment-experienced adult patients, is co-administered with ritonavir, an antiretroviral drug associated with hepatotoxicity. In general, HIV antiretroviral medications are associated with liver enzyme elevations, however, for some medications, an association with hepatotoxicity is more firmly established.

Healthcare providers should conduct appropriate hepatic laboratory testing prior to and after starting patients on Prezista. Patients should promptly seek medical attention if they experience unexplained fatigue, anorexia, nausea, jaundice, abdominal pain or dark urine. Healthcare professionals should consider interrupting or discontinuing Prezista if evidence of new or worsening liver injury arises.
近日，美国食品药品管理局（FDA）和强生公司联合发布警告说，抗艾药Prezista可损害患者肝脏，甚至导致死亡。

强生Tibotec疗法部在FDA网站上表示，自2006年6月Prezista (darunavir)获批上市后，公司陆续收到肝损伤和死亡报告。参加临床试验的3063名患者中，有15名出现药物性肝炎。

然而，Tibotec还说明，发生肝损伤的患者大都是同时接受其它药物治疗的艾滋病晚期患者，以及慢性活动性乙型或丙型肝炎患者。慢性活动性乙型或丙型肝炎可加大肝损伤发生几率。Prezista是和雅培的Norvir (ritonavir)结合使用的，因此上述损伤和Prezista之间的因果关联并不能建立。

Tibotec称，医生在建议患者服用Prezista前需做测试，并不断监测患者肝酶水平。

摘自：http://www.chnmed.com/html/2008/0314/10373.html