Kao Louise W, Kirk Mark A, Evers Stephanee J, Rosenfeld Stephen H
Division of Medical Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA.
Ann Emerg Med. 2003 Apr;41(4):546-58. doi: 10.1067/mem.2003.110.
Droperidol is a butyrophenone commonly used as an antiemetic and antipsychotic in the United States since US Food and Drug Administration (FDA) approval in 1970. Its labeling has recently been revised, with a black box warning for cases of QT prolongation leading to torsades de pointes and death. A black box warning is applied when serious adverse drug reactions are uncovered for medications. We sought to examine the evidence of a causal association suggested by the black box warning to aid clinicians in their risk-benefit analyses regarding further use of droperidol.
A literature search was undertaken to determine the evidence regarding the association between droperidol and QT prolongation or torsades de pointes. The evidence was then evaluated by using evidence-based medicine principles. In addition, a review of the FDA regulatory process is presented.
Three clinical studies, 1 published abstract, and 7 case reports were reviewed. Available postmarketing surveillance data (MedWatch reports) were also reviewed. Applying the criteria of evidence-based medicine and Hill's criteria, the evidence is not convincing for a causal relationship between therapeutic droperidol administration and life-threatening cardiac events.
The recent black box warning appears to have originated from postmarketing surveillance data rather than data reported in the peer-reviewed medical literature. Ongoing monitoring of drug safety and more definitive study appear appropriate.
氟哌利多是一种丁酰苯类药物，自1970年获得美国食品药品监督管理局（FDA）批准以来，在美国常用作止吐药和抗精神病药。其标签最近已修订，有黑框警告提示其可导致QT间期延长，进而引发尖端扭转型室速和死亡。当发现药物存在严重不良反应时会应用黑框警告。我们试图审查黑框警告所提示的因果关联证据，以帮助临床医生在对氟哌利多的进一步使用进行风险效益分析时提供参考。
进行文献检索以确定有关氟哌利多与QT间期延长或尖端扭转型室速之间关联的证据。然后运用循证医学原则对证据进行评估。此外，还介绍了FDA的监管过程。
审查了三项临床研究、一篇发表的摘要和七篇病例报告。还审查了上市后监测数据（MedWatch报告）。应用循证医学标准和希尔标准，治疗剂量的氟哌利多给药与危及生命的心脏事件之间存在因果关系的证据并不令人信服。
最近的黑框警告似乎源于上市后监测数据，而非同行评审医学文献中报告的数据。持续监测药物安全性并开展更具确定性的研究似乎是合适的。
