Droperidol, QT prolongation, and sudden death: what is the evidence?
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kao
Louise W
LW
Division of Medical Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA. Lkao@clarian.org
Kirk
Mark A
MA
Evers
Stephanee J
SJ
Rosenfeld
Stephen H
SH
D016907:Adverse Drug Reaction Reporting Systems; D000932:Antiemetics / Q000009:adverse effects*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D015984:Causality; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology*; D004329:Droperidol / Q000009:adverse effects*; D017277:Drug Approval / Q000458:organization & administration; D004348:Drug Labeling; D016903:Drug Monitoring; D004562:Electrocardiography; D019317:Evidence-Based Medicine; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D011358:Product Surveillance, Postmarketing; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D012449:Safety; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
D000932:Antiemetics; D014150:Antipsychotic Agents; D004329:Droperidol