FAQ
Haloperidol and cardiovascular concerns Recent News
On September 17, 2007, a warning about cardiovascular risks associated with haloperidol was announced by Johnson and Johnson and the U.S. Food and Drug Administration (FDA). Several case reports of patients receiving intravenous haloperidol at higher-than-recommended doses have documented QT prolongation, Torsades de Pointes (TdP), and even sudden death.
Haloperidol use
Haloperidol lactate injection, approved for intramuscular administration, is indicated for use in schizophrenia and for the control of tics and vocal utterances associated with Tourette’s Disorder. Haloperidol is commonly administered off-label as an intravenous injection for delirium, although it is not FDA-approved for this route of administration or indication. The Society of Critical Care Medicine and the American College of Critical Care Medicine consider haloperidol the drug of choice for the treatment of delirium in critically ill patients.
Delirium may occur in 10% to 30% of hospitalized patients, and symptoms may last more than 2 months. Antipsychotics are generally considered the drugs of choice for delirium, and haloperidol is considered first-line due to its relatively tolerable adverse effect profile and extensive clinical experience with its use. Intravascular administration is considered most effective for achieving sedation in emergency situations or when oral access is limited.
Cardiovascular concerns with haloperidol tend to be associated with its use in delirium due to intravascular administration and higher doses. The optimal dose for delirium has not been established, and a large range of doses have been used. Doses as low as 0.25 mg every 4 hours may be sufficient for geriatric patients with delirium; however, there are reports of adult patients who have required single intravenous doses up to 50 mg or total daily dosages of 500 mg.
Reports of cardiovascular risks
The mechanism by which haloperidol affects the cardiac conduction system is unclear; however, it has been shown to block the cardiac sodium and aortic calcium channels in animal studies. Numerous case reports in medical literature have demonstrated QT prolongation, TdP, and fatality associated with haloperidol use. Seventy-three cases of TdP, 11 of which were fatal, were reported in a post-marketing analysis of adverse events related to oral or injectable haloperidol. The sponsor reported concomitant QT-prolonging drugs or medical conditions in many of these cases. Another post-marketing investigation examined cardiac adverse events with haloperidol decanoate, the long-acting intramuscular formulation. Thirteen cases of TdP, QT prolongation, ventricular arrhythmias and/or sudden death were reported.
Case-control studies have demonstrated a dose-dependent relationship between intravenous haloperidol and subsequent TdP. Along with increased risks of other adverse effects with higher dosages, some evidence suggests that the risk of TdP increases at total daily dosages of 35 to 50 mg or more. Limited evidence suggests the incidence of TdP in patients receiving haloperidol intravenously is about 0.4% to 3.6%, but it may increase to greater than 10% at intravenous doses of 35 mg or more per day.
Recommendations
Due to cardiovascular risks associated with the use of IV haloperidol and other antipsychotic agents, recommendations from Hassaballa, Balk, and the FDA to prevent adverse events include:
Conclusion
Haloperidol is the drug of choice for delirium, and it has been widely used intravenously off-label for this use. Case reports indicate the risk of TdP, QT prolongation, and possible sudden death. The likelihood of these events is typically associated with higher-than-recommended intravenous doses. However, they have also been reported at lower doses. Baseline and periodic ECGs should be performed in patients receiving haloperidol, and special precautions should be taken in patients at higher risk for developing QT prolongation.
References
Information for healthcare professionals for haloperidol. U.S. Food and Drug Administration. Available at http://www.fda.gov/cder/drug/InfoSheets/HCP/haloperidol.htm. Accessed 01/16/08.
Gupta, A. Lawrence, K. Krishnan, C. Kavinsky, R. Trohman. Current concepts in the mechanisms and management of drug-induced QT prolongation and torsade de pointes. Am Heart J. 2007 Jun;153(6):891-9.
Haloperidol [package insert]. Bedford, OH: Bedford Laboratories; 2005.
Hassaballa HA, Balk RA. Torsade de pointes associated with the administration of intravenous haloperidol. Am J Ther. 2003 Jan-Feb;10(1):58-60.