Information for Healthcare Professionals
Haloperidol (marketed as Haldol, Haldol Decanoate and Haldol Lactate)
ALERT [9/2007]: This Alert highlights revisions to the labeling
for haloperidol (marketed as Haldol, Haldol Decanoate and Haldol
Lactate). The updated labeling includes WARNINGS stating that Torsades de Pointes and QT
prolongation have been observed in patients receiving haloperidol,
especially when the drug is administered intravenously or in higher
doses than recommended. Haloperidol is not approved for intravenous use.
information reflects FDA’s current analysis of data available to FDA
concerning this drug. FDA intends to update this sheet when additional
information or analyses become available.
report any unexpected adverse or serious events associated with the use
of this drug, please contact the FDA MedWatch program and complete a
form on line at http://www.fda.gov/medwatch/report/hcp.htm
or report by fax to 1-800-FDA-0178, by mail using the postage-paid
address form provided on line, or by telephone to 1-800-FDA-1088.
advisory addresses the risk of QT prolongation and Torsades de Pointes
(TdP) in patients treated with haloperidol (a butryphenone
antipsychotic), especially when given intravenously.
Recommendations and considerations for healthcare professionals:
Although injectable haloperidol is approved by the FDA only for intramuscular injection, there is considerable evidence from the medical literature that intravenous administration of
haloperidol is a relatively common “off-label” clinical practice,
primarily for treatment of severe agitation in intensive care units.
Due to a number of case reports of sudden death, TdP and QT
prolongation in patients treated with haloperidol (especially when the
drug is given intravenously or at doses higher than recommended), the
sponsor has updated the labeling for haloperidol. The updated
WARNINGS note that:
doses and intravenous administration of haloperidol appear to be
associated with a higher risk of QT prolongation and TdP.
cases of sudden death, TdP and QT prolongation have been reported even
in the absence of predisposing factors, particular caution is advised
in treating patients using any formulation of haloperidol who:
- have other QT-prolonging conditions, including electrolyte imbalance (particularly hypokalemia and hypomagnesemia),
- have underlying cardiac abnormalities, hypothyroidism, or familial long QT syndrome, or
- are taking drugs known to prolong the QT interval.
- Because of this risk of TdP and QT prolongation, ECG monitoring is recommended if haloperidol is given intravenously.
- Haloperidol is not approved for intravenous administration.
are at least 28 case reports of QT prolongation and TdP in the medical
literature, some with fatal outcome in the context of off-label
intravenous use of haloperidol. In addition to these cases,
case-control studies have demonstrated a dose-response relationship
between intravenous haloperidol dose and subsequent TdP. Based on
this information, as well as the biologic plausibility of QT
prolongation with intravenous haloperidol, FDA has strengthened
warnings in the haloperidol labeling with regard to the risk of TdP and
QT prolongation with intravenous haloperidol use.
the request of the Pharmacovigilance Department of the Italian Drug
Agency (AIFA), the sponsor (Johnson & Johnson) performed two
post-marketing analyses of QT interval prolongation and TdP with
haloperidol administration (oral or injectable). In one analysis,
the sponsor searched their Benefit Risk Management worldwide safety
database for QT prolongation -related adverse event reports received
through June 30, 2005. This search identified 229 reports, many
of which the sponsor described as confounded by concomitant
QT-prolonging drugs or medical conditions. The reports included
73 cases of TdP, eleven of which were fatal. Eight of the eleven
fatal cases involved intravenous administration of various doses of
In March 2007 the sponsor
submitted to FDA the results of a second post-marketing investigation
conducted for the Italian drug authority1. This report
examined cardiac adverse events with haloperidol decanoate received by
the sponsor as of July 30, 2005. The sponsor found thirteen
reports including TdP, QT prolongation, ventricular arrhythmias and/or
Based on case
reports alone, we are unable to estimate the frequency with which QT
prolongation or TdP occur following administration of these
professionals should consider this new risk information when making
individual treatment decisions for their patients. FDA will
continue to monitor post-marketing reports for QT prolongation and
Torsades de Pointes in patients treated with haloperidol, and will
analyze any additional data for this as well as other important adverse
events. FDA will consider further regulatory action and
communication as additional information becomes available.
NDA 20-919 (Haloperidol). QT Prolongation in Association with the
Use of Haloperidol Decanoate: a Response to the Pharmacovigilance
Department of the Italian Drug Agency. Prepared by Johnson &
Johnson Pharmaceutical Research and Development, L.L.C. Dated
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Date created: September 17, 2007