The Food and Drug Administration (FDA) issued a safety alert to health care
professionals regarding the risk of arrhythmias and sudden death associated
with haloperidol administered intravenously or at a higher-than-recommended
Haloperidol injection, available as a decanoate salt and a lactate salt, is
approved for intramuscular administration only, but intravenous use is a"
relatively common offlabel" use to treat severe agitation in
intensive care units, according to the FDA.
The agency cited at least 28 cases of torsades de pointes and prolongation
of the QT interval, some resulting in death, associated with intravenous use
of haloperidol in the medical literature. In postmarketing analyses conducted
by Johnson and Johnson, the manufacturer of the brand-name product Haldol, 229
reports of adverse events related to QT prolongation were identified with all
formulations and uses of the drug in their worldwide safety database up to
June 2005, including cases that the company described as "confounded by
concomitant QT-prolonging drugs or medical conditions."
The analyses and reports had been requested by the Italian equivalent of
the FDA. The reports included 73 cases of torsades de pointes, 11 of which
resulted in death. Eight of these 11 deaths involved intravenously
administered haloperidol. A second postmarketing safety analysis, which the
company also conducted for the Italian agency and submitted to the FDA in
March, included 13 cases involving torsades de pointes, QT prolongation,
ventricular arrhythmias, and/or sudden death, according to the FDA. The FDA
alert states that the frequency of these adverse effects cannot be estimated
based on these case reports.
In September, the FDA approved labeling revisions to include an additional
warning about the risks of sudden death, QT prolongation, and torsades de
pointes. The updated warning advises caution in using any formulation of
haloperidol in patients who "have other QT-prolonging conditions,
including electrolyte imbalance; have underlying cardiac abnormalities,
hypothyroidism, or familial long QT syndrome"; or are taking concomitant
drugs with QT-prolonging effects. The new label also recommends ECG monitoring
if haloperidol is given intravenously.
The prescribing information for haloperidol recommends an intramuscular
dosage of 2 to 5 mg for acutely agitated schizophrenia patients with
moderately severe to very severe symptoms. "Depending on the response of
the patient, subsequent doses may be given, administered as often as every
hour, although 4- to 8-hour intervals may be satisfactory," according to
the package insert. No definition of high dose for intravenous haloperidol is
given in the FDA alert.
The updated prescribing information had not been posted on the FDA's Web
site by press time.