The US Food and Drug Administration (FDA) has recently issued a safety alert which highlights the potential increased risk of QT prolongation and torsade de pointes (TdP) with the use of intravenous (IV) administration of haloperidol.

Although injectable haloperidol is approved by the FDA only to be used as an intramuscular injection, there is considerable evidence from the medical literature that IV haloperidol is a relatively common ‘off-label' clinical practice, primarily to treat cases of severe agitation in intensive care units.

There 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 IV administration of haloperidol. Additionally, case control studies performed have demonstrated a dose-response relationship between intravenous haloperidol dosing and subsequent TdP.

Johnson & Johnson recently (sponsor of the proprietary brand of haloperidol, Haldol® in the US) conducted two post-marketing studies analysing QT prolongation and TdP with the administration of haloperidol (both oral and injectable). In the first study, Johnson & Johnson performed a search of their Benefit Risk Management worldwide safety database. The results revealed 73 cases of TdP, of which 11 of these cases lead to fatalities. Eight of these fatalities involved the IV administration of haloperidol. The second study involved a post-marketing investigation that examined reports of cardiac events that involved haloperidol received by the company as of 30 July 2005. Thirteen of these haloperidol related cardiac events reported involved the occurrence of TdP, QT prolongation, ventricular arrhythmia and/or sudden death.

Based on these recent findings, the labelling of Haldol® products in the US were revised to include the following warnings:

• Higher doses and IV administration of haloperidol appear to be associated with a higher risk of QT prolongation and TdP.
  
• Although 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 hypokalaemia 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.
  
  
  

HSA has not received any local reports of prolonged QTc or TdP involving the use of haloperidol, and will continue to monitor the situation. The FDA in its safety update stated that based on case reports alone, it was unable to estimate the frequency with which QT prolongation or TdP occur following administration of haloperidol and will continue to monitor post-marketing reports for such adverse events and further regulatory actions and communications will be effected as additional information becomes available.

It advised that healthcare professionals should take into consideration the above new safety information when making individual treatment decisions for their patients.