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Comparative safety of antipsychotics in the WHO pharmacovigilance database: the haloperidol case

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Abstract

Background Starting in 2007, regulatory agencies strengthened label warnings for intravenous haloperidol. Based on adverse drug reaction (ADR) reports of QT prolongation and torsades de pointes, regulatory agencies recommended the use of continuous telemetry or advising against the intravenous administration in general. Intravenous haloperidol is commonly used as a first line treatment for acute delirium. Consequently, the extended warning has caused uncertainty among health care professionals. Objective The aim of this study is to critically evaluate the WHO global individual case safety report (ICSR) database VigiBase for QT prolongation, torsades and/or cardiac arrest involving intravenous haloperidol compared to other routes of administration and the antipsychotics olanzapine and quetiapine. Method All WHO safety reports (1972–2010) of cardiac reactions associated with haloperidol, quetiapine and olanzapine were evaluated, including dose, route of administration and patient risk factors. Reporting odds ratios for the 3 antipsychotics were calculated. Main outcome measure Number of submitted reports on different antipsychotics. Results The absolute number of ICSR regarding QT prolongation, torsades and/or cardiac arrest were: haloperidol (365 cases), olanzapine (489) and quetiapine (520). Reporting rates of haloperidol did not increase over the last two decades. 32% of the haloperidol cases involved oral, 16.4% intramuscular and 22.7% intravenous administration. The difference of the reporting odds ratios of haloperidol and quetiapine were not statistically significant. Olanzapine was associated with a slightly lower reporting odds ratio. Conclusion While regulatory agencies advise against the use of intravenous haloperidol, review of VigiBase does not reveal that the intravenous route is any more likely to be associated with cardiac adverse events. Furthermore, our results do not demonstrate any additional risk associated with haloperidol when compared with alternative agents. Although pharmacovigilance data does not routinely include a denominator regarding frequency of use, regulatory agencies are currently advising against the use of intravenous haloperidol based on pharmacovigilance, but the number of overall reports is greater for quetiapine and olanzapine when compared to haloperidol. Improved pharmacovigilance approaches are needed to more accurately address the safe, effective use of medicines.

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Acknowledgments

The authors would like to thank Louise Mallet, Pharm D, Certified Geriatric Pharmacist, Professor of Clinical Pharmacy at the University of Montreal and Clinical Pharmacist in Geriatrics at the Royal Victoria Hospital in Montreal for the provision of vast background knowledge on geriatric delirium.

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None.

Conflicts of interest

The authors don’t have any conflict of interest whatsoever to report.

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Authors and Affiliations

  1. Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland

    Carla Meyer-Massetti, Simone Vaerini & Christoph R. Meier

  2. Regional Pharmacovigilance Center and Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland

    Alexandra E. Rätz Bravo

  3. Hospital Pharmacy, University Hospital Basel, Basel, Switzerland

    Christoph R. Meier

  4. Department of Clinical Pharmacy, School of Pharmacy, University of California San Francisco, San Francisco, CA, USA

    B. Joseph Guglielmo

Authors
  1. Carla Meyer-Massetti
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  2. Simone Vaerini
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  4. Christoph R. Meier
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  5. B. Joseph Guglielmo
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Corresponding author

Correspondence to Carla Meyer-Massetti.

Additional information

Carla Meyer-Massetti and Simone Vaerini are co-first-authors.

The data on which this work is based were obtained from the WHO Collaborating Centre for International Drug Monitoring, Uppsala, Sweden. The information contained in this work is not homogeneous at least with respect to origin or likelihood that the pharmaceutical product caused the adverse reaction. The information contained in this work does not represent the opinion of the World Health Organization.

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Meyer-Massetti, C., Vaerini, S., Rätz Bravo, A.E. et al. Comparative safety of antipsychotics in the WHO pharmacovigilance database: the haloperidol case. Int J Clin Pharm 33, 806–814 (2011). https://doi.org/10.1007/s11096-011-9541-y

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