Pharmacokinetic drug interactions with oral haloperidol in adults: dose correction factors from a combined weighted analysis

Ian McGrane, Edoardo Spina, Christoph Hiemke, Jose de Leon

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations


Introduction: Pharmacokinetic (PK) drug-drug interactions (DDIs) of oral haloperidol, a first-generation antipsychotic, are systematically reviewed. Areas covered: After exclusions, the search for DDIs with oral haloperidol provided 47 articles as victim and 7 as perpetrator. Changes in mean haloperidol concentration-to-dose (C/D) ratios after weighting each study’s size were used to calculate the effects of other drugs (inhibitors/inducers) on haloperidol. These changes of haloperidol C/D ratio were used to estimate dose-correction factors (<1 for inhibitors and >1 for inducers). Expert opinion: A box summarizes our recommendations for clinicians regarding our current knowledge of haloperidol PK DDIs, which will need to be updated as new information becomes available. Moderate to strong inducers (carbamazepine, phenobarbital, phenytoin, or rifampin) should be avoided since they required dose-correction factors of 2–5. Smoking appeared to be a weak inducer (dose-correction factor 1.2). Fluvoxamine, promethazine, and combinations of CYP3A4 and CYP2D6 inhibitors should be avoided. There are no long-term studies on fluoxetine to provide a dose correction factor. Limited information suggests that valproate may be an inhibitor (dose-correction factor 0.6). In most patients, haloperidol may not have clinically relevant effects as a perpetrator, but in vitro and clinical studies suggest it is a weak CYP2D6 inhibitor.

Original languageEnglish
Pages (from-to)135-149
Number of pages15
JournalExpert Opinion on Drug Metabolism and Toxicology
Issue number2
StatePublished - 2022

Bibliographical note

Funding Information:
I McGrane has received royalties from Hogrefe Publishing Group and received honoraria from the American College of Clinical Pharmacy (2019 and 2021) and from the College of Psychiatric and Neurologic Pharmacists (2017). J de Leon personally develops his presentations for lecturing, has never lectured using any pharmaceutical or pharmacogenetic company presentations, and has never been a consultant for pharmacogenetic or pharmaceutical companies. J de Leon has, in the past, received researcher-initiated grants from Eli Lilly (2003 and 2007), Roche Molecular Systems, Inc. (2007), and in collaboration with Genomas, Inc., from the NIH Small Business Innovation Research program (2010). He has also been on the advisory boards of Bristol-Myers Squibb (2003/2004) and AstraZeneca (2003). Roche Molecular Systems has also supported one of his educational presentations, which was published in a peer-reviewed journal (2005). His lectures were supported once by Sandoz (1997), twice by Lundbeck (both 1999), twice by Pfizer (both 2001), three times by Eli Lilly (2003, and two in 2006), twice by Janssen (2000 and 2006), once by Bristol-Myers Squibb (2006), seven times by Roche Molecular Systems, Inc. (once in 2005 and six times in 2006). E Spina has participated in speakers/advisory boards and lectured, supported by Arcapharma, Janssen Pharmaceuticals, Lundbeck, Otsuka and Recordati. C Hiemke has received speaker or consultancy fees from Otsuka and declares no conflict of interest related to this article. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Funding Information:
This paper was not funded. The authors acknowledge Lorraine Maw from the Mental Health Research Center at Eastern State Hospital, who helped in editing the article.

Publisher Copyright:
© 2022 Informa UK Limited, trading as Taylor & Francis Group.


  • antidepressive agents
  • antipsychotic agents
  • cytochrome P-450 enzyme inducers
  • cytochrome P-450 enzyme inhibitors
  • drug interactions
  • haloperidol/blood
  • haloperidol/pharmacokinetics
  • haloperidol/therapeutic use
  • smoking
  • valproate

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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