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

5 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


  • 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


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