Melatonin Interaction Resulting in Severe Sedation


  • Brian C Foster University of Ottawa
  • Kosta Cvijovic University of Toronto
  • Heather S Boon University of Toronto
  • Teresa W Tam University of Ottawa
  • Rui Liu University of Ottawa
  • Mano Murty Health Canada
  • Duc Vu Health Canada
  • Walter Jaeger University of Vienna
  • Ross T Tsuyuki University of Alberta
  • Joanne Barnes University of Auckland
  • Sunita Vohra University of Alberta



Purpose. Natural health products (NHPs), including melatonin, are widely used products. Despite the widespread assumption that all NHPs are safe, they contain pharmacologically active substances and can therefore have adverse effects and/or interact with pharmaceuticals. Objective: To investigate the mechanism underlying NHP interactions identified through the Pharmacy SONAR active surveillance study. Methods: Active surveillance was undertaken in community pharmacies to identify adverse events in patients who had recently taken NHPs together with conventional pharmaceuticals. For suspected NHP-pharmaceutical interactions, the possible mechanism of action was explored by in vitro analysis of samples of different products to identify cytochrome P450 enzyme (CYP) inhibition potential. Results: Active surveillance identified a 19-year-old male taking citalopram, nortriptyline and oxycodone concomitantly and who experienced severe sedation when melatonin was added to this regimen. In vitro analysis involving several melatonin products showed product-dependent inhibition of CYP1A2, CYP2C19 and CYP3A7. Conclusion: The adverse event was likely due to a primary pharmacokinetic interaction between melatonin and citalopram; although mechanistically, interactions affecting cytochrome P450-mediated metabolism may have occurred with all of these health products. A pharmacodynamic interaction may also be possible, but beyond the capacity of this study to establish.

Key words: Melatonin, citalopram, nortriptyline, oxycodone, drug interaction.


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Author Biographies

Brian C Foster, University of Ottawa

Faculty of Medicine, Adjunct Professor

Kosta Cvijovic, University of Toronto

Leslie Dan Faculty of Pharmacy

Heather S Boon, University of Toronto

Leslie Dan Faculty of Pharmacy

Teresa W Tam, University of Ottawa

Faculty of Medicine

Rui Liu, University of Ottawa

Faculty of Medicine

Mano Murty, Health Canada

Marketed Health Products Directorate

Duc Vu, Health Canada

Marketed Health Products Directorate

Ross T Tsuyuki, University of Alberta

Faculty of Medicine and Dentistry

Joanne Barnes, University of Auckland

School of Pharmacy

Sunita Vohra, University of Alberta

CARE Program, Faculty of Medicine and School of Public Health




How to Cite

Foster, B. C., Cvijovic, K., Boon, H. S., Tam, T. W., Liu, R., Murty, M., … Vohra, S. (2015). Melatonin Interaction Resulting in Severe Sedation. Journal of Pharmacy & Pharmaceutical Sciences, 18(2), 124–131.



Pharmaceutical Sciences; Review Articles