Melatonin Interaction Resulting in Severe Sedation
Open accessAbstract
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.
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Caution should be exercised when melatonin is taken with one or more medications; otherwise, adverse side effects like extreme sedation can result.
“Caution should be exercised when melatonin is taken with one or more medications; otherwise, adverse side effects (like extreme sedation) can result [303].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [303]
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- Authors
- Foster, B. C., Cvijovic, K., Boon, H. S., Tam, T. W., Liu, R., Murty, M., Vu, D., Jaeger, W., Tsuyuki, R. T., Barnes, J., & Vohra, S.
- Affiliations
- University of Ottawa (CA)
- University of Toronto (CA)
- Health Canada (CA)
- University of Vienna (AT)
- University of Alberta (CA)
- University of Auckland (NZ)
- Venue
- Journal of Pharmacy & Pharmaceutical Sciences
- Publisher
- Frontiers Media SA
- Published
- 2015-04-20
- Volume
- 18
- Issue
- 2
- Pages
- 124
- ISSN
- 1482-1826 (ISSN-L)
- OpenAlex
- W2146859352
- Cited by
- 17
- References
- 38
- Citations by year
- 2026: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 3 · 2016: 2 · 2015: 2
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Pharmacy & Pharmaceutical Sciences (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Canadian Patient Safety Institute
- Alberta Innovates
- Health Canada
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- melatonin, natural health products, drug interactions, sedation, citalopram, nortriptyline, oxycodone, cytochrome P450 inhibition, CYP1A2, CYP2C19, CYP3A7, pharmacokinetic interactions, adverse drug reactions, active surveillance, community pharmacy
- MeSH terms
- Administration, Oral, Cytochrome P-450 Enzyme System, Dose-Response Relationship, Drug, Humans, Male, Melatonin, Nortriptyline, Oxycodone, Structure-Activity Relationship, Citalopram, Deep Sedation, Young Adult, Watchful Waiting, Cytochrome P-450 Enzyme Inhibitors
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