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Article

Impact of Drug-Gene-Interaction, Drug-Drug-Interaction, and Drug-Drug-Gene-Interaction on (es)Citalopram Therapy: The PharmLines Initiative

1
Department of PharmacoTherapy, -Epidemiology & -Economics, University of Groningen, 9713 AV Groningen, The Netherlands
2
Faculty of Pharmacy, Universitas Hasanuddin, Makassar 90245, Indonesia
3
Department of Genetics, Groningen, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands
4
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands
*
Author to whom correspondence should be addressed.
J. Pers. Med. 2020, 10(4), 256; https://doi.org/10.3390/jpm10040256
Received: 9 October 2020 / Revised: 11 November 2020 / Accepted: 14 November 2020 / Published: 28 November 2020
(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)
We explored the association between CYP2C19/3A4 mediated drug-gene-interaction (DGI), drug-drug-interaction (DDI) and drug-drug-gene-interaction (DDGI) and (es)citalopram dispensing course. A cohort study was conducted among adult Caucasians from the Lifelines cohort (167,729 participants) and linked dispensing data from the IADB.nl database as part of the PharmLines Initiative. Exposure groups were categorized into (es)citalopram starters with DGI, DDI and DDGI. The primary outcome was drug switching and/or dose adjustment, and the secondary was early discontinuation after the start of (es)citalopram. Logistic regression modeling was applied to estimate adjusted odd ratios with their confidence interval. We identified 316 (es)citalopram starters with complete CYP2C19/3A4 genetic information. The CYP2C19 IM/PM and CYP3A4 NM combination increased risks of switching and/or dose reduction (OR: 2.75, 95% CI: 1.03–7.29). The higher effect size was achieved by the CYP2C19 IM/PM and CYP3A4 IM combination (OR: 4.38, 95% CI: 1.22–15.69). CYP2C19/3A4 mediated DDIs and DDGIs showed trends towards increased risks of switching and/or dose reduction. In conclusion, a DGI involving predicted decreased CYP2C19 function increases the need for (es)citalopram switching and/or dose reduction which might be enhanced by co-presence of predicted decreased CYP3A4 function. For DDI and DDGI, no conclusions can be drawn from the results. View Full-Text
Keywords: (es)citalopram; drug-gene-interaction; drug-drug-interaction; drug-drug-gene-interaction; the PharmLines initiative (es)citalopram; drug-gene-interaction; drug-drug-interaction; drug-drug-gene-interaction; the PharmLines initiative
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MDPI and ACS Style

Bahar, M.A.; Lanting, P.; Bos, J.H.J.; Sijmons, R.H.; Hak, E.; Wilffert, B. Impact of Drug-Gene-Interaction, Drug-Drug-Interaction, and Drug-Drug-Gene-Interaction on (es)Citalopram Therapy: The PharmLines Initiative. J. Pers. Med. 2020, 10, 256. https://doi.org/10.3390/jpm10040256

AMA Style

Bahar MA, Lanting P, Bos JHJ, Sijmons RH, Hak E, Wilffert B. Impact of Drug-Gene-Interaction, Drug-Drug-Interaction, and Drug-Drug-Gene-Interaction on (es)Citalopram Therapy: The PharmLines Initiative. Journal of Personalized Medicine. 2020; 10(4):256. https://doi.org/10.3390/jpm10040256

Chicago/Turabian Style

Bahar, Muh. A., Pauline Lanting, Jens H.J. Bos, Rolf H. Sijmons, Eelko Hak, and Bob Wilffert. 2020. "Impact of Drug-Gene-Interaction, Drug-Drug-Interaction, and Drug-Drug-Gene-Interaction on (es)Citalopram Therapy: The PharmLines Initiative" Journal of Personalized Medicine 10, no. 4: 256. https://doi.org/10.3390/jpm10040256

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