Cargando…

The impact of CYP2D6 mediated drug–drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine

AIM: Metoprolol (a CYP2D6 substrate) is often co‐prescribed with paroxetine/fluoxetine (a CYP2D6 inhibitor) because the clinical relevance of this drug–drug interaction (DDI) is still unclear. This review aimed to systematically evaluate the available evidence and quantify the clinical impact of the...

Descripción completa

Detalles Bibliográficos
Autores principales: Bahar, Muh. Akbar, Kamp, Jasper, Borgsteede, Sander D., Hak, Eelko, Wilffert, Bob
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255988/
https://www.ncbi.nlm.nih.gov/pubmed/30248178
http://dx.doi.org/10.1111/bcp.13741
_version_ 1783374062081277952
author Bahar, Muh. Akbar
Kamp, Jasper
Borgsteede, Sander D.
Hak, Eelko
Wilffert, Bob
author_facet Bahar, Muh. Akbar
Kamp, Jasper
Borgsteede, Sander D.
Hak, Eelko
Wilffert, Bob
author_sort Bahar, Muh. Akbar
collection PubMed
description AIM: Metoprolol (a CYP2D6 substrate) is often co‐prescribed with paroxetine/fluoxetine (a CYP2D6 inhibitor) because the clinical relevance of this drug–drug interaction (DDI) is still unclear. This review aimed to systematically evaluate the available evidence and quantify the clinical impact of the DDI. METHOD: Pubmed, Web of Science, Cochrane Library and Embase were searched for studies reporting on the effect of the DDI among adults published until April 2018. Data on pharmacokinetics, pharmacodynamics and clinical outcomes from experimental, observational and case report studies were retrieved. The protocol of this study was registered in PROSPERO (CRD42018093087). RESULTS: We found nine eligible articles that consisted of four experimental and two observational studies as well as three case reports. Experimental studies reported that paroxetine increased the AUC of metoprolol three to five times, and significantly decreased systolic blood pressure and heart rate of patients. Case reports concerned bradycardia and atrioventricular block due to the DDI. Results from observational studies were conflicting. A cohort study indicated that the DDI was significantly associated with the incidence of early discontinuation of metoprolol as an indicator of the emergence of metoprolol‐related side effects. In a case–control study, the DDI was not significantly associated with bradycardia. CONCLUSION: Despite the contradictory conclusions from the current literature, the majority of studies suggest that the DDI can lead to adverse clinical consequences. Since alternative antidepressants and beta‐blockers with comparable efficacy are available, such DDIs can be avoided. Nonetheless, if prescribing the combination is unavoidable, a dose adjustment or close monitoring of the metoprolol‐related side effects is necessary.
format Online
Article
Text
id pubmed-6255988
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-62559882018-12-03 The impact of CYP2D6 mediated drug–drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine Bahar, Muh. Akbar Kamp, Jasper Borgsteede, Sander D. Hak, Eelko Wilffert, Bob Br J Clin Pharmacol Systematic Review and Meta‐analysis AIM: Metoprolol (a CYP2D6 substrate) is often co‐prescribed with paroxetine/fluoxetine (a CYP2D6 inhibitor) because the clinical relevance of this drug–drug interaction (DDI) is still unclear. This review aimed to systematically evaluate the available evidence and quantify the clinical impact of the DDI. METHOD: Pubmed, Web of Science, Cochrane Library and Embase were searched for studies reporting on the effect of the DDI among adults published until April 2018. Data on pharmacokinetics, pharmacodynamics and clinical outcomes from experimental, observational and case report studies were retrieved. The protocol of this study was registered in PROSPERO (CRD42018093087). RESULTS: We found nine eligible articles that consisted of four experimental and two observational studies as well as three case reports. Experimental studies reported that paroxetine increased the AUC of metoprolol three to five times, and significantly decreased systolic blood pressure and heart rate of patients. Case reports concerned bradycardia and atrioventricular block due to the DDI. Results from observational studies were conflicting. A cohort study indicated that the DDI was significantly associated with the incidence of early discontinuation of metoprolol as an indicator of the emergence of metoprolol‐related side effects. In a case–control study, the DDI was not significantly associated with bradycardia. CONCLUSION: Despite the contradictory conclusions from the current literature, the majority of studies suggest that the DDI can lead to adverse clinical consequences. Since alternative antidepressants and beta‐blockers with comparable efficacy are available, such DDIs can be avoided. Nonetheless, if prescribing the combination is unavoidable, a dose adjustment or close monitoring of the metoprolol‐related side effects is necessary. John Wiley and Sons Inc. 2018-09-24 2018-12 /pmc/articles/PMC6255988/ /pubmed/30248178 http://dx.doi.org/10.1111/bcp.13741 Text en © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Systematic Review and Meta‐analysis
Bahar, Muh. Akbar
Kamp, Jasper
Borgsteede, Sander D.
Hak, Eelko
Wilffert, Bob
The impact of CYP2D6 mediated drug–drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine
title The impact of CYP2D6 mediated drug–drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine
title_full The impact of CYP2D6 mediated drug–drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine
title_fullStr The impact of CYP2D6 mediated drug–drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine
title_full_unstemmed The impact of CYP2D6 mediated drug–drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine
title_short The impact of CYP2D6 mediated drug–drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine
title_sort impact of cyp2d6 mediated drug–drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine
topic Systematic Review and Meta‐analysis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255988/
https://www.ncbi.nlm.nih.gov/pubmed/30248178
http://dx.doi.org/10.1111/bcp.13741
work_keys_str_mv AT baharmuhakbar theimpactofcyp2d6mediateddrugdruginteractionasystematicreviewonacombinationofmetoprololandparoxetinefluoxetine
AT kampjasper theimpactofcyp2d6mediateddrugdruginteractionasystematicreviewonacombinationofmetoprololandparoxetinefluoxetine
AT borgsteedesanderd theimpactofcyp2d6mediateddrugdruginteractionasystematicreviewonacombinationofmetoprololandparoxetinefluoxetine
AT hakeelko theimpactofcyp2d6mediateddrugdruginteractionasystematicreviewonacombinationofmetoprololandparoxetinefluoxetine
AT wilffertbob theimpactofcyp2d6mediateddrugdruginteractionasystematicreviewonacombinationofmetoprololandparoxetinefluoxetine
AT baharmuhakbar impactofcyp2d6mediateddrugdruginteractionasystematicreviewonacombinationofmetoprololandparoxetinefluoxetine
AT kampjasper impactofcyp2d6mediateddrugdruginteractionasystematicreviewonacombinationofmetoprololandparoxetinefluoxetine
AT borgsteedesanderd impactofcyp2d6mediateddrugdruginteractionasystematicreviewonacombinationofmetoprololandparoxetinefluoxetine
AT hakeelko impactofcyp2d6mediateddrugdruginteractionasystematicreviewonacombinationofmetoprololandparoxetinefluoxetine
AT wilffertbob impactofcyp2d6mediateddrugdruginteractionasystematicreviewonacombinationofmetoprololandparoxetinefluoxetine