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.; Wilffert, Bob

doi:10.1111/bcp.13741

Cited by 26 publications

(18 citation statements)

References 61 publications

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“…This study does not provide data on how many unwanted drug combinations that have been captured during the dispensing process. If the impact of being scored as PM or UM is also taken into consideration, the balance between "monitor closely" and "serious use alternate" might change significantly towards the latter, which recently has been substantiated for opioids [17,36] and for metoprolol [37]. It should be mentioned that other drug-interaction checkers might score the warnings shown in Table 5 differently from that obtained in this study, e.g., "Interaktionsdatabasen" provided by the Danish Medicines Agency (http://www.interaktionsdatabasen.dk/); however, it is the author's opinion that the principles outlined above still will be valid.…”

Section: Discussionmentioning

confidence: 99%

Drug Use in Denmark for Drugs Having Pharmacogenomics (PGx) Based Dosing Guidelines from CPIC or DPWG for CYP2D6 and CYP2C19 Drug–Gene Pairs: Perspectives for Introducing PGx Test to Polypharmacy Patients

Westergaard

Nielsen

Jørgensen

et al. 2020

JPM

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Background: The cytochrome P450 drug metabolizing enzymes CYP2D6 and CYP2C19 are the major targets for pharmacogenomics (PGx) testing and determining for drug response. Clinical dosing guidelines for specific drug-gene interactions (DGI) are publicly available through PharmGKB. The aim of this register study was to map the use of drugs in Denmark for drugs having actionable dosing guidelines (AG) i.e., dosing recommendations different from standard dosing for CYP2D6 or CYP2C19 DGI in terms of consumption. Methods: The Danish Register of Medicinal Product Statistics was the source to retrieve consumption in Defined Daily Dose (DDD) i.e., the assumed average maintenance dose per day for a drug used for its main indication in adults and number of users (2017 data). Clinical dosing guidelines were available from the PharmGKB website. Results: Forty-nine drugs have guidelines corresponding to 14.5% of total sales in DDD. Twenty-eight drugs have AG corresponding to 375.2 million DDD. Pantoprazole, lansoprazole, omeprazole, clopidogrel, and metoprolol constituted fifty-eight percent of the consumption in DDD of drugs having AG. The consumption of antidepressant drugs, opioids, and antipsychotic drugs were 157.0 million DDD; with 441,850 users, 48.9 million DDD; with 427,765 users, and 23.7 million DDD; with 128,935 users, respectively. Age distributions of consumption of drugs and drug combinations, e.g., for sertraline redeemed either alone or in combination with metoprolol and tramadol, are presented. Conclusion: This exploratory register study clearly showed that a large fraction of the Danish population, especially the elderly, are exposed to drugs or drug combinations for which there exist AG related to PGx of CYP2D6 or CYP2C19.

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Section: Discussionmentioning

confidence: 99%

Drug Use in Denmark for Drugs Having Pharmacogenomics (PGx) Based Dosing Guidelines from CPIC or DPWG for CYP2D6 and CYP2C19 Drug–Gene Pairs: Perspectives for Introducing PGx Test to Polypharmacy Patients

Westergaard

Nielsen

Jørgensen

et al. 2020

JPM

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“…Similar considerations can be applied for the other combinations shown in Table 4. If the impact of phenoconversion are taken into consideration the balance between "monitor closely" and "serious use alternate" might change significantly towards the latter, which recently have been substantiated for opioids [40,41] and metoprolol [42]. That phenoconversion constitutes a clinical challenge in polypharmacy patients as exemplified both in this study and in our previous study [24] as well as by others [22,43] further substantiates the need for alignment of drug interaction trackers with regard to severity scoring as well as incorporation of gene scores thereby taking phenoconversion into consideration.…”

Section: Discussionmentioning

confidence: 99%

Drug Use among Nursing Home Residents in Denmark for Drugs Having Pharmacogenomics Based (PGx) Dosing Guidelines: Potential for Preemptive PGx Testing

Vermehren

Nielsen

Jørgensen

et al. 2020

JPM

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Background: Polypharmacy is most prevalent among the elderly population and in particular among nursing home residents. The frequency of the use of drugs with pharmacogenomics (PGx)-based dosing guidelines for CYP2D6, CYP2C9, CYP2C19 and SLCO1B1 were measured among nursing home residents in the Capital Region of Denmark as well as drug–drug interactions. The aim was to evaluate the potential of applying PGx-test as a supportive tool in medication reviews. Methods: Drug use among nursing home residents during 2017–2018 in the Capital Region of Copenhagen, for drugs with PGx-based dosing guidelines available through the PharmGKB website, were measured. Drug–drug interactions were scored in severity by using drug interaction checkers. Results: The number of residents using drugs with PGx-based actionable dosing guidelines (AG) were 119 out of 141 residents (84.3%). Of these 119 residents, 87 residents used drugs with AG for CYP2C19, 47 residents for CYP2D6, and 42 residents for SLCO1B1. In addition, 30 residents used two drugs with an AG for CYP2C19, and for CYP2D6, it was only seven residents. The most used drugs with AG were clopidogrel (42), pantoprazole (32), simvastatin (30), metoprolol (25), and citalopram (24). The most frequent drug interactions found with warnings were combinations of proton pump inhibitors and clopidogrel underscoring the potential for phenoconversion. Conclusion: this study clearly showed that the majority of the nursing home residents were exposed to drugs or drug combinations for which there exist PGx-based AG. This indeed supports the notion of accessing and accounting for not only drug–gene but also drug–drug–gene interactions as a supplement to medication review.

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“…However, co-administration of sertraline and metoprolol increases the blood concentration of metoprolol. Therefore, we adjusted the dose of metoprolol in the sertraline and metoprolol groups in this study ( Bahar et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

An Integrative Pharmacology-Based Strategy to Uncover the Mechanism of Xiong-Pi-Fang in Treating Coronary Heart Disease with Depression

Zhang

Zhu

et al. 2021

Front. Pharmacol.

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Objectives: This study aimed to explore the mechanism of Xiong-Pi-Fang (XPF) in the treatment of coronary heart disease (CHD) with depression by an integrative strategy combining serum pharmacochemistry, network pharmacology analysis, and experimental validation.Methods: An ultrahigh performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) method was constructed to identify compounds in rat serum after oral administration of XPF, and a component-target network was established using Cytoscape, between the targets of XPF ingredients and CHD with depression. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to deduce the mechanism of XPF in treating CHD with depression. Finally, in a chronic unpredictable mild stress (CUMS)-and isoproterenol (ISO)-induced rat model, TUNEL was used to detect the apoptosis index of the myocardium and hippocampus, ELISA and western blot were used to detect the predicted hub targets, namely AngII, 5-HT, cAMP, PKA, CREB, BDNF, Bcl-2, Bax, Cyt-c, and caspase-3.Results: We identified 51 compounds in rat serum after oral administration of XPF, which mainly included phenolic acids, saponins, and flavonoids. Network pharmacology analysis revealed that XPF may regulate targets, such as ACE2, HTR1A, HTR2A, AKT1, PKIA, CREB1, BDNF, BCL2, BAX, CASP3, cAMP signaling pathway, and cell apoptosis process in the treatment of CHD with depression. ELISA analysis showed that XPF decreased Ang-II content in the circulation and central nervous system, inhibited 5-HT levels in peripheral circulation, and increased 5-HT content in the central nervous system and cAMP content in the myocardia and hippocampus. Meanwhile, western blot analysis indicated that XPF could upregulate the expression levels of PKA, CREB, and BDNF both in the myocardia and hippocampus. TUNEL staining indicated that the apoptosis index of myocardial and hippocampal cells increased in CUMS-and ISO-induced CHD in rats under depression, and XPF could increase the expression of Bcl-2, inhibit the expression of Bax, Cyt-c, and caspase-3, and rectify the injury of the hippocampus and myocardium, which exerted antidepressant and antimyocardial ischemia effects.Conclusion: Our study proposed an integrated strategy, combining serum pharmacochemistry and network pharmacology to investigate the mechanisms of XPF in treating CHD with depression. The mechanism of XPF in treating CHD with depression may be related to the activation of the cAMP signaling pathway and the inhibition of the apoptosis.

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

Cited by 26 publications

References 61 publications

Drug Use in Denmark for Drugs Having Pharmacogenomics (PGx) Based Dosing Guidelines from CPIC or DPWG for CYP2D6 and CYP2C19 Drug–Gene Pairs: Perspectives for Introducing PGx Test to Polypharmacy Patients

Drug Use in Denmark for Drugs Having Pharmacogenomics (PGx) Based Dosing Guidelines from CPIC or DPWG for CYP2D6 and CYP2C19 Drug–Gene Pairs: Perspectives for Introducing PGx Test to Polypharmacy Patients

Drug Use among Nursing Home Residents in Denmark for Drugs Having Pharmacogenomics Based (PGx) Dosing Guidelines: Potential for Preemptive PGx Testing

An Integrative Pharmacology-Based Strategy to Uncover the Mechanism of Xiong-Pi-Fang in Treating Coronary Heart Disease with Depression

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