The burden and management of cytochrome P450 2D6 (CYP2D6)‐mediated drug–drug interaction (DDI): co‐medication of metoprolol and paroxetine or fluoxetine in the elderly

Bahar, Muh. Akbar; Bos, Jens; Borgsteede, Sander D.; Wilffert, Bob

doi:10.1002/pds.4200

Cited by 21 publications

(30 citation statements)

References 60 publications

(72 reference statements)

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“…Bahar et al reported that among all co‐prescriptions of beta‐blockers with paroxetine/fluoxetine during 1994–2014 for elderly patients in the community pharmacies in the Netherlands, 52% of them was metoprolol‐paroxetine/fluoxetine combination. The numbers of other beta‐blockers combined with paroxetine/fluoxetine were 17%, 12% and 19% for atenolol, bisoprolol and any other beta‐blockers respectively .…”

Section: Introductionmentioning

confidence: 99%

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

Bahar

Kamp

Borgsteede³

et al. 2018

Brit J Clinical Pharma

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AimMetoprolol (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.MethodPubmed, 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).ResultsWe 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.ConclusionDespite 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.

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Section: Introductionmentioning

confidence: 99%

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

Bahar

Kamp

Borgsteede³

et al. 2018

Brit J Clinical Pharma

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“…Similar to other clinical settings, in psychiatric practice, DDIs present a serious, constantly increasing clinical problem, especially in older patients. Previous studies identified DDIs in psychiatric hospitalization but focused on antidepressants (Markowitz & Devine, ) and drugs with action on cytochrome P450 (CYP) 2D6 and 3A4 (Bahar et al., ; Davies, Eayrs, Pratt, & Lennard, ), as well as inpatients in General Hospitals and psychiatric units (Sinclair et al., ). These studies did not analyse DDI in view of nursing care of psychiatric patients, considering the impact on patient safety.…”

Section: Introductionmentioning

confidence: 99%

Potential drug–drug interactions and polypharmacy in institutionalized elderly patients in a public hospital in Brazil

Castilho

Reis

Borges

et al. 2017

Psychiatric Ment Health Nurs

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Introduction Despite the impact on patient safety and the fact that prevalence is higher in older patients, previous research did not analyse drug-drug interactions (DDIs) in view of nursing care of elderly psychiatric patients. Aim To identify potential drug-drug interactions and polypharmacy in prescriptions of aged inpatients with psychiatric disorders and analyse associated factors. Methods In this retrospective cross-sectional study, we analysed the medical records of institutionalized patients diagnosed with psychiatric disorders (n = 94), aged >60 years, and prescribed multiple medications. Drug prescriptions were checked at admission, midway through and the last prescription. Factors associated with DDI occurrence were assessed using multivariable logistic regression analysis. Results A DDI prevalence potential of 67.0%, 74.5% and 80.8% occurred in patients at admission, midway through hospitalization and the last prescription, respectively. Most of the prescribed drugs were nervous system agents. A high percentage of serious and contraindicated potential DDIs occurred. Age between 60 and 69 years, use of cardiovascular and respiratory system drugs, and the number of medications contributed significantly to DDI. Implications for mental health nursing Knowledge on the factors associated with DDIs in patients with mental disorders can contribute to the improvement of effectiveness and safety of nursing care.

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“…In the Netherlands, despite the fact that computerized DDI alerting systems have been incorporated in the electronic prescription systems and applied before the dispensing process in the pharmacy, the combination of metoprolol‐paroxetine/fluoxetine is still common in older patients . One possible reason is that there is a conflicting response of the applied surveillance systems in assessing the DDI because of the contrasting evidence in the clinical consequences of metoprolol and paroxetine/fluoxetine interaction . The G‐standard, a product from the “Royal Dutch Association for the Advancement of Pharmacy” (KNMP) and used by approximately 45% of the pharmacies, does alert the interaction, but the Pharmabase, a product from the Health Base Foundation and used by approximately 55% of the pharmacies, has been stopping alerting the combination since 2005 .…”

Section: Discussionmentioning

confidence: 99%

“…Clinically relevant cytochrome P450 mediated drug‐drug interactions (DDI) are prevalent in geriatric patients with multiple comorbidities such as cardiovascular and psychiatric diseases . Metoprolol and paroxetine/fluoxetine as the drugs of choice for treating these chronic illnesses consecutively are often observed to be co‐prescribed in the elderly . Several studies have reported that the combination triggers cytochrome P450 2D6 (CYP2D6) mediated pharmacokinetic DDI .…”

Section: Introductionmentioning

confidence: 99%

Discontinuation and dose adjustment of metoprolol after metoprolol‐paroxetine/fluoxetine co‐prescription in Dutch elderly

Bahar

Wang

Bos

et al. 2018

Pharmacoepidemiology and Drug

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PurposeCo‐prescription of paroxetine/fluoxetine (a strong CYP2D6 inhibitor) in metoprolol (a CYP2D6 substrate) users is common, but data on the clinical consequences of this drug‐drug interaction are limited and inconclusive. Therefore, we assessed the effect of paroxetine/fluoxetine initiation on the existing treatment with metoprolol on the discontinuation and dose adjustment of metoprolol among elderly.MethodsWe performed a cohort study using the University of Groningen IADB.nl prescription database (www.IADB.nl). We selected all elderly (≥60 years) who had ever been prescribed metoprolol and had a first co‐prescription of paroxetine/fluoxetine, citalopram (weak CYP2D6 inhibitor), or mirtazapine (negative control) from 1994 to 2015. The exposure group was metoprolol and paroxetine/fluoxetine co‐prescription, and the other groups acted as controls. The outcomes were early discontinuation and dose adjustment of metoprolol. Logistic regression was applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).ResultsCombinations of metoprolol‐paroxetine/fluoxetine, metoprolol‐citalopram, and metoprolol‐mirtazapine were started in 528, 673, and 625 patients, respectively. Compared with metoprolol‐citalopram, metoprolol‐paroxetine/fluoxetine was not significantly associated with the early discontinuation and dose adjustment of metoprolol (OR = 1.07, 95% CI:0.77‐1.48; OR = 0.87, 95% CI:0.57‐1.33, respectively). In comparison with metoprolol‐mirtazapine, metoprolol‐paroxetine/fluoxetine was associated with a significant 43% relative increase in early discontinuation of metoprolol (OR = 1.43, 95% CI:1.01‐2.02) but no difference in the risk of dose adjustment. Stratified analysis by gender showed that women have a significantly high risk of metoprolol early discontinuation (OR = 1.62, 95% CI:1.03‐2.53).ConclusionParoxetine/fluoxetine initiation in metoprolol prescriptions, especially for female older patients, is associated with the risk of early discontinuation of metoprolol.

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The burden and management of cytochrome P450 2D6 (CYP2D6)‐mediated drug–drug interaction (DDI): co‐medication of metoprolol and paroxetine or fluoxetine in the elderly

Abstract: Despite the signalling software, metoprolol-paroxetine/fluoxetine combinations are still observed in the elderly population. The clinical impact of these interactions needs further investigation. Copyright © 2017 John Wiley & Sons, Ltd.

Cited by 21 publications

References 60 publications

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

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

Potential drug–drug interactions and polypharmacy in institutionalized elderly patients in a public hospital in Brazil

Discontinuation and dose adjustment of metoprolol after metoprolol‐paroxetine/fluoxetine co‐prescription in Dutch elderly

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