CYP2D6-inhibiting drugs and risk of fall injury after newly initiated therapy with beta-blockers—a register-based case-crossover study

Abstract We assessed whether concomitant use of CYP2D6-inhibiting drugs associates with increased risk of fall injuries after newly initiated therapy with beta-blockers. A case-crossover study design was applied which eliminates confounding from individual fixed characteristics by pairing cases with...

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Main Authors: Karin Leander, M.-L. Dahl, M. Vikström, J. Möller, K. Söderberg-Löfdal
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-09617-4
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author Karin Leander
M.-L. Dahl
M. Vikström
J. Möller
K. Söderberg-Löfdal
author_facet Karin Leander
M.-L. Dahl
M. Vikström
J. Möller
K. Söderberg-Löfdal
author_sort Karin Leander
collection DOAJ
description Abstract We assessed whether concomitant use of CYP2D6-inhibiting drugs associates with increased risk of fall injuries after newly initiated therapy with beta-blockers. A case-crossover study design was applied which eliminates confounding from individual fixed characteristics by pairing cases with themselves across time. Data on prescribed and dispensed beta-blockers and hospitalizations for first-time fall injuries in the Swedish population aged ≥ 20 for the period 2006-01-01–2013-12-31 were extracted from national registers. Odds ratios (OR) with 95% confidence interval (CI) of fall injury associated with newly initiated beta-blocker therapy (prescription dispensed within the 28 days preceding the fall injury) while considering concomitant use of CYP2D6-inhibiting drugs, were estimated. Newly initiated beta-blocker therapy (any type) with concomitant use of CYP2D6-inhibiting drugs (any type) was associated with an increased risk of fall injury (OR 1.37, 1.24–1.52). This risk became elevated after restriction to concomitant use of moderate (OR 1.63, 1.26–2.10) or strong CYP2D6 inhibitors (OR 2.25, 1.39–3.63). The results remained similar independent of the beta-blockers’ degree of CYP2D6 metabolism (none, partial or major). Our study indicates the presence of drug-drug interaction for concomitant use of beta-blockers and CYP2D6 inhibitors in relation to the risk of fall injury, irrespective of degree of CYP2D6 metabolism.
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spelling doaj-art-5331bfd9aa7d4641b084dacc593ef8712025-08-20T04:02:46ZengNature PortfolioScientific Reports2045-23222025-07-011511810.1038/s41598-025-09617-4CYP2D6-inhibiting drugs and risk of fall injury after newly initiated therapy with beta-blockers—a register-based case-crossover studyKarin Leander0M.-L. Dahl1M. Vikström2J. Möller3K. Söderberg-Löfdal4Institute of Environmental Medicine, Unit of Cardiovascular and Nutritional Epidemiology, Karolinska InstitutetDivision of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University HospitalInstitute of Environmental Medicine, Unit of Cardiovascular and Nutritional Epidemiology, Karolinska InstitutetDepartment of Global Public Health, Karolinska InstitutetDivision of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University HospitalAbstract We assessed whether concomitant use of CYP2D6-inhibiting drugs associates with increased risk of fall injuries after newly initiated therapy with beta-blockers. A case-crossover study design was applied which eliminates confounding from individual fixed characteristics by pairing cases with themselves across time. Data on prescribed and dispensed beta-blockers and hospitalizations for first-time fall injuries in the Swedish population aged ≥ 20 for the period 2006-01-01–2013-12-31 were extracted from national registers. Odds ratios (OR) with 95% confidence interval (CI) of fall injury associated with newly initiated beta-blocker therapy (prescription dispensed within the 28 days preceding the fall injury) while considering concomitant use of CYP2D6-inhibiting drugs, were estimated. Newly initiated beta-blocker therapy (any type) with concomitant use of CYP2D6-inhibiting drugs (any type) was associated with an increased risk of fall injury (OR 1.37, 1.24–1.52). This risk became elevated after restriction to concomitant use of moderate (OR 1.63, 1.26–2.10) or strong CYP2D6 inhibitors (OR 2.25, 1.39–3.63). The results remained similar independent of the beta-blockers’ degree of CYP2D6 metabolism (none, partial or major). Our study indicates the presence of drug-drug interaction for concomitant use of beta-blockers and CYP2D6 inhibitors in relation to the risk of fall injury, irrespective of degree of CYP2D6 metabolism.https://doi.org/10.1038/s41598-025-09617-4Accidental fallsBeta-blocking agentsCytochrome P450 CYP2D6 inhibitorsDrug interactions
spellingShingle Karin Leander
M.-L. Dahl
M. Vikström
J. Möller
K. Söderberg-Löfdal
CYP2D6-inhibiting drugs and risk of fall injury after newly initiated therapy with beta-blockers—a register-based case-crossover study
Scientific Reports
Accidental falls
Beta-blocking agents
Cytochrome P450 CYP2D6 inhibitors
Drug interactions
title CYP2D6-inhibiting drugs and risk of fall injury after newly initiated therapy with beta-blockers—a register-based case-crossover study
title_full CYP2D6-inhibiting drugs and risk of fall injury after newly initiated therapy with beta-blockers—a register-based case-crossover study
title_fullStr CYP2D6-inhibiting drugs and risk of fall injury after newly initiated therapy with beta-blockers—a register-based case-crossover study
title_full_unstemmed CYP2D6-inhibiting drugs and risk of fall injury after newly initiated therapy with beta-blockers—a register-based case-crossover study
title_short CYP2D6-inhibiting drugs and risk of fall injury after newly initiated therapy with beta-blockers—a register-based case-crossover study
title_sort cyp2d6 inhibiting drugs and risk of fall injury after newly initiated therapy with beta blockers a register based case crossover study
topic Accidental falls
Beta-blocking agents
Cytochrome P450 CYP2D6 inhibitors
Drug interactions
url https://doi.org/10.1038/s41598-025-09617-4
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