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

## TL;DR

This study found that using beta-blockers with CYP2D6-inhibiting drugs increases the risk of fall injuries, regardless of how much the beta-blockers rely on CYP2D6 metabolism.

## Contribution

The study identifies a drug-drug interaction between beta-blockers and CYP2D6 inhibitors that increases fall injury risk, independent of the beta-blocker's CYP2D6 metabolism level.

## Key findings

- Concomitant use of CYP2D6 inhibitors with beta-blockers was associated with a 37% increased risk of fall injury.
- Strong CYP2D6 inhibitors increased the risk by 125% compared to no inhibitors.
- The risk was consistent regardless of the beta-blocker's CYP2D6 metabolism level.

## 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.

The online version contains supplementary material available at 10.1038/s41598-025-09617-4.