Fall-risk in genetic variable cytochrome P450 enzymes and exposure to anticholinergic drugs – a pilot-analysis from the ADRED-study

Aims The use of anticholinergic (AC) drugs in older adults is associated with falls, but it is not clear how to differentiate the individual risk. The aim was to analyze associations of pharmacogenetic slow CYP2D6 and CYP2C19 metabolism of AC drugs with falls in older adults.Patients and methods Cohort study of adverse drug reactions in emergency departments (ADRED-study). Patients ≥65 years, with use of ≥three drugs, and pharmacogenetic results for CYP2D6 and CYP2C19. Anticholinergic burden scores (ABS) derived from medication were analyzed, differentiating for ABS derived from drugs metabolized via CYP2D6 (ABS2D6) and CYP2C19 (ABS2C19).Results N = 659 patients were included. ABS2D6 showed a significant association with falls in logistic regression analysis of OR 1.57 [95%CI 1.09–2.26]. Intermediate and poor CYP2D6 metabolizers had a high chance of 3.32 [1.58–6.99] to present with a fall, while normal and ultra-rapid CYP2D6 metabolizers had not (1.19 [0.71–1.98]). CYP2C19 metabolizers were not found to be associated with a higher chance of falls (1.10 [0.59–2.04]).Conclusions This hypothesis-generating-study identifies pharmacogenetic slow CYP2D6 metabolizers as high‑risk patients for falls with the use of AC drugs. Our study may help to individualize recommendations on anticholinergic drug treatment to optimize drug safety in older adults.Trial registration DRKS00008979.