We present a novel, evidence-based methodology to identify ‘severe’ drug-drug interactions (DDIs) that may result in adverse health outcomes.

In our study, approximately one-quarter of older (≥ 70 years) participants were potentially exposed to at least one ‘severe’ cardiovascular or central nervous system DDI. Polypharmacy and depression were significantly associated with potential exposure to these DDIs.

Older adults dispensed warfarin, escitalopram, atorvastatin, furosemide, or clarithromycin had the highest burden of potential exposure to multiple DDIs examined. These older patients should be the focus of medication review/optimisation interventions.