Detecting Hidden Drug Risks by AI Powered Multiple-Drug-Drug Interaction (MDDI) Analysis: The Apixaban Case

Introduction The “clinical implications of co-administering apixaban with key interacting medications” were recently published by Favatella et al. in 2024 [1]. The authors stated that the multiple organ and metabolic pathways for apixaban clearance are expected to minimize the potential for large increases in apixaban exposure. However, this opinion might not apply when multiple mechanisms of drug clearance and inactivation are inhibited concomitantly as Isoherranen et al. have pointed to in a very convincing manner [2] and as shown in the in-vivo studies by Niemi et al. demonstrating huge increases of drug exposure caused by multiple enzyme inhibition in the triple drug interactions “repaglinide – itraconazole – gemfibrozil” and “loperamide – itraconazole – gemfibrozil” [3,4] (Table 1).