Detection and management of clinically relevant drug-drug interactions with direct oral anticoagulants in ambulatory care: a prospective interventional study in community pharmacies

Abstract Background/Introduction Direct oral anticoagulants (DOACs) are increasingly used but can be involved in clinically relevant drug-drug interactions (DDIs) that increase the risk of major bleeding or thromboembolism. Community pharmacists, who have access to patients’ complete medication profiles, including over-the-counter medication and medication from different prescribers, can play a crucial role in detecting and managing DDIs with DOAC in ambulatory care. Purpose This study aimed to detect and manage DDIs with DOAC in ambulatory care, because such real-life clinical practice studies are currently lacking. Methods A prospective interventional study was conducted between October 2021 and August 2022 in 201 community pharmacies in Belgium. On random days, every patient purchasing a DOAC or an interacting drug was screened for the presence of a DDI with DOAC. The pharmacist contacted the physician to discuss the management of the interaction. For the screening and management of DDI with DOAC, a previously developed practice-oriented DDI list for ambulatory care was used [1]. Results In total, 751 patients (74.5±10.7 years) were included, in whom 875 DDIs were identified. The three most commonly involved interacting drugs were (selective) serotonin (norepinephrine) reuptake inhibitors (32.9%), antiplatelets (30.9%), and non-steroidal anti-inflammatory drugs (28.9%). Most DDIs (83.1%) were not new (patients were already using these drugs) and 8.7% of interacting drugs were dispensed over-the-counter. In almost one-third of DDIs (28.0%), the interacting drug and the DOAC were prescribed by different physicians. Prescribers rated the clinical risks of the identified DDIs as high (15.9%), moderate (33.1%), and low (38.7%), whereas 12.3% were unaware of the potential risks. Remarkably, in 18 patients who were concomitantly taking an antiplatelet and DOAC, the prescriber reported forgetting to stop the antiplatelet or not being aware that the patient was taking both medications. Three patients were also found to be using another anticoagulant along with DOAC due to miscommunication between prescribers. When discussing how to manage the DDI, pharmacotherapy was mostly unchanged (60.2%). Physicians cited reasons such as the interacting drug being deemed necessary (37.2%), the patient already using a proton pump inhibitor (PPI) (19.5%), or the patient using both interacting drugs already for a long time without problems (18.6%). However, in 39.8% of cases, the discussion resulted in a pharmacotherapy change. The most common changes included stopping the interacting drug (21.5%), initiating a PPI (17.6%), or replacing the interacting drug with a safer alternative (14.5%). Conclusion This study illustrated that community pharmacists, in collaboration with physicians, can contribute to reducing avoidable patient harm from DDIs with DOACs.