Drug interactions with the available oral anticoagulant warfarin are prominent in clinical practice, with more than 50% of patients tak- ing potentially warfarin-interacting drugs. The objective of this review is to summarize data on drug interactions with warfarin in rela- tion to the bleeding risk, their mechanisms and significance, and to present new data on the current problem. In 2021, the results of the largest systematic review and meta-analysis of 72 studies evaluating clinically significant drug interactions with warfarin leading to bleeding were published. The most significant groups of drugs that in combined use with warfarin increase the risk of bleeding include antiplatelets, non-steroidal anti-inflammatory drugs (NSAIDs), some antibiotics, selective serotonin reuptake inhibitors (SSRIs), and the mechanism of these interactions is largely pharmacodynamic. There was no statistically sig-nificant increase in the bleeding risk when warfarin was combined with amiodarone, but an increase in all-cause mortality was found. A decrease in clinically significant bleeding when warfarin was combined with proton pump inhibitors was found. Thus, antiplatelets, NSAIDs, SSRIs may increase the risk of bleed- ing when combined with warfarin, and their concomitant use should be routinely evaluated. Data on drug interactions with warfarin is constantly updated and replenished, so it is very important for clinicians to regularly receive up-to-date information to address issues of rational and safe treatment of patients receiving warfarin. Qualified management of drug interactions with warfarin will help improve clinical outcomes and prevent adverse complications in patients taking warfarin.

Keywords: antiplate-lets selective serotonin reuptake inhibitors, drug interactions, non-steroidal anti-inflammatory drugs, proton pump inhibitors, bleeding, amiodarone, warfarin