Even though direct oral anticoagulants (DOAC) are at risk for drug-drug interactions, they are barely mentioned in the dose adjustment guidelines and contradictory information is found in the summary of product characteristics of individual DOACs. This represents a significant issue for general and internal medicine clinicians, as it is well established that patients with atrial fibrillation receive numerous co-medications, and that polymedication increases the bleeding risk. Our multidisciplinary team (composed of clinical pharmacologists and pharmacists, internal medicine and hemostasis physicians) proposes here practical recommendations for pharmacokinetic drug-drug interactions with DOAC, based on the best available clinical and pharmacological evidence that can be easily implemented at the bedside. These recommendations aim pragmatically to more clearly define the situations that require the clinician's attention and provide suggestions for appropriate action in presence of drug-drug interactions with DOAC.