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Compared to vitamin K antagonists, DOACs have significant advantages, although their drug\u2013drug interaction (DDI) profile may complicate drug efficacy and safety. This narrative review addresses the clinical challenges posed by these DDIs and the potential pharmacological alternatives and monitoring strategies available.<\/jats:p><jats:p>A PubMed search was conducted (1 January 2000\u201331 December 2023) including human DDI studies on DOAC use and CYP3A4\/P\u2010gp inducers in adult patients, evaluating patient outcome data and recommendations for DDI management.<\/jats:p><jats:p>Twenty\u2010two studies were included. Case reports (<jats:italic>n<\/jats:italic>\u2009=\u20096) indicated that antiepileptic drugs such as carbamazepine, phenobarbital and phenytoin may be associated with thromboembolic events. The nested case\u2013control studies (<jats:italic>n<\/jats:italic>\u2009=\u20092) and cohort studies (<jats:italic>n<\/jats:italic>\u2009=\u20099) found that co\u2010administration of DOACs and CYP3A4\/P\u2010gp inducers, particularly carbamazepine and phenytoin, increased the risk of thromboembolic events. Pharmacovigilance database analyses indicated a significant association between DOAC DDIs and increased reported stroke rates. Management recommendations in systematic reviews (<jats:italic>n<\/jats:italic>\u2009=\u20095) highlighted monitoring when DOACs were combined with inducers. Strategies included using alternative drugs with a weaker or preferentially absent inducing profile. Limited evidence suggests that edoxaban may be an acceptable option in case of DOAC and CYP3A4\/P\u2010gp inducer interactions; however, robust clinical data confirming safety are needed.<\/jats:p><jats:p>Present literature indicates a higher thromboembolic risk in patients on DOAC treatment combining CYP3A4\u2010 and\/or P\u2010gp inducers. 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