Theoretically, the concurrent use of P-gp or CYP3A4 inducers could decrease DOAC benefits, but the panel was unable to estimate the magnitude of decrease, if any. Harms and burden. Theoretically, the concurrent use of P- gp or CYP3A4 inhibitors could increase risk for bleeding for patients being treated with DOACs, but the panel was unable to estimate the magnitude of increase, if any. Use of P-gp/CYP inhibitors was associated with an increased risk of major bleeding and intracranial hemorrhage but not a significant change in the safety or efficacy of rivaroxaban compared with warfarin.28 Other EtD criteria and considerations. The panel de- termined that the acceptability of using DOACs for patients requiring P-gp or CYP3A4 inhibitors or inducers varies depending on factors such as the specific DOAC, whether the interacting medication was a strong inhibitor or inducer, the underlying bleeding or thromboembolic risk of the patient, comorbid disease states such as renal dysfunction, and patient preferences. The panel was unable to identify any evidence regarding other considerations. Conclusions and research needs for this recommendation. The guideline panel was unable to determine whether using DOACs concomitantly with P-gp or CYP3A4 inhibitors or inducers would result in a net health benefit or harm. Given the lack of evidence, we suggest that clinicians consider using an alternative anticoagulant (such as VKA or LMWH) rather than DOACs for patients requiring administration of P-gp inhibitors or inducers or strong inhibitors or inducers of CYP enzymes (conditional recommendation based on very low certainty in the evidence about effects). The recommen- dation places a high value on avoiding the uncertainty in DOAC anticoagulant response associated with coadministration of the interacting drug and a low value on avoiding the burden of warfarin or LMWH therapy. 