Direct Oral Anticoagulants (DOACs) like rivaroxaban, apixaban, dabigatran, and edoxaban offer effective anticoagulation with fewer monitoring requirements compared to traditional therapies like acenocoumarol and warfarin. However, managing drug-drug interactions (DDIs) involving DOACs, especially in hospitalized patients with complex medical conditions, poses unique challenges. This resource provides an overview of how healthcare professionals can handle these interactions in a hospital setting to minimize risks and optimize patient outcomes. In this literature update an overview is given of an article by Zaria et al.

DOACs and DDIs Overview

DOACs are frequently used in patients with conditions like atrial fibrillation and venous thromboembolism. However, moderate to strong inhibitors or inducers of the CYP3A4 enzyme and P-glycoprotein (P-gp) can significantly alter the pharmacokinetics of DOACs. This can increase the risk of either thrombotic or hemorrhagic events. For example, co-administration with drugs like clarithromycin, a potent CYP3A4 inhibitor, can heighten the risk of major bleeding, while inducers like rifampin can reduce DOAC effectiveness, increasing the risk of clot formation.

Study Insights A study conducted at Brigham and Women's Hospital reviewed 23,280 hospitalizations from January to June 2021, identifying 197 cases (5%) where patients had clinically relevant DOAC DDIs. Among these:

• o 63% had no changes made to their medication regimen based on the interaction at discharge.
• o 37% required adjustments, including stopping the interacting drug (73%), stopping the DOAC (15%), or holding the DOAC temporarily (4%).
• o Interestingly, only 4% of these interactions prompted an automated alert from the hospital’s electronic health record (EHR), highlighting a potential gap in alert systems.

Management Practices

The majority of DOAC DDIs in hospitalized patients were managed by either continuing or adjusting the dose of the DOAC or interacting drug. Adjustments typically included dose reductions or discontinuations of either the DOAC or the interacting medication. For instance, when apixaban was prescribed alongside azithromycin, the dose was lowered to minimize bleeding risk. Outcomes and Risks Among patients whose regimens were adjusted due to a DDI, there was no statistically significant difference in rehospitalization or mortality compared to those whose regimens were not adjusted. However, rehospitalizations and deaths within 90 days were slightly higher in the group with medication changes (25% vs. 16% for mortality).

Practical Application for Healthcare Professionals

For healthcare providers managing hospitalized patients on DOACs, it is critical to regularly assess the potential for DDIs, particularly when new therapies are introduced. While DOACs are generally safe, interactions with other drugs, especially those metabolized by CYP3A4 and P-gp, can lead to serious adverse effects. Steps for Managing DOAC DDIs:

• • Review and Reconcile Medications: Conduct thorough medication reviews upon admission, paying attention to CYP3A4 or P-gp inhibitors and inducers.
• • Monitor for Alerts: Ensure that electronic health record systems are updated to prompt alerts for high-risk interactions, and review these carefully.
• • Dose Adjustments: Be proactive in adjusting doses of either the DOAC or the interacting drug when necessary. Monitor for signs of bleeding or clotting.
• • Consult Pharmacists: Pharmacist-led medication reconciliation can be invaluable in identifying potential interactions and managing DDIs effectively during care transitions.

Conclusion

Clinically significant DDIs with DOACs occur infrequently but require careful management. The findings suggest that many DOAC-DDIs can be managed without discontinuing the anticoagulant, though greater awareness and improved alert systems in hospitals could further enhance patient safety. With the increasing complexity of patient care, especially in older adults with polypharmacy, healthcare providers must remain vigilant about potential drug interactions to ensure optimal therapeutic outcomes.

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