Drug–drug interactions with DOACs persist despite computerized alerts

Clinicians vary as to how they manage drug–drug interactions (DDIs) with direct oral anticoagulants (DOACs) in clinical practice, with potentially substantial DDIs with DOACs still occurring despite computerized alerts, according to a study.

“When major DDIs with a DOAC occur, the benefit–risk evaluation should be made based on clinical relevance of DDIs as well as patient-specific factors,” the researchers said.

This retrospective chart review was conducted at the Brookdale University Hospital and Medical Center (BUHMC) in New York, US, from January 2014 to November 2016. All adult patients admitted to the BUHMC who received a DOAC for at least 3 days were screened. Those who received selected interacting drugs at any time during DOAC therapy were eligible for the study.

A total of 165 patients (mean age, 73 years) and 233 cases were included. Aspirin (58 percent) was the most commonly used concomitant drug with a DOAC, followed by amiodarone (16 percent) and P2Y₁₂ inhibitors (11 percent). [J Pharm Pract 2020;33:136-141]

Eighteen cases (6 percent) were identified to have used the combination of dual antiplatelet therapy and a DOAC. About a third of these cases were classified as the “avoidance” category.

Significant DDIs with DOACs occurred partly because of insufficient clinical data regarding DOAC DDIs, resulting in a wide variation across guideline recommendations, the researchers said. [J Thromb Thrombolysis 2016;41:206-232; Eur Heart J 2017;38:2137-2149; JCOM 2015;22:550-564]

“The mechanisms of DOAC DDIs mediated by P-gp and/or CYP3A4 are well described in the literature and widely understood among healthcare professionals,” they noted. “The incidence and clinical significance of these DDIs are not yet clearly established.” [Ther Adv Drug Saf 2017;8:319-328; Signa Vitae 2017;13(suppl 1):68-70]

This then led to a lack of consensus among international guidelines as well as drug information resources on how to manage clinically relevant DOAC DDIs. [Ther Adv Drug Saf 2017;8:319-328]

In a recent Australian study, Forbes and colleagues found that potential DDIs with DOACs were relatively common among inpatients aged >65 years (37 percent). This was consistent with the results of the current study, which found that potential DDIs with DOACs occurred in inpatients with an average age of 73 years (~30 percent). [Ther Adv Drug Saf 2017;8:319-328]

A retrospective study also found an increased risk of major bleeding when a DOAC was given with amiodarone, fluconazole, rifampin and phenytoin. The current study reported nearly 70 percent of patients receiving DOACs plus antiplatelet agents. [JAMA 2017;318:1250-1259]

According to the researchers, most patients who experienced significant bleeding events received antiplatelet agents concomitantly with DOACs.

“It would be reasonable for institutions to integrate key aspects from multiple clinical practice guidelines into practice until further studies provide conclusive evidence related to the appropriate use of DOACs including drug interactions,” they noted.