Jurisdictional Guidance on DOAC Use—Will It Affect Practice? A Comparison of European, American, and Canadian Product Monographs

Abstract

Objective: To identify clinically relevant areas of concordance and discordance between product monographs for 4 direct oral anticoagulants (DOACs) approved by regulatory authorities in Europe, the United States, and Canada. Data Sources: For each DOAC (apixaban, dabigatran, edoxaban, rivaroxaban), manufacturer product monographs were retrieved from the European Medicines Database, US Food and Drug Administration, and Health Canada Drug Product Database. Data Extraction: Monographs for each DOAC were independently reviewed by 2 investigators to identify areas of concordance and discordance. Discordance existed if it was deemed that a potentially clinically relevant difference existed. A heat map summarizing the data was created to identify areas of complete concordance, partial concordance (concordance between 2 of 3 monographs), and complete discordance. Data Synthesis: The areas of concordance were indications for use, use in extremes of weight, and switching to/from the DOAC. Areas of discordance included the following: differing recommendations for use/dosing with renal dysfunction; contraindication or use with caution with drug interactions, pregnancy, and hepatic/renal dysfunction; and timing of DOAC with spinal/epidural anesthesia after a procedure or traumatic puncture. Relevance to Patient Care and Clinical Practice: Concordance was most evident for uncomplicated patients with atrial fibrillation or venous thromboembolism, whereas discordance emerged for those having characteristics/factors wherein clinicians may seek clarification within product monographs (eg, impaired renal/hepatic function, drug interactions). As such, clinicians must be familiar with product information within their country of practice. Conclusion: Variability between jurisdictions was evident, and variability of DOAC use is likely to increase with expanding worldwide uptake.

Potential Drug Interactions between Recombinant Interleukin-2 and Direct Oral Anticoagulants: Indirect Evidence from In Vivo Animal Studies

“…15,16 This becomes more prominent when considering that the indications for DOAC are extending and ranging from non-valvular atrial fibrillation, acute coronary syndrome, recurrent VTE prevention, and VTE prevention in total hip/knee arthroplasty to chronic coronary or peripheral arterial disease. 17 Since the indications of rIL-2 extend and the use of DOAC increases globally, it will become more likely that some patients may use them concurrently. In this perspective, concerns exist on the safety of DOAC-treated patients being exposed to drugs which were not adequately represented in phase III trials or not investigated for potential interactions in ad hoc phase I pharmacokinetic studies.…”