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

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. 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. 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. 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. 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. Variability between jurisdictions was evident, and variability of DOAC use is likely to increase with expanding worldwide uptake.