How to Switch from Xarelto to Warfarin

New oral anticoagulants (NOACs) have several advantages over warfarin.

For instance, patients on warfarin often dislike undergoing regular coagulation monitoring, and many switch to NOACs to eliminate INR assessment. NOACs also have more rapid onset/offset of action, fewer drug-food interactions, and predictable pharmacokinetics. Plus, warfarin dosing can be complex if regimens are frequently adjusted or if patients have to take multiple tablets or half tablets on certain days, while NOACs are dosed identically day to day.

Although NOACs are an excellent choice for some patients, warfarin has clear advantages in certain individuals. For instance, its long half-life allows patients who often miss doses to remain anticoagulated for much longer than NOACs. Furthermore, although some studies have shown NOACs’ benefit regarding bleeding risk, with the exception of dabigatran, there are no commercially available reversal agents available for NOACs. Additionally, some patients benefit from close warfarin monitoring and opt to remain on warfarin even if they’re candidates for a NOAC.

For these reasons, there are often circumstances where patients are switched from a NOAC like rivaroxaban (Xarelto) to warfarin.

Unfortunately, to the best of my knowledge, no clinical trial data are available to guide this switch. According to Xarelto’s package insert, one approach is to discontinue Xarelto and begin both a parenteral anticoagulant and warfarin at the time the next dose of Xarelto would’ve been taken. In this case, parenteral therapy should be continued for ≥5 days and until INR ≥2 for ≥24 hours, according to the American College of Chest Physicians.

Although both patients and providers often find parental anticoagulation unappealing, the evidence on coadministering warfarin and NOACs is relatively sparse. Some literature recommends starting coadministration on day -4 and stopping rivaroxaban on day 0, based on pharmacokinetic data.^1,2

For a patient with a CrCl >50, the transition from Xarelto to warfarin would look like this:

• Day -4: Start warfarin, continue Xarelto
• Day -3: Continue warfarin and Xarelto
• Day -2: Continue warfarin and Xarelto
• Day -1: Continue warfarin and Xarelto
• Day 0: Stop Xarelto, continue warfarin
• Day 1+: Continue warfarin

An alternative method used in Europe involves continuing rivaroxaban and starting warfarin until INR ≥2. It recommends concurrent use for ≥2 days. Because rivaroxaban affects INR, providers using this method shouldn’t check INR until ≥24 hours after the prior rivaroxaban dose.³

Recent research results support this method, stating that as a general rule, either approach (stop NOAC and then start warfarin, or overlap warfarin with NOAC, measure INR just before next NOAC dose, and stop NOAC when INR ≥2.0) can be used for all NOAC to warfarin transitions.⁴

Notably, warfarin shouldn’t be started without a period of coadministration with another anticoagulant. Patients in the ROCKET-AF trial who were switched from Xarelto to warfarin without a period of bridging/coadministration had higher rates of stroke than those maintained on warfarin.

References

• Strasser KM, et al. Switching between oral anticoagulants. Hosp Pract. 2014;42(3):68-74.
• Schulman S, et al. How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch. Blood. 2012;119(13): 3016-3023.
• Moore KT, et al. Switching from rivaroxaban to warfarin: an open label pharmacodynamic study in healthy subjects. Br J Clin Pharmacol. 2015;79(6):907-917.
• Burnett AE, et al. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis. 2016;41(1):206-232.