Switching oral anticoagulants

  • Ensure continuous, adequate anticoagulation while minimising bleeding risk, when switching anticoagulants.
  • Plan switching anticoagulants to start on a Sunday or Monday so that INR testing can be done during the week (and avoid weekend INR testing).
  • Although all newer anticoagulants can contribute to an elevated INR, the INR is not a measure of their anticoagulant effect.
  • Provide clear instructions to the patient to avoid missed or double doses during switching.
    Note: Rivaroxaban is once daily dosing while apixaban and dabigatran are both twice daily dosing.
  • Advise patients to return any oral anticoagulant medicine no longer required to their doctor or pharmacist for safe disposal when switching is completed.

FROM warfarin

The switch from warfarin to another oral anticoagulant is largely guided by the patient's INR (international normalised ratio).[1–6]

FROM warfarin TO apixaban[1]

Stop Wait Then start
Warfarin
Until INR < 2.0[A] apixaban

FROM warfarin TO dabigatran[2]

Stop Wait Then start
Warfarin
Until INR < 2.0[A] dabigatran

FROM warfarin TO rivaroxaban[3]

Stop Wait Then start
Warfarin

Until INR ≤ 3.0[A] in AF or

INR ≤ 2.5[A] in prevention or treatment of DVT
rivaroxaban
[A] However, expert consensus recommends wait until INR ≤ 2.0 before starting a new oral anticoagulant.[5]


TO warfarin

The protocol for switching to warfarin depends on the oral anticoagulant being used.[1–4]

FROM apixaban TO warfarin[1]

  • Switching guided by INR, limited clinical trial data available to guide the process 
Start
When should INR be done?[B]
Wait
Then STOP
Continue

START warfarin concurrently, using standard initial dosing on days 1 and 2

Daily from day 3 onwards warfarin dose is guided by INR

During co-administration, obtain the INR  just before the next scheduled dose of apixaban.
 

Until INR ≥ 2.0

STOP apixaban

Once the INR is ≥ 2.0 and stable, continue routine monitoring to guide warfarin dose.

See Starting warfarin therapy for a guide to achieving and maintaining INR in therapeutic range

[B] The first INR obtained on day 3 of warfarin medication is for the purpose of identifying an excessive INR resulting in more caution with warfarin dosing.[6]


FROM dabigatran TO warfarin[2,6]

  • Switching guided by renal function
Start Wait Then STOP
When should INR be done?
Check renal function[C]


Review INR at least 2 days after the last dose of dabigatran when it will better reflect the effect of warfarin
On day 1: START warfarin concurrently[D] 3 days if CrCl > 50 mL/min
On day 4: STOP dabigatran
2 days if CrCl 31–50 mL/min On day 3: STOP dabigatran
1 day if CrCl 15–30 mL/min[E] On day 2: STOP dabigatran

[C] Cockcroft–Gault formula was used in the clinical trials. This method is recommended when assessing patient CrCl (mL/min) before and during dabigatran treatment.

A free online CrCl calculator is available on the Austrailan Medicines Handbook website (go to www.amh.net.au/online/misc/creatinineclearancecalculator.php)

[D] Initial warfarin dosing recommendations are not provided in the dabigatran Product Information. Use a standard initial dose for days 1–2 then adjust according to INR.

[E] Note dabigatran is contraindicated in patients with CrCl < 30 mL/min.


FROM rivaroxaban TO warfarin[3,6]

  • Switching guided by INR, limited clinical trial data available to guide the process 
Start
When should INR be done?[B] Wait
Then STOP
Continue[6]

START warfarin concurrently, using standard initial dosing on days 1 and 2.

Daily from day 3 onwards warfarin dose is guided by INR.[F]

During co-administration obtain INR  just before the next scheduled rivaroxaban dose.

An INR obtained at least 24 hours after the last rivaroxaban dose will better reflect the effect of warfarin.

Until INR ≥ 2.0

rivaroxaban

Once the INR is ≥2.0 and stable continue routine INR monitoring to guide warfarin dose.

See Starting warfarin therapy for a guide to achieving and maintaining INR in therapeutic range.

[F] Point-of-care INR monitors should not be used to assess the INR during transitions between rivaroxaban and warfarin. Rivaroxaban will increase the prothrombin time to differing extents, based on difference in the sensitivity of the coagulometer and the prothrombin reagent.[3,6]


FROM apixaban, dabigatran or rivaroxaban TO apixaban, dabigatran or rivaroxaban[7]

Limited experience or guidance available. Start the first dose of apixaban, dabigatran or rivaroxaban when the next dose of the preceding newer oral anticoagulant would have been due.[7]

Consider a longer interval between stopping the current anticoagulant and starting one of the newer oral anticoagulants in situations where higher-than therapeutic plasma concentrations are expected, e.g. a patient with impaired renal function (half-life of the anticoagulant will be increased).[7]

Note: The information on this page is based on information current at the time of publication.

References

  1. Bristol-Myers Squibb Australia Pty Ltd. Eliquis (apixaban) Product Information. 29 April 2013.
  2. Boehringer Ingelheim Pty Limited. Pradaxa (dabigatran etexilate) Product Information. 15 April 2013.
  3. Bayer Australia Limited. Xarelto (rivaroxaban) Product Information. 27 June 2013.
  4. Australian medicines handbook. Adelaide: Australian Medicines Handbook Pty Ltd, 2012.
  5. Alberts MJ, Eikelboom JW, Hankey GJ. Antithrombotic therapy for stroke prevention in non-valvular atrial fibrillation. Lancet neurology 2012;11:1066–81.
  6. Schulman S, Crowther MA. How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch. Blood 2012;119:3016–23.
  7. Heidbuchel H, et al. European Hearth Rhythm Association practical guide on the use of the new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace: 2013;15:625–51.