Direct Oral Anticoagulants (DOACs)

Dabigatran Rivaroxaban Apixaban Edoxaban

(Pradaxa) (Xarelto) (Eliquis) (Savaysa)
Drug Classification Selective thrombin inhibitor Selective direct Xa inhibitor Selective direct Xa inhibitor Selective direct Xa inhibitor
FDA Approved - Nonvalvular AF - Nonvalvular AF - Nonvalvular AF - Nonvalvular AF
Indications - Treatment of VTE - Treatment of VTE - Treatment of VTE - Treatment of VTE
- Reduce risk of recurrent VTE - Reduce risk of recurrent VTE - Reduce risk of recurrent VTE
- VTE prophylaxis (hip) - VTE prophylaxis (hip & knee) - VTE prophylaxis (hip & knee)
Half-life 12-17 hrs 5-9 hrs 8-15 hrs 10-14 hrs
14-17 hrs (elderly) 9-12 hrs (elderly)
Time to max effect 2 hrs 2-4 hrs 3 hrs 1-2 hrs
Renal Clearance 80% renal 66% renal 25% renal 50% renal
20% biliary 33% biliary 75% biliary 50% biliary
Dosage AF: AF: AF: AF:
 150 mg BID  20 mg DAILY with PM meal  5 mg BID  60 mg DAILY

VTE treatment & Recurrent VTE: VTE treatment: VTE treatment: VTE treatment:
 150 mg BID after 5-10 days of  15 mg BID x 21 days, then 20  10 mg BID x 7 days, then 5  60 mg daily after 5-10 days of
parenteral anticoagulant mg DAILY with PM meal mg BID parenteral anticoagulant

VTE Prophylaxis: Recurrent VTE: Recurrent VTE: 2.5 mg BID

 110 mg 1-4 hrs post hip  20 mg daily with PM meal
surgery then 220 mg daily x VTE prophylaxis:
35 days VTE prophylaxis:  Hip surgery: 2.5 mg BID x 35
 Hip surgery: 10 mg daily x 35 days
days  Knee surgery: 2.5 mg BID x
 Knee surgery: 10 mg daily x 12 12 days
days
Dosing Adjustments and AF: CrCl 15-30: 75 mg BID AF: CrCl 15-50: 15 mg daily AF: if 2 of 3 criteria met then AF: CrCl > 95: avoid use
Considerations CrCl < 15: avoid use CrCl < 15: avoid use decrease to 2.5 mg BID: CrCl 15 – 30: 30 mg daily
 Age > 80 CrCl < 15: avoid use
VTE: CrCl < 30: avoid use VTE Treatment and Prophylaxis:  Wt < 60 kg
CrCl < 30: avoid use  Creatinine > 1.5 VTE: CrCl 15 – 30: 30 mg daily
CrCl < 15: avoid use
Hemodialysis: 5 mg BID (reduce
dose if 2 of 3 criteria above met)

VTE Treatment and Prophylaxis:

CrCl < 15: avoid use
Contraindications - Avoid in pregnancy, breastfeeding or in severe liver disease
Monitoring No lab testing available. All DOACs affect the INR. Measuring INRs during co-administration may not be useful for determining an appropriate
dose of warfarin.
Peri-procedure Pre- - Standard bleed risk procedure - Standard bleed risk procedure - Standard bleed risk procedure - Standard bleed risk procedure
use op  CrCl ≥ 50: stop 1-2 days prior  CrCl > 30: stop 24 hrs prior  Scr ≥ 50: stop 24 hrs prior  CrCl ≥ 50: stop 24 hrs prior
(see U-Connect  CrCl < 50: stop 3-5 days prior  CrCl < 30: stop 48 hrs prior  Scr < 50: stop 48 hrs prior  CrCl < 50: stop 48 hrs prior
 Direct Oral Anticoagulants (DOACs)
for UW guidelines)
- High bleed risk procedure: - High bleed risk procedure: - High bleed risk procedure: - High bleed risk procedure:
 CrCl ≥ 50: stop 2-4 days prior  CrCl > 30: stop 48 hrs prior  CrCl ≥ 50: stop 48 hrs prior  CrCl ≥ 50: stop 48 hrs prior
 CrCl < 50: stop > 5 days prior  CrCl < 30: stop 72 hrs prior  CrCl < 50: stop 72 hrs prior  CrCl < 50: stop 72 hrs prior
Post- - For low bleed risk surgery restart within 24 hrs post-op if ok with surgeon
op - For high bleed risk surgery restart within 72 hrs post-op if ok with surgeon
Switching from DOAC to - If CrCl > 50: start warfarin 3 days Initiate warfarin & a parenteral If continuous anticoagulation is - If taking 60 mg, reduce to 30 mg
warfarin prior to stopping dabigatran anticoagulant 24 hrs after necessary, stop apixaban & and begin warfarin
- If CrCl 31-50: start warfarin 2 stopping rivaroxaban begin both a parenteral - If taking 30 mg, reduce to 15 mg
days prior to stopping dabigatran anticoagulant & warfarin when and begin warfarin
- If CrCl 15-30: start warfarin 1 day next dose is due; stop parenteral - measure INR at least weekly and
prior to stopping dabigatran anticoagulant when INR at goal just prior to the use of edoxaban
- when INR > 2.0 stop edoxaban
Switching from DOAC to - If CrCl >30, start UFH or - If CrCl >30, start UFH or Start UFH or enoxaparin 12 hrs D/c edoxaban and start parenteral
IV UFH or enoxaparin enoxaparin 12 hrs after last dose enoxaparin 12 hrs after last dose after the last apixaban dose AC at the time of next dose of
- If CrCl <30, consider starting - If CrCl <30, consider starting edoxaban
UFH or enoxaparin 24 hrs after last UFH or enoxaparin 24 hrs after
dose last dose
Switching from warfarin Allow INR to drop to < 2.0 before Allow INR to drop to < 3.0 before Allow INR to drop to < 2.0 before Start when INR is < 2.5
to DOAC initiating initiating initiating
Switching from  Start DOAC 2 hrs before the time to next subcutaneous anticoagulant dose  Discontinue LMWH and start
parenteral AC to DOAC  Start DOAC at the time of IV heparin discontinuation edoxaban at the time of next
schedule dose LMWH
 - Discontinue heparin drip and
start edoxaban 4 hrs later
Recommendations for - Only DOAC with antidote: - For all DOACs hemostasis expected within 12-24 hrs after last dose
bleeding besides blood Idarucizumab - Oral activated charcoal given within 2 hrs may decrease plasma concentrations
products (see UW - Only DOAC that can be
guidelines on U-Connect) moderately reversed by dialysis
Missed Dose - Take missed dose ASAP, but if - If taking 15 mg BID: Take - Take missed dose ASAP on same day
next dose is < 6 hrs away, skip ASAP to ensure 30 mg daily - The dose should not be doubled to make up for a missed dose
the missed dose - For daily dose: Take missed
- Do not take 2 doses at the same dose immediately
time
Drug Interactions - P-gp & strong CYP3A4 inhibitors (amiodarone, cyclosporine, ketoconazole, quinidine, verapamil, azole antifungals, nicardipine, ritonavir), may 
serum concentration
- P-gp & strong CYP3A4 inducers (carbamazepine, dexamethasone, phenytoin, prazosin, rifampin, nafcillin, rifampin) may decrease the serum
concentration
Use for electrical Demonstrated to be effective anti-coagulant in the setting of cardioversion with guidelines similar to warfarin
cardioversion
Nonbleeding Side Dyspepsia (5-10%) None
Effects
Advantages - Fixed dose
- No bridging
- No INR monitoring required
- No food restrictions & fewer drug interactions
 Direct Oral Anticoagulants (DOACs)
Disadvantages - Cost
- Lack of antidote & difficult to manage bleeding
- Difficult to determine compliance
- Missed dose may place pt at increased risk of thromboembolic event
- Renal monitoring and dose adjustment required
Lab Frequency follow- Yearly: Hgb, renal and liver function
up 6 monthly: Renal function if CrCl 30-60 ml/min, or if on dabigatran and > 75 years or fragile
3 monthly: If co-morbidity or condition that may impact renal or hepatic function

References:
 European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation (2013) 15, 625-651.
 Chest Supplement, Antithrombotic Therapy and Prevention of Thrombosis, 9th edition, ACCP.
 RE-LY trial: NEJM 2009; 361:1139
 ROCKET-AF trial: NEJM 2011: 365:883.
 ARISTOTLE trial: NEJM 2011: 365:981.
 Package inserts from Pradaxa, Xarelto, Eliquis, Savaysa

Developed by Kathy Wackerle, APRN-BC

Reviewed by Dr. Craig January
October 2015