DOAC At-a-Glance Reference updated: August 2018

1 DOAC At-a-Glance Reference updated: August 2018 DOAC_At-a-Glance_8-27-2018 MGH Anticoagulation Management Service file owner: L B Oertel Page 1 of 4 Dabigatran PI March 2018 Indication Dose Modifiers Renal Hepatic Impairment Child-Pugh Class: Pregnancy Reversal Lactation DABIGATRAN Halflife: 12-17h Tmax: 1-2h NVAF CrCl>30mL/min 150mg twice daily AVOID P-gp inducer rifampin *dronedarone or ketoconazole HD: Avoid B: large inter-subject variability. No evidence of consistent change in exposure or pharmacodynamics May increase risk of bleeding in fetus and neonate For life threatening emergencies or urgent surgery: idarucizumab (Praxbind ) IV in 2 divided doses Hemodialysis can remove CrCl 15-30 mL/min 75 mg twice daily CrCl <15 or HD No recommendation CrCl 30-50 AND P-gp inhib* 75 mg twice daily CrCl 15-30 AND P-gp inhib* AVOID VTE CrCl >30 mL/min 150mg twice daily AFTER 5-10 (7 MGH AMS) day lead-in with parenteral agent CrCl 30 or HD No recommendation Breastfeeding NOT recommended CrCl <50 and P-gp inhibitor AVOID VTE risk reduction CrCl >30mL/min 150 mg twice daily CrCl 30 or HD No recommendation CrCl<50 and P-gp inhibitor AVOID VTE prophylaxis (HIP) Hip Replacement CrCl >30mL/min 110mg for first day, then 220 mg once daily for 28-35 days CrCl <50 AND P-gp inhibitor AVOID CrCl 30 or HD No recommendation Transition from warfarin Discontinue warfarin and start dabigatran when the INR is <2 Transition to warfarin CrCl 50 mL/min: start warfarin 3 days before discontinuing NOTE.

2 Dabigatran can increase the INR, INR will better reflect warfarin s effect after dabigatran stopped for at least 2 days CrCl 30-50 mL/min: start warfarin 2 days before discontinuing CrCl 15-30 mL/min: start warfarin 1 days before discontinuing CrCl < 15 mL/min: No recommendations Transition from OR to Parenterals Currently on parenteral: Start 0 2 hours before the time of next dose of parenteral drug or at time of d/c of IV heparin Currently on dabigatran: If CrCl 30 - wait 12 hours, if CrCl <30 - wait 24 hours after last dose of dabigatran before initiating parenteral Interruptions for Surgery or Invasive Procedures (especially epidural or spinal) Discontinue dabigatran 1-2 days (CrCl 50) or 3-5 days (CrCl <30). (MGH AMS at least 48 hrs but based on patient risk assessment) Consider longer time if major surgery, spinal puncture or spinal or epidural catheter placement. Restart after adequate hemostasis established. Patient Education Highlights (see Patient and Family Education Medication Guide for Dabigatran in Partners Handbook or EED anticoag portal page or Epic) Must remain in original container.

3 Use open bottle within 120 days. Blister packs available. Swallow capsules whole, do NOT open, break or chew. Take with full glass water. May take with or without food. Do NOT double up for a missed dose. DOAC At-a-Glance Reference updated: August 2018 DOAC_At-a-Glance_8-27-2018 MGH Anticoagulation Management Service file owner: L B Oertel Page 2 of 4 Rivaroxaban PI June 2018 Indication Dose Modifiers Renal Hepatic Impairment Child-Pugh Class: Pregnancy Reversal Lactation RIVAROXABAN Halflife: 5-9h Tmax: 2-4h NVAF CrCl>50 mL/min 20mg daily with food AVOID concomitant P-gp and strong CYP3A4 inhibitors (ketoconazole, ritonavir) AVOID concomitant P-gp and strong CYP3A4 inducers (carbamazepine, phenytoin, rifamptin, St.)

4 John s wort) ESRD on HD: Not adequately studied in large-scale clinical trial, use in this population should be avoided whenever possible. Am J Med. 2017; 130(9):1015-1023 B: AVOID C: AVOID Use caution due to potential for obstetric hemorrhage and/or emergent delivery Coagulation Factor Xa (recombinant) (Andexxa ), approved 2018 Indication: life-threatening or uncontrolled bleeding IV bolus followed by continuous IV infusion CrCl 15-50 mL/min 15mg daily with food CrCl <15 AVOID CrCl 15-80 mL/min AND combined P-gp + moderate CYP3A4 inhibitors (eg. erythromycin) AVOID VTE CrCl>30 mL/min 15 mg twice daily with food for first 21 days after 21 days, transition to Has been detected in human milk. Insufficient data for recommendations 20 mg once daily with food for remaining treatment CrCl<30 mL/min AVOID VTE risk reduction 10mg daily with or without food after at least 6 months standard anticoagulant therapy VTE prophylaxis Hip Replacement 10mg daily with or without food for 35 days Knee Replacement 10mg daily with or without food for 12 days CrCl <30 mLmin AVOID Transition from warfarin Discontinue warfarin and start rivaroxaban when the INR is <3 (MGH AMS <2) Transition to warfarin No data available.

5 One approach is to d/c rivaroxaban and begin both a parenteral anticoagulant and warfarin at the time of the next dose of rivaroxaban would have been taken. NOTE: Rivaroxaban affects INR Transition from rivaroxaban to anticoagulants other than warfarin D/C rivaroxaban Give the first dose of the other anticoagulant (oral or parenteral) at the time the next rivaroxaban dose would have been taken Transition from anticoagulants other than warfarin to rivaroxaban Start rivaroxaban 0-2 hr prior to next scheduled evening administration of the drug Omit administration of other drug (LMWH or non-warfarin oral anticoagulant) Start rivaroxaban Stop IV heparin infusion at same time Interruptions for Surgery or Invasive Procedures (especially epidural or spinal) Stop at least 24 hours (MGH AMS 48 hrs) before procedure. Restart after adequate hemostasis. Patient Education Highlights (see Patient and Family Education Medication Guide for Rivaroxaban in Partners Handbook or EED anticoag portal page or Epic) Take 15 and 20mg dose with food.

6 May crush pills and mix with applesauce or water if trouble swallowing or delivery via NG or gastric tube; follow with meal or enteral feeding. If taking 15 mg twice daily, can double up for missed dose same day. Do not double if on a daily dose. DOAC At-a-Glance Reference updated: August 2018 DOAC_At-a-Glance_8-27-2018 MGH Anticoagulation Management Service file owner: L B Oertel Page 3 of 4 Apixaban PI June 2018 Indication Dose Modifiers Renal Hepatic Impairment Child-Pugh Class: Pregnancy Reversal Lactation APIXABAN Halflife: ~12h Tmax: ~3h NVAF Recommended dose 5mg twice daily If taking 5mg or 10mg twice daily, decrease dose by 50% if: concomittant CYP3A4 and P-gp inhibitors (ketoconazole, itraconazole, ritonavir).

7 AVOID if dose already at mg twice daily. AVOID concomitant strong inducers of CYP3A4 and P-gp (rifampin, carbamazipine, phenytoin, St. John s wort). ESRD on HD: Not adequately studied in large-scale clinical trial, use in this population should be avoided whenever possible. Am J Med. 2017; 130(9):1015-1023 B: No advice C: AVOID Cat B Coagulation Factor Xa (recombinant) (Andexxa ), approved 2018 Indication: life-threatening or uncontrolled bleeding IV bolus followed by continuous IV infusion Activated oral charcoal absorption of apixaban and plasma concentration. If two of the following: Age 80 yr, Wt 60 kg, or sCr mg/dl twice daily VTE 10 mg twice daily for first 7 days after 7 days, transition to Unknown if excreted in human milk, D/C breastfeeding or drug 5mg twice daily VTE risk reduction twice daily AFTER at least 6mo Trt. dose VTE prophylaxis Hip Replacement (initial dose 12-24 h after surgery) twice daily for 35 days Knee Replacement (initial dose 12-24 h after surgery) twice daily for 12 days Transition from warfarin Discontinue warfarin and start apixaban when the INR is <2 Transition to warfarin One approach is to d/c apixaban and begin both a parenteral anticoagulant and warfarin at the time of the next dose of apixaban would have been taken.

8 D/C parenteral agent when INR reaches acceptable range. NOTE: apixaban affects INR Transition from apixaban to anticoagulants other than warfarin (oral or parenteral) Stop apixaban Begin taking new anticoagulant other than warfarin at usual time of the next dose of apixaban Transition from anticoagulants other than warfarin to apixiban Stop the anticoagulant Begin apixaban at the usual time of the next dose of the anticoagulant other than warfarin Temporary interruptions for Surgery or Invasive Procedures (especially epidural or spinal) Stop at least 48 hours prior with moderate or high risk of bleeding, at least 24 hours if low risk. Restart after adequate hemostasis established. Patient Education Highlights (see Patient and Family Education Medication Guide for Apixaban in Partners Handbook or EED anticoag portal page or Epic) Take with or without food. Can crush tablets and add to applesauce or D5W if trouble swallowing or can deliver via NG tube. DOAC At-a-Glance Reference updated: August 2018 DOAC_At-a-Glance_8-27-2018 MGH Anticoagulation Management Service file owner: L B Oertel Page 4 of 4 Edoxaban PI September 2017 Indication Dose Modifiers Renal Impairment Hepatic Impairment Child-Pugh Class: Pregnancy Reversal Lactation EDOXABAN Halflife: 10-14h Tmax: 1-2h NVAF CrCl >95mL/min AVOID AVOID rifampin HD: No data B: AVOID C: AVOID Insufficient data None CrCl 51-95mL/min 60 mg once daily CrCl 15-50 mL/min 30mg once daily CrCl <15 AVOID VTE CrCl >50 mL/min 60 mg once daily AFTER 5-10 day (7 MGH AMS) lead-in with parenteral agent *In Hokusai VTE, dose to 30mg if concomitant.

9 Verapamil, quinidine, azithromycin, clarithromycin, erythromycin, itraconazole or ketoconazole Breastfeeding is NOT recommended CrCl 15-50 mL/min 30mg once daily CrCl <15 AVOID If Weight 60kg 30mg once daily P-gp inhibitor * 30mg once daily Transition from warfarin Discontinue warfarin and start edoxaban when the INR is (MGH AMS <2) Transition to warfarin Oral option: If taking 60mg, dose to 30mg: Begin warfarin concomitantly. Once stable INR 2, D/C edoxaban. NOTE: Measure INR at least weekly and just prior to daily edoxaban to minimize influence on INR value. Oral option: If taking 30mg, dose to 15mg: Begin warfarin concomitantly. Once stable INR 2, D/C edoxaban. Parenteral option: D/C edoxaban Begin parenteral and warfarin at time of next scheduled edoxaban dose. Once stable INR 2, D/C parenteral. Transition from OR to Parenterals or DOAC Currently on LMWH or DOAC: D/C other anticoagulant or LMWH and start edoxaban at time of next scheduled dose Currently on IV Heparin: D/C infusion and start edoxaban 4 hours later Currently on edoxaban: If CrCl 30 - wait 12 hours, if CrCl <30 - wait 24 hours after last dose of dabigratran before initiating parenteral Interruptions for Surgery or Invasive Procedures (especially epidural or spinal) Discontinue edoxaban at least 24 hours (MGH AMS 48 hrs) before.

10 Restart after adequate hemostasis established. Patient Education Highlights (see Patient and Family Education Medication Guide for Edoxaban in Partners Handbook or EED anticoag portal page or Epic) Can take with or without food. Do not double up for missed dose. No data available regarding crushing and/or mixing edoxaban into food, liquids or NG tube administration.