Recommendations for Anticoagulation Therapies Anticoagulation and Thrombophilia Clinic 800 East 28th Street, Minneapolis, MN 55407 612-863-6800 allinahealth.org/mhi | mplsheart.com AKN S414386 281375 Table of Contents Recommendations for Anticoagulation Therapies Direct Oral Anticoagulants (DOACs) Guide .............................................................................................................................. 3–14 Management of Bleeding Associated with Direct Oral Anticoagulants (DOACs) ................................................................... 15–25 Switching To and From Anticoagulants .................................................................................................................................. 26–32 Management of Periprocedural Anticoagulation ..................................................................................................................... 33-50 Warfarin ................................................................................................................................................................. 34 DOACs ...............................................................................................................................................................35-37 Bleeding Risks ........................................................................................................................................................ 38 Thrombotic Risks ................................................................................................................................................... 39 Cardiac Electrophysiology ..................................................................................................................................40-44 Cardiac Catheterization Lab ............................................................................................................................. 45-46 Neuraxial Access or Peripheral Nerve Procedures ................................................................................ 47-50 DVT and PE Prophylaxis in Medically Ill Patients ..........................................................................................................................51-61 Thromboprophylaxis for Congenital Heart Patients ......................................................................................................................61-62 DVT and PE Anticoagulation Management Recommendations ....................................................................................................63-69 Thrombophilia Work-up Recommendations ..................................................................................................................................70-79 Watchman (Left Atrial Appendage Occluder Device) Non-Implanter Reference ............................................................................80-82 Access the most recent version online on the AKN at Abbott Northwestern Hospital > Excellian patient care quick links. Anticoagulation and Thrombophilia Clinic 800 East 28th Street, Minneapolis, MN 55407 612-863-6800 | Reviewed August 2016, June 2018, July 2019 allinahealth.org/mhi | mplsheart.com Direct Oral Anticoagulants (DOACs) Guide Anticoagulation and Thrombophilia Clinic, Minneapolis Heart Institute®, Abbott Northwestern Hospital. Tel: 612-863-6800 S414386A 281375 0517 ©2017 ALLINA HEALTH SYSTEM. TM A TRADEMARK OF ALLINA HEALTH SYSTEM. MINNEAPOLIS HEART INSTITUTE® AND MHI® ARE TRADEMARKS OF MINNEAPOLIS HEART INSTITUTE®, INC. 3 Direct Oral Anticoagulants (DOACs) Guide Direct Thrombin Direct Factor Xa Inhibitors (Factor IIa) Inhibitor apixaban edoxaban rivaroxaban betrixaban dabigatran (Pradaxa®) (Eliquis®) (Savaysa®) (Xarelto®) (Byvexxa®) NVAF NVAF NVAF Prophylaxis of VTE in NVAF FDA Approved 5 mg PO BID CrCl > 95 mL/min: CrCl > 50 mL/min: 20 mg adults hospitalized for CrCl >30 mL/min: 150 Indications and 2.5 mg PO BID: If ≥ 2 of NOT recommended PO daily with evening meal acute medical illness mg PO BID Dosage the following: age ≥80 (drug may be cleared CrCl ≤ 50 mL/min: 15 mg with moderate or CrCl 15-30 mL/min: 75 years, weight ≤60 kg or too rapidly and PO daily with evening meal severe restricted mg PO BID Cr ≥ 1.5 mg/dL adequate drug levels mobility CrCl < 15 mL/min: not not attained) VTE treatment 160 mg PO initial recommended Usage if Cr > 2.5 mg/dL CrCl ≥30 mL/min: CrCl 51-95 mL/min: single dose, or CrCl < 25 mL/min is 15 mg PO BID for 21 days, VTE treatment and 60 mg PO once daily followed by 80 mg based on then 20 mg PO daily secondary prevention pharmacokinetics and CrCl 15-50 mL/min: same time daily For VTE treatment, an CrCl < 30 mL/min: not on clinical studies. 30 mg PO once daily with food for 35 to initial 5-10 days of Caution is advised. not recommended 42 days CrCl < 15 mL/min: not parenteral CrCl 15-29 mL/min: VTE treatment recommended VTE secondary prevention anticoagulation is 80 mg PO initial 10 mg PO BID for 7 days, CrCl ≥ 30 mL/min: required before VTE treatment single dose, initiating dabigatran then 5 mg PO BID 10 mg PO daily, with or Begin after 5-10 days followed by 40 mg CrCl >30 mL/min: 150 No dose adjustment without food, after at least of initial therapy with a same time daily mg PO BID based on renal function 6 months of standard parenteral with food for 35 to CrCl ≤30 mL/min: not Usage if CrCl < 25 treatment. anticoagulant 42 days recommended mL/min is based on CrCl > 50 mL/min: 60 CrCl < 30 mL/min: CrCl < 15 mL/min: pharmacokinetics and not mg PO once daily not recommended not recommended VTE prophylaxis in THR CrCl >30 mL/min: 110 on clinical studies. CrCl 15-50 mL/min or With concomitant Caution is advised. VTE prophylaxis in THR/TKR mg for the first day, then weight ≤60 kg or on P- Start 6-10 hours post-op use of P-gp gp inhibitor§: 30 mg PO inhibitor§: 80 mg PO 220 mg PO daily VTE secondary prevention THR: 10 mg PO daily for once daily initial single dose, CrCl ≤30 mL/min or on 2.5 mg PO BID 35 days followed by 40 mg dialysis: dosing CrCl < 25 mL/min: no VTE secondary TKR: 10 mg PO daily for same time daily recommendations not clinical studies prevention 12 days with food for 35 to available VTE prophylaxis in Not approved Avoid if CrCl < 30 mL/min 42 days CrCl <50 mL/min with THR/TKR VTE prophylaxis in concomitant use of P-gp Start 12-24 hours postop § THR/TKR Reduction of Risk of Major inhibitor : avoid co- THR: 2.5 mg BID PO for Not approved Cardiovascular Events administration 35 days Chronic CAD and/or PAD: VTE prophylaxis in TKR TKR: 2.5 mg BID PO for 2.5 mg PO BID in Not approved 12 days combination with aspirin CrCl < 30 mL/min: no 81 mg PO daily clinical studies 4 Direct Oral Anticoagulants (DOACs) Guide Direct Thrombin Direct Factor Xa Inhibitors (Factor IIa) Inhibitor apixaban edoxaban rivaroxaban betrixaban dabigatran (Pradaxa®) (Eliquis®) (Savaysa®) (Xarelto®) (Byvexxa®) Capsules: 75 mg, 110 mg, 150 mg Keep in original container; remove only at time of use. Close bottle immediately Tablets: 15 mg, 30 mg, Tablets: 2.5 mg, 10 mg, 15 mg, Tablets: 2.5 mg, 5 mg Capsules: 40 mg, 80 mg after use. Keep tightly Dosage Forms 60 mg 20 mg closed. Do not put in pillbox or medication organizer. Use within 4 months after opening bottle. Yes No data are available Yes May dissolve in No water or apple juice, Both 2.5 mg and 5 regarding The 15 mg and 20 mg Do not chew, break, or or mix with mg tablets may be bioavailability upon tablets may be crushed open capsules applesauce. For crushed and crushing and/or and mixed with (bioavailability increases by administration by suspended in 60 mL mixing edoxaban applesauce for oral use 75% if capsule is opened) NG or feeding tube, D5W and tablets into food, or with 50 mL of water Able to Crush liquids, or dissolve in water. Medication immediately for NG or gastric tube delivered through an administration feeding (avoid if distal to After NGT through feeding the stomach). After administration, oral tubes. or enteral feeding No information available administration, oral or should immediately regarding oral enteral feeding should follow the dose. administration of immediately follow the crushed and suspended dose. tablets 20 mg: with food Administration with 15 mg: with food With or without food With or without food With food With or without food food 2.5 mg,10 mg: with or without food Half-life 8-15 hours 10-14 hours 5-13 hours 19-27 hours 12-17 hours T-max 3-4 hours 1-2 hours 2-4 hours 3-4 hours 1-3 hours Renal 27% Renal 50% Renal 50% Feces: 85% Renal 80% Hepatic unchanged drug Metabolism Hepatic 73% Metabolism, biliary/intestinal 50% 1/3 eliminated non- Renal: 11-18% metabolized 5 Direct Oral Anticoagulants (DOACs) Guide Direct Thrombin Direct Factor Xa Inhibitors (Factor IIa) Inhibitor apixaban edoxaban rivaroxaban betrixaban dabigatran (Pradaxa®) (Eliquis®) (Savaysa®) (Xarelto®) (Byvexxa®) Bleeding Bleeding Bleeding Bleeding Bleeding Thrombocytopenia GI: dyspepsia, abdominal Thrombocytopenia Hypokalemia Abnormal LFTs Hypersensitivity and epigastric pain reaction Side Effects Hypersensitivity reaction Rash Hypertension GI bleed Stevens-Johnson Thrombocytopenia Headache Anemia Syndrome Hypersensitivity reaction Agranulocytosis Hypersensitivity Hepatitis reaction Not studied and Not studied and Not studied and should No data in pregnancy Not studied and should be should be avoided should be avoided be avoided but treatment likely to avoided increase risk of Lactation: not Lactation: not