New Oral Anticoagulants

Transcription

1 New Oral Anticoagulants A Resource Guide Brought to you by ADVANCE October 2015 advanceweb.com This resource highlights new oral anticoagulant drugs by brand name, generic name and drug classification. This includes indications, clinical actions, warnings/contraindications, drug administration and monitoring. Refer to complete prescribing information on use in these special populations: children, pregnancy, lactation, elderly, liver disease and kidney disease. THINKSTOCK/VISUAL GENERATION INC. Compiled by Yvonne Phan, PharmD, BCPS, assistant professor of Clinical Pharmacy, Philadelphia College of Pharmacy, University of the Sciences and Cardiology Pharmacy, Cardiology Pharmacy Specialist at the Hospital of University of Pennsylvania - Perelman Heart and Vascular Center; Hoan Hoang, PharmD Candidate, Philadelphia College of Pharmacy, University of the Sciences; and Joseph Cavanaugh, PharmD candidate, University of the Sciences, Philadelphia College of Pharmacy.

2 2 NEW ORAL ANTICOAGULANTS RESOURCE GUIDE Novel Oral Anticoagulants BRAND NAME DRUG CLASSIFICATION Factor Xa Inhibitor Eliquis GENERIC NAME Apixaban BRAND NAME DRUG CLASSIFICATION Direct Thrombin Inhibitor Pradaxa GENERIC NAME Dabigatran Etexilate BRAND NAME DRUG CLASSIFICATION Factor Xa Inhibitor Savaysa GENERIC NAME Edoxaban BRAND NAME DRUG CLASSIFICATION Xarelto GENERIC NAME THINKSTOCK/GETTY IMAGES Factor Xa Inhibitor Rivaroxaban

3 3 NEW ORAL ANTICOAGULANTS RESOURCE GUIDE Novel Oral Anticoagulants by Indication Indications Reduce risk of stroke and systemic embolism in patients with NVAF Treatment for DVT, PE, and reduction in the risk of recurrence of DVT and of PE Prophylaxis of DVT, which may lead to PE, following hip or knee replacement surgery Pradaxa (Dabigatran etexilate) Xarelto (Rivaroxaban) Eliquis (Apixaban) Savaysa (Edoxadan) + + NVAF: nonvalvular atrial fibrillation; DVT: deep venous thrombosis; PE: pulmonary embolism + = FDA approved indication Your No. 1 Job Resource Turn to our job board for the latest career opportunities in every specialty and practice setting. Save your searches, sign up for job alerts, create or upload a resume, apply in seconds and track your applications. You can do it all at JEFFREY LEESER

4 4 NEW ORAL ANTICOAGULANTS RESOURCE GUIDE Guidelines for Individual Drug or Drug Classes Pradaxa (Dabigatran etexilate) Indications Reduce risk of stroke and systemic embolism in patients with NVAF Treatment for DVT, PE, and reduction in the risk of recurrence of DVT and of PE Clinical actions Warnings/ contraindications Reversible direct thrombin inhibitor, inhibiting both free and fibrin bound thrombin Contraindicated in patients with known serious hypersensitivity reactions to dabigatran; discontinue dabigatran in patients with active pathological bleeding; avoid in patients with mechanical heart valve. [U.S. Boxed Warning] An increased risk of thrombotic events may occur with premature discontinuation of dabigatran. [U.S. Boxed Warning] Consider risks of spinal or epidural hematoma in patients who are receiving neuraxial anesthesia or undergoing spinal puncture. Dosing for treatment of DVT, PE, and reduction in the risk of recurrence of DVT and of PE Pregnancy Category C Treatment of DVT and PE: If CrCl > 30 ml/min, take 150 mg orally twice daily after 5-10 days of parenteral anticoagulation. Reduction in the risk of recurrence of DVT and PE: If CrCl > 30 ml/min, take 150 mg orally twice daily after previous treatment. Dosing for NVAF to reduce risk of stroke and systemic embolism Avoid use if CrCl < 50 ml/min and already receiving concomitant P-gp inhibitors (verapamil, quinidine, amiodarone, ritonavir, tacrolimus, cyclosporine). If CrCl > 30 ml/min, take 150 mg orally twice daily. If CrCl ml/min, take 75 mg orally twice daily. CrCl < 15 ml/min or on dialysis, dosing recommendation cannot be provided. If also taking dronedarone (Multaq) or systemic ketoconazole AND CrCl between ml/min, consider reducing dose to 75 mg orally twice daily. Drug interactions P-gp inducers rifampin: Avoid coadministration with dabigatran P-gp inhibitors in patients with CrCl ml/min: Consider reducing dose or avoid P-gp inhibitors in patients with CrCl < 30 ml/min: Not recommended Increased risk of bleeding with concomitant use of other drugs that increase the risk of bleeding (e.g., anti-platelet agents, heparin, fibrinolytic therapy, and chronic use of NSAIDs). Monitoring Monitor for signs and symptoms of bleeding (e.g., a drop in hemoglobin and/or hematocrit, hypotension). Check SCr and BUN in patients at risk for a decline in renal function. Clinical Pearls Must be used within 120 days of opening the bottle. Keep capsules in the original bottle to protect from moisture. Do not put in pill boxes or pill organizers. Administer with a full glass of water without regard to meals. Do not break, chew, or open capsules. Hepatic impairment: No dosage adjustment required (Note: RELY trial excluded patients with active hepatitis and persistent ALT, AST, Alk Phos greater than twice the upper limit of the normal range.)

5 5 NEW ORAL ANTICOAGULANTS RESOURCE GUIDE Pradaxa (Dabigatran etexilate) cont d. Conversion between other oral anticoagulants Converting to warfarin CrCl > 50 ml/min CrCl ml/min CrCl ml/min Initiate warfarin 3 days before stopping dabigatran Initiate warfarin 2 days before stopping dabigatran Initiate warfarin 1 day before stopping dabigatran Converting from warfarin Discontinue warfarin and initiate dabigatran when INR < 2.0 Management of acute bleeding/overdose Discontinuing prior to surgery/interventions 1 Activated charcoal within 2 hours of dabigatran administration No specific antidote; however reversal agents and/or platelet concentrates have been used and can be considered per institution s protocol. Hemodialysis (removes 68% in 4 hours): evidence supporting its use is limited. CrCl > 50 ml/min CrCl ml/min CrCl < 30 ml/min Standard Bleeding Risk Discontinue dabigatran 1 day before the procedure. Discontinue dabigatran > 2 days before the procedure. Discontinue dabigatran 2 to 5 days before the procedure. CrCl > 50 ml/min CrCl ml/min CrCl < 30 ml/min High Bleeding Risk Discontinue dabigatran 2 to 4 days before the procedure. Discontinue dabigatran 4 days before the procedure. Discontinue dabigatran > 5 days before the procedure. Xarelto (Rivaroxaban) Indications Reduce risk of stroke and systemic embolism in patients with NVAF Treatment for DVT, PE, and reduction in the risk of recurrence of DVT and of PE Prophylaxis of DVT, which may lead to PE, following hip or knee replacement surgery Clinical actions Direct factor Xa inhibitor that inhibits both free and clot-bound factor Xa Warnings/ Contraindicated in patients with known severe hypersensitivity reactions to rivaroxaban or any component of the formulation, and active pathological bleeding contraindications [U.S. Boxed Warning] An increased risk of thrombotic events may occur with premature discontinuation of rivaroxaban. [U.S. Boxed Warning] Consider risks of spinal or epidural hematoma in patients who are receiving neuraxial anesthesia or undergoing spinal puncture. Dosing for treatment of DVT, PE, and reduction in the risk of recurrence of DVT and of PE Dosing for NVAF to reduce risk of stroke and systemic embolism Pregnancy Category C Administer 15 mg orally twice a day with food for 21 days, then transition to 20 mg once daily with food, for remaining treatment. Patients with CrCl < 30 ml/min were excluded from the studies. If CrCl > 50 ml/min, take 20 mg once daily with evening meal. If CrCl ml/min, take 15 mg once daily with evening meal. If CrCl < 15 ml/min, avoid use.

6 6 NEW ORAL ANTICOAGULANTS RESOURCE GUIDE Xarelto (Rivaroxaban) cont d. Prophylaxis of DVT Hip replacement surgery: 10 mg once daily for a duration of 10 to 14 days (up to an extended duration of 35 days) following hip or knee replacement surgery Knee replacement surgery: 10 mg once daily for a minimum duration of 12 to 14 days (up to an extended duration of 35 days) Drug interactions Combined P-gp and strong CYP3A4 inhibitors and inducers: Avoid concomitant use. Anticoagulants: Avoid concomitant use. Monitoring Monitor for signs and symptoms of bleeding (e.g., a drop in hemoglobin and/or hematocrit, hypotension). Check SCr and BUN in patients at risk for a decline in renal function. Monitor for hepatic function (AST and ALT). Clinical Pearls Administer with the evening meal for nonvalvular atrial fibrillation. Can crush tablet and combine with a small amount of applesauce, followed by food. Conversion between other oral anticoagulants Converting to warfarin No clinical trial data are available to guide converting patients for rivaroxaban to warfarin. One approach is to discontinue rivaroxaban and begin both a parenteral anticoagulant and warfarin at the next scheduled dose of rivaroxaban. Discontinue the parenteral anticoagulant when INR reaches an acceptable range. Converting from warfarin Discontinue warfarin and initiate rivaroxaban when INR < 3.0. Management of acute bleeding/overdose Discontinuing prior to surgery/interventions (20 mg once daily) 2 Activated charcoal within 2 hours of rivaroxaban administration No specific antidote; however, reversal agents and/or platelet concentrates have been used and can be considered per institution s protocol. CrCl > 30 ml/min CrCl ml/min Standard Bleeding Risk Last dose of rivaroxaban 2 days before the procedure Last dose of rivaroxaban 3 days before the procedure CrCl > 30 ml/min CrCl ml/min High Bleeding Risk Last dose of rivaroxaban 3 days before the procedure Last dose of rivaroxaban 4 days before the procedure Eliquis (Apixaban) Indications Reduce risk of stroke and systemic embolism in patients with NVAF Treatment for DVT, PE, and reduction in the risk of recurrence of DVT and of PE Prophylaxis of DVT, which may lead to PE, following hip or knee replacement surgery Clinical actions Direct factor Xa inhibitor that inhibits both free and clot-bound factor Xa Warnings/ Contraindicated in patients with severe hypersensitivity reactions to apixaban or any component of the formulation, and active pathological bleeding contraindications [U.S. Boxed Warning] An increased risk of thrombotic events may occur with premature discontinuation of apixaban. [U.S. Boxed Warning] Consider risks of spinal or epidural hematoma in patients who are receiving neuraxial anesthesia or undergoing spinal puncture. Pregnancy Category B

7 7 NEW ORAL ANTICOAGULANTS RESOURCE GUIDE Eliquis (Apixaban) cont d. Dosing for treatment of DVT, PE, and reduction in the risk of recurrence of DVT and of PE Dosing for NVAF to reduce risk of stroke and systemic embolism Prophylaxis of DVT following hip or knee replacement surgery Administer 10 mg orally twice daily for 7 days, followed by 5 mg twice daily thereafter. May reduce to 2.5 mg twice daily after 6 months of previous therapy. Patients with CrCl < 25 ml/min or SCr > 2.5 mg/dl were excluded from the studies. Administer 5 mg orally twice daily. If patients have at least 2 of the following characteristics: age > 80 years, body weight < 60 kg, or serum creatinine > 1.5 mg/dl, then reduce dose to 2.5 mg orally twice daily. ESRD on hemodialysis: 5 mg orally twice daily; reduce to 2.5 mg twice daily if age 80 years or body weight 60 kg Hip replacement surgery: 2.5 mg twice daily beginning 12 to 24 hours postoperatively for 35 days Knee replacement surgery: 2.5 mg twice daily beginning 12 to 24 hours postoperatively for 12 days Drug interactions Strong dual inhibitors of CYP3A4 and P-gp: Reduce dose or avoid coadministration. Simultaneous use of strong dual inducers of CYP3A4 and P-gp: avoid concomitant use. Monitoring Monitor for signs and symptoms of bleeding (e.g., a drop in hemoglobin and/or hematocrit, hypotension). Check SCr and BUN in patients at risk for a decline in renal function. Clinical Pearls Twice daily dosing Dose reduction based on age > 80 years old, weight < 60 kg, and SCr > 1.5mg/dl Avoid concurrent use with antifungals (azoles), ritonavir, carbamazepine, phenytoin, St. John s Wort. Avoid use in moderate to severe hepatic impairment (Child Pugh Class B-C). Conversion between other oral anticoagulants Converting to warfarin No clinical trial data are available to guide converting patients for apixaban to warfarin. One approach is to discontinue apixaban and begin both a parenteral anticoagulant and warfarin at the next scheduled dose of apixaban. Discontinue the parenteral anticoagulant when INR reaches an acceptable range. Converting from warfarin Discontinue warfarin and initiate apixaban when INR < 2.0. Management of acute bleeding/overdose Activated charcoal within 2 hours of apixaban administration. No specific antidote; however, reversal agents and/or platelet concentrates can be considered per institution s protocol. Discontinuing prior to surgery/interventions (5 mg once daily) 2 CrCl > 50 ml/min CrCl ml/min CrCl > 50 ml/min CrCl ml/min Standard Bleeding Risk Last dose apixaban 2 days before the procedure Last dose of apixaban 3 days before the procedure High Bleeding Risk Last dose of apixaban 3 days before the procedure Last dose of apixaban 4 days before the procedure

8 8 NEW ORAL ANTICOAGULANTS RESOURCE GUIDE Savaysa (Edoxadan) Indications Reduce risk of stroke and systemic embolism in patients with NVAF Treatment for DVT, PE, and reduction in the risk of recurrence of DVT and of PE Clinical actions Warnings/ contraindications Direct factor Xa inhibitor that inhibits both free and clot-bound factor Xa Contraindicated in patients with active pathological bleeding [U.S. Boxed Warning] An increased risk of thrombotic events may occur with premature discontinuation of edoxaban. [U.S. Boxed Warning] Increased risk of ischemic stroke in non-valvular atrial fibrillation patients with CrCl > 95 ml/minute Pregnancy Category C Dosing for treatment of DVT, PE, and reduction in the risk of recurrence of DVT and of PE Dosing for NVAF to reduce risk of stroke and systemic embolism Initiate after 5-10 days of parental anticoagulation: If CrCl > 50 ml/min, take 60 mg orally once daily if CrCl > 50 ml/min. If CrCl ml/min OR body weight < 60 kg OR concomitant administration of P-gp inhibitors, take 30 mg orally once daily. If CrCl < 15mL/min: Avoid use. If CrCl > 50 to < 95 ml/min, take 60 mg orally once daily. If CrCl ml/min, take 30 mg orally once daily. If CrCl > 95 ml/min or < 15mL/min: Avoid use. Drug interactions Anticoagulants: Avoid concomitant use Rifampin: Avoid concomitant use Monitoring Monitor for signs and symptoms of bleeding (e.g., a drop in hemoglobin and/or hematocrit, hypotension). Check SCr and BUN in patients at risk for a decline in renal function. Clinical Pearls Once daily dosing Not recommended in patients with CrCl > 95 ml/min because of increased risk of ischemic stroke compared to warfarin at the highest dose studied (60 mg) Concomitant therapy with specific P-gp inhibitors requires dose adjustment: verapamil, quinidine; the short-term use of azithromycin, clarithromycin, erythromycin, oral itraconazole, oral ketoconazole Conversion between other oral anticoagulants Converting to warfarin If taking 60 mg once daily Reduce to 30 mg once daily and begin warfarin concomitantly If taking 30 mg once daily Reduce to 15 mg once daily and begin warfarin concomitantly Monitor INR at least weekly and discontinue edoxaban once a stable INR > 2 is achieved Converting from warfarin Discontinue warfarin and initiate edoxaban when INR < 2.5. Management of acute bleeding/overdose Discontinuing prior to surgery/interventions Activated charcoal within 2 hours of edoxaban administration No specific antidote; however, reversal agents and/or platelet concentrates can be considered per institution s protocol. Hold edoxaban at least 24 hours before invasive or surgical procedure because of the risk of bleeding.

9 9 NEW ORAL ANTICOAGULANTS RESOURCE GUIDE APPENDIX OF ACRONYMS NVAF: Nonvalvular atrial fibrillation CrCl: Creatinine clearance CYP3A4: Hepatic cytochrome P450 enzyme; affects drug metabolism INR: International normalized ratio DVT: Deep vein thrombosis PE: Pulmonary embolism P-gp: P-glycoprotein transporter; affects drug metabolism ESRD: End-stage renal disease AST: Aspartate transaminase ALT: Alanine transaminase Alk Phos: Alkaline phosphatase REFERENCES: 1. GJ Hankey et al. Dabigatran etexilate: a new oral thrombin inhibitor. Circulation. 2011;123: Spyropoulos AC, Douketis JD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood Oct 11;120(15): Prescribing Information. Pradaxa. 1/2015 ed. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT: Prescribing information. Xarelto. 1/2015 ed. Janssen Pharmaceuticals, Inc. Titusville, NJ: Prescribing information. Eliquis. 8/2014 ed. Bristol-Myers Squibb Company. Princeton, NJ: 2014 and Pfizer Inc. New York, NY: Prescribing information. Savaysa. 1/2015. Daiichi Sankyo, Inc. Parsippany, NJ: 2015 For more resources on a variety of topics, visit