Oral Anticoagulation Drug Class Prior Authorization Protocol Line of Business: Medicaid P & T Approval Date: February 21, 2018 Effective Date: April 1, 2018 This policy has been developed through review of medical literature, consideration of medical necessity, generally accepted medical practice standards, and approved by the IEHP Pharmacy and Therapeutics Subcommittee. Drug Requiring Prior Authorization Review: Eliquis (apixaban), Pradaxa (dabigatran), Savaysa (edoxaban), Xarelto (rivaroxaban) Formulary Alternative: Coumadin (warfarin) Criteria: A. Drug: Eliquis, Xarelto 1. Diagnosis: Prophylaxis Deep Venous Thrombosis (DVT) and/or Pulmonary Embolism (PE) *CODE 1* (please see Code 1 drug list here for details) 2. Diagnosis: Prophylaxis DVT following hip or knew replacement surgery *CODE 1* (please see Code 1 drug list here for details) 3. Diagnosis: Prophylaxis Non-Valvular Atrial Fibrillation (to prevent stroke and systemic embolism). Criteria: Failure or clinically significant adverse effects to warfarin. Duration of Therapy: 1 year (365 days)
B. Drug: Pradaxa b. Confirmed stability or no adverse effect (bleeding episode). Duration of Reauthorization: 1 year (365 days) 1. Diagnosis: Prophylaxis Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE) Criteria: Confirmed Diagnosis Duration of Therapy: 1 year (365 days) b. Confirmed stability or no adverse effect (bleeding episode). c. IEHP Pharmacist Review Required Duration of Reauthorization: 1 year (365 days) 2. Diagnosis: Prophylaxis DVT following hip or knee replacement surgery b. Xarelto Duration of Therapy: 2 months (60 days) b. Confirmed stability or no disease progression. c. IEHP Pharmacist Review Required Duration of Reauthorization: 2 months (60 days)
3. Diagnosis: Treatment of Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE) b. Xarelto Duration of Therapy: 6 months (180 days) b. Confirmed stability or no disease progression. c. IEHP Pharmacist Review Required Duration of Reauthorization: 6 months (180 days) 4. Diagnosis: Prophylaxis Non-Valvular Atrial Fibrillation (to prevent stroke and systemic embolism) b. Xarelto C. Drug: Savaysa Duration of Therapy: 1 year (365 days) b. Confirmed stability or no adverse effect (bleeding episode). Duration of Reauthorization: 1 year (365 days) 1. Diagnosis: Treatment of Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE)
b. Xarelto Duration of Therapy: 6 months (180 days) b. Confirmed stability or no disease progression. c. IEHP Pharmacist Review Required Duration of Reauthorization: 6 months (180 days) 2. Diagnosis: Non-Valvular Atrial Fibrillation (to prevent stroke and systemic embolism) b. Xarelto Duration of Therapy: 1 year (365 days) b. Confirmed stability or no adverse events (bleeding episodes). Duration of Reauthorization: 1 year (365 days)
Clinical Justification: Comparison of FDA Approved Indications Coumadin (warfarin) Eliquis (apixaban) Pradaxa (dabigatran) Xarelto (rivaroxaban) Savaysa (edoxaban) Usual Dosage Routine Lab Anticoagulant Monitoring Reversal Agent Dietary Consideration Time to maximum concentration Stroke prevention in nonvalvular atrial fibrillation (AF) VTE prophylaxis following hip or knee replacement VTE treatment Reduction in the risk of VTE recurrence Thromboembolism prevention in heart valve replacement Post myocardial infarction X X X X X X X X X X X X (Hip surgery) X X X X X X X X Dabigatran Rivaroxaban Apixaban Edoxaban Warfarin AF: 150mg AF: 60mg daily bid VTE tx: 60mg VTE tx: daily 150mg bid AF: 20mg daily VTE tx: 15mg bid x21 days, then 20mg daily VTE ppx: 10mg daily AF: 5 mg bid VTE tx: 10mg bid x 7 days, then 5mg bid VTE ppx: 2.5mg bid No No No No Yes Yes No No No Yes No 1-2 hours (no bridging required) Yes, take with evening meal for doses > 10mg 2-4 hours (no bridging required) AF: once daily titrate to INR 2-3 Mechanical mitral valve or mechanical aortic and mitral valves: INR 2.5-3.5 No No Yes; consistency with vitamin K food 3-4 hours (no bridging required) 1-2 hours (no bridging required) Peak effect delayed 72-96 hours
Bridging required (e.g. LMWH) Half-Life 12-17 hours 5-9 hours 12 hours 10-14 hours ~40 hours Renal Dosing Adjustment AF: CrCl 15-30 ml/min: 75mg bid RELY: CrCl <30mL/min: excluded VTE tx: CrCl 30 ml/min: avoid use Atrial Fibrillation AF: CrCl 15-50 ml/min: 15mg once daily ROCKET AF: CrCl<30mL/mi n excluded VTE tx: CrCl<30mL/mi n: avoid use VTE ppx: CrCl<30ml/min : avoid use AF: SCr 1.5 mg/dl and one of the following: Age 80, wt 60kg: 2.5mg bid VTE tx: no adjustment VTE ppx: no adjustment AF: Should not used in patients with CrCl>95 ml/min AF/VTE tx: CrCl 15-50mL/min: 30mg once daily. CrCl <15mL/min: avoid use 2016 American College of Chest Physicians (ACCP) CHEST Guidelines: Titrate to INR 2-3 Studies show that patients with non-valvular atrial fibrillation may have a higher risk of GI bleed with dabigatran, rivaroxaban and edoxaban over warfarin. 2014 American Heart Association (AHA), American College of Cardiology (ACC) and Heart Rhythm Society (HRS) Guideline for the Management of Patients with Atrial Fibrillation: Executive Summary: In patients with nonvalvular AF, the CHADS2-VASc score is recommended for assessment of stroke risk. (Level of Evidence: B) For patients with AF who have mechanical heart valves, warfarin is recommended, and the target INR intensity (2.0 to 3.0 or 2.5 to 3.5) should be based on the type and location of the prosthesis. (Level of Evidence: B) For patients with nonvalvular AF with prior stroke, transient ischemic attack (TIA), or a CHADS 2-VASc score of 2 or greater, oral anticoagulants are recommended. Options include warfarin (INR 2.0 to 3.0) (Level of Evidence: A), dabigatran (Level of Evidence: B), rivaroxaban (Level of Evidence: B), or apixaban (Level of Evidence: B)
Renal function should be evaluated before initiation of direct thrombin for factor Xa inhibitors and should be reevaluated when clinically indicated and at least annually. (Level of Evidence: B) For patients with nonvalvular AF with a CHA 2 DS 2 -VASc score of 2 or greater and who have end-stage chronic kidney disease (CKD) (creatinine clearance <15 ml/min) or are on hemodialysis, it is reasonable to prescribe warfarin (INR 2.0 to 3.0) for oral anticoagulation. (Level of Evidence: B) 1. According to the three pivotal large clinical trials, RELY, ROCKET AF and ARISTOTLE, dabigatran, rivaroxaban and apixaban, respectively, demonstrated noninferior efficacy in the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Furthermore, dabigatran and apixaban were shown to be superior to warfarin for their primary composite endpoint of stroke or systemic embolism. Favorable mortality benefits were noted with all three newer agents than warfarin. 2. There is no head-to-head comparison study among the newer oral anticoagulant agents. 3. Dabigatran is associated with increased gastrointestinal bleeding, particularly in patients of age 75 years and older. 4. Despite concerns of post-marketing reports of bleeding, dabigatran did not appear to associate with higher bleeding rates than warfarin according to the FDA statement issued in November 2012. Venous Thromboembolism (VTE) Treatment 2016 ACCP CHEST Guidelines: Dabigatran, rivaroxaban, apixaban or edoxaban are preferred over warfarin in the treatment of VTE in patients with no cancer (Grade 2B). In patients with VTE and cancer, low-molecular-weight heparins are preferred over warfarin (Grade 2B). For patients with proximal DVT or PE provoked by surgery or a nonsurgical transient risk factor, the duration of anticoagulant should be limited to 3 months (Grade 1B). VTE Prophylaxis in Total Knee Replacement and Total Hip Replacement 2012 ACCP CHEST Guidelines: LMWH is preferred over rivaroxaban or dabigatran in the prevention of VTE in patients undergoing total knee or total hip replacement (Grade 2B), given the lack of long term safety data with the newer agents. 2011 American Academy of Orthopedia Surgeons Guidelines:
No preference for one agent over another for VTE prophylaxis for total knee replacement or total hip replacement. Rivaroxaban, apixaban and dabigatran have demonstrated noninferior efficacy as enoxaparin 40mg once daily for VTE prophylaxis in patients undergoing total hip replacement with comparable major bleeding rates. References: 1. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-51. 2. Connolly SJ, Wallentin L, Ezekowitz MD, et al. The long-term multicenter observational study of dabigatran treatment in patients with atrial fibrillation (RELY-ABLE) Study. Circulation. 2013;128:237-43. 3. Coumadin [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2017. 4. Eliquis [package insert]. New York, NY: Bristol-Myers Squibb, Princeton NJ and Pfizer Inc.; 2012. 5. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients. CHEST 2012;141(2)(Suppl):e278S-325S. 6. FDA. Medical Review for dabigatran. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512orig1s000medr.pdf. Accessed January 7, 2018. 7. Furie KL, Goldstein LB, Albers GW, et al. Oral antithrombotic agents for the prevention of stroke in nonvalvular atrial fibrillation: a science advisory for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43:3442-53. 8. Guyatt GH, Akl EA, Crowther M, et al. Executive Summary: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Chest. Feb 2012;141(2 Suppl):7S-47S. 9. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation, Journal of the American College of Cardiology (2014), doi: 10.1016/j.jacc.2014.03.022. 10. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-52. 11. Mont MA, Jacobs JJ, Boggio LN, et al. Preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Am Acad Orthop Surg. 2011;19(12):768-76. 12. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation (ROCKET AF). N Engl J Med. 2011; Sep 8;365(10):883-91. 13. Pradaxa [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2013. 14. Savaysa [package insert]. Basking Ridge, NJ: Daiichi Sankyo, Inc.; 2017. 15. Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2013.
Change Control Date Change 02/21/2018 Added approval duration and re-authorization criteria Added indication of VTE prophylaxis to Eliquis, Xarelto and Pradaxa