1. Newer Anticoagulants Drug Class Nicole N. Nguyen, PharmD Senior Clinical Pharmacist Health Care Services October 16, 2013

2. Newer Anticoagulants Apixaban Dabigatran etexilate Rivaroxaban 2

3. February 2013 P & T Motion After considering the evidence of safety, efficacy and special populations for newer anticoagulant drugs for the prevention of stroke or systemic embolism in patients who are medically ill, undergoing surgery or with nonvalvular atrial fibrillation, I move that apixaban, dabigatran, and rivaroxaban are safe and efficacious for their approved indications. Apixaban, dabigatran, and rivaroxaban cannot be subject to therapeutic interchange in the Washington preferred drug list. 3

4. Criteria FDA approved indications and dosing Initial criteria includes trial of warfarin or reason given why unable to use warfarin (includes patient or provider refusal). – This was added due to new products on market without long term safety, and ability to reverse anticoagulant effect if needed. 4

5. Eliquis (apixaban) Indication: Non-valvular atrial fibrillation, to reduce the risk of stroke and systemic embolism Dosing: 5 mg BID – 2.5mg BID if at least 2 of the following: age ≥ 80 years, body weight ≤ 60kg, or serum creatinine ≥ 1.5 mg/dL 5

6. Pradaxa (dabigatran etexilate) Indication: Non-valvular atrial fibrillation, to reduce the risk of stroke and systemic embolism Dosing: – 150mg BID if creatinine clearance (CrCl) >30 mL/min – 75mg BID if CrCl 15 -30 mL/min 6

7. Xarelto (rivaroxaban) Indications: – Non-valvular atrial fibrillation, to reduce the risk of stroke and systemic embolism – Treatment of deep vein thrombosis (DVT) – Treatment of pulmonary embolism (PE) – Reduction in the risk of recurrence of DVT and PE after initial 6 months treatment for DVT and/or PE – prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery 7

8. Xarelto (rivaroxaban) continued Dosing: – A-fib: CrCl >50 mL/min: 20mg QD CrCl 15 to 50 mL/min: 15mg QD – Treatment DVT and PE: 15mg BID x 21 days, then 20mg QD – Reduction in risk of recurrence of DVT/PE: 20mg QD – Hip replacement: 10mg QD x 35 days – Knee replacement: 10mg QD x 12 days 8

9. Medicaid experience with PA For all newer anticoagulants there are requests for off-label use, including valvular a-fib. For all newer anticoagulants there are requests for incorrect dosing. Pradaxa approved first & have limited to non-valvular a-fib. Have received requests for valvular a-fib. 9

10. continued Pradaxa FDA warning issued not to use in patients with mechanical prosthetic heart valves due to increased risk of strokes, heart attacks, and blood clots forming on the mechanical heart valves than users of the anticoagulant warfarin. The use of Pradaxa valve replacement made of natural biological tissue, known as a bioprosthetic valves, has not been evaluated and cannot be recommended. 10

11. Questions? Clinical questions specific to Newer Anticoagulants? 11

12. Source of Criteria Current criteria in these drug classes was established through HCA’s internal Drug Evaluation Matrix Committee, prior to selection as PDL classes Not previously brought to the DUR Board under Authorization program because criteria are specific to FDA labeling and use of less costly alternatives 12

13. DUR Board review As per previous presentation: Use of generic(s) as first line agents for PDL classes explicitly requires review under RCW (unlike authorization program) Limiting product selection / endorser DAW according to FDA labeled indications requires review under RCW 13

14. Agency Recommendations Newer Anticoagulants -Approve requirement to use warfarin first line, with lenient exceptions including preference, convenience, or compliance factors -Approve requirement for use within FDA labeling and dosing -Eliminate DAW, requiring clinical justification by prescriber for selection of non-preferred product 14

15. Stakeholder Input Newer Anticoagulants 15

16. Motion: Newer Anticoagulants Require warfarin first line? Limit use to FDA labeling, including dosing requirements? Remove DAW privelige? Modifications to criteria by DUR Board? 16

17. Questions? More Information: http://www.hca.wa.gov/medicaid/billing/pages/prescription_drug_program.aspx or http://www.hca.wa.gov/medicaid/pharmacy/Pages/index.aspx Nicole N. Nguyen PharmD, Senior Clinical Pharmacist Health Care Services nicole.nguyen@hca.wa.gov Tel: 360-725-1757 17