ZONTIVITY, Vorapaxar Sulfate Form

Vorapaxar (Zontivity®) is a protease-activated receptor-1 antagonist. FDA Approved Indication(s) Zontivity is indicated for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD). Zontivity has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke, and urgent coronary revascularization. Policy/Criteria Provider must submit documentation (including such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Zontivity is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Cardiovascular Event Prophylaxis (must meet all):

1. Member has history of MI and/or diagnosis of PAD;
   2. Prescribed by or in consultation with a cardiologist;
   3. Member must use in combination with at least one of the following (a or b):
      a. aspirin (generic preferred);
      b. clopidogrel (generic preferred);
2. Dose does not exceed both of the following (a and b):
   a. 2.08 mg per day; b. 1 tablet per day. Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):

3. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace; or Page 1 of 5

   CLINICAL POLICY
   Zontivity b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace; or

4. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace. II. Continued Therapy A. Cardiovascular Event Prophylaxis (must meet all):
   
   1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
   2. Member is responding positively to therapy;
   3. If request is for a dose increase, new dose does not exceed both of the following (a and b):
      a. 2.08 mg per day;
      b. 1 tablet per day.
      Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):
5. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace; or

6. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace.
   III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – HIM.PA.154 for health insurance marketplace or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration Page 2 of 5

   CLINICAL POLICY
   Zontivity MI: myocardial infarction PAD: peripheral arterial disease Appendix B: Therapeutic Alternatives
   This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
   Drug Name Dosing Regimen Dose Limit/ Maximum Dose 75 mg/day 100 mg/day clopidogrel (Plavix®) aspirin 75 mg PO QD 75 to 100 mg PO QD Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o History of stroke, transient ischemic attack, or intracranial hemorrhage o Active pathologic bleeding • Boxed warning(s): bleeding risk; do not use Zontivity in patients with history of stroke, TIA, or intracranial hemorrhage or active pathological bleeding.
   V. Dosage and Administration
   Indication Cardiovascular event prophylaxis 2.08 mg (1 tablet) PO QD
   Dosing Regimen Maximum Dose 2.08 mg/day VI. Product Availability
   Tablet: 2.08 mg VII.