ARIXTRA, Fondaparinux Sodium Form

Fondaparinux (Arixtra®) is a synthetic factor Xa inhibitor. FDA Approved Indication(s) Arixtra is indicated: • For prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing: o Hip fracture surgery, including extended prophylaxis;
o Hip replacement surgery; o Knee replacement surgery; o Abdominal surgery who are at risk for thromboembolic complications. • For treatment of acute DVT when administered in conjunction with warfarin sodium. • For treatment of acute PE when administered in conjunction with warfarin sodium when initial therapy is administered in the hospital. 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 Arixtra is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Thrombosis/Thromboembolism* (must meet all):

1. Any of the following indications (a, b, or c): a. Thrombosis or thromboembolism prevention associated with any of the following conditions: i. Cancer (see Appendix D); ii. Unstable angina or myocardial infarction; iii. Major surgery - orthopedic or non-orthopedic; iv. Critical illness related to ICU admissions or events; v. Restricted mobility associated with acute illnesses or conditions; vi. Implanted devices-vascular (e.g., central venous access device, umbilical venous catheter, devices/fistulas related to hemodialysis, ventricular assist devices); b. Thrombosis or thromboembolism treatment; c. Short-term prophylaxis for transition to or from oral anticoagulation; Page 1 of 9

   CLINICAL POLICY Fondaparinux

   2. Failure of a trial of enoxaparin unless (a, b, or c): a. Enoxaparin is contraindicated; b. History of clinically significant adverse effects or allergy to low molecular weight heparin (LMWH; enoxaparin or dalteparin) or heparin (e.g., history of heparin- induced thrombocytopenia [HIT]); c. The requested use is FDA labeled for fondaparinux but not for enoxaparin (i.e., hip fracture surgery prophylaxis; PE treatment);
   3. If request is for Arixtra, member must use generic fondaparinux, unless contraindicated or clinically significant adverse effects are experienced. Approval duration:
      Medicaid/HIM - 6 months Commercial – 6 months or duration of request, whichever is less ___ *Includes off-label use for adults and pediatrics. B. Anticoagulation in Pregnancy: Ante- and Postpartum (off-label) (must meet all):
   4. Any of the following indications: a. Acute venous thrombosis during current pregnancy; b. Prior venous thrombosis; c. Receiving long-term therapy with a vitamin K antagonist (e.g., warfarin); d. Prosthetic heart valve; e. Inherited thrombophilia; f. Antiphospholipid antibody syndrome; g. Development of severe ovarian hyperstimulation syndrome post assisted reproduction; h. Cesarean section – current pregnancy and request is for the postpartum period; i. Any other indication not listed here that is listed in section I.A.
   5. Member is pregnant or < 6 months postpartum;

2. History of clinically significant adverse effects or allergy to LMWH or heparin (e.g. HIT);

   4. If request is for Arixtra, member must use generic fondaparinux unless contraindicated or clinically significant adverse effects are experienced. Approval duration: Medicaid/HIM – Antepartum (to estimated delivery date); postpartum (6 months)
      Commercial – 6 months or duration of request, whichever is less C. 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: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or Page 2 of 9

   CLINICAL POLICY Fondaparinux b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

   2. 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: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid. II. Continued Therapy A. Thrombosis/Thromboembolism (must meet all):
3. 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);
4. Member is responding positively to therapy;
5. Continued use is limited to any of the following indications (a, b, or c):
   a. Venous thrombosis prophylaxis or treatment in the presence of cancer; b. Past history of failed anticoagulation therapy (clot development) on warfarin; c. Any other indication in section I.A where bridging to warfarin is inappropriate or member has a contraindication to warfarin and extended (indefinite duration) anticoagulation therapy is required;
   4. If request is for Arixtra, member must use generic fondaparinux, unless contraindicated or clinically significant adverse effects are experienced. Approval duration:
      Medicaid/HIM - 6 months Commercial – 6 months or duration of request, whichever is less B. Anticoagulation in Pregnancy: Ante- and Postpartum (off-label) (must meet all):
   5. 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);
6. Member is responding positively to therapy;
7. See Section II.A for continued anticoagulation therapy beyond 6 months postpartum;

8. If request is for Arixtra, member must use generic fondaparinux, unless contraindicated or clinically significant adverse effects are experienced. Approval duration: Medicaid/HIM – Antepartum (to estimated delivery date); postpartum (6 months)
   Commercial – 6 months or duration of request, whichever is less
   Page 3 of 9

   CLINICAL POLICY Fondaparinux C. Other diagnoses/indications (must meet 1 or 2):

   1. 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: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; 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: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
   2. 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 2 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
      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 – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
      IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key DVT: deep vein thrombosis HIT: heparin-induced thrombocytopenia LMWH: low molecular weight heparin NCCN: National Comprehensive Cancer Network
      PE: pulmonary embolism 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 Dose as specified; duration may vary. enoxaparin (Lovenox®)
      Adults: DVT prophylaxis in abdominal surgery 40 mg SC once daily DVT prophylaxis in knee replacement surgery 30 mg SC every 12 hours
      DVT prophylaxis in hip replacement surgery 30 mg SC every 12 hours or 40 mg SC once daily Page 4 of 9

   CLINICAL POLICY Fondaparinux Drug Name Dosing Regimen Dose Limit/ Maximum Dose DVT prophylaxis in medical patients 40 mg SC once daily Inpatient treatment or acute DVT with or without PE 1 mg/kg SC every 12 hours or 1.5 mg/kg SC once daily Outpatient treatment of acute DVT without PI 1 mg/kg SC every 12 hours Unstable angina and non-Q wave MI 1 mg/kg SC every 12 hours (with aspirin) Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
   o Severe renal impairment (creatinine clearance [CrCl] <30 mL/min) in prophylaxis or treatment of venous thromboembolism
   o Active major bleeding o Bacterial endocarditis o Thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of fondaparinux sodium o Body weight < 50 kg (venous thromboembolism [VTE] prophylaxis only) o History of serious hypersensitivity reaction (e.g., angioedema, anaphylactoid/anaphylactic reactions) to Arixtra • Boxed warning(s): Spinal/epidural hematomas Appendix D: General information • Per National Comprehensive Cancer Network (NCCN) guidelines for cancer-associated venous thromboembolic disease, fondaparinux is recommended for: o Anticoagulation for acute and chronic management of acute superficial vein thrombosis, management of chronic splanchnic vein thrombosis in cancer patients, management of acute splanchnic vein thrombosis, anticoagulation for acute DVT, acute catheter-related DVT, and/or acute pulmonary embolism in cancer patients with no contraindication to anticoagulation:
    as monotherapy  for 5 - 10 days given concurrently with warfarin monotherapy o Anticoagulation for cancer patients following progression on therapeutic anticoagulation: heparin sodium, low-molecular weight heparin, warfarin sodium, apixaban, dabigatran, edoxaban, or rivaroxaban o Venous thromboembolism prophylaxis for adult patients with cancer (excluding basal/squamous cell skin cancer) or those for whom a clinical suspicion of cancer exists who are admitted for medical or surgical hospitalizations with no contraindication to anticoagulation Page 5 of 9

   CLINICAL POLICY Fondaparinux o Initial treatment for suspected or confirmed heparin-induced thrombocytopenia following discontinuation of heparin-based products in clinically stable patients with no contraindications and without hemodynamically unstable pulmonary embolism, limb-threatening thrombosis, or planned invasive procedures o Transition to alternative therapy (direct oral anticoagulants preferred) for patents with heparin-induced thrombocytopenia who have been stabilized on initial treatment with a direct thrombin inhibitor or fondaparinux and have no contraindications or invasive procedures planned
   V. Dosage and Administration
   Indication Adults DVT prophylaxis following hip fracture, hip replacement, and knee replacement surgery and abdominal surgery Acute DVT/PE treatment Dosing Regimen Maximum Dose 2.5 mg SC per day 2.5 mg per day SC based on body weight: < 50 kg: 5 mg per day 50 to 100 kg: 7.5 mg per day

   100 kg: 10 mg per day 10 mg per day VI. Product Availability
   Single-dose, prefilled syringes: 2.5 mg, 5 mg, 7.5 mg, 10 mg VII.