Enoxaparin (Lovenox) Form

Enoxaparin (Lovenox®) is a low molecular weight heparin (LMWH). FDA Approved Indication(s) Lovenox is indicated: • For prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism pulmonary embolism (PE): o In patients undergoing  Abdominal surgery who are at risk for thromboembolic complications;  Hip replacement surgery, during and following hospitalization;  Knee replacement surgery; o In medical patients who are at risk for thromboembolic complications due to severely restricted mobility during acute illness. • For treatment of acute DVT: o Inpatient treatment of acute DVT with or without PE, when administered in conjunction with warfarin sodium. o Outpatient treatment of acute DVT without pulmonary embolism when administered in conjunction with warfarin sodium. • For prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin. • For treatment of acute ST-elevation myocardial infarction (STEMI). 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 Lovenox 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. Atrial fibrillation or prosthetic heart valve; Page 1 of 9

   CLINICAL POLICY Enoxaparin iv. Major surgery – orthopedic or non-orthopedic; v. Critical illness related to ICU admissions or events; vi. Restricted mobility associated with acute illnesses or conditions; vii. 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;

   2. If request is for Lovenox, member must use generic enoxaparin, 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):
   3. 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.
   4. Member is pregnant or < 6 months postpartum;

2. If request is for Lovenox, member must use generic enoxaparin, 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):

   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: Page 2 of 9

   CLINICAL POLICY Enoxaparin 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 a non- LMWH (e.g., failed therapy on heparin, fondaparinux, warfarin, apixaban, dabigatran, edoxaban, rivaroxaban); LMWHs include enoxaparin and dalteparin 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 Lovenox, member must use generic enoxaparin, 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 Lovenox, member must use generic enoxaparin, unless contraindicated or clinically significant adverse effects are experienced.
   Approval duration:
   Medicaid/HIM – Antepartum (to estimated delivery date); postpartum (6 months)
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   CLINICAL POLICY Enoxaparin Commercial – 6 months or duration of request, whichever is less 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 LMWH: low molecular weight heparin NCCN: National Comprehensive Cancer Network Appendix B: Therapeutic Alternatives
      Not applicable PE: pulmonary embolism STEMI: ST-elevation myocardial infarction Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
      o Active major bleeding o History of immune-mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in the presence of circulating antibodies o Known hypersensitivity to enoxaparin sodium (e.g., pruritus, urticaria, anaphylactic/anaphylactoid reactions) o Known hypersensitivity to heparin or pork products Page 4 of 9

   CLINICAL POLICY Enoxaparin o Known hypersensitivity to benzyl alcohol (which is in only the multidose formulation of Lovenox) • Boxed warning(s): spinal/epidural hematomas Appendix D: General information • Per National Comprehensive Cancer Network (NCCN) guidelines for cancer-associated venous thromboembolic disease, enoxaparin is recommended for: o Anticoagulation for acute and chronic management of acute superficial vein thrombosis, consider for 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 (preferred for patients with gastric or gastroesophageal lesions):
    administered as monotherapy  administered for at least 45 days given concurrently with warfarin until transition to warfarin monotherapy, prior to switching to edoxaban, prior to switching to dabigatran if preferred regimens not appropriate or unavailable o Anticoagulation for cancer patients following therapeutic anticoagulation failure with: heparin sodium, fondaparinux, warfarin sodium, apixaban, dabigatran, edoxaban, or rivaroxaban o Venous thromboembolism prophylaxis:  For adults 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 and no contraindication to anticoagulation
    For adults with cancer (excluding basal/squamous cell skin cancer) or those for whom a clinical suspicion of cancer exists who are admitted for surgical hospitalizations and requires preoperative dosing for high-risk surgery (e.g. abdominal/pelvic surgery) and no contraindication to anticoagulation
    For adults with advanced unresectable and metastatic pancreatic cancer receiving/starting systemic therapy for their cancer that are ambulatory with post- medical oncology discharge and assessed as intermediate or high risk for VTE based on Khorana score > 2
    For adults with cancer who are at risk in the ambulatory setting after discharge for up to 4 weeks postoperative following high-risk surgery (e.g. abdominal/pelvic) V. Dosage and Administration
   Indication Adults DVT prophylaxis in abdominal surgery DVT prophylaxis in knee replacement surgery DVT prophylaxis in hip replacement surgery Dosing Regimen Maximum Dose 40 mg SC once daily 30 mg SC every 12 hours 30 mg SC every 12 hours or 40 mg SC once daily Dose as specified; duration may vary.
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   CLINICAL POLICY Enoxaparin Indication Adults DVT prophylaxis in medical patients Inpatient treatment or acute DVT with or without PE Outpatient treatment of acute DVT without PI Unstable angina and non-Q wave MI Cancer-associated venous thromoemoblic disease Acute STEMI in patient < 75 years of age
   Acute STEMI in patient ≥ 75 years of age
   Dosing Regimen Maximum Dose 40 mg SC once daily 1 mg/kg SC every 12 hours or 1.5 mg/kg SC once daily 1 mg/kg SC every 12 hours 1 mg/kg SC every 12 hours (with aspirin) 1 mg/kg SC every 12 hours or 1.5 mg/kg SC once daily after first month 30 mg single IV bolus plus a 1 mg/kg SC dose followed by 1 mg/kg SC every 12 hours (with aspirin) 0.75 mg/kg SC every 12 hours (no bolus) (with aspirin) VI. Product Availability
   • Prefilled syringes: 30 mg/0.3 mL, 40 mg/0.4 mL • Graduated prefilled syringes: 60 mg/0.6 mL, 80 mg/0.8 mL,100 mg/1 mL, 120 mg/0.8 mL, 150 mg/1 mL • Multiple-dose vial: 300 mg/3 mL VII.