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Prior Authorization Protocol
Injectable Anticoagulants - Low Molecular Weight Heparins (LMWH)

FRAGMINR(dalteparin) / LOVENOXR(enoxaparin) / ARIXTRAR(fondaparinux)

NATL

Coverage of drugs is first determined by the member’s pharmacy or medical benefit. Please consult with or refer to the Evidence of Coverage document.
  1. FDA Approved Indications:

    SUMMARY OF FDA APPROVED INDICATIONS
    Indication
    Fragmin
    Lovenox
    Arixtra
    Prophylaxis of DVT (deep vein thrombosis) that may lead to PE (pulmonary embolism)
    • In abdominal surgery
    X
    X
    X
    • In hip replacement
    X
    X
    X
    • In knee replacement
    *
    X
    X
    • In patients with severely restricted mobility during acute illness
    X
    X
    • In moderate risk surgery patients
    • In high risk surgery patients
    *
    *
    • In orthopedic surgery
    *
    *
    • In hip fracture surgery
    *
    *
    X
    • In neurosurgery
    • In major trauma
    *
    *
    • In acute spinal cord injury
    *
    *
    • In ischemic stroke with impaired mobility
    *
    *
    • In general medical patients at risk (congestive heart failure (CHF), cancer, severe lung disease, restricted to bed)
    *
    *
    *
    • In pregnancy related thromboembolism
    *
    *
    Treatment of acute DVT
    Treatment of acute DVT with warfarin
    X
    Treatment of VTE (venous thromboembolism) with warfarin
    *
    Treatment of acute PE with warfarin
    X
    Extended treatment of symptomatic VTE in patients with cancer
    X
    Prophylaxis of ischemic complications in unstable angina and non-Q-wave MI (myocardial infarction)
    X
    X
    *
    Acute ST-segment elevated myocardial infarction (STEMI)
    X
    *
    Percutaneous angioplasty, acute coronary syndrome
    *
    *
    *
    Anticoagulation for dialysis
    *

    X FDA approved indication
    * Sufficient data exist to support off-label use.
  2. Health Net Approved Indications and Usage Guidelines:
    Health Net considers the use of low-molecular-weight heparins (LMWHs) medically appropriate in clinical settings in which they have been found to offer improved safety and efficacy over unfractionated heparins (UFHs). Consistent with recommendations from the Ninth Edition of the American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Evidence-Based Clinical Practice Guidelines, Health Net, Inc. approves coverage of LMWHs for the following indications:


    For Fragmin and Lovenox: Prevention of venous thromboembolism in adults for any of the following:
    • Hip surgery including replacement and hip fracture
    • Knee replacement surgery
    • Other major orthopedic procedures
    • Members who are acutely ill and are hospitalized for severe respiratory infection or congestive heart failure or who are non-ambulatory and over 65 years of age, have a history of VTE, have active cancer, have severe respiratory disease, or congestive heart failure
    • Acute multiple trauma
    • Acute spinal cord injury
    • Acute thromboembolic stroke with impaired mobility
    • Active malignancy with recurrent VTE (venous thromboembolism) on oral anticoagulants with a therapeutic INR (international normalized ratio)
    • Thrombophilia or congenital prethrombotic defects precluding use of oral anticoagulants or with recurrent VTE on oral anticoagulants with a therapeutic INR
    • Acute ST-segment elevated myocardial infarction (STEMI) (Lovenox only- See Arixtra indications below)
    • Pregnancy under the following conditions:
      • Single previous idiopathic VTE
      • Single previous VTE that was estrogen or pregnancy related
      • Anti-thrombin-deficient women (G20210A, factor V Leiden)
      • Two or more previous VTE
      • Antiphospholipid antibodies and multiple previous miscarriages or a history of VTE
      • Other congenital thrombophilic defects with recurrent miscarriages, second-trimester or later loss, severe or recurrent preeclampsia, or abruption
      • Mechanical heart valve (DOSE MUST BE ADJUSTED TO ANTI-Xa LEVELS)
    OR

    Prevention of thromboembolism in pediatric members 2 months of age and older for any of the following reasons:
    • Short term prophylaxis in high-risk situations such as immobility, major surgery, or trauma
    • Congenital prethrombotic states such as antithrombin deficiency or homozygous protein C and S deficiency
    OR
    • Treatment of venous thrombosis and prophylaxis of extension of venous thrombosis when inpatient care can be diverted to an outpatient setting
    OR
    • Use as short-term, preoperative therapy when a member on oral anticoagulation needs to be put on a drug with a shorter duration of action prior to surgery or as prophylaxis or treatment as a transition to oral anticoagulation
    OR
    • Unstable angina, acute non-Q wave MI, acute coronary syndrome, or percutaneous angioplasty

    For Arixtra: Prevention of venous thromboembolism in adults for any of the following:
    • Hip surgery including replacement and hip fracture
    • Knee replacement surgery
    • Abdominal surgery
    • Other orthopedic surgery in patients at high-risk for thromboembolism.
    • Members who are acutely ill and are hospitalized for severe respiratory infection or congestive heart failure or who are non-ambulatory and over 65 years of age, have a history of VTE, have active cancer, have severe respiratory disease, or congestive heart failure
    OR
    • Treatment of venous thrombosis and prophylaxis of extension of venous thrombosis when inpatient care can be diverted to an outpatient setting
    OR
    • Unstable angina
    • Treatment of arterial thrombosis resulting in acute coronary syndrome
    • Acute ST-segment elevated myocardial infarction (STEMI)
    OR
    • Treatment of heparin-induced thrombocytopenia (see general information)
  3. Coverage is Not Authorized For:
    • Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section unless there is sufficient documentation of efficacy and safety in the published literature.
  4. General Information:
    • LMWHs are not interchangeable with heparin or each other on a unit for unit basis. Each of these medicines has its own instructions for use.
    • When transitioning patients to warfarin, a minimum of 4 to 5 days of overlapping therapy with a LMWH or fondaparinux is suggested. LMWH or fondaparinux should not be discontinued until a therapeutic INR has been achieved on two successive measurements.
    • LMWH, with the exception of Arixtra should not be used in patients with heparin-induced thrombocytopenia as a cross-reaction occurs.
    • Caprini Risk Assessment Score estimates VTE risk by adding points for various VTE risk factors. This scoring system was validated in a large retrospective study in a sample of general, vascular, and urological surgery patients and adapted by the CHEST guidelines committee to categorize VTE risk as being very low (0-1 point), low (2 points), moderate (3-4 points), or high (≥5 points)
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose

    Heparin

    Prophylaxis of VTE:
    5000 U SC Q 8-12 H or adjusted dose to
    therapeutic aPTT depending on procedure,
    and patient risk factors.

    Treatment of VTE:
    5000 U IV, then 20,000 to 40,000 units/24 hours
    continuous infusion.

    This field intentionally left blank.

    Warfarin

    Oral Prophylaxis and Treatment:
    Dose adjusted to therapeutic INR (2-3 for treatment of VTE)
    based on procedure, condition, and patient risk factors.

    This field intentionally left blank.

    ArgatrobanR
    (argatroban)

    Treatment of VTE:
    2 mcg/kg/min IV infusion adjusted to
    therapeutic aPTT.

    This field intentionally left blank.

    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit
    Hip fracture or replacement

    Arixtra:
    2.5 mg QD
    Fragmin:
    Preoperative varies,
    Postoperative 5,000 IU/day
    Lovenox:
    30 mg Q 12 H or 40 mg QD

    35 days

    Abdominal surgery

    Arixtra:
    2.5 mg QD
    Fragmin:
    2500-5000 IU QD
    Lovenox:
    40 mg QD

    Arixtra:
    10 days
    Fragmin:
    10 days
    Lovenox:
    12 days

    Knee replacement

    Arixtra:
    2.5 mg QD
    Lovenox:
    30 mg Q 12 H

    35 days

    High risk surgery/major gynecologic surgery or
    surgery with malignancy

    Fragmin
    5000 IU QD
    Lovenox
    40 mg QD
    4 weeks

    Acute medical illness

    Arixtra:
    2.5 mg QD
    Fragmin:
    5000 IU QD
    Lovenox:
    40 mg QD

    Arixtra:
    14 days until illness resolves
    and/or ambulatory
    Fragmin:
    14 days until illness resolves
    and/or ambulatory
    Lovenox:
    14 days until illness resolves
    and/or ambulatory

    Acute multiple trauma

    Lovenox:
    30 mg BID

    Lovenox:
    Hospital discharge unless
    major impaired mobility

    Acute spinal cord injury

    Fragmin:
    5000 IU QD
    Lovenox:
    30 mg BID or 40 mg QD

    Fragmin:
    Continue to the end of
    rehabilitation phase of therapy
    Lovenox:
    Continue to the end of
    rehabilitation phase of therapy

    Embolic stroke

    Lovenox:
    30 mg BID

    Lovenox:
    Acute phase until ambulatory

    Recurrent DVT on oral anticoagultion or
    oral therapy precluded

    Fragmin:
    200 IU/kg QD (max 18,000 IU/day)
    Lovenox:
    1 mg/kg Q 12 H
    Indefinite

    Unstable angina/non-Q wave MI

    Fragmin:
    120 IU/kg Q 12 H (max 10,000 IU Q12 H)
    Lovenox:
    1 mg/kg Q 12 H

    Fragmin:
    8 days
    Lovenox:
    13 days

    Acute coronary syndrome

    Lovenox:
    1 mg/kg Q 12 H

    Lovenox:
    8 days or until clincal stabilization

    Pregnancy
    (prophylaxis)

    Fragmin:
    5000 IU QD
    Lovenox:
    40 mg Q12 H or QD

    Fragmin:
    6 weeks post partum
    Lovenox:
    6 weeks post partum

    Treatment of VTE
    Arixtra:
    Weight based:
    5 mg, 7.5 mg, 10 mg QD
    Lovenox:
    1 mg/kg Q 12 H
    Lovenox :
    17 days with conversion to oral vitamin K antagonist (VKA)
    Arixtra:
    5 days until INR 2-3 achieved with warfarin


    Extended treatment of symptomatic VTE
    in patients with cancer

    Fragmin:
    Month 1: 200 IU/kg QD
    Month 2: 150 IU/kg QD
    Max 18,000 IU/day

    6 months

    Short-term prophylaxis for transition
    to /from oral anticoagulation

    Lovenox:
    High-risk of clot: 1 mg/kg Q 12 H
    Low-risk of clot: 30 mg BID or 40 mg QD

    Lovenox:
    Preoperative 3 days following
    discontinuation of oral VKA,
    5 days post-operatively conversion to VKA

    Pediatric patients treatment

    Fragmin:
    129 IU/kg QD
    Lovenox:
    < 2 mo 1.5 mg/kg Q12 H
    > 2 mo 1 mg/kg Q 12 H

    Consult literature for appropriate
    duration based on intended use

    Pediatric patients prophylaxis

    Fragmin:
    92 IU/kg QD
    Lovenox:
    < 2 mo 0.75 mg/kg Q 12 H
    > 2 mo 0.5 mg/kg Q 12 H

    Consult literature for appropriate
    duration based on intended use

  7. Product Availability:

    Arixtra: Solution for injection, prefilled syringe: 2.5 mg/0.5 mL, 5 mg/0.4 mL, 7.5 mg/0.6 mL, 10 mg/0.8 mL
    Fragmin: Single-dose prefilled syringe: 2,500 IU/0.2 mL, 5,000 IU/0.2 mL, 7,500 IU/0.3 mL, 10,000 IU/0.4 mL, 12,500 IU/0.5 mL, 15,000 IU/0.6 mL, 18,000 IU/0.72 mL. Single-dose graduated syringe: 10,000 IU/1 mL. Multiple dose vial: 95,000 IU/3.8mL, 95,000 IU/9.5 mL
    Lovenox: Solution for injection, vial: 300 mg/3 ml. Prefilled syringes: 30 mg/0.3 mL, 40 mg/0.4 mL, 60 mg/0.6 mL, 80 mg/0.8 mL, 100 mg/1 mL, 120 mg/0.8 mL, 150 mg/1 mL

  8. References:
    1. Lovenox prescribing information, Sanofi-Aventis, October 2013.
    2. Fragmin prescribing information, Eisai, January 2015.
    3. Arixtra prescribing information, GlaxoSmithKline, July 2014.
    4. The Seventh ACCP Consensus Conference on Antithrombotic Therapy. The seventh ACCP conference on antithrombotic and thrombolytic therapy: evidence-based guidelines. Chest.2004;126(3 Suppl):174S-703S.
    5. Hirsh J, Hoak J. Statement for Healthcare Professionals From the Council on Thrombosis (in Consultation With the Council on Cardiovascular Radiology), American Heart Association. Management of Deep Vein Thrombosis and Pulmonary Embolism. Circulation. 1996;93:2212-2245.
    6. Hirsh J, MD; Fuster V. AHA Medical/Scientific Statement: Guide to Anticoagulant Therapy Part 1: Heparin. Circulation. 1994;89:1449-1468.
    7. Nurmohamed MT, ten Cate H, ten Cate JW. Low molecular weight heparin(oid)s. Clinical investigations and practical recommendations. Drugs. 1997;53(5):736-751.
    8. Pineo GF, Hull RD. Low-molecular-weight heparin: Prophylaxis and treatment of venous thromboembolism. Annu Rev Med. 1997;48:79-91.
    9. Kakkar VV, Boeckl O, Boneu B, et al. Efficacy and safety of a low-molecular-weight heparin and standard unfractionated heparin for prophylaxis of postoperative venous thromboembolism: European multicenter trial. World J Surg. 1997;21(1):2-8.
    10. Baglin TP. Low-molecular-weight heparins and new strategies for the treatment of patients with established venous thrombosis. Hemostasis. 1996;26(Suppl 2):10-15.
    11. Koopman MMW, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med. 1996;334(11):682-687.
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    13. Fauno P, Suomalainen O, Rehnberg V, et al. Prophylaxis for the prevention of venous thromboembolism after total knee arthroplasty. A comparison between unfractionated and low-molecular-weight heparin. J Bone Joint Surg Am. 1994;76(12):1814-1818.
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    17. Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low molecular weight heparin or unfractionated heparin. N Engl J Med. 1995;332(20):1330-1335.
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The material provided to you are guidelines used by this plan to authorize, modify or determine coverage for persons with similar illnesses or conditions. Specific care and treatment may vary depending on individual need and the benefits covered under your contract.