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Prior Authorization Protocol

NEUPOGENR (filgrastim), ZARXIOTM (filgrastim-sndz)


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:
    • Myelosuppressive chemotherapy - To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever.
    • Acute myeloid leukemia (AML) - For reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of adults with AML.
    • Severe chronic neutropenia - For chronic administration to reduce the incidence and duration of sequelae of neutropenia (e.g., fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital, cyclic or idiopathic neutropenia.
    • Bone marrow transplant - To reduce the duration of neutropenia and neutropenia-related clinical sequelae, eg febrile neutropenia, in patients with non-myeloid malignancies undergoing myeloablative chemo-therapy followed by marrow transplantation.
    • Peripheral blood progenitor cell collection - For mobilization of hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis.
    • Neupogen: Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome)
  2. Health Net Approved Indications and Usage Guidelines:
    • Patient is receiving myelosuppressive chemotherapy (primary prophylaxis)

    AND

    • Chemotherapy regimen is expected to cause febrile neutropenia
    OR
    • Patient is at higher risk for chemotherapy-induced infectious complications including, but not limited to one of the following:
      1. Pre-existing neutropenia due to disease, extensive prior chemotherapy
      2. Decreased immune function
      3. Previous radiation to areas containing large amounts of bone marrow
      4. Active tissue infection(s)
      5. Open wound(s)
      6. Age greater than 65 years old

    OR

    • Patient is receiving myelosuppressive chemotherapy (secondary prophylaxis)

    AND

    • Patient has a history of febrile neutropenia following a previous course of chemotherapy

    OR

    • Patient has a history of prolonged neutropenia, causing dose reduction or delay in chemotherapy

    OR any of the following:

    • AML (receiving induction or consolidation chemotherapy)
    • Severe chronic neutropenia
    • Bone marrow transplant
    • Peripheral blood progenitor cell collection
    • Myelodysplastic syndrome (supportive care)
    • To treat AIDS patients who have severe neutropenia resulting from the use of antiviral agents.
    • Acute drug-induced neutropenia not recovered with dose reduction or withdrawal of the causative agent within 3 weeks.
    • Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome)
  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:
    • The development of febrile neutropenia is a common dose-limiting toxicity of many chemotherapy regimens. This risk is directly related to the intensity of the chemotherapy regimen. Chemotherapy regimens that have an incidence of febrile neutropenia greater than 20% in clinical trials in chemotherapy naove patients are considered by the National Comprehensive Cancer Network (NCCN) panel at high risk. Prophylaxis with myeloid growth factors is recommended at this level of risk. In addition to chemotherapy regimens, other risk factors such as: treatment-related, patient related, cancer-related, and co-morbidities have also been associated with an increased risk of febrile neutropenia. Therefore, the type of chemotherapy regimen is only one component of the risk assessment.
    • For chemotherapy patients, continuing filgrastim until the ANC has reached 10,000/mm3 following the expected chemotherapy-induced neutrophil nadir (as specified in the G-CSF package insert), is known to be safe and effective. However, a shorter duration of administration that is sufficient to achieve clinically adequate neutrophil recovery is a reasonable alternative, considering issues of patient convenience and cost.5
    • Evidence supports dose reduction of pegylated interferon according to FDA approved labeling as treatment for neutropenia occurring in hepatitis C patients treated with combination therapy (pegylated interferon + ribavirin). Treatment with filgrastim is not FDA approved or recommended by current hepatitis C treatment guidelines except in patients with decompensated cirrhosis.
    • There are insufficient data to support the use of filgrastim to treat febrile neutropenia in patients who have received prophylactic Neulasta.
    • In a randomized, double-blind, multi-center safety and efficacy study of 218 breast cancer patients receiving chemotherapy with a high risk of neutropenia, Zarxio was non-inferior to Neupogen on the primary endpoint of duration of severe neutropenia (1.17 days for Zarxio and 1.20 days for Neupogen).
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose

    NeulastaR (pegfilgrastim)*

    Myelosuppressive chemotherapy:
    6 mg SC once per 21-day chemotherapy cycle

    1 dose per cycle of chemotherapy

    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit

    Neupogen, Zarxio

    Myelosuppressive chemotherapy
    5 mcg/kg SC bolus injection, by short IV infusion (15 to 30 minutes), or
    by continuous SC or continuous IV infusion QD
    Dose may be increased in increments of 5 mcg/kg for each chemotherapy cycle,
    according to the duration ands severity of the ANC nadir
    Do not administer 24 hours before and after chemotherapy

    Acute myeloid leukemia
    5 mcg/kg SC QD

    Severe chronic neutropenia
    Congenital:
    6 mcg/kg SC BID
    Idiopathic or cyclic:
    5 mcg/kg SC QD

    Bone marrow transplant
    10 mcg/kg IV infusion of 4 or 24 hours, or as a continuous 24 hours SC infusion QD
    Reduce to 5 mcg/kg/day when ANC > 1000/mm3 for 3 consecutive days
    Discontinue if ANC remains > 1000/ mm3 for 3 more consecutive days
    Resume at 5mcg/kg/day if ANC decreases to < 1000/mm3

    Peripheral blood progenitror cell collection
    10 mcg/kg SC bolus or a continuous infusion QD

    Myelodysplastic syndrome
    0.3 mcg/kg SC QD

    AIDS Patients
    5-10 mcg/kg SC QD

    Drug-Induced
    4 to 10 mcg/kg SC QD

    Patients acutely exposed to myelosuppressive doses of radiation:
    10 mcg/kg SC QD
    Myelosuppressive chemotherapy
    Up to 2 weeks, OR until the ANC has reached 10,000/ mm3 following chemotherapy cycle

    Acute myeloid leukemia
    Up to 35 days

    Severe chronic
    neutropenia
    30 day supply/month, up to 6 months

    Bone marrow transplant

    14 days

    Peripheral blood progenitror cell collection

    7 days

    Myelodysplastic syndrome

    3 months

    AIDS Patients

    Length of benefit (For AHCS requests: One Year)

    Drug-Induced Neutropenia
    15 days

    Patients acutely exposed to myelosuppressive doses of radiation:
    Length of Benefit
  7. Product Availability:
    Neupogen: 300 mcg/ml and 480 mcg/1.6 ml vials, 300 mcg/0.5 ml and 480 mcg/0.8 ml prefilled syringes
    Zarxio: 300 mcg/0.5 mL and 480 mcg/0.8 ml prefilled syringes
  8. References:
    1. Neupogen [package insert]. Thousand Oaks, CA: Amgen Inc; March 2015.
    2. Zarxio [package insert]. Princeton, NJ: Sandoz, Inc. March 2015.
    3. Shiffman ML, Di Bisceglie AM, Lindsay KL, et al for the HALT-C Trial Group. Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology 2004;126:1015-1023.
    4. American Society of Clinical Oncology Recommendations for the use of hematopoietic colony- stimulating factors: Evidence-based, clinical practice guidelines. J Clin Oncology 1994;12:11: 2471-2508.
    5. American Society of Clinical Oncology 2006 Update of Recommendations for the Use of White Blood Cell Growth Factors: An Evidence-Based Clinical Practice Guideline. J Clin Oncology. 2006; 24: 3187-3205.
    6. National Comprehensive Cancer Network: Myeloid Growth Factors Version 2.2014. Available at: http://www.nccn.org/professionals/physician_gls/pdf/myeloid_growth.pdf. Accessed July 7, 2015.
    7. American Association for the Study of Liver Disease Recommendations for Testing,Managing, and Treating Hepatitis C; July 2015 (accessed at: http://www.hcvguidelines.org)
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.