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Prior Authorization Protocol

EPOGENR, PROCRITR(epoetin alfa), ARANESPR (darbepoetin alfa), MIRCERAR (methoxypolyethylene glycol epoetin beta)


HNCA

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:
    • Treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and patients not on dialysis to decrease the need for red blood cell (RBC) transfusion.
    • For the treatment of anemia due to zidovudine administered at < 4200 mg per week in HIV-infected patients with endogenous serum erythropoietin levels of < 500 mUnits/mL. (Epogen/Procrit only)
    • For the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy.
    • To reduce the need for allogeneic RBC transfusions among patients with perioperative hemoglobin > 10 to ≤ 13 g/dL who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery. It is not indicated for patients who are willing to donate autologous blood pre-operatively. (Epogen/Procrit only)
    • Limitations of Use:
      • Have not been shown to improve quality of life, fatigue, or patient well-being.
      • Not indicated for use:
        • In patients with cancer receiving hormonal agents, biologic products, or radiotherapy, unless also receiving concomitant myelosuppressive chemotherapy.
        • In patients with cancer receiving myelosuppressive chemotherapy when the outcome is cure.
        • In patients scheduled for surgery who are willing to donate autologous blood.
        • In patients undergoing cardiac or vascular surgery.
        • As a substitute for RBC transfusions in patients who require immediate correction of anemia.
    • For the treatment of anemia associated with chronic kidney disease (CKD) in adult patients on dialysis and patients not on dialysis
  2. Health Net Approved Indications and Usage Guidelines:
    • For Procrit, Epogen, or Aranesp: Diagnosis of ONE of the following:
      • Anemia of CKD (both dialysis and non-dialysis patients)
      • Zidovudine (AZT) therapy induced anemia (Epogen/Procrit only)
      • Chemotherapy-induced anemia in patients with non-myeloid malignancies
      • Surgery patients at high risk for perioperative allogeneic RBC transfusions with significant, anticipated blood loss during elective, noncardiac, nonvascular surgery (typically pre-operative use for hip or knee surgery), and patient is not a candidate for autologous blood donation (Epogen/Procrit only)
      • Patient is on combination therapy (pegylated interferon and ribavirin) for treatment of hepatitis C to maintain the recommended ribavirin dose (Epogen/Procrit only)
      • Myelodysplastic syndrome
    OR
    • For Mircera: Diagnosis of anemia of CKD (both dialysis and non-dialysis patients)
    AND
    • For Epogen/Aranesp/Mircera requests: Failure or clinically significant adverse effects to Procrit.
  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
    • Mircera is not indicated and is not recommended in the treatment of anemia due to cancer chemotherapy

  4. General Information:
    • The therapeutic effects of erythropoietin are dependent upon dose, however, a greater biologic response is not observed at doses exceeding 300 units/kilogram three times weekly.
    • American Society of Clinical Oncology/American Society of Hematology 2010 Clinical Practice Guideline Update on the Use of Epoetin and Darbepoetin states: The use of epoetin or darbepoetin is recommended as a treatment option for patients with chemotherapy- associated anemia and a Hgb concentration that has decreased to less than 10 g/dL to decrease transfusions. An optimal target Hgb concentration cannot be definitively determined from the available literature. Modification to reduce the erythropoiesis-stimulating agents (ESA) dose is appropriate when Hgb reaches a level sufficient to avoid transfusion or the increase exceeds 1 g/dL in any 2-week period to avoid excessive ESA exposure.
    • Because it takes several days for erythropoiesis, a clinically significant increase in hematocrit is usually not observed in less than 2 weeks and may require up to 6 weeks in some patients.
    • Based on HALT-C trial data, there is a greater chance of achieving a sustained viral response (SVR) in patients with hepatitis C if the ribavirin dose can be maintained during the first 20 weeks of combination therapy.
    • Clinical response in the treatment of myelodysplastic syndrome may include any of the following: Hgb increase of at least 1 g/dL from baseline or maintenance of Hgb between 10-12 g/dL.
    • Black box warnings include:
      • Chronic Kidney Disease: In controlled trials, patients experienced greater risks for death, serious cardiovascular reactions and stroke when administered ESAs to target a hemoglobin level of greater than 11 g/dL. No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks. Use the lowest dose sufficient to reduce the need for red blood cell transfusions.
      • Cancer: ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in some clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers. To decrease these risks, as well as the risk of serious cardio-and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusion. Because of these risks, prescribers and hospitals must enroll in and comply with the Assisting Providers and Cancer Patients with Risk Information for the Safe use of ESAs (APRISE). Oncology Program to prescribe and/or dispense Epogen/Procrit . Use ESAs only for treatment of anemia due to concomitant myelosuppressive chemotherapy. ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure. Discontinue following the completion of a chemotherapy course.
      • Perisurgery: Increased the rate of deep venous thrombosis in patients not receiving prophylactic anticoagulation. Deep venous thrombosis prophylaxis is recommended.
      • A dose-ranging trial of Mircera in 153 patients who were undergoing chemotherapy for non-small cell lung cancer was terminated prematurely because more deaths occurred among patients receiving Mircera than another ESA.
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose
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    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit
    ProcritR (epoetin alfa)* (preferred) and EpogenR (epoetin alfa)*
    Chronic Kidney Disease patients on dialysis
    Adults:
    50-100 units/kg IV or SC TIW
    CKD patients not on dialysis
    Adults:
    50-100 units/kg IV or SC TIW
    CKD (dialysis and non-dialysis patients)
    Do not increase dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently.

    Use the lowest dose that will maintain a Hgb level sufficient to reduce the need for RBC transfusions.
    6 months or to member's renewal date, whichever is longer
    Procrit (epoetin alfa)* (preferred) and Epogen (epoetin alfa)*
    Zidovudine-treated patients
    Initial:
    100 units/kg IV or SC TIW
    If Hgb does not increase after 8 weeks of therapy, increase dose by approximately 50 to 100 units/kg at 4 to 8 week intervals
    until Hgb reaches a level needed to avoid RBC transfusions or 300 units/kg.

    Withhold if Hgb exceeds 12 g/dL. Resume therapy at a dose 25% below the previous dose
    when Hgb declines to less than 11 g/dL.

    Discontinue if an increase in Hgb is not achieved at a dose of 300 units/kg for 8 weeks.

    6 months or to member's renewal date, whichever is longer

    Procrit (epoetin alfa)* (preferred) and Epogen (epoetin alfa)*
    Cancer Patients on Chemotherapy
    Initial Dose:
    150 units/kg SC TIW or 40,000 units SC weekly until completion of a chemotherapy course.
    Reduce dose by 25% if Hgb increases greater than 1 g/dL in any 2 week period or Hgb reaches a level needed to avoid RBC transfusion.
    Withhold dose if Hgb exceeds a level needed to avoid RBC transfusion.
    Reinitiate at a dose 25% below the previous dose when Hgb approaches a level where RBC transfusions may be required.

    After the initial 4 weeks of therapy, if Hgb increases by less than 1g/dL and remains below 10 g/dL, increase dose to 300 units/kg TIW or 60,000 units/week in adults.

    Discontinue if after 8 weeks of therapy, there is no response as measured by Hgb levels or if RBC transfusions are still required.
    Authorized until the completion of chemotherapy course,
    6 months or to member's renewal date, whichever is longer
    Procrit (epoetin alfa)* (preferred) and Epogen (epoetin alfa)*
    Surgery Patients
    300 units/kg/day SC for 10 days prior to surgery, on the day of surgery, continuing for 4 days after surgery OR
    600 units/kg SC in once weekly doses 21, 14 and 7 days before surgery plus a 4th dose on day of surgery

    Up to 15 doses

    Procrit (epoetin alfa)* (preferred) and Epogen (epoetin alfa)*
    Hepatitis C Patients on combination therapy (pegylated interferon and ribavirin)
    40,000 units/week SC, may increase to 60,000 units SC once weekly if hemoglobin level has not increased by at least 1 g/dL after 4 weeks of treatment
    Coincide with duration of ribavirin authorization to maintain greater than or equal to 80% of the original ribavirin dose.

    Procrit (epoetin alfa)* (preferred) and Epogen (epoetin alfa)*
    Myelodysplastic syndrome
    150-300 units/kg/day SC (a 40,000 U weekly dose was also studied in some clinical trials)

    6 months or to member's renewal date, whichever is longer

    Aranesp

    Anemia in CKD patients on dialysis:
    Initial: 0.45 mcg/kg IV or SC weekly, or 0.75 mcg/kg once every 2 weeks. IV route is recommended for patients on hemodialysis.

    If the Hgb level approaches or exceeds 11 g/dL, reduce or interrupt the dose.
    Anemia in CKD patients not on dialysis:
    Initial: 0.45 mcg/kg IV or SC once at four week intervals.

    If the Hgb level exceeds 10 g/dL, reduce or interrupt the dose and use the lowest dose of Aranesp sufficient to reduce the need for RBC transfusions
    CKD (dialysis and non-dialysis patients):
    Do not increase dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently.

    If Hgb rises rapidly (e.g. more than 1 g/dL in any 2 week period), reduce the dose by 25% or more as needed to reduce rapid responses.

    For patients who do not respond adequately, if the Hgb has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%.

    Use the lowest dose that will maintain a Hgb level sufficient to reduce the need for RBC transfusions.
    6 months or to member's renewal date, whichever is longer

    Aranesp

    Chemotherapy-induced anemia
    Starting dose is 2.25 mcg/kg SC once weekly or 500 mcg SC every 3 weeks until completion of chemotherapy course
    If Hgb increases greater than 1 g/dL in any 2 week period or if Hgb reaches a level needed to avoid RBC transfusion, reduce dose by 40% (both weekly and every 3 week schedule)
    If Hgb exceeds a level needed to avoid RBC transfusion, withhold dose until Hgb approaches a level where RBC transfusions may be required. Then reinitiate at a dose of 40% below the previous dose (both weekly and every 3 week schedule).

    If Hgb increases by less than 1 g/dL and remains below 10 g/dL after 6 weeks of therapy, increase dose to 4.5mcg/kg/week (weekly schedule). No dose adjustment is needed for every 3 week schedule.

    Discontinue Aranesp if there is no response as measured by the Hgb levels or if RBC transfusions are still required after 8 weeks of therapy or following completion of a chemotherapy course.

    Use the lowest dose necessary to avoid RBC transfusions.
    Authorized until the completion of chemotherapy course,
    6 months or to member's renewal date, whichever is longer

    Aranesp

    Myelodysplastic syndromes
    150-300 mcg/week SC
    6 months or to member's renewal date, whichever is longer

    MirceraR (methoxypolyethylene glycol epoetin beta)

    Anemia in CKD (dialysis and non-dialysis patients):
    0.6 mcg/kg SC or IV every two weeks.

    Anemia in CKD patients on dialysis:
    If the Hgb level approaches or exceeds 11 g/dL, reduce or interrupt the dose.

    Anemia in CKD patients not on dialysis:
    If the Hgb level exceeds 10 g/dL, reduce or interrupt the dose and use the lowest dose of Mircera sufficient to reduce the need for RBC transfusions

    6 months or to member's renewal date, whichever is longer

  7. Product Availability:
    • Epogen/Procrit:
      • 1 ml Single dose, preservative free solution: 2000 units/ml, 3000 units/ml, 4000 units/ml, 10,000 units/ml, 40,000 units/ml (Procrit only)
      • 1 ml Multidose, preserved solution: 20,000 units/ml
      • 2 ml Multidose, preserved solution: 10,000 units/ml
    • Aranesp:
      • Vial for injection (single dose, polysorbate): 25 mcg/ml, 40 mcg/ml, 60 mcg/ml, 100 mg/ml, 150 mcg/0.75 ml, 200 mcg/ml, 300 mcg/ml, 500 mcg/ml
      • Prefilled syringes: (single dose polysorbate): 25 mcg/0.42 ml, 40 mcg/0.4 ml, 60 mcg/0.3 ml, 100 mcg/0.5 ml, 150 mcg/ 0.3 ml, 200 mcg/0.4 ml, 300 mcg/0.6 ml, 500 mcg/ml
    • Mircera:
      • Prefilled syringe containing: 50 mcg, 75 mcg, 100 mcg, 150 mcg, 200 mcg, or 250 mcg in 0.3 mL solution
  8. References:
    1. Procrit [Prescribing information].Thousand Oaks, CA: Amgen Inc; December 2013.
    2. Epogen [Prescribing information].Thousand Oaks, CA: Amgen Inc; April 2014.
    3. Aranesp [Prescribing information]. Thousand Oaks, CA: Amgen Inc; March 2015.
    4. Mircera [Product Information] South San Francisco, CA, Genentech USA. October 2014
    5. Seidenfeld J, et al. Epoetin treatment of anemia associated with cancer therapy: a systematic review and meta-analysis of controlled clinical trials. J Natl Cancer Inst 2001;93:1204-1214.
    6. National Comprehensive Cancer Network. Cancer and Chemotherapy Induced Anemia Version 2.2015. Available at: http://www.nccn.org/professionals/physician gls/pdf/anemia.pdf. Accessed May 21, 2015.
    7. Afdhal NH, Dieterich DT, Pockros PJ, et al for the Proactive Study Group. Epoetin alfa maintains ribavirin dose in HCV-infected patients: a prospective, double-blind, randomized controlled study. Gastroenterology. 2004;128:1302-1311.
    8. 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.
    9. FDA Strengthens Safety Information for Erythropoiesis-Stimulating Agents (ESAs). Available at: http://www.fda.gov/. Accessed May 21, 2015.
    10. Rizzo JR, Somerfield MR, Hagerty KL, et al. American Society of Clinical Oncology/American Society of Hematology 2007 Clinical Practice Guideline Update on the Use of Epoetin and Darbepoetin. Blood DOI 10.1182/blood-2007-08-109488.
    11. Procrit/Epogen. In DrugPoints. System [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed July 11, 2014.
    12. Kidney Disease Outcomes Quality Initiative. Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. 2006 Available at: http://www2.kidney.org/professionals/KDOQI/guidelines_anemiaUP. Accessed May 21, 2015.
    13. National Comprehensive Cancer Network. Myelodysplastic Syndrome Version 2.2014. Available at: http://www.nccn.org/professionals/physician_gls/pdf/mds.pdf. Accessed May 21, 2015.
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.