HN Logo
Prior Authorization Protocol

ALOXIR (palonosetron), ANZEMETR (dolasetron), SANCUSOR, GRANISOLTM (granisetron)





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:
    Aloxi injection
    Anzemet injection
    Anzemet tablet
    Granisetron injection
    Granisetron tablet & Granisol
    Sancuso patch
    Moderately emetogenic cancer chemotherapy (MEC)-prevention of acute nausea & vomiting associated with initial and repeat courses
    X
    Also approved for delayed nausea and vomiting
    X
    X
    X
    X
    Patient is receiving chemotherapy regimens up to 5 consecutive days duration
    Highly emetogenic cancer chemotherapy (HEC)-prevention of acute nausea & vomiting associated with initial and repeat courses.
    X
    X
    X
    X
    Patient is receiving chemotherapy regimens up to 5 consecutive days duration
    Prevention of nausea & vomiting associated with radiation (RINV), including total body irradiation and fractionated abdominal radiation
    X
    Prevention of postoperative nausea and vomiting (PONV).
    X
    Used for up to 24 hours following surgery. Efficacy beyond 24 hours has not been demonstrated
    X
    X
    Treatment of postoperative nausea and vomiting (PONV)
    X
    X
  2. Health Net Approved Indications and Usage Guidelines:
    Prevention of nausea and vomiting associated with cancer chemotherapy for Anzemet tablet, Granisetron injection and tablet, Granisol and Sancuso patch:
    • Patient has received, or will receive, highly or moderately emetogenic chemotherapy
    AND
    • Failure or clinically significant adverse events to ondansetron or Aloxi
    Prevention of nausea and vomiting associated with radiation therapy (RINV) for Granisetron tablet and Granisol:
    • Patient will receive radiation therapy
    AND
    • Failure or clinically significant adverse events to ondansetron
    Prevention of postoperative nausea and vomiting (PONV) for Aloxi, Anzemet injection and Granisetron injection:
    • Patient is undergoing surgery
    AND
    • Failure or clinically significant adverse events to ondansetron
    Treatment of PONV for Anzemet injection and Granisetron injection:
    • Patient underwent surgery
    AND
    • 5-HT3antagonist was not used for prevention of PONV
  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
    • Anzemet injection solution is contraindicated in adult and pediatric patients for the prevention of nausea and vomiting associated with the initial and repeat courses of emetogenic cancer chemotherapy
  4. General Information:
    • The NCCN Antiemesis guidelines Version 1.2012 added Aloxi as the preferred 5HT-3 antagonist for highly or moderately emetogenic chemotherapy
    • Anzemet injection solution prolongs the QT interval in a dose dependent fashion. Torsades de Pointes has been reported during post-marketing experience. Avoid Anzemet in patients with congenital long QT syndrome, hypokalemia or hypomagnesemia.
    • Serotonin subtype 3 (5-HT3) receptor antagonist may cause serotonin syndrome alone but particularly with concomitant use of serotonergic drugs.
    • According to the 2011 American Society of Clinical Oncology (ASCO) Guideline for Antiemetics in Oncology, the Update Committee recommends the following:
      • For chemotherapy of high emetic risk - three-drug combination of 5-hydroxytryptamine-3 (5-HT3) serotonin receptor antagonist, dexamethasone, and aprepitant
      • For chemotherapy of moderate emetic risk - two-drug combination of a 5-HT3 serotonin receptor antagonist and dexamethasone
    • Per practice guidelines from the National Comprehensive Cancer Network (NCCN), selection of emetogenic agents used should be based on the emetic risk of the therapy , prior experience with antiemetics, as well as patient risk factors.
    • The following table is NCCN's classification for emetogenic potential of significant chemotherapy and other agents.

    Agents
    Frequency of Emesis
    AC combination defined as either doxorubicin or epirubicin with cyclophosphamide, carmustine > 250 mg/m2, cisplatin, cyclophosphamide > 1,500 mg/m2, doxorubicin ≥ 60mg/m2, epirubicin >90mg/m2, ifosfamide ≥ 2gm/m2 per dose, dacarbazine, mechlorethamine, streptozocin
    High Emetic Risk
    >90%
    aldesleukin > 12-15 million IU/m2, amifostine > 300 mg/m2, arsenic trioxide, azacitidine, bendamustine, busulfan, carboplatin, carmustine 250 mg/m2, clofarabine, cyclophosphamide 1500 mg/m2, cytarabine > 200mg/m2, dactinomycin, daunorubicin, doxorubicin < 60 mg/m2, epirubicin 90mg/m2, idarubicin, ifosfamide < 2gm/m2 per dose, interferon alpha ≥ 10 million IU/m2, irinotecan, melphalan, MTX ≥ 250 mg/m2, oxaliplatin, temozolomide
    Moderate Emetic Risk
    30-90%
    ado-trastuzumab emtansine, amifostine 300 mg, aldesleukin 12 million IU/m2, brentuximab vedotin, cabazitaxel, carfilzomib, cytarabine (low dose) 100 - 200 mg/m2, docetaxel, doxorubicin (liposomal), eribulin, etoposide, 5-fluorouracil, floxuridine, gemcitabine, interferon alpha > 5 <10 million IU/m2, ixabepilone, MTX > 50 mg/m2 < 250 mg/m2, mitomcyin, mitoxantrone, omacetaxine, paclitaxel, paclitaxel-albumin, pemetrexed, pentostatin, pralatrexate, romidepsin, thiotepa, topotecan, ziv-aflibercept
    Low Emetic Risk
    10-30%
    alemtuzumab, asparaginase, bevacizumab, bleomycin, bortezomib, cetuximab, 2-chlorodeoxyadenosine (cladribine), cytarabine < 100mg/m2, decitabine, denileukin diftitox, dexrazoxane, fludarabine, interferon alpha 5 million IU/m2, ipilimumab, MTX 50 mg/m2, nelarabine, ofatumumab, panitumumab, pegaspargase, peginterferon, pertuzumab, rituximab, temsirolimus, trastuzumab, valrubicin, vinblastine, vincristine, vincristine (liposomal), vinorelbine
    Minimal Emetic Risk
    <10%
    altretamine, busulfan (≥ 4 mg/d), crizotinib, cyclophosphamide (≥ 100 mg/m2/d), estramustine, etoposide, lomustine (single day), mitotane, procarbazine, temozolomide (> 75 mg/m2/d), vismodegib
    Emetogenic potential of oral antineoplastic agents: Moderate to High
    axitinib, bexarotene, bosutinib, busulfan (< 4 mg/d), cabozantinib, capecitabine, chlorambucil, cyclophosphamide (< 100 mg/m2/d), dasatinib, dabrafenib, erlotinib, everolimus, fludarabine, gefitinib, hydroxyurea, imatinib, lapatinib, lenalidomide, melphalan, mercaptopurine, methotrexate, nilotinib, pazopanib, pomalidomide, ponatinib, regorafenib, ruxolitinib, sorafenib, sunitinib, temozolomide (75 mg/m2/d), thalidomide, thioguanine, topotecan, trametinib, tretinoin, vandetanib, vemurafenib, vorinostat
    Emetogenic potential of oral antineoplastic agents: Minimal to low

  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose

    5-HT3 serotonin receptor antagonist

    ondansetron (ZofranR)*
    MEC:
    Adults and children 12 years and older:
    8 mg PO BID administered 30 minutes before the start of chemotherapy, with a subsequent dose 8 hours after the first dose; continue 8 mg PO BID for 1 to 2 days after completion of chemotherapy.

    Adults:
    Three 0.15 mg/kg IV doses up to a maximum of 16 mg per dose. The first dose is infused over 15 minutes beginning 30 minutes before the start of chemotherapy and subsequent doses are administered 4 and 8 hours after the first dose

    Children 4-11 years:
    4 mg PO TID administered 30 minutes before the start of chemotherapy, with subsequent doses 4 and 8 hours after the first dose; continue 4 mg PO TID for 1 to 2 days after completion of chemotherapy.
    Children 6 months-18 years:
    Three 0.15 mg/kg IV administered 30 minutes before the start of chemotherapy, with subsequent doses 4 and 8 hours after the first dose. Each dose is infused over 15 minutes.
    As specified by length of chemotherapy

    5-HT3 serotonin receptor antagonist

    ondansetron (ZofranR)*
    HEC:
    Adults:
    24 mg (given as three 8 mg tablets) PO administered 30 minutes before the start of single-day chemotherapy.

    Adults:
    Three 0.15 mg/kg IV doses up to a maximum of 16 mg per dose. The first dose is infused over 15 minutes beginning 30 minutes before the start of chemotherapy and subsequent doses are administered 4 and 8 hours after the first dose.

    Children 6 months-18 years:
    Three 0.15 mg/kg IV administered 30 minutes before the start of chemotherapy, with subsequent doses 4 and 8 hours after the first dose. Each dose is infused over 15 minutes.
    As specified by length of chemotherapy

    5-HT3 serotonin receptor antagonist

    ondansetron (ZofranR)*
    RINV:
    Total body irradiation:
    Adults: 8 mg PO given 1 to 2 hours before each fraction of radiotherapy administered each day.

    Single high dose fraction radiotherapy to the abdomen:

    Adults: 8 mg PO given 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose; continue 1 to 2 days after completion of radiotherapy.

    Daily fractionated radiotherapy to the abdomen:
    Adults:

    8 mg PO given 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiation is given


    Prevention of PONV:
    Adults:
    16 mg (given as two 8 mg tablets) PO 1 hour before induction of anesthesia

    Adults:

    4 mg undiluted IV infused over 2 to 5 minutes before induction of anesthesia

    Children 1 month-12 years:

    0.1 mg/kg IV dose (for patients weighing 40 kg or less) or 4 mg IV dose (for patients weighing more than 40 kg) infused over 2 to 5 minutes before induction of anesthesia
    RINV:
    As specified by prescriber
    Maximum 8 mg PO TID for up to 3 days per cycle.


    Prevention of PONV:
    One day

    substance P/neurokinin 1 (NK1) receptor antagonist
    EmendR (aprepitant)
    MEC and HEC:
    125 mg PO 1 hour prior to chemotherapy and 80 mg on Day 2, 3

    Emend 115 mg IV may be substituted for Emend 125 mg PO 30 minutes prior to chemotherapy on day 1 only of the CINV regimen as an infusion administered over 15 minutes.


    1 x 125 mg capsule (or 1 x 115 mg IV) and 2 x 80 mg capsules per cycle

    substance P/neurokinin 1 (NK1) receptor antagonist
    EmendR (aprepitant)
    Prevention of PONV:
    40 mg PO within 3 hours prior to induction of anesthesia
    One day
    Corticosteroid
    Dexamethasone (DecardronR)

    20 mg PO (pre-chemotherapy) and 8 mg PO daily on Day 2, 3

    Various chemotherapy dosage regimens

    40 mg/day

    Phenothiazine
    Promethazine (PhenerganR)


    Oral, Rectal, IM
    12.5 mg-25 mg q 4-6 hours PRN

    100 mg/day

    Phenothiazine
    Prochlorperazine (CompazineR)

    Oral: 5-10 mg PO q 6-8 hours.
    Rectal: 25 mg q12 hours
    IM: 5-10 mg initially, repeat q 3-4 hours PRN

    40 mg PO/day

    Benzodiazepine
    Lorazepam (AtivanR)

    0.5-2 mg PO or IV q 4-6 hours PRN

    Various chemotherapy dosage regimens

    10 mg/day

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

    Aloxi

    MEC and HEC:
    Adults:
    0.25 mg IV infused over 30 seconds beginning 30 minutes prior to chemotherapy.

    Pediatrics (1 month to less than 17 years):

    20 mcg/kg (max 1.5 mg) infused over 15 minutes beginning 30 minutes prior to chemotherapy


    Prevention of PONV:
    Adults: 0.075 mg IV infused over 10 seconds immediately before the induction of the anesthesia

    Efficacy beyond 24 hours has not been demonstrated.
    MEC and HEC:
    As specified by length of chemotherapy



    Prevention of PONV:
    One day

    Anzemet

    Prevention of Cancer Chemotherapy Induced Nausea and Vomiting
    Adults:
    100 mg PO given within 1 hour prior to chemotherapy.
    Children 2-16 years:
    1.8 mg/kg up to a maximum of 100 mg PO given within 1 hour prior to chemotherapy

    Safety and effectiveness in pediatric patients under 2 years of age have not been established.

    As specified by length of chemotherapy

    Anzemet

    Prevention or treatment of PONV:
    Adults:
    12.5 mg IV 15 minutes prior to cessation of anesthesia (prevention) or as soon as nausea or vomiting presents (treatment).
    Children 2-16 years:
    0.35 mg/kg up to a maximum of 12.5 mg IV given as a single dose approximately 15 minutes before the cessation of anesthesia or as soon as nausea or vomiting presents. The injection may also be given as an oral administration mixed in apple juice as 1.2mg/kg up to a maximum 100mg dose given within two hours before surgery.

    Safety and effectiveness in pediatric patients under 2 years of age have not been established.

    One day

    Granisetron, Granisol

    MEC and HEC:
    Adults:
    2 mg QD PO 1 hour prior to chemotherapy OR 1 mg PO BID 1 hour prior to chemotherapy and then 12 hours later

    Adults:
    10 mcg/kg IV infused over 30 seconds beginning 30 minutes prior to chemotherapy

    Children 2-16 years:
    10 mcg/kg IV prior to chemotherapy

    Safety and effectiveness in pediatric patients under 2 years of age has not been established
    As specified by length of chemotherapy

    Granisetron, Granisol

    Prevention of PONV
    Adults:
    1 mg IV infused over 30 seconds prior to induction of anesthesia or immediately before reversal of anesthesia

    Treatment of PONV
    Adults:
    1 mg administered IV over 30 seconds

    PONV:
    One day

    Granisetron, Granisol

    RINV:
    Adults: 2 mg PO QD within 1 hour of radiation

    As specified by prescriber
    Maximum 2 mg per day on days of radiation

    Sancuso
    MEC and HEC:
    Adults:
    Apply a single patch to the upper outer arm from 24 to 48 hours before chemotherapy. Remove the patch a minimum of 24 hours after completion of chemotherapy.

    The patch can be worn for up to 7 days depending on the duration of chemotherapy regimen.
    As Specified by Length of Chemotherapy
  7. Product Availability:
    Aloxi: 0.25 mg/5 ml (single-use 5 ml vial), 0.075 mg/1.5 ml (single-use 1.5 ml vial)
    Anzemet: 50 mg, 100 mg tablets
    Anzemet: 12.5 mg/ 0.625 ml single use vial
    Anzemet: 100 mg/5 ml (single-use 5 ml vial) and 500 mg/25 ml (multidose 25 ml vial)
    Granisetron: 1 mg tablets
    Granisetron: 1 mg/ml (single-use 1 ml vial, multidose 4 ml vial) and 0.1 mg/ml (single-use 1 ml vial)
    Granisol: 2 mg/10 mL oral solution 30 mL bottle
    Sancuso: 3.1 mg/24 hours transdermal patch
  8. References:
    1. Aloxi [package insert].Switzerland:Helsinn Healthcare; September 2014.
    2. Anzemet Tablets [package insert] Bridgewater, NJ: Sanofi-Aventis; September, 2014.
    3. AnzemetInjection[package insert] Bridgewater, NJ: Sanofi-Aventis; September, 2014.
    4. GranisolTM [package insert] Califon NJ: PediatRx, Inc; November 2010.
    5. Kytril Tablets [package insert] Nutley, NJ: Roche Pharmaceuticals October, 2009.
    6. Kytril Injection [package insert] Nutley, NJ: Roche Pharmaceuticals; April 2011.
    7. Sancuso Transdermal System [package insert] Bedminster, NJ: ProStrakan;September 2014.
    8. Zofran Injection [package insert] Research Triangle Park, NC: GlaxoSmithKline September 2014.
    9. Zofran Tablet/ODT/Oral Solution [package insert] Research Triangle Park,NC: GlaxoSmithKline September 2014..
    10. Emend capsules [package insert] Whitehouse Station, NJ: Merck December 2012.
    11. Emend injection [package insert] Whitehouse Station, NJ: Merck December 2012.
    12. ASHP Therapeutic Guidelines on the Pharmacologic Management of Nausea and Vomiting in Adult and Pediatric Patients Receiving Chemotherapy or Radiation Therapy or undergoing Surgery. Am J Health Syst Pharm.1999;56:730-764.
    13. Gan TJ, Diemunsch, P, Habib AS, et al. Consensus Guidelines for the Management of Postoperative Nausea and Vomiting. Anesth Analg 2014;118:85-113.
    14. 14. Basch E, Prestrud AA, Hesketh, PJ, et al. Antiemetics: American Society of Clinical Oncology (ASCO) Clinical Practice Guideline Update 2011J Clin Oncol 29:4189-4198.
    15. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology - Antiemesis Version 1.2012. NCCN Web site. Available at: http://www.nccn.org/. Accessed July 7, 2014.
    16. Aloxi. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 21, 2015.
    17. Anzemet. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 21, 2015.
    18. Granisetron. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 21, 2015.
    19. Micromedex Web site. Available at: http://www.thomsonhc.com/home/dispatch. Acceseed June 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.