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Prior Authorization Protocol

ZOFRANR, ZUPLENZR (ondansetron)

NATL

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

    Zofran injection
    Zofran tablets, (orally disintegrating tablets) ODT & oral solution
    Zuplenz oral soluble film
    Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy (HEC) including cisplatin > 50mg/m2
    X
    X
    Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC)
    X
    X
    Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including high-dose cisplatin.
    X
    Prevention of nausea and vomiting associated with radiotherapy (RINV) in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen
    X
    X
    Prevention of postoperative nausea and/or vomiting (PONV)
    X
    X
    X

  2. Health Net Approved Indications and Usage Guidelines:
    • Patient has received or will receive highly or moderately emetogenic cancer chemotherapy
    OR
    • Patient will receive radiation therapy
    OR
    • Patient suffers from hyperemesis due to pregnancy (hyperemesis grayidarum)

    OR

    • Patient requires for prevention of postoperative nausea and vomiting
    OR
    • Pediatric patients with gastroenteritis
  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 maximum injectable dose of Zofran is 16 mg. A 32 mg single intravenous dose of Zofran (ondansetron) may affect the electrical activity of the heart (QT interval prolongation), which could pre-dispose patients to develop an abnormal and potentially fatal heart rhythm known as Torsades de Pointes.
    • Micromedex has a Class IIA recommendation for oral ondansetron use for pediatric patients from 6 months to 12 years presenting with gastroenteritis
    • 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, 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, dacarbazine, doxorubicin ≥ 60 mg/m2, or epirubicin >90 mg/m2, ifosfamide ≥ 2gm/m2 per dose,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 > 200 mg/m2, dactinomycin, daunorubicin, doxorubicin <60 mg/ m2, epirubicin 90 mg/m2, idarubicin, ifosfamide <2 gm/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, ipilimumab, interferon alpha 5 million IU/m2, 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 Antagonists
    AloxiR (palonosetron)*

    MEC and HEC:
    Adults:
    0.25 mg IV infused over 30 seconds beginning 30 minutes prior to chemotherapy.
    Pediactrics (1 month to less than 17 years):
    20 mcg/kg (max 1.5 mg) infused over 15 minutes beginning 30 minutes prior to chemotherapy.

    As specified by length of chemotherapy

    5-HT3 Serotonin Antagonists
    AloxiR (palonosetron)*


    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.

    Postoperative nausea and vomiting: One day

    5-HT3 Serotonin Antagonists
    AnzemetR (dolasetron)*
    Prevention of cancer chemotherapy induced nausea and vomiting
    Adults
    100 mg PO 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
    5-HT3 Serotonin Antagonists
    AnzemetR (dolasetron)*
    Prevention of PONV:
    Adults:
    12.5 mg IV 15 minutes prior to cessation of anesthesia or as soon as nausea or vomiting presents

    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 1.2 mg/kg up to a maximum 100 mg dose given within two hours before surgery.
    Safety and effectiveness in pediatric patients under 2 years of age have not been established

    Postoperative nausea and vomiting: One day

    5-HT3 Serotonin Antagonists
    Granisetron*
    MEC and HEC
    Adults:
    2 mg QD PO 1 hour prior to chemotherapy OR 1 mg BID PO 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 have not been established
    As specified by length of chemotherapy
    5-HT3 Serotonin Antagonists
    Granisetron*
    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 admininstered IV over 30 seconds

    Postoperative nausea and vomiting: One day

    5-HT3 Serotonin Antagonists
    SancusoR (granisetron)*
    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
    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 if the CINV regimen as an infusion administered over 15 minutes.

    1 x 125 mg capsule (or 1 x 115mg IV) and 2 x 80 mg capsules per cycle
    NK1 Receptor Antagonist
    EmendR (aprepitant)*

    Prevention of PONV
    40 mg PO within 3 hours prior to induction of anesthesia
    Prevention of postoperative nausea and vomiting:
    One day
    Oral Corticosteroids
    Dexamethasone (DecadronR)


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

    various chemotherapy dosage regimens


    40 mg/day

    Phenothiazines
    Promethazine (PhenerganR)


    Oral, Rectal, IM
    :
    12.5 mg-25 mg q4-6 hours prn


    100 mg/day

    Phenothiazines
    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/day

    Benzodiazepines
    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

    Ondansetron (ZofranR)


    MEC/ORAL
    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 BID for 1 to 2 days after completion of chemotherapy
    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 TID for 1 to 2 days after completion of chemotherapy

    MEC/IV
    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 prior to 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 doses IV doses up to a maximum of 16 mg per dose. The first dose is administered 30 minutes before
    the start of chemotherapy, with subsequent
    doses 4 and 8 hours after the first dose.
    Each dose is infused IV over 15 minutes.
    As specified by length of chemotherapy

    Ondansetron (ZofranR)

    HEC:
    Adults:
    24 mg (given as three 8 mg tablets) PO administered 30 minutes before the start of single-day chemotherapy.
    Use for multi-day, single-dose administration of 24 mg not established.
    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 doses up to a maximum of 16 mg per dose.
    The first dose is administered 30 minutes before the start of chemotherapy, with subsequent doses 4 and 8 hours after the first dose.
    Each dose is infused IV over 15 minutes.
    As specified by length of chemotherapy

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


    Maximum 8 mg PO TID for up to 3 days per cycle.

    Ondansetron (ZofranR)


    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 immediately before induction of anesthesia or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery.
    Alternatively, 4 mg undiluted may be administered intramuscularly as a single injection.
    Children 1 month - 12 years:
    0.1 mg/kg IV dose (for patients weighing 40kg or less) or 4 mg IV dose (for patients weighing more than 40 kg) infused over 2 to 5 minutes immediately before or following induction of anesthesia, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery.


    One time

    Ondansetron (ZofranR)


    Hyperemesis due to pregnancy
    8 mg PO every 8 hours as needed
    Up to 90 tablets per month through expected date of delivery.

    ZuplenzR (ondansetron)


    MEC
    Adults and children 12 years and older:
    One 8 mg PO film 30 minutes before chemotherapy followed by an 8mg PO dose 8 hours later.
    Administer one 8 mg PO film BID (every 12 hours) for 1 to 2 days after completion of chemotherapy
    Children 4-11 years:
    One 4 mg PO film TID.
    Administer the first dose 30 minutes before chemotherapy, with subsequent doses of 4 and 8 hours later.
    Administer one 4 mg PO film TID (every 8 hours) for 1 to 2 days after completion of chemotherapy
    As specified by length of chemotherapy

    ZuplenzR (ondansetron)

    HEC
    Adults:
    24 mg PO given successively as three 8 mg films 30 minutes before the start of chemotherapy
    As specified by length of chemotherapy

    ZuplenzR (ondansetron)

    RINV
    Adults:
    One 8 mg PO film TID


    Maximum 8 mg PO TID

    ZuplenzR (ondansetron)


    Prevention of PONV
    Adults:
    16 mg PO given successively as two 8 mg films 1 hour before anesthesia


    One time

    Ondansetron ODT

    Pediatric Gastroenteritis - Vomiting

    (body weight 8 to 15 kg) 2 mg, (body weight 15 to 30 kg) 4 mg, and (body weight over 30 kg) 8 mg (0.13 to 0.26 mg/kg), dissolved orally on the tongue usually as a single dose

    One time

  7. Product Availability:
    Ondansetron (Zofran) Tablet: 4 mg, 8 mg,
    Ondansetron (Zofran) Orally disintegrating Tablet (ODT): 4 mg, 8 mg
    Ondansetron (Zofran) Oral Solution: 4 mg/5 ml (50 ml bottle)
    Ondansetron (Zofran) Injection: 2 mg/ml (20 ml multidose vial)
    Zuplenz (ondansetron) oral soluble film: 4 mg, 8 mg (package size 10)
  8. References:
    1. Zofran injection. [package insert]. Research Triangle Park, NC: GlaxoSmithKline; September 2014
    2. Zofran tablets/oral solution/ ODT. [package insert]. Research Triangle Park,NC: GlaxoSmithKline; September 2014
    3. Zuplenz oral soluble film. [package insert]. Morrisville, NC: Praelia Pharmaceuticals;September 2014.
    4. Sullivan CA, Johnson CA, Roach H, et al. A pilot study of intravenous ondansetron for hyperemesis gravidarum. Am J Obstet Gynecol 1996;174:1565-8.
    5. Siu SSN, Yip SK, Cheung CW, et al. Treatment of intractable hyperemesis gravidarum by ondansetron. Eur J Obstet Gynecol Reprod Biol 2002;105:73-4.
    6. Guikontes E, Spantideas A, Diakakis J, et al. Ondansetron and hyperemesis gravidarum. Lancet. 1992;340:1223.
    7. World MJ. Ondansetron and hyperemesis gravidarum. Lancet 1993;341:185.
    8. Basch E, Prestrud AA, Hesketh, PJ, et al. Antiemetics: American Society of Clinical Oncology (ASCO) Clinical Practice Guideline Update 2011 J Clin Oncol 29:4189-4198.
    9. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology  Antiemesis Version 1.2012. NCCN Web site. Available at: http://www.nccn.org/. Accessed June 22, 2015.
    10. Clinical Pharmacology Web site. Available at: http://cpip.gsm.com/. Accessed June 22, 2015.
    11. MicromedexR Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed June 22, 2015.
    12. Ondansetron. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed July 1, 2014
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.