Ondansetron (Zuplenz) Form

Ondansetron (Zuplenz®) is a serotonin (5-HT3) receptor antagonist.
FDA Approved Indication(s) Zuplenz is indicated for the prevention of:
• Nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m2, in adults • Nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy in adults and pediatric patients 4 years of age and older • Nausea and vomiting associated with radiotherapy in adult patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen • Postoperative nausea and/or vomiting (PONV) in adults Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Zuplenz is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Prevention of Nausea and Vomiting (must meet all):

1. Prescribed for the prevention of nausea/vomiting due to one of the following (a, b, or c): a. Cancer chemotherapy (see Appendix D);
   b. Radiation therapy; c. Surgery;
2. Member meets one of the following: a. For moderately emetogenic cancer chemotherapy: Age ≥ 4 years; b. For highly emetogenic cancer chemotherapy: Age ≥ 18 years; c. For total body irradiation: Age ≥ 18 years; d. For PONV: Age ≥ 18 years;

3. Member meets one of the following (a or b): a. Both of the following (i and ii): i. Member is contraindicated or has experienced clinically significant adverse effects to the excipients in all formulary generic ondansetron products (regular tablet, orally disintegrating tablet, oral solution); Page 1 of 9

   CLINICAL POLICY Ondansetron ii. Documentation supports member’s inability to use all formulary generic ondansetron products (regular tablet, orally disintegrating tablet, oral solution); b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E);

4. Dose does not exceed one of the following (a or b): a. Chemotherapy, radiation therapy: both of the following (i and ii): i. 24 mg per day; ii. 3 films per day; b. Postoperative: both of the following (i and ii): i. 16 mg as a single dose; ii. 2 films. Approval duration:
   Chemotherapy-induced nausea/vomiting: Projected course of chemotherapy up to 72 hours after completion of chemotherapy Radiation therapy-induced nausea/vomiting: Projected course of radiation therapy up to 48 hours after completion of radiation therapy
   Postoperative nausea/vomiting: One time approval (3 days) B. Other diagnoses/indications (must meet 1 or 2):
5. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

6. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Nausea and Vomiting Associated with Chemotherapy or Radiation Therapy (must meet all):

   1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B); Page 2 of 9

   CLINICAL POLICY Ondansetron

7. Member is responding positively to therapy;
   3. Member continues to receive cancer chemotherapy (see Appendix D) or radiation therapy;
8. If request is for a dose increase, new dose does not exceed both of the following (a and b): a. 24 mg per day; b. 3 films per day. Approval duration:
   Chemotherapy-induced nausea/vomiting: Projected course of chemotherapy up to 72 hours after completion of chemotherapy Radiation therapy-induced nausea/vomiting: Projected course of radiation therapy up to 48 hours after completion of radiation therapy B. Postoperative Nausea and Vomiting
9. Re-authorization is not permitted. Members must meet the initial approval criteria. Approval duration: Not applicable C. Other diagnoses/indications (must meet 1 or 2):
10. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

11. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key 5-HT3: serotonin 5-hydroxytryptamine, type 3 ASCO: American Society of Clinical Oncology FDA: Food and Drug Administration Page 3 of 9

    CLINICAL POLICY Ondansetron NCCN: National Comprehensive Cancer PONV: postoperative nausea and vomiting Network
    Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Dosing Regimen Drug Name Dose Limit/ Maximum Dose PO: 24 mg/day
    IV: 16 mg/day ondansetron (Zofran®, Zofran ODT) Prevention of nausea and vomiting associated with moderately emetogenic chemotherapy 8 mg PO given 30 min prior to chemotherapy, then repeat dose 8 hrs after initial dose, then 8 mg PO BID for 1 to 2 days after chemotherapy completion
    Prevention of nausea and vomiting associated with highly emetogenic chemotherapy 24 mg PO given 30 min prior to start of single- day chemotherapy Prevention of nausea and vomiting associated with emetogenic chemotherapy 0.15 mg/kg/dose IV given 30 min prior to chemotherapy, then repeat dose 4 and 8 hrs after initial dose Treatment of nausea and vomiting associated with chemotherapy* 16 to 24 mg PO daily or 8 to 16 mg IV Prevention of nausea and vomiting associated with radiation therapy Total body irradiation: 8 mg PO given 1 to 2 hrs prior to radiotherapy Single high-dose radiotherapy: 8 mg PO given 1 to 2 hrs prior to irradiation, then 8 mg PO Q8H for 1 to 2 days after completion of radiotherapy Daily fractionated radiotherapy: 8 mg PO given 1 to 2 hrs prior to irradiation, then 8 mg PO Q8H for each day of radiotherapy Prevention of PONV 16 mg PO given 1 hr prior to anesthesia or 4 mg IM/IV as a single dose given 30 min before end of anesthesia Page 4 of 9

    CLINICAL POLICY Ondansetron Drug Name Dosing Regimen Dose Limit/ Maximum Dose Treatment of PONV 4 mg IV as a single dose Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Off-label Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o Known hypersensitivity (e.g., anaphylaxis) to ondansetron or any components of the formulation o Concomitant use of apomorphine • Boxed warning(s): none reported Appendix D: American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) Recommendations in Oncology • Minimal emetic risk chemotherapy: No routine prophylaxis is recommended. • Low emetic risk chemotherapy: Recommended options include dexamethasone (recommended by both ASCO and NCCN) or metoclopramide, prochlorperazine, or a 5- HT3 receptor antagonist (recommended by NCCN only). NK1 receptor antagonists are not included in low risk antiemetic recommendations. • Moderate emetic risk chemotherapy: 5-HT3 receptor antagonists and dexamethasone may be used in combination and with or without NK1 receptor antagonists. Olanzapine may also be used in combination with palonosetron and dexamethasone. o Examples of moderate emetic risk chemotherapy: azacitidine, bendamustine, carboplatin, clofarabine, cyclophosphamide ≤ 1,500 mg/m2, cytarabine > 200 mg/m2, daunorubicin, doxorubicin < 60 mg/m2, epirubicin ≤ 90 mg/m2, idarubicin, ifosfamide, irinotecan, oxaliplatin • High emetic risk chemotherapy: NK1 receptor antagonists are recommended for use in combination with 5-HT3 receptor antagonists and dexamethasone. Olanzapine may also be used in combination with 5-HT3 receptor antagonists, dexamethasone, and/or NK1 receptor antagonists. o Examples of high emetic risk chemotherapy: carmustine, cisplatin, cyclophosphamide

    1,500 mg/m2, dacarbazine, mechlorethamine, streptozocin • Breakthrough emesis: Per NCCN, an agent from a different drug class is recommended to be added to the current antiemetic regimen. Drug classes include atypical antipsychotics (olanzapine), benzodiazepines (lorazepam), cannabinoids (dronabinol, nabilone), phenothiazines (prochlorperazine, promethazine), 5-HT3 receptor antagonists (dolasetron, ondansetron, granisetron), steroids (dexamethasone), or haloperidol, metoclopramide, scopolamine. An NK1 receptor antagonist may be added to the prophylaxis regimen of the next chemotherapy cycle if not previously included.
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    CLINICAL POLICY Ondansetron Appendix E: States with Regulations against Redirections in Stage IV or Metastatic Cancer State Step Therapy Prohibited? Yes Yes FL GA Notes For stage 4 metastatic cancer and associated conditions. For stage 4 metastatic cancer. Redirection does not refer to review of medical necessity or clinical appropriateness. For standard of care stage 4 cancer drug use, supported by peer- reviewed, evidence-based literature, and approved by FDA. For stage 4 advanced, metastatic cancer or associated conditions. Exception if “clinically equivalent therapy, contains identical active ingredient(s), and proven to have same efficacy. Stage 3 and stage 4 cancer patients for a prescription drug to treat the cancer or any symptom thereof of the covered person Applies to Commercial and HIM requests only For stage 4 metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer For advanced metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer and associated conditions IA LA NV OH PA TN TX Yes Yes Yes Yes Yes Yes Yes V. Dosage and Administration
    Indication Prevention of nausea and vomiting associated with cancer chemotherapy Prevention of nausea and vomiting associated with radiotherapy Prevention of postoperative nausea Dosing Regimen Moderately emetogenic cancer chemotherapy:
    Age 12 years or older: 8 mg PO given 30 min prior to chemotherapy, then repeat dose 8 hrs after initial dose, then 8 mg PO BID for 1 to 2 days after chemotherapy completion
    Age 4 to 11 years: 4 mg PO given 30 min prior to chemotherapy, then repeat dose 4 and 8 hrs after initial dose, then 4 mg PO TID for 1 to 2 days after chemotherapy completion Highly emetogenic cancer chemotherapy:
    Age 18 or older: 24 mg PO given 30 min prior to start of single-day chemotherapy Total body irradiation: 8 mg PO given 1 to 2 hrs prior to each daily fraction of radiotherapy Single high-dose radiotherapy: 8 mg PO given 1 to 2 hrs prior to irradiation, then 8 mg PO Q8H for 1 to 2 days after completion of radiotherapy Daily fractionated radiotherapy: 8 mg PO given 1 to 2 hrs prior to irradiation, then 8 mg PO Q8H for each day of radiotherapy 16 mg PO given 1 hr prior to anesthesia
    Maximum Dose 24 mg/day 24 mg/day 16 mg/dose Page 6 of 9

    CLINICAL POLICY Ondansetron Indication and vomiting Dosing Regimen Maximum Dose VI. Product Availability
    Oral soluble film: 4 mg, 8 mg
    VII.