Granisetron (Sancuso, Sustol) Form

Granisetron (Sancuso®, Sustol®) is a serotonin (5-HT3) receptor antagonist.
FDA Approved Indication(s) Granisetron intravenous injection is indicated for: • Prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin • Prevention and treatment of postoperative nausea and vomiting (PONV) in adults Granisetron tablet is indicated for the prevention of: • Nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin • Nausea and vomiting associated with radiation, including total body irradiation and fractionated abdominal radiation Sancuso is indicated for the prevention of nausea and vomiting in patients receiving moderately and/or highly emetogenic chemotherapy of up to 5 consecutive days duration. Sustol is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MED) for anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. 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 granisetron, Sancuso, and Sustol are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Nausea and Vomiting Associated with Cancer Chemotherapy (must meet all):

1. Prescribed for the prevention or treatment of chemotherapy-induced nausea/vomiting;

   2. For Sancuso or Sustol: Age ≥ 18 years;
   3. Member is scheduled to receive cancer chemotherapy (see Appendix D);
   4. Member must use generic granisetron, unless contraindicated or clinically significant adverse effects are experienced; Page 1 of 11

   CLINICAL POLICY Granisetron

2. Member meets one of the following (a or b): a. Failure of a formulary 5-HT3 receptor antagonist (ondansetron is preferred) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
   b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E);
3. Dose does not exceed one of the following (a, b, c, or d): a. Intravenous injection: 10 mcg/kg;
   b. Tablet: 2 mg (2 tablets) per day; c. Sustol: 10 mg per 7 days; d. Sancuso: 1 patch per 7 days. Approval duration: Projected course of chemotherapy up to 72 hours after completion of chemotherapy B. Nausea and Vomiting Associated with Radiation Therapy (must meet all):
4. Request is for granisetron tablet;
   2. Prescribed for the prevention of radiation-induced nausea/vomiting;
   3. Age ≥ 18 years;
   4. Member is scheduled to receive radiation therapy;
   5. Member meets one of the following (a or b): a. Failure of a formulary 5-HT3 receptor antagonist (ondansetron is preferred) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
      b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E);
5. Dose does not exceed 2 mg (2 tablets) per day. Approval duration: Projected course of radiation therapy up to 48 hours after completion of radiation therapy C. Postoperative Nausea and Vomiting (must meet all):
6. Request is for granisetron IV injection;
   2. Prescribed for the prevention or treatment of PONV;
   3. Age ≥ 18 years;
   4. Member is scheduled to undergo surgery;
   5. Member meets one of the following (a or b): a. For prevention: Failure of a formulary 5-HT3 receptor antagonist (ondansetron is preferred) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
      b. For treatment: Member did not receive a preoperative 5-HT3 receptor antagonist (e.g., ondansetron);

7. Dose does not exceed 1 mg once. Approval duration: One time approval (3 days) Page 2 of 11

   CLINICAL POLICY Granisetron D. Other diagnoses/indications (must meet 1 or 2):

8. 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
9. 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);
   2. Member is responding positively to therapy;
   3. Member must use generic granisetron, unless contraindicated or clinically significant adverse effects are experienced;
10. Member meets one of the following (a or b): a. Member continues to receive cancer chemotherapy (see Appendix D); b. Member continues to receive radiation therapy;

11. If request is for a dose increase, new dose does not exceed one of the following (a, b, c, or d): a. Intravenous injection: 10 mcg/kg;
    b. Tablet: 2 mg (2 tablets) per day; c. Sustol: 10 mg per 7 days; d. Sancuso: 1 patch per 7 days. 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 Page 3 of 11

    CLINICAL POLICY Granisetron B. Postoperative Nausea and Vomiting

12. 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):
13. 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

14. 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 FDA: Food and Drug Administration NCCN: National Comprehensive Cancer ASCO: American Society of Clinical Network
    Oncology PONV: postoperative nausea and vomiting 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 5-HT3 Serotonin Antagonists Akynzeo® (fosnetupitant/ palonosetron) Prevention of nausea and vomiting associated with highly emetogenic chemotherapy 1 vial/chemotherapy cycle Page 4 of 11

    Dose Limit/ Maximum Dose 1 capsule or vial/chemotherapy cycle 100 mg/day
    Chemo-induced N/V prophylaxis: 0.25 mg/day
    PONV prophylaxis: 0.075 mg/day PO: 24 mg/day
    IV: 16 mg/dose (up to 3 doses/day) CLINICAL POLICY Granisetron Drug Name Dosing Regimen Akynzeo® (netupitant/ palonosetron) Anzemet® (dolasetron) Aloxi® (palonosetron) ondansetron (Zofran®, Zofran® ODT, Zuplenz®) 1 vial IV given 30 min prior to chemotherapy on day 1 Prevention of nausea and vomiting associated with highly emetogenic chemotherapy 1 capsule PO given 1 hour prior to initiation of chemotherapy on day 1 (in combination with dexamethasone) or 1 vial IV given 30 min prior to initiation of chemotherapy on day 1 Prevention of nausea and vomiting associated with chemotherapy 100 mg PO within 1 hr prior to chemotherapy Prevention of nausea and vomiting associated with chemotherapy 0.25 mg IV given 30 min prior to chemotherapy Prevention of PONV 0.075 mg IV given immediately prior to anesthesia Prevention of nausea and vomiting associated with moderately emetogenic 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 8 mg PO TID 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 Page 5 of 11

    CLINICAL POLICY Granisetron Drug Name Dosing Regimen Dose Limit/ Maximum 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 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 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 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 Sustol is contraindicated in patients with hypersensitivity to granisetron, any of the components of Sustol, or to any of the other 5-HT3 receptor antagonists. o Sancuso is contraindicated in patients with known hypersensitivity to granisetron or to any of the components of the patch. • 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. Page 6 of 11

    CLINICAL POLICY Granisetron 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.
    Appendix E: States with Regulations against Redirections in Stage IV or Metastatic Cancer State Step Therapy Prohibited? Yes Yes FL GA IA LA NV OH PA TN TX Yes Yes Yes Yes Yes Yes Yes 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 V. Dosage and Administration
    Drug Name Indication Dosing Regimen Granisetron tablet Prevention of nausea and vomiting associated with chemotherapy Prevention of nausea and vomiting associated with radiotherapy 2 mg PO QD or 1 mg PO BID only on days chemotherapy is given 2 mg PO QD given within 1 hr of radiation Maximum Dose 2 mg/day 2 mg/day Page 7 of 11

    CLINICAL POLICY Granisetron Drug Name Indication Dosing Regimen Granisetron injection Prevention of Chemotherapy-Induced Nausea and Vomiting Prevention and treatment of postoperative nausea and vomiting Prevention of nausea and vomiting associated with cancer chemotherapy Granisetron (Sancuso) Granisetron (Sustol) Prevention of nausea and vomiting associated with cancer chemotherapy 10 mcg/kg IV within 30 minutes before initiation of chemotherapy, and only on the day(s) chemotherapy is given. 1 mg IV before induction of anesthesia or immediately before reversal of anesthesia Apply 1 patch to upper outer arm 24 to 48 hrs prior to chemotherapy; Remove patch at least 24 hrs after completion of chemotherapy 10 mg SC 30 minutes prior to the initiation of MED or AC combination chemotherapy on Day 1.
    Maximum Dose 10 mcg/kg 1 mg/operation 1 patch/7 days 10 mg/7 days VI. Product Availability
    Drug Name Granisetron Granisetron (Sancuso) Granisetron (Sustol) Availability Tablet: 1 mg Injection: 0.1 mg/mL, 1 mg/mL Transdermal system: 3.1 mg/24 hours Extended-release pre-filled syringe: 10 mg/0.4 mL
    VII.