ANZEMET, Dolasetron Mesylate Form

Dolasetron (Anzemet®) is a serotonin (5-HT3) receptor antagonist.
FDA Approved Indication(s) Anzemet is indicated for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy, including initial and repeat courses in adults and children 2 years and older. 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 Anzemet is 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. Age ≥ 2 years;
   3. Member is scheduled to receive cancer chemotherapy (see Appendix D);
   4. 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);
2. Dose does not exceed both of the following (a and b): a. 100 mg per day; b. 1 tablet per day.
   Approval duration: Projected course of chemotherapy up to 72 hours after completion of chemotherapy
   B. Other diagnoses/indications (must meet 1 or 2):

3. 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): Page 1 of 7

   CLINICAL POLICY Dolasetron 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

4. 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 Cancer Chemotherapy (must meet all):
5. 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 continues to receive cancer chemotherapy (see Appendix D);
   4. If request is for a dose increase, new dose does not exceed both of the following (a and b): a. 100 mg per day; b. 1 tablet per day. Approval duration: Projected course of chemotherapy up to 72 hours after completion of chemotherapy
      B. Other diagnoses/indications (must meet 1 or 2):
6. 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

7. 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 Page 2 of 7

   CLINICAL POLICY Dolasetron 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
   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) Akynzeo® (netupitant/ palonosetron) 1 vial IV given 30 min prior to chemotherapy on day 1 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 0.25 mg IV given 30 min prior to chemotherapy 1 vial/ chemotherapy cycle 1 capsule or vial/chemotherapy cycle 0.25 mg/day Aloxi® (palonosetron) granisetron (Kytril®) Tablet: 2 mg PO QD given 1 hr prior to chemotherapy, or 1 mg PO BID (one dose given 1 hr prior to chemotherapy and then 12 hours later) PO: 2 mg/day
   IV: 10 mcg/kg/day
   Injection: 10 mcg/kg IV given within 30 min prior to chemotherapy (on days chemotherapy is given) ondansetron (Zofran®, Zofran® ODT, Zuplenz®) 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
   PO: 24 mg/day
   IV: 16 mg/dose (up to 3 doses/day) Page 3 of 7

   CLINICAL POLICY Dolasetron Drug Name Dosing Regimen Dose Limit/ Maximum Dose 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 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. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): known hypersensitivity to the drug • 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 Dolasetron 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
   Indication Prevention of chemotherapy-induced nausea and vomiting Dosing Regimen Adults: 100 mg PO given within 1 hour before chemotherapy Maximum Dose 100 mg/day Pediatrics (age 2 to 16 years): 1.8 mg/kg PO given within 1 hour before chemotherapy VI. Product Availability
   Tablets: 50 mg, 100 mg
   VII.