Aprepitant (Emend, Cinvanti), Fosaprepitant (Emend for injection) Form

Aprepitant (Aponvie™, Emend®, Cinvanti®) and Fosaprepitant (Emend® for injection, Focinvez®) are substance P/neurokinin 1 (NK1) receptor antagonists. ____ *For Health Insurance Marketplace (HIM), if request is through the pharmacy benefit, Aponvie, Emend, fosaprepitant (Emend for injection, Focinvez), and Cinvanti are non-formulary and should not be approved using these criteria; refer to the formulary exception policy, HIM.PA.103.
FDA Approved Indication(s) Aponvie, Emend, Cinvanti, and Focinvez are indicated: • In combination with other antiemetic agents for adults (Cinvanti), patients 6 months of age and older (Emend oral suspension and injection, Focinvez), or 12 years of age and older (Emend capsules), for prevention of: o Acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin o Nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) (Cinvanti and Emend oral suspension/capsules only)
o Delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) (Emend injection, Focinvez, and Cinvanti only). • For prevention of postoperative nausea and vomiting (PONV) in adults (generic aprepitant capsules and Aponvie only) Limitation(s) of use:
• Aponvie, Emend, Cinvanti, and Focinvez have not been studied for treatment of established nausea and vomiting. • Chronic continuous administration of Emend oral suspension/capsules is not recommended. 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 Aponvie, Emend, Cinvanti, and Focinvez are medically necessary when the following criteria are met:
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CLINICAL POLICY Aprepitant, Fosaprepitant I. Initial Approval Criteria
A. Prevention of Nausea and Vomiting Associated with Cancer Chemotherapy (must meet all):

1. Request is for generic aprepitant capsules, Emend, Cinvanti, or Focinvez;
2. Prescribed for the prevention of chemotherapy-induced nausea/vomiting;
3. Member meets one of the following (a, b, or c): a. Emend oral suspension, Emend for injection, or Focinvez: age ≥ 6 months; b. Emend capsules: age ≥ 12 years; c. Cinvanti: age ≥ 18 years;
   4. Member is scheduled to receive moderately to highly emetogenic cancer chemotherapy (see Appendix D);
   5. Prescribed in combination with a serotonin (5-HT3) receptor antagonist (ondansetron is preferred) and dexamethasone;
   6. If request is for brand Emend, Focinvez, or Cinvanti, one of the following (a or b):
      a. Member must use generic aprepitant or fosaprepitant, 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);
   7. Dose does not exceed one of the following (a, b, or c): a. Emend oral suspension or capsules, both of the following (i and ii):
      i. 125 mg on Day 1, followed by 80 mg on Days 2 and 3 per chemotherapy cycle; ii. If age ≥ 6 months and < 12 years: 3 mg/kg on Day 1, followed by 2 mg/kg on Days 2 and 3 per chemotherapy cycle;
      b. Emend for injection or Focnivez, one of the following (i or ii):
      i. Single-dose regimen, all of the following (1, 2, and 3): 1) 150 mg on Day 1; 2) If age 2 years to < 12 years: 4 mg/kg on Day 1;
      3) If age 6 months to < 2 years: 5 mg/kg on Day 1
      ii. 3-day regimen, both of the following (1 and 2):
      1) 115 mg on Day 1; 2) If age 6 months to < 12 years: 3 mg/kg on Day 1
      c. Cinvanti, one of the following (i or ii):
      i. Single-dose regimen: 130 mg on Day 1 for HEC and MEC; ii. 3-day regimen: 100 mg on Day 1 for MEC. Approval duration:
      Medicaid – Projected duration of chemotherapy
      HIM – Projected duration of chemotherapy (refer to HIM.PA.103 for Emend, fosaprepitant (Emend for injection, Focinvez), and Cinvanti if pharmacy benefit) B. Prevention of Postoperative Nausea and Vomiting (must meet all):
   8. Request is for generic aprepitant capsules or Aponvie;
4. Prescribed for the prevention of PONV;
5. Age ≥ 18 years;

6. Member is scheduled to receive surgery;
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   CLINICAL POLICY Aprepitant, Fosaprepitant

   5. Failure of a 5-HT3 receptor antagonist (ondansetron is preferred) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
   6. Dose does not exceed one of the following (a or b): a. Generic aprepitant capsules: 40 mg (1 capsule) once; b. Aponvie: 32 mg (one vial) once. Approval duration:
      Medicaid – 3 days (one time dose)
      HIM – 3 days (one time dose) (refer to HIM.PA.103 for Aponvie if pharmacy benefit) C. Other diagnoses/indications (must meet 1 or 2):
   7. 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: 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: 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 of business: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Prevention of Nausea and Vomiting Associated with Cancer Chemotherapy (must meet all):
8. 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);
9. Member is responding positively to therapy;

10. Member continues to receive moderately to highly emetogenic cancer chemotherapy (see Appendix D);

    4. Prescribed in combination with a 5-HT3 receptor antagonist (ondansetron is preferred) and dexamethasone;
    5. If request is for brand Emend, Focinvez, or Cinvanti, one of the following (a or b): a. Member must use generic aprepitant or fosaprepitant, 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); Page 3 of 12

    CLINICAL POLICY Aprepitant, Fosaprepitant

    6. If request is for a dose increase, new dose does not exceed one of the following (a, b, or c): a. Emend oral suspension or capsules, both of the following (i and ii):
       i. 125 mg on Day 1, followed by 80 mg on Days 2 and 3 per chemotherapy cycle; ii. If age ≥ 6 months and < 12 years: 3 mg/kg on Day 1, followed by 2 mg/kg on Days 2 and 3 per chemotherapy cycle;
       b. Emend for injection or Focinvez:, one of the following (i or ii):
       i. Single-dose regimen, all of the following (1, 2, and 3): 1) 150 mg on Day 1; 2) If age 2 years to < 12 years: 4 mg/kg on Day 1;
       3) If age 6 months to < 2 years: 5 mg/kg on Day 1
       ii. 3-day regimen, both of the following (1 and 2):
       1) 115 mg on Day 1; 2) If age 6 months to < 12 years: 3 mg/kg on Day 1;
       c. Cinvanti, one of the following (i or ii):
       i. Single-dose regimen: 130 mg on Day 1 for HEC and MEC; ii. 3-day regimen: 100 mg on Day 1 for MEC. Approval duration:
       Medicaid – Projected duration of chemotherapy
       HIM – Projected duration of chemotherapy (refer to HIM.PA.103 for Emend, fosaprepitant (Emend for injection, Focinvez), and Cinvanti if pharmacy benefit) B. Prevention of Postoperative Nausea and Vomiting
    7. 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):
    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: 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: 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: 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 – Page 4 of 12

    CLINICAL POLICY Aprepitant, Fosaprepitant 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 MEC: moderately emetogenic cancer chemotherapy ASCO: American Society of Clinical NCCN: National Comprehensive Cancer Oncology
    Network
    FDA: Food and Drug Administration HEC: highly emetogenic cancer NK1: neurokinin 1 PONV: postoperative nausea and vomiting chemotherapy 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 granisetron (Kytril®) ondansetron (Zofran®, Zofran® ODT) Prevention of PONV 0.35 to 3 mg (5 to 20 mcg/kg) IV at the end of surgery Prevention of PONV 16 mg PO given 1 hour prior to anesthesia or 4 mg IM/IV as a single dose given 30 min before end of anesthesia 20 mcg/kg/dose
    PO: 16 mg/dose
    IV: 4 mg/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): known hypersensitivity, concurrent use with pimozide • 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, or 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 5 of 12

    CLINICAL POLICY Aprepitant, Fosaprepitant o Examples of moderate emetic risk chemotherapy: 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, fam-trastuzumab deruxtecan-nxki • 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 OK PA TN TX Yes 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 Applies to HIM requests only For advanced 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 postoperative nausea and vomiting
    Drug Name Aprepitant (Aponvie) Dosing Regimen 32 mg IV prior to induction of anesthesia Maximum Dose 32 mg Page 6 of 12

    CLINICAL POLICY Aprepitant, Fosaprepitant Drug Name Aprepitant (Cinvanti) Aprepitant (Emend)
    Indication Prevention of chemotherapy- induced nausea and vomiting Prevention of chemotherapy- induced nausea and vomiting Prevention of postoperative nausea and vomiting
    Fosaprepitant (Emend for injection)
    Prevention of chemotherapy- induced nausea and vomiting Dosing Regimen HEC or MEC (single- dose regimen): 130 mg IV on Day 1 Maximum Dose Single-dose: 130 mg/dose 3-day regimen: 100 mg/dose Per chemotherapy cycle: Day 1: 125 mg Days 2 and 3: 80 mg 40 mg/dose Adult or pediatric single-dose: 150 mg/dose
    Pediatric, multi-day regimen: 115 mg/dose on Day 1 MEC (3-day regimen): 100 mg IV on Day 1 Capsules: 125 mg PO on Day 1, then 80 mg PO on Days 2 and 3 of each chemotherapy cycle Oral suspension: 3 mg/kg PO on Day 1, then 2 mg/kg PO on Days 2 and 3 Capsules: 40 mg PO within 3 hours prior to induction of anesthesia Adults: HEC or MEC (single- dose):
    150 mg IV over 20 to 30 minutes on Day 1 Pediatric: HEC or MEC (single- dose regimen): 12 to 17 years: 150 mg IV over 30 minutes
    2 years to < 12 years: 4 mg/kg IV over 60 minutes 6 months to < 2 years: 5 mg/kg IV over 60 minutes HEC or MEC (3-day regimen): 12 to 17 years: 115 mg IV over 30 minutes on day 1, followed by Emend capsules PO Days 2 and 3 Page 7 of 12

    CLINICAL POLICY Aprepitant, Fosaprepitant Drug Name Indication Dosing Regimen Maximum Dose Fosaprepitant (Focinvez) Prevention of chemotherapy- induced nausea and vomiting Adult or pediatric single-dose: 150 mg/dose
    Pediatric, multi-day regimen: 115 mg/dose on Day 1 6 months to < 12 years: 3 mg/kg IV over 60 minutes on Day 1, followed by Emend for oral suspension on Days 2 and 3 Adults: HEC or MEC (single- dose):
    150 mg IV over 20 to 30 minutes on Day 1 Pediatric: HEC or MEC (single- dose regimen): 12 to 17 years: 150 mg IV over 30 minutes
    2 years to < 12 years: 4 mg/kg IV over 60 minutes 6 months to < 2 years: 5 mg/kg IV over 60 minutes HEC or MEC (3-day regimen): 12 to 17 years: 115 mg IV over 30 minutes on Day 1, followed by Emend capsules PO Days 2 and 3 6 months to < 12 years: 3 mg/kg IV over 60 minutes on Day 1, followed by Emend for oral suspension on Days 2 and 3 Page 8 of 12

    CLINICAL POLICY Aprepitant, Fosaprepitant VI. Product Availability
    Drug Name Aprepitant (Aponvie) Aprepitant (Cinvanti) Aprepitant (Emend)
    Fosaprepitant (Emend for injection) Fosaprepitant (Focinvez) Availability Single-dose vial, injectable emulsion: 32 mg/4.4 mL Single-dose vial, injectable emulsion: 130 mg/18 mL Capsules: 40 mg, 80 mg, 125 mg Capsule therapy pack: 80 mg/125 mg Powder for oral suspension: 125 mg Single-dose vial for injection, powder for reconstitution: 150 mg Single-dose vial for injection: 150 mg/50 mL
    VII.