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Antiemetic Injection Therapy Notification

Commercial Drug Policy
Version Date: March 2024

Restricted Product(s):

  • Fosnetupitant/palonosetron (Akynzeo® ) intravenous infusion for administration by a healthcare professional 
  • Palonosetron (Aloxi® ) intravenous infusion for administration by a healthcare professional 
  • Aprepitant (Cinvanti® ) intravenous injection or infusion for administration by a healthcare professional 
  • Fosaprepitant (Emend® ) intravenous infusion for administration by a healthcare professional 
  • Fosaprepitant (Focinvez™) intravenous infusion for administration by a healthcare professional 
  • Granisetron (Sustol® ) extended-release subcutaneous injection for administration by a healthcare professional 

FDA Approved Use:

  • Fosnetupitant/palonosetron (Akynzeo® ) 
    • For use in combination with dexamethasone, in adults, for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy 
    • Limitations of use: Not for prevention of nausea and vomiting associated with anthracycline plus cyclophosphamide chemotherapy
  • Palonosetron (Aloxi® ) 
    • Adult patients 
      • For prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) 
      • For prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) 
    • Pediatric patients aged 1 month to less than 17 years 
      • For prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy (HEC) 
  • Aprepitant (Cinvanti® ) 
    • For use in combination with other antiemetic agents, in adults, for prevention of:
      • Acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin as a single-dose regimen 
      • Delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen 
      • Nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen 
    • Limitations of use: Not for treatment of established nausea and vomiting
  • Fosaprepitant (Emend® ) 
    • For use in combination with other antiemetic agents, in adults and pediatric patients 6 months of age and older, for prevention of:
      • Acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin
      • Delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) 
    • Limitations of use: Not for treatment of established nausea and vomiting 
  • Fosaprepitant (Focinvez™) 
    • For use in combination with other antiemetic agents, in adults and pediatric patients 6 months of age and older, for prevention of: 
      • Acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin
      • Delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) 
    • Limitations of use: Not for treatment of established nausea and vomiting 
  • Granisetron (Sustol® ) 
    • For use in combination with other antiemetics, in adults, for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens 

 

Criteria for Medical Necessity:

The restricted product(s) may be considered medically necessary when the following criteria are met:

  1. The request is for Akynzeo (fosnetupitant and palonosetron); AND 
    1. The patient is 18 years of age or older; AND
    2. The requested agent is being prescribed in combination with dexamethasone, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly and/or moderately emetogenic cancer chemotherapy; AND
      1. There is documented use of a highly and/or moderately emetogenic cancer chemotherapy agent(s) listed in the most recent NCCN Guidelines (refer to guidelines on pages 8-10); AND 
    3. ONE of the following:
      1. The patient has experienced a therapeutic failure or inadequate response to fosaprepitant (Emend); OR
      2. The patient has a contraindication to fosaprepitant (Emend); AND 
    4. ONE of the following:
      1. The patient has experienced a therapeutic failure or inadequate response to oral or intravenous granisetron OR oral or intravenous ondansetron; OR
      2. The patient has a contraindication to oral or intravenous granisetron OR oral or intravenous ondansetron; OR 
  2. The request is for Aloxi (palonosetron); AND 
    1. ONE of the following:
      1. The patient is 1 month to less than 17 years of age; AND
        1. The requested agent is being prescribed for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy; AND 
          1. There is documented use of a highly emetogenic cancer chemotherapy agent(s) listed in the most recent NCCN Guidelines (refer to guidelines on pages 8-10); OR
      2. The patient is 17 years of age or older; AND 
        1. The requested agent is being prescribed for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly and/or moderately emetogenic cancer chemotherapy; AND
          1. There is documented use of a highly and/or moderately emetogenic cancer chemotherapy agent(s) listed in the most recent NCCN Guidelines (refer to guidelines on pages 8-10); AND
    2. If the requested agent is being prescribed for patients with documented use of a low or minimally emetogenic cancer chemotherapy agent(s), then ONE of the following:
      1. The patient has experienced a therapeutic failure or inadequate response to oral or intravenous granisetron OR oral or intravenous ondansetron; OR
      2. The patient has a contraindication to oral or intravenous granisetron OR oral or intravenous ondansetron; OR
  3. The request is for Cinvanti (aprepitant); AND 
    1. The patient is 18 years of age or older; AND 
    2. The requested agent is being prescribed in combination with other antiemetic agents [i.e., 5-HT3 antagonist (e.g., granisetron, ondansetron, palonosetron) and corticosteroid (i.e., dexamethasone)], for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly and/or moderately emetogenic cancer chemotherapy, including high-dose cisplatin; AND
      1. There is documented use of a highly and/or moderately emetogenic cancer chemotherapy agent(s) listed in the most recent NCCN Guidelines (refer to guidelines on pages 8-10); AND
    3. ONE of the following:
      1. The patient has experienced a therapeutic failure or inadequate response to fosaprepitant (Emend); OR
      2. The patient has a contraindication to fosaprepitant (Emend); AND 
    4. If the requested agent is being prescribed for patients with documented use of a low or minimally emetogenic cancer chemotherapy agent(s), then ONE of the following:
      1. The patient has experienced a therapeutic failure or inadequate response to oral or intravenous granisetron OR oral or intravenous ondansetron; OR
      2. The patient has a contraindication to oral or intravenous granisetron OR oral or intravenous ondansetron; OR
  4. The request is for Emend (fosaprepitant) or Focinvez (fosaprepitant); AND 
    1. The patient is 6 months of age or older and weighs at least 6 kg; AND 
    2. The requested agent is being prescribed in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly and/or moderately emetogenic cancer chemotherapy, including highdose cisplatin; AND
      1. There is documented use of a highly and/or moderately emetogenic cancer chemotherapy agent(s) listed in the most recent NCCN Guidelines (refer to guidelines on pages 8-10); AND 
    3. If the requested agent is being prescribed for patients with documented use of a low or minimally emetogenic cancer chemotherapy agent(s), then ONE of the following:
      1. The patient has experienced a therapeutic failure or inadequate response to oral or intravenous granisetron OR oral or intravenous ondansetron; OR
      2. The patient has a contraindication to oral or intravenous granisetron OR oral or intravenous ondansetron; OR
  5. The request is for Sustol (granisetron); AND
    1. The patient is 18 years of age or older; AND
    2. The requested agent is being prescribed in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens; AND 
      1. There is documented use of a moderately emetogenic cancer chemotherapy agent(s) listed in the most recent NCCN Guidelines (refer to guidelines on pages 8-10) OR documented use of an anthracycline and cyclophosphamide (AC) combination chemotherapy regimen; AND 
    3. If the requested agent is being prescribed for patients with documented use of a low or minimally emetogenic cancer chemotherapy agent(s), then ONE of the following: 
      1. The patient has experienced a therapeutic failure or inadequate response to oral or intravenous granisetron OR oral or intravenous ondansetron; OR
      2. The patient has a contraindication to oral or intravenous granisetron OR oral or intravenous ondansetron; AND
  6. The requested quantity (dose) and treatment duration (and maximum units) is within FDA labeled dosing for the requested indication or NCCN 1 or 2A compendia supported dosing for the requested indication.

Duration of Approval: 365 days (1 year)

NOTE:

Use of antiemetic injection therapy may be considered medically necessary for clinical indications not listed above when the drug is prescribed for the treatment of cancer either:

  1. In accordance with FDA label (when clinical benefit has been established, and it is not determined to be investigational as defined in the Blue Cross NC Corporate Medical Policy (CMP), “Investigational (Experimental) Services.” [please refer to CMP “Investigational (Experimental) Services” for a summary of evidence standards from nationally recognized compendia]; OR
  2. In accordance with specific strong endorsement or support by nationally recognized compendia, when such recommendation is based on strong/high levels of evidence, and/or uniform consensus of clinical appropriateness has been reached.

FDA Label Reference:

MedicationIndicationDosingHCPCS
Fosnetupitant/palonosetron (Akynzeo® ) intravenous (IV) infusionPrevention of nausea and vomiting associated with emetogenic cancer chemotherapyIV: One vial (235 mg fosnetupitant/0.25 mg palonosetron) 30 minutes before chemotherapy J1454
Palonosetron (Aloxi® ) intravenous (IV) infusionPrevention of nausea and vomiting associated with emetogenic cancer chemotherapy

IV: 

  • Adults: 0.25 mg as a single dose 30 minutes before chemotherapy 
  • Pediatric patients (1 month to < 17 years): 20 mcg/kg (maximum 1.5 mg) as a single dose 30 minutes before chemotherapy
J2469
Aprepitant (Cinvanti® ) intravenous (IV) injection or infusion Prevention of nausea and vomiting associated with emetogenic cancer chemotherapy

IV: 

  • HEC and MEC (single-dose regimen): 130 mg on Day 1, 30 minutes before chemotherapy 
  • MEC (3-day regimen): 100 mg on Day 1, 30 minutes before chemotherapy. Aprepitant capsules (80 mg) are then given by mouth on Days 2 and 3. 
  • Used as part of a regimen that includes a corticosteroid and a 5- HT3 antagonist 
J0185
Fosaprepitant (Emend® ) intravenous (IV) infusionPrevention of nausea and vomiting associated with emetogenic cancer chemotherapy

IV:

  • Adults: 150 mg on Day 1, 30 minutes before chemotherapy
  • Pediatric patients (6 months to 17 years, Wt ≥ 6 kg): See package labeling
J1453
Fosaprepitant (Focinvez™) intravenous (IV) infusionPrevention of nausea and vomiting associated with emetogenic cancer chemotherapy

IV: 

  • Adults: 150 mg on Day 1, 30 minutes before chemotherapy 
  • Pediatric patients (6 months to 17 years, Wt ≥ 6 kg): See package labeling 

C9399**

J3490**

J3590**

J9999**

Granisetron (Sustol® ) extendedrelease subcutaneous (SC) injectionPrevention of nausea and vomiting associated with emetogenic cancer chemotherapySC: 10 mg as a single injection at least 30 minutes before chemotherapy on Day 1. Do not administer more frequently than once every 7 days. J1627

**Non-specific assigned HCPCS codes, must submit requested product NDC

***Oncology-specific HCPCS codes: S0353, S0354

Other codes that may be applicable to this policy: Diagnoses (ICD-10 codes) that are subject to medical necessity review: C00.0-C49.9, C4A.0-C4A.9, C50.011-C79.9, C7A.00-C7A.8, C7B.00-C7B.8, C80.0-C86.6, C88.2-C96.Z, D00.00-D09.9, D47.01, D47.02, D47.09, Z51.11, Z51.12

NCCN Guidelines Version 1.2024 Antiemesis

Emetogenic Potential of Parental Anticancer Agents

  • AC combination defined as any chemotherapy regimen that contains an anthracycline and cyclophophamide
  • Carboplatin AUC ≥4
  • Carmustine >250 mg / m2 
  • Cisplatin
  • Cyclophosphamide >1500  mg / m2
  • Dacarbazine
  • Doxorubicin ≥60 mg / m2
  • Epirubicin >90 mg / m2
  • Fam-trastuzumab deruxtecan-nxki
  • Ifosfamide ≥2 g / m2 per dose
  • Mechlorethamine
  • Melphalan ≥140 mg / m2
  • Sacituzumab govitecan-hziy
  • Streptozicin

 

  • Aldesleukin >12 - 15 million IU / m2
  • Amifostin >300 mg / m2
  • Bendamustine
  • Busulfan
  • Carboplatinb AUC <4
  • Carmustineb ≤250 mg / m2
  • Clofarabine
  • Cyclophophamideb ≤1500 mg / m2
  • Cytarabine >200 mg / m2
  • Dactinomycinb
  • Daunorubicinb
  • Dinutuximab
  • Doxorubicinb <60 mg/m2
  • Dual - drug liposomal encapsulation of cytarabine and daunorubicin
  • Epirubicinb ≤90 mg / m2
  • Idarubicinb
  • Ifosfamideb <2 g / m2 per dose
  • Irinotecanb
  • Irinotecan (liposomal)
  • Lurbinectedin
  • Melphalan <140 mg / m2
  • Methotrexateb ≥250 mg / m2 
  • Mirvetuximab soravtansine-gynx
  • Naxitamab-gqgk 
  • Oxaliplatinb
  • Romidepsin
  • Temozolomide
  • Trabectedinb

  • Ad-trastuzumab emtansine
  • Aldesleukin ≤12 million IU / m2
  • Amifostine ≤300 mg / m2
  • Amivantamab-vmjw
  • Arsenic trioxide
  • Axicabtagene ciloleuceld
  • Azacitidine
  • Bellnostat
  • Brentuximab vedotin
  • Brexucabtagene autoleuceld
  • Cabazitaxel
  • Carfilzomib
  • Ciltacabtagene autoleuceld
  • Copanlisib
  • Cytarabine (low dose) 100 mg / m2 - 200 mg / m2
  • Docetaxel
  • Doxorubicin (liposomal)
  • Enfortumab vedotin-ejfv
  • Eribulin
  • Etoposide
  • Floxuridine
  • 5-Fluorouracil (5-FU)
  • Gemcitabine
  • Gemtuzumab ozogamicin
  • Idecabtagene vicleuceld
  • Inotuzumab ozogamicin
  • Isatuximab-irfc
  • Ixabepilone
  • Lisocabtagene maraleuceld
  • Loncastuximab tesirine-lpyl
  • Methotrexate >50 mg / m2 - <250 mg / m2
  • Mitomycin
  • Mitomycin pyelocalyceal solution
  • Mitoxantrone
  • Mogamulizumab-kpkc
  • Mosunetuzumab-axgb
  • Necitumumab
  • Omacetaxine
  • Paclitaxel
  • Paclitaxel-albumin
  • Pemetrexed
  • Pentostatin
  • Polatuzumab vedotin-piig
  • Pralatrexate
  • Tafasitamab-cxix
  • Tagraxofusp-erzs
  • Talimogene laherparepvec
  • Tebentafusp-tebn
  • Thiotepa
  • Tisagenlecleuceld
  • Tisotumab bedotin-tftv
  • Topotecan
  • Ziv-afilbercept    

  • Alemtuzumab
  • Asparaginasee
  • Atezolizumab
  • Avelumab
  • Bevacizumab
  • Bleomycin
  • Blinatumomab
  • Bortezomib
  • Cemiplimab-rwlc
  • Cetuximab
  • Cladribine
  • Cytarabine <10 mg / m2
  • Daratumumab
  • Daratumumab and hylaruronidase-fihj
  • Decitabine
  • Degarelix
  • Dexrazoxane
  • Dostarlimab-gxly
  • Durvalumab
  • Elotuzumab
  • Epcoritamab-bysp
  • Fludarabine
  • Fulvestrant
  • Glofitamab-gxbm
  • Goserelin
  • Histrelin
  • Ipilimumab
  • Lanreotide
  • Leuprolide
  • Luspatercept-aamt
  • Margetuximab-cmkb
  • Methotrexate ≤50 mg / m2
  • Nelarabine
  • Nivolumab
  • Nivolumab / relatlimab-rmbw
  • Obinutuzumab
  • Octreotide
  • Ofatumumab
  • Panitumumab
  • Pembrolizumab
  • Pertuzumab
  • Pertuzumab / trastuzumab and hyaluronidase-zzxf
  • Ramucirumab
  • Retifanlimab-dlwr
  • Rituximab
  • Rituximab and hyaluronidase
  • Siltuximab
  • Sirolimus-albumin
  • Teclistamab-cqyv
  • Temsirolimus
  • Trastuzumab
  • Trastuzumab and hyaluronidase-oysk
  • Tremelimumab-actl
  • Triptorelin
  • Valrubicin
  • Vinblastine
  • Vincristine
  • Vincristine (liposomal)
  • Vinorelbine

Emetogenic Potential of Oral Anticancer Agents

  • Azacitidinew
  • Busulfan ≥4 mg / day
  • Ceritinib
  • Cyclophosphamide ≥100 mg / m2 / day
  • Fedratinib
  • Lomustine (single day)
  • Midostaurin
  • Mitotane
  • Selinexorx
  • Temozolomide >75 mg / m2 / day

  • Adagrasib
  • Avapritinib
  • Binimetinib
  • Bosutinib >400 mg / day
  • Cabozantinib
  • Crizotinib
  • Dabrafenib
  • Elacestrant
  • Enasidenib
  • Encorafenib
  • Estramustine
  • Etoposide
  • Imatinib >400 mg / day
  • Lenvatinib >12 mg / day
  • Niraparib
  • Olaparib
  • Procarbazine
  • Rucaparib

  • Abemacicilib
  • Abiraterone
  • Acalabrutinib
  • Afatinib
  • Alectinib
  • Alpelisib
  • Anastrozole
  • Apalutamide
  • Asciminib
  • Axitinib
  • Belzutifan
  • Bexarotene
  • Bicalutamide
  • Bosutinib ≤400 mg / day
  • Brigatinib
  • Busulfan <4 mg / day
  • Capecitabine
  • Chlorambucil
  • Cobimetinib
  • Cyclophosphamide <100 mg / m2 / day
  • Dacomitinib
  • Darolutamide
  • Dasatinib
  • Decitabine and cedazuridine
  • Duvelisib
  • Entrectinib
  • Enzalutamide
  • Erdafitinib
  • Eroltinib
  • Everolimus
  • Exemestane
  • Fludarabine
  • Fultamide
  • Futibatinib
  • Gefitinib
  • Gilteritinib
  • Glasdegib
  • Hydroxyurea
  • Ibrutinib
  • Idelalisib
  • Imatinib ≤400 mg / day
  • Ivosidenib
  • Ixazomib
  • Lapatinib
  • Larotrectinib
  • Lenalidomide
  • Lenvatinib ≤12 mg / day
  • Letrozole
  • Lorlatinib
  • Megestrol
  • Melphalan
  • Mercaptopurine
  • Methotrexate
  • Momelotinib
  • Neratinib
  • Nilotinib
  • Nilutamide
  • Olutasidenib
  • Osimertinib
  • Pacritinib
  • Palbocicib
  • Pazopanib
  • Pemigatinib
  • Pexidartinib
  • Pirtobrutinib
  • Pomalidomide
  • Ponatinib
  • Pralsetinib
  • Regorafenib
  • Relugolix
  • Repotrectinib
  • Ribociclib
  • Ripretinib
  • Ruxolitinib
  • Selpercatinib
  • Sonidegib
  • Sorafenib
  • Sotorasib
  • Sunitinib
  • Talazoparib tosylate
  • Tamoxifen
  • Tazemetostat
  • Temozolomide ≤76 mg / m2 / dayy
  • Tepotinib
  • Thalidomide
  • Thioguanine
  • Tivozanib
  • Topotecan
  • Toremifene
  • Trametinib
  • Tretinoin
  • Trifluridine / tipiracil
  • Tucatinib
  • Vandetanib
  • Vemurafenib
  • Venetoclax
  • Vismodegib
  • Vorinostat
  • Zanubrutinib

References:

All information referenced is from FDA package insert unless otherwise noted below.

  1. Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2017;35(28):3240-3261.
  2. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Guidelines for Supportive Care. Antiemesis. Version 1.2024. Fort Washington, PA: NCCN, 12/13/23. Available at: http://www.nccn.org/. Accessed January 2024. 

Policy Implementation / Update Information:

Criteria and treatment protocols are reviewed annually by the Blue Cross NC P&T Committee, regardless of change. This policy is reviewed in Q3 annually. 

March 2024: Criteria change: Added newly approved Focinvez (fosaprepitant) to policy, and associated dosing and HCPCS codes C9399, J3490, J3590, and J9999 to FDA label reference table. Adjusted trial and failure requirements for Cinvanti to require trial of Emend (fosaprepitant), and trial of granisetron or ondansetron for low to minimally emetogenic cancer chemotherapy regimens. Adjusted indication for Emend per FDA label to include pediatric patients 6 months of age or older weighing at least 6 kg. Updated NCCN Emetogenic Potential of Intravenous and Oral Antineoplastic Agents tables. Medical policy formatting change. Policy notification given 1/29/2024 for effective date 3/29/2024.

Further historical criteria changes and updates available upon request from Medical Policy and/or Corporate Pharmacy.

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