Antiemetics - NC Standard

Commercial Medical Policy

Last Review: September 2023

Restricted Product(s)

Restriction applies to brand and generic products

Akynzeo®(netupitant/palonosetron)
Anzemet® (dolasetron mesylate)
Emend® (aprepitant)
Sancuso® (granisetron)
Varubi® (dolasetron mesylate)
Zuplenz® (onsansetron)

FDA Approved Use

Akynzeo:
- For the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy.
Anzemet:
- Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy in adults and children ≥2 years of age.
Emend:
- For the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (in combination with other antiemetics) in patients ≥12 years of age (capsules) and in patients ≥6 months of age (oral suspension).
- For the prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (in combination with other antiemetics) in patients ≥12 years of age (capsules) and in patients ≥6 months of age (oral suspension).
- Prevention of postoperative nausea and vomiting (PONV) in adults. Note: The PONV indication was removed from the Emend capsule US prescribing information; however, it remains in the labeling for generic aprepitant capsules.
Sancuso:
- For the prevention of nausea and vomiting in patients receiving moderately and/or highly emetogenic chemotherapy for up to 5 consecutive days.
Varubi:
- For the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy in adults (in combination with other antiemetic agents).
Zuplenz:
- For the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy.
- For the prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
- For the prevention of nausea and vomiting associated with radiotherapy in patients receiving total body irradiation, single high-dose fraction to abdomen, or daily fractions to the abdomen.
- For the prevention of postoperative nausea and/or vomiting.

Criteria for Approval of Restricted Product(s)

The request is for Akynzeo; AND
1. The patient is ≥18 years of age; AND
2. Akynzeo is being prescribed for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy; AND
  1. There is documented use of an emetogenic cancer chemotherapy agent listed in the most recent NCCN guidelines (refer to guidelines on pages 7-9); AND
  2. If prescribing highly and/or moderately emetogenic intravenous chemotherapy and a neurokinin-1 (NK1) antagonist,
    1. The patient has experienced a therapeutic failure or inadequate response to generic oral ondansetron, generic oral granisetron, or generic oral aprepitant; OR
    2. The patient has a contraindication to generic oral ondansetron, generic oral granisetron, or generic oral aprepitant; AND
    3. The patient has experienced a therapeutic failure or inadequate response to oral rolapitant (Varubi); OR
    4. The patient has a contraindication to oral rolapitant (Varubi); OR
  3. If prescribing low and/or minimal emetogenic intravenous chemotherapy and/or emetogenic oral chemotherapy,
    1. The patient has experienced a therapeutic failure or inadequate response to generic oral ondansetron or generic oral granisetron; OR
    2. The patient has a contraindication to generic oral ondansetron or generic oral granisetron; AND
    3. The patient has experienced a therapeutic failure or inadequate response to oral rolapitant (Varubi); OR
    4. The patient has a contraindication to oral rolapitant (Varubi); OR
The request is for Anzemet; AND
1. The patient is ≥2 years of age; AND
2. Anzemet is being prescribed for nausea and vomiting secondary to pregnancy; OR
3. Anzemet is being prescribed for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy; AND
4. There is documented use of a moderately emetogenic cancer chemotherapy agent listed in the most recent NCCN guidelines (refer to guidelines on pages 7-9); AND
5. The patient has experienced a therapeutic failure or inadequate response to generic oral ondansetron or generic oral granisetron; OR
  1. The patient has a clinical contraindication to generic oral ondansetron or generic oral granisetron; OR
The request is for Emend; AND
1. ONE of the following:
  1. Emend 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 emetogenic cancer chemotherapy (HEC) including high dose-cisplatin; AND
    1. For Emend capsules, the patient is ≥ 12 years of age or < 12 years of age who weigh at least 30kg; AND
    2. For Emend suspension, the patient is 6 months of age or older; AND
    3. There is documented use of a highly emetogenic cancer chemotherapy agent listed in the most recent NCCN guidelines (refer to guidelines on pages 7-9); AND
    4. If prescribing highly emetogenic oral chemotherapy, the patient has experienced a therapeutic failure or inadequate response to generic oral ondansetron or generic oral granisetron; OR
    5. The patient has a contraindication to generic oral ondansetron or generic oral granisetron; OR
  2. Emend is being prescribed in combination with other antiemetic agents, for the prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC); AND
    1. For Emend capsules, the patient is ≥ 12 years of age or < 12 years of age who weigh at least 30kg; AND
    2. For Emend suspension, the patient is 6 months of age or older; AND
    3. There is documented use of a highly emetogenic cancer chemotherapy agent listed in the most recent NCCN guidelines (refer to guidelines on pages 7-9); AND
    4. If prescribing highly emetogenic oral chemotherapy, the patient has experienced a therapeutic failure or inadequate response to generic oral ondansetron or generic oral granisetron; OR
    5. The patient has a contraindication to generic oral ondansetron or generic oral granisetron; OR
  3. Emend is being prescribed as capsules for the prevention of postoperative nausea and vomiting (PONV) in adults ≥ 18 years of age; AND
    1. The patient has experienced a therapeutic failure or inadequate response to generic oral ondansetron or generic oral granisetron; OR
    2. The patient has a contraindication to generic oral ondansetron or generic oral granisetron; OR
The request is for Sancuso; AND
1. The patient is ≥18 years of age; AND
2. Sancuso is being prescribed for nausea and vomiting secondary to pregnancy; OR
3. Sancuso is being prescribed for the prevention of nausea and vomiting in a patient receiving moderately and/or highly emetogenic chemotherapy; AND
  1. There is documented use of a moderately and/or highly emetogenic cancer chemotherapy agent, as listed in the most recent NCCN guidelines (refer to guidelines on pages 7-9), for up to 5 consecutive days; AND
4. The patient has experienced a therapeutic failure or inadequate response to generic oral ondansetron or generic oral granisetron; OR
5. The patient has a contraindication to generic oral ondansetron or generic oral granisetron; OR
The request is for Varubi; AND
1. The patient is ≥18 years of age; AND
2. Varubi is being prescribed, in combination with other antiemetic agents, for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic cancer chemotherapy (HEC); AND
  1. There is documented use of an emetogenic cancer chemotherapy agent listed in the most recent NCCN guidelines (refer to guidelines on pages 7-9); AND
  2. If prescribing highly and/or moderately emetogenic intravenous chemotherapy and a neurokinin-1 (NK1) antagonist,
    1. The patient has experienced a therapeutic failure or inadequate response to Emend; OR
    2. The patient has a contraindication to Emend; AND
  3. If prescribing low and/or minimal emetogenic intravenous chemotherapy and/or emetogenic oral chemotherapy,
    1. The patient has experienced a therapeutic failure or inadequate response to generic oral ondansetron or generic oral granisetron; OR
    2. The patient has a contraindication to generic oral ondansetron or generic oral granisetron; OR
The request is for Zuplenz; AND
1. The patient is ≥18 years of age; AND
2. Zuplenz is being prescribed for at least one of the following:
  1. Nausea and vomiting secondary to pregnancy
  2. Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy and there is documented use of a highly emetogenic cancer chemotherapy agent listed in the most recent NCCN guidelines (refer to guidelines on pages 7-9)
  3. Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy and there is documented use of a moderately emetogenic cancer chemotherapy agent listed in the most recent NCCN guidelines (refer to guidelines on pages 7-9)
  4. Prevention of nausea and vomiting associated with radiotherapy in patients receiving total body irradiation, single high-dose fraction to abdomen, or daily fractions to the abdomen
  5. Prevention of postoperative nausea and/or vomiting; AND
3. The patient has experienced a therapeutic failure or inadequate response to generic oral ondansetron or generic oral granisetron; OR
4. The patient has a contraindication to generic oral ondansetron or generic oral granisetron; AND
For formularies that exclude (non-formulary) the requested medication, Non-formulary Exception Criteria applies.

Duration of Approval: 365 days (1 year)

Quantity Limitations

Quantity limitations apply to brand and associated generic products.

Medication	Quantity per 30 Days
Akynzeo (netupitant/palonosetron) 300 mg netupitant/0.5 mg palonosetron capsule	2 capsules
Anzemet (dolasetron mesylate) 50 mg tablet	7 tablets
Anzemet (dolasetron mesylate) 100mg tablet	7 tablets
Emend (aprepitant) 40 mg capsule	4 capsules
Emend (aprepitant) 80 mg capsule	4 capsules
Emend (aprepitant) 125 mg strength capsule	2 capsules
Emend (aprepitant) Therapy Pack (1 x 125mg capsule; 2 x 80mg capsules)	2 therapy packs
Emend (aprepitant) 125mg suspension	6 suspension packets
Sancuso (granisetron transdermal system) 52 cm2 patch containing 34.3 mg of granisetron delivering 3.1 mg per 24 hours	1 patch
Varubi (rolapitant) 90mg tablet	4 tablets per 28 days
Zuplenz (ondansetron) 4 mg and 8 mg oral soluble film	20 films (2 boxes of 10)

Quantity Limit Exception Criteria:

The patient has cancer chemotherapy related nausea and vomiting and will be receiving chemotherapy more than 7 days per month; OR
The patient has delayed emesis in highly emetogenic chemotherapy; OR
The quantity (dose) requested is for documented titration purposes at the initiation of therapy (authorization for a 90-day titration period); AND
The prescribed dose cannot be achieved using a lesser quantity of a higher strength; AND
The quantity (dose) requested does not exceed the maximum FDA labeled dose, when specified, or to the safest studied dose per the manufacturer’s product insert; OR
The prescriber has submitted documentation in support of the requested therapeutic use and quantity for the requested medication; OR
If the quantity (dose) requested exceeds the maximum FDA labeled dose, when specified, or to the safest studied dose per the manufacturer’s product insert, then the prescriber must submit documentation in support of therapy with a higher dose for the intended diagnosis (submitted documentation may include medical records OR fax form which reflects medical record documentation that shows the length of time the requested dose has been used, and what other medications and doses have been tried and failed).

Duration of Approval: 365 days (1 year)

NCCN Guidelines Version 2.2023 Antiemesis

Emetogenic Potential of Parental Anticancer Agents

LEVEL	AGENT
High emetic risk (>90% frequency of emesis)^a	AC combination defined as any chemotherapy regimen that contains an anthracycline and cyclophosphamide 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 Streptozocin
Moderate emetic risk (>30%—90% frequency of emesis)^a	Aldesleukin >12—15 million IU/m² Amifostine >300 mg/m² Bendamustine Busulfan Carboplatin^b AUC <4 Carmustine^b ≤250 mg/m² Clofarabine Cyclophosphamide^b ≤1500 mg/m² Cytarabine >200 mg/m² Dactinomycin^b Daunorubicin^b Dinutuximab Doxorubicin^b <60 mg/m² Dual-drug liposomal encapsulation of cytarabine and daunorubicin Epirubicin^b ≤90 mg/m² Idarubicin^b Ifosfamide^b <2 g/m² per dose Irinotecan^b Irinotecan (liposomal) Lurbinectedin Melphalan <140 mg/m² Methotrexate^b ≥250 mg/m² Naxitamab-gqgk Oxaliplatin^b Romidepsin Temozolomide Trabectedin^b
Low emetic risk (10%—30% frequency of emesis)^a,c	Ado-trastuzumab emtansine Aldesleukin ≤12 million IU/m² Amifostine ≤300 mg/m² Amivantamab-vmjw Arsenic trioxide Axicabtagene ciloleucel^d Azacitidine Belinostat Brexucabtagene autoleucel^d Brentuximab vedotin Cabazitaxel Carfilzomib Ciltacabtagene autoleucel^d Copanlisib Cytarabine (low dose) 100 mg/m²—200 mg/m² Docetaxel Doxorubicin (liposomal) Enfortumab vedotin-ejfv Eribulin Etoposide 5-Fluorouracil (5-FU) Floxuridine Gemcitabine Gemtuzumab ozogamicin Idecabtagene vicleucel^d Inotuzumab ozogamicin Isatuximab-irfc Ixabepilone Lisocabtagene maraleucel^d Loncastuximab tesirine-lpyl Methotrexate >50 mg/m²—<250 mg/m² Mitomycin Mitomycin pyelocalyceal solution Mitoxantrone Mogamulizumab-kpkc Moxetumomab pasudotox-tdfk Necitumumab Omacetaxine Paclitaxel Paclitaxel-albumin Pemetrexed Pentostatin Polatuzumab vedotin-piig Pralatrexate Tafasitamab-cxix Tagraxofusp-erzs Talimogene laherparepvec Tebentafusp-tebn Thiotepa Tisagenlecleucel^d Tisotumab vedotin-tftv Topotecan Ziv-aflibercept
Minimal emetic risk (<10% frequency of emesis) ^a,c	Alemtuzumab Asparaginase^e Atezolizumab Avelumab Belantamab mafodotin•blmf Bevacizumab Bleomycin Blinatumomab Bortezomib Cemiplimab-rwlc Cetuximab Cladribine Cytarabine <100 mg/m² Daratumumab Daratumumab and hyaluronidase•fihj Decitabine Dexrazoxane Dostarlimab-gxly Durvalumab Elotuzumab Fludarabine Ipilimumab Luspatercept-aamt Margetuximab-cmkb Methotrexate ≤50 mg/m² Nelarabine Nivolumab Nivolumab/relatlimab-rmbw Obinutuzumab Ofatumumab Panitumumab Pembrolizumab Pertuzumab Pertuzumab/trastuzumab and hyaluronidase-zzxf Ramucirumab Rituximab Rituxirnab and hyaluronidase Siltuximab Sirolimus-albumin Teclistamab-cqyv Temsirolimus Trastuzumab Trastuzumab and hyaluronidase-oysk Tremelimumab-actl Valrubicin Vinblastine Vincristine Vincristine (liposomal) Vinorelbine

NCCN Guidelines Version 2.2023 Antiemesis

Emetogenic Potential of Oral Anticancer Agents

LEVEL	AGENT
Moderate to high emetic risk^a (≥30% frequency of emesis): prophylaxis required on days of oral anticancer agent administration	Azacitidine^w Busulfan ≥4 mg/day Ceritinib Cyclophosphamide ≥100 mg/m²/day Fedratinib Lomustine (single day) Midostaurin Mitotane Mobocertinib Selinexor^x Temozolomide >75 mg/m²/day
Moderate to high emetic risk^a,v (≥30% frequency of emesis): As needed (PRN) dosing is initially appropriate on days of oral anticancer agent administration	Avapritinib Binimetinib Bosutinib >400 mg/day Cabozantinib Crizotinib Dabrafenib Enasidenib Encorafenib Estramustine Etoposide Imatinib >400 mg/day Lenvatinib >12 mg/day Niraparib Olaparib Procarbazine Rucaparib
Minimal to low emetic risk^a (<30% frequency of emesis)	Abemaciclib Acalabrutinib Afatinib Alectinib Alpelisib Asciminib Axitinib Belzutifan Bexarotene Bosutinib ≤400 mg/day Brigatinib Busulfan <4 mg/day Capecitabine Capmatinib Chlorambucil Cobimetinib Cyclophosphamide <100 mg/m²/day Dacomitinib Dasatinib Decitabine and cedazuridine Duvelisib Entrectinib Erdafitinib Erlotinib Everolimus Fludarabine Futibatinib Gefitinib Gilteritinib Glasdegib Hydroxyurea Ibrutinib Idelalisib Imatinib ≤400 mg/day Ivosidenib Ixazomib Lapatinib Larotrectinib Lenalidomide Lenvatinib ≤12 mg/day Lorlatinib Melphalan Mercaptopurine Methotrexate Nilotinib Neratinib Osimertinib Pacritinib Palbociclib Pazopanib Pemigatinib Pexidartinib Pomalidomide Ponatinib Pralsetinib Regorafenib Ribociclib Ripretinib Ruxolitinib Selpercatinib Sonidegib Sorafenib Sotorasib Sunitinib Talazoparib tosylate Tazemetostat Temozolomide ≤75 mg/m²/day^y Tepotinib Thalidomide Thioguanine Tivozanib Topotecan Trametinib Tretinoin Trifluridine/tipiracil Tucatinib Vandetanib Vemurafenib Venetoclax Vismodegib Vorinostat Zanubrutinib

References:

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

NCCN Clinical Practice Guidelines in Oncology. Antiemesis Version 2.2023. https://www.nccn.org/

Nausea and vomiting of pregnancy. ACOG Practice Bullentin No. 189. American College of Obetetricians and Gynecologists. Obstet Gynecol 2018; 131:e15-30.

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 Q2 annually.

September 2023: Criteria update: Update to Emetogenic Potential of Intravenous and Oral Antineoplastic Agents Table.

September 2021: Criteria update: Combined Akynzeo, Anzemet, Emend, Sancuso, Varubi, Zuplenz into one policy.

June 2021: Criteria update (Varubi): Update QL to 4 per 28 days.

February 2021: Criteria update: Update to Emetogenic Potential of Intravenous and Oral Antineoplastic Agents Table; Reformat and review criteria.

January 2020: Criteria change: Added requirement of a therapeutic failure/inadequate response/contraindication to Varubi.

January 2019: Update to Emetogenic Potential of Intravenous and Oral Antineoplastic Agents Table; Review and reformat criteria

December 2018: Update to Emetogenic Potential of Intravenous and Oral Antineoplastic Agents Table

October 2016: Reviewed for ASO Net Results and Essential formularies. Removed verbiage in regard to restricted access for
Enhanced and Basic Open formularies. Non-formulary verbiage added.

January 2016: Original utilization management criteria issued.

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