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Aprepitant (Cinvanti™), Fosaprepitant Dimeglumine (Emend®), Granisetron (Sustol®), and Rolapitant (Varubi®)
08.01.41d

Policy

MEDICALLY NECESSARY

Intravenous aprepitant (Cinvanti™) is considered medically necessary and, therefore, covered for individuals 18 years of age or older when all of the following criteria are met:
  • The individual is prescribed intravenous aprepitant (Cinvantiin combination with other antiemetic agents for one of the following indications whose appropriate regimen is also listed in Attachment A of this Policy*:
    • Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin 
    • Prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen
    • Prevention of​ nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen
  • Intravenous aprepitant (Cinvanti) will be used in combination with dexamethasone and a 5-hydroxytryptamine3 (5-HT3) antagonist (e.g., granisetron [Sustol®], ondansetron [Zofran®], palonosetron [Aloxi®]) before intravenous anticancer therapy, unless the individual is intolerant of, or has a contraindication to, those drugs 
Intravenous fosaprepitant dimeglumine (Emend®) is considered medically necessary and, therefore, covered for individuals 6 months of age or older for one of the following indications whose appropriate regimen is also listed in Attachment A of this Policy*​:
  • Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of HEC, including high-dose cisplatin, in combination with dexamethasone and a 5-HTantagonist (e.g., granisetron [Sustol®], ondansetron [Zofran®], palonosetron [Aloxi®]) in adult individualsand with or without a corticosteroid on chemotherapy day 1 for pediatric individuals, unless the individual is intolerant of, or has a contraindication to, those drugs
  • Prevention of delayed nausea and vomiting associated with initial and repeat courses of MEC​ in combination with dexamethasone and a 5-HTantagonist (e.g., granisetron [Sustol®], ondansetron [Zofran®], palonosetron [Aloxi®]) in adult individualsand with or without a corticosteroid on chemotherapy day 1 for pediatric individuals, unless the individual is intolerant of, or has a contraindication to, those drugs
  • Prevention of delayed nausea and vomiting associated with​ MEC and HEC, if not previously given,​ intravenous fosaprepitant dimeglumine (Emend®) will be used ​as a four-drug regimen (in combination with olanzapine, serotonin receptor antagonist, and dexamethasone) administered before parenteral anticancer therapy if emesis occurred during a previous cycle of anticancer treatment with a three-drug regimen (olanzapine or neurokinin-1 receptor antagonist [NK1RA]-containing regimen) 
  • For high emetic risk, in combination with dexamethasone and a 5-HT3 antagonist (with or without lorazepam, histamine-2 blockers, or proton pump inhibitors) before parenteral anticancer therapy with olanzapine (National Comprehensive Care Network [NCCN] preferred regimen​​​)​ or without olanzapine ​
  • For moderate emetic risk, for select individuals with additional risk factors or previous treatment failure with a corticosteroid and 5-HT3 antagonist alone ​in combination with dexamethasone and a 5-HT3 antagonist (with or without lorazepam, histamine-2 blockers, or proton pump inhibitors) before parenteral anticancer therapy 
Granisetron (Sustol®) is considered medically necessary and, therefore, covered in individuals 18 years of age or older for the prevention of acute and delayed nausea and vomiting when all of the following criteria are met:
  • Granisetron (Sustol®) will be given for one of the following indications whose appropriate regimen is also listed in Attachment A of this Policy*
    • In combination with other antiemetics for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens
    • ​​Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin 
    • In combination with dexamethasone before parenteral anticancer therapy with high emetic risk with olanzapine and either aprepitant (PO or IV), fosaprepitant, or rolapitant (all preferred) or high emetic risk with either aprepitant (PO or IV), fosaprepitant, or rolapitant for moderate emetic risk (SQ route preferred)
    • ​​Prevention of nausea and vomiting​ associated with moderate emetic risk, with either aprepitant (PO or IV), fosaprepitant, or rolapitant for select individuals with additional risk factors or previous treatment failure with a corticosteroid plus a serotonin receptor antagonist alone (may use with or without lorazepam, histamine-2 blockers, or proton pump inhibitors)
    • For high or moderately emetogenic chemotherapy if not previously given, ​granisetron (Sustol®) may be used as a four-drug regimen [in combination with olanzapine, NK1RA, and dexamethasone] given before parenteral anticancer therapy if emesis occurred during a previous cycle of anticancer therapy with a 3-drug regimen (olanzapine or NK1RA-containing regimen) 
  • ​​​The individual has a documented failure, contraindication, or intolerance to generic formulations of 5-HTantagonists (e.g., granisetron, ondansetron, palonosetron)​ 
  • Granisetron (Sustol®) will be used in combination with other antiemetics (e.g., dexamethasone, fosaprepitant dimeglumine [Emend®])unless the individual is intolerant of, or has a contraindication to, those drugs​ 
Granisetron (Sustol®) is considered medically necessary and, therefore, covered in individuals 18 years of age or older for the prevention of postoperative nausea and vomiting and the individual​ has a documented failure, contraindication, or intolerance to generic formulations of 5-HTantagonists (e.g., granisetron, ondansetron, palonosetron)​ ​ 

Intravenous rolapitant (Varubi®) is considered medically necessary and, therefore, covered for individuals 18 years of age or older when all of the following criteria are met:
  • The individual is taking rolapitant (Varubi®) for one of the following indications whose appropriate regimen is also listed in Attachment A of this Policy*:
    • Prevention of delayed nausea and vomiting associated with initial and repeat courses of highly and moderately emetogenic cancer chemotherapy in combination with dexamethasone and a 5-HTantagonist (e.g., granisetron [Sustol®], ondansetron [Zofran®], palonosetron [Aloxi®]), unless the individual is intolerant of, or has a contraindication to, those drugs ​
    • In combination with dexamethasone and a serotonin receptor antagonist before parenteral anticancer therapy with high emetic risk with or without olanzapine (preferred with olanzapine) or moderate emetic risk, for select individuals with additional risk factors or previous treatment failure with a corticosteroid plus serotonin receptor antagonist alone (may use with or without lorazepam, histamine-2 blockers, or proton pump inhibitors) 
    • For high or moderately emetogenic chemotherapy if not previously given, may be used in a four-drug regimen (in combination with olanzapine, serotonin receptor antagonist, and dexamethasone) administered before parenteral anticancer therapy if emesis occurred during a previous cycle of anticancer treatment with a three-drug regimen (olanzapine or NK1RA-​containing regimen) 
* To define emetogenicity risk of chemotherapy agents/regimens, see Attachment A, Risk of Emesis Without Prophylaxis

EXPERIMENTAL/INVESTIGATIONAL

All other uses for aprepitant (Cinvanti), fosaprepitant dimeglumine (Emend®), granisetron (Sustol®) and rolapitant (Varubi®) including use for the treatment of established nausea and vomiting, are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

MANDATES 

PENNSYLVANIA MEMBERS

In accordance with the Commonwealth of Pennsylvania's Act 6 of 2020 or Fair Access to Cancer Treatment Act, for members who are enrolled in Pennsylvania commercial products who have Stage 4, advanced metastatic cancer, refer to the Medical Policy titled "Coverage of Anticancer Prescription Oral and Injectable Drugs and Biologics and Supportive agents (08.01.08)" for additional information regarding the applicable coverage of drugs and biologics.


Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, aprepitant (Cinvanti), fosaprepitant dimeglumine (Emend®), granisetron (Sustol®), and rolapitant (Varubi®) are covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Aprepitant (Cinvanti) was approved by the FDA on November 9, 2017 for use in adults, 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
  • Nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC)
Fosaprepitant dimeglumine (Emend®) was approved by the FDA on January 25, 2008 for use in adults and pediatric individuals 6 months of age and older, on April 3, 2018 in combination with other antiemetic agents, for the prevention of:
  • Acute and delayed nausea and vomiting associated with initial and repeat courses of HEC, including high-dose cisplatin
  • Delayed nausea and vomiting associated with initial and repeat courses of MEC
Granisetron (Sustol®) was approved by the FDA on August 9, 2016 for use in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of MEC or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. The safety and effectiveness of granisetron (Sustol®) have not been established in pediatric patients.

Rolapitant (Varubi®) was approved by the FDA on October 25, 2017 for use in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, HEC. The safety and effectiveness of rolapitant (Varubi®) have not been established in pediatric patients.

Description

Chemotherapy-induced nausea and vomiting may be a serious adverse effect of chemotherapy. There are three types of chemotherapy-induced nausea and vomiting:
  • Acute emesis: occurs within 1 to 2 hours of chemotherapy and usually peaks in 4 to 6 hours
  • Delayed emesis: occurs more than 24 hours after chemotherapy
  • Anticipatory emesis: occurs prior to chemotherapy as a conditioned response in individuals who had previously experienced significant nausea and vomiting during previous cycles
The risk of emesis without prophylaxis has been defined by the National Comprehensive Cancer Network (NCCN) for chemotherapy agents and their regimens. Based on these data, decisions regarding antiemetic prophylaxis (e.g., when to initiate, which antiemetic agents to use) can be made:
  • Highly emetic: more than 90% risk of emesis
  • Moderately emetic: 30% to 90% risk of emesis
  • Low emetogenicity: 10% to 30% risk of emesis
  • Minimally emetic: less than 10% risk of emesis
Examples of options for chemotherapy-induced antiemetic prophylaxis include oral, injectable, transdermal, or intravenous infusions of:
  • 5-Hydroxytryptamine (5-HT3) receptor antagonists (e.g., granisetron [Kytril®, Sustol®], ondansetron [Zofran®], palonosetron [Aloxi®])
  • Neurokinin-1 receptor (NK1R) antagonists (e.g., aprepitant [Cinvanti], aprepitant or fosaprepitant dimeglumine [Emend®], rolapitant [Varubi®])
  • Dexamethasone
  • Olanzapine (Zyprexa®)

APREPITANT (CINVANTI)

Aprepitant (Cinvanti) was approved by the US Food and Drug Administration (FDA) on November 9, 2017 for use in adults, 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
  • Nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC)
Aprepitant (Cinvanti) is a substance P/neurokinin-1 (NK1) receptor antagonist. Aprepitant (Cinvanti) has been shown to augment the antiemetic activity of dexamethasone and a 5-HT3receptor antagonist. Aprepitant (Cinvanti) is an intravenous infusion that is administered on Day 1 of chemotherapy over a period of 30 minutes, approximately 30 minutes prior to chemotherapy. Aprepitant (Cinvanti) is administered in a regimen with dexamethasone and a 5-HT3 antagonist.

FOSAPREPITANT DIMEGLUMINE (EMEND®)

Fosaprepitant dimeglumine (Emend®) was approved by the FDA on January 25, 2008 for use in adults and pediatric individuals 6 months of age and older, on April 3, 2018 in combination with other antiemetic agents, for the prevention of:
  • Acute and delayed nausea and vomiting associated with initial and repeat courses of HEC including high-dose cisplatin
  • Delayed nausea and vomiting associated with initial and repeat courses of MEC
Fosaprepitant dimeglumine (Emend®) is a prodrug of aprepitant, which is a substance P/neurokinin-1 (NK1) receptor antagonist. Aprepitant has been shown to augment the antiemetic activity of dexamethasone and a 5-HT3receptor antagonist. Fosaprepitant dimeglumine (Emend®) is an intravenous infusion that is administered on Day 1 of chemotherapy over a period of 20 to 30 minutes, approximately 30 minutes prior to chemotherapy. Fosaprepitant dimeglumine (Emend®) is administered in a regimen with dexamethasone and a 5-HT3 antagonist.

GRANISETRON (SUSTOL®)

Granisetron (Sustol®) was approved by the FDA on August 9, 2016 for use in adults, in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of MEC or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.

Granisetron (Sustol®) is a selective serotonin-3 (5-HT3) receptor antagonist. When binding to 5-HT3 receptors, granisetron (Sustol®) inhibits the release of serotonin from its receptors and stops the process of vomiting.

Granisetron (Sustol®) is administered as a slow subcutaneous injection in combination with dexamethasone at least 30 minutes before the initiation of MEC or AC combination chemotherapy. It is administered on Day 1 of chemotherapy and not more frequently than once every 7 days because of the extended-release properties of the formulation.

ROLAPITANT (VARUBI®)

Rolapitant (Varubi®) was approved by the FDA on October 25, 2017 for use in combination with other antiemetic agents in adults 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.

Rolapitant (Varubi®) is a substance P/neurokinin-1 (NK1) receptor antagonist. Rolapitant (Varubi®) has been shown to augment the antiemetic activity of dexamethasone and a 5-HT3–​receptor antagonist. Rolapitant (Varubi®) is an intravenous infusion that is administered on Day 1 of chemotherapy over a period of 30 minutes, given 2 hours prior to the initiation of chemotherapy. Rolapitant (Varubi®) is administered in a regimen with dexamethasone and a 5-HT3 antagonist.

OFF-LABEL INDICATION

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

Cinvanti™ (aprepitant). [prescribing information]. San Diego, CA: Heron Therapeutics; updated 03/2022. Available at: http://cinvanti.com/. Accessed July 15, 2022.

Elsevier’s Clinical Pharmacology Compendium. Aprepitant (Cinvanti™). [Clinical Key Web site].05/09/22. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed July 15, 2022.

Elsevier’s Clinical Pharmacology Compendium. Fosaprepitant dimeglumine (Emend®). [Clinical Key Web site].05/09/22. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed July 15, 2022.

Elsevier’s Clinical Pharmacology Compendium. Granisetron (Sustol®). [Clinical Key Web site].05/11/22. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed July 15, 2022.

Elsevier’s Clinical Pharmacology Compendium. Rolapitant (Varubi®). [Clinical Key Web site].11/01/17. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed July 15, 2022.

Emend® (fosaprepitant dimeglumine). [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp. 05/2022. Available at: http://www.emend.com/. Accessed July 15, 2022.

Hesketh PJ. Prevention and treatment of chemotherapy-induced nausea and vomiting in adults. [UpToDate Web Site]. Updated 10/15/18. Available at: https://www.uptodate.com/contents/prevention-and-treatment-of-chemotherapy-induced-nausea-and-vomiting-in-adults?source=search_result&search=fosaprepitant&selectedTitle=5~14 [via subscription only]. Accessed July 15, 2022.

Lexi-Drugs Compendium. Aprepitant (Cinvanti™)[Lexicomp Online Website]. 07/19/22. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 15, 2022.

Lexi-Drugs Compendium. Fosaprepitant dimeglumine (Emend®)[Lexicomp Online Website]. 07/19/22. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 15, 2022.

Lexi-Drugs Compendium. Granisetron (Sustol®). [Lexicomp Online Website]. 07/26/22. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 15, 2022.

Lexi-Drugs Compendium. Rolapitant (Varubi®). [Lexicomp Online Website]. 07/18/22. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Fosaprepitant dimeglumine (Emend®). [NCCN Web site]. 2022. Available at: https://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Granisetron (Sustol®). [NCCN Web site]. 2022. Available at: https://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed July 15, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Antiemesis. V.2.2022. [NCCN Web site]. 03/23/22. Available at: https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf [via free subscription]. Accessed July 15, 2022.

Sustol® (granisetron). [prescribing information] Redwood City, CA: Heron Therapeutics; updated 08/2016. Available at: http://sustol.com/hcp/healthcare-professionals. Accessed July 15, 2022.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Aprepitant (Cinvanti™). Greenwood Village, CO. [Micromedex® Solutions Web site]. Last modified: 07/15/22. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed July 15, 2022.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Fosaprepitant dimeglumine (Emend®). Greenwood Village, CO. [Micromedex® Solutions Web site]. Last modified: 07/15/22. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed July 15, 2022.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Granisetron (Sustol®). Greenwood Village, CO. [Micromedex® Solutions Web site]. Last modified: 07/24/22​. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed July 25, 2022.

Truven Health Analytics. Micromedex® DrugDex® Compendium. rolapitant (Varubi®). Greenwood Village, CO. [Micromedex® Solutions Web site]. Last modified: 05/11/22. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed July 15, 2022.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Aprepitant (Cinvanti™) prescribing information and approval letter [FDA Web site]. Updated 03/2022. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed July 15, 2022.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Fosaprepitant dimeglumine (Emend®) prescribing information and approval letter [FDA Web site]. Updated 05/2022. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed July 15, 2022.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Granisetron (Sustol®) prescribing information and approval letter [FDA Web site]. Updated 08/2016. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed July 15, 2022.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Rolapitant (Varubi®) prescribing information and approval letter [FDA Web site]. updated 08/19/2020. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=208399. Accessed July 15, 2022.

Varubi® (Rolapitant). [prescribing information]. Waltham, MA: Tesaro, Inc.; updated 08/2020. Available at: http://www.varubirx.com/en. Accessed July 15, 2022​.

Coding

CPT Procedure Code Number(s)
N/A

ICD - 10 Procedure Code Number(s)
N/A

ICD - 10 Diagnosis Code Number(s)
R11.0 Nausea

R11.11 Vomiting without nausea

R11.2 Nausea with vomiting, unspecified

T45.1X5A Adverse effect of antineoplastic and immunosuppressive drugs, initial encounter

T45.1X5D Adverse effect of antineoplastic and immunosuppressive drugs, subsequent encounter

T45.1X5S Adverse effect of antineoplastic and immunosuppressive drugs, sequela

T66.XXXA Radiation sickness, unspecified, initial encounter

T66.XXXD Radiation sickness, unspecified, subsequent encounter

T66.XXXS Radiation sickness, unspecified, sequela

Z51.0 Encounter for antineoplastic radiation therapy

Z51.11 Encounter for antineoplastic chemotherapy

HCPCS Level II Code Number(s)
J0185 Injection, aprepitant, 1 mg

J1453 Injection, fosaprepitant, 1 mg

J1627 Injection, granisetron, extended-release, 0.1 mg

J2797 Injection, rolapitant, 0.5 mg

Revenue Code Number(s)
N/A




Coding and Billing Requirements


Policy History

11/29/2022
11/29/2022
08.01.41
Medical Policy Bulletin
Commercial
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No