Medicare Advantage

Medical Policy

Title:

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

Policy #:

MA08.091e

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 (Cinvanti™) in 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®]), 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-HT3 antagonist (e.g., granisetron [Sustol®], ondansetron [Zofran®], palonosetron [Aloxi®]) in adult individuals, and 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 moderately emetogenic cancer chemotherapy (MEC) in combination with dexamethasone and a 5-HT3 antagonist (e.g., granisetron [Sustol®], ondansetron [Zofran®], palonosetron [Aloxi®]) in adult individuals, and 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 [NKR1]-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 Cancer 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-HT₃antagonist 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 administered 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 MEC 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 three-drug regimen (olanzapine or NK1RA-containing regimen)

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

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-HT3 antagonist (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.

Guidelines

BENEFIT APPLICATION

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

There is no Medicare coverage determination addressing intravenous aprepitant (Cinvanti™), fosaprepitant dimeglumine (Emend®), granisetron (Sustol®), and rolapitant (Varubi®); therefore, the Company policy is applicable.

For Medicare Advantage members, certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when intravenous aprepitant (Cinvanti™), fosaprepitant dimeglumine (Emend®), granisetron (Sustol®), and rolapitant (Varubi®) are covered under a member's medical benefit (Part B benefit). It does not address instances when intravenous aprepitant (Cinvanti™), fosaprepitant dimeglumine (Emend®), granisetron (Sustol®), and rolapitant (Varubi®) are covered under a member’s pharmacy benefit (Part D benefit).

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 one to two hours of chemotherapy and usually peaks in four to six 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 this data, decisions regarding antiemetic prophylaxis (e.g., when to initiate, which antiemetic agents to use) can be made:

Highly emetic: more than 90 percent risk of emesis
Moderately emetic: 30 to 90 percent risk of emesis
Low emetogenicity: 10 to 30 percent risk of emesis
Minimally emetic: less than 10 percent 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-HT₃-receptor 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-HT₃antagonist.

FOSAPREPITANT DIMEGLUMINE (EMEND®)

Fosaprepitant dimeglumine (Emend®) was approved by the FDA on January 25, 2008 for use in adults, and pediatric individuals six 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 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)

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-HT₃-receptor 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-HT₃antagonist.

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 moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.

Granisetron (Sustol®) is a selective serotonin-3 (5-hydroxytryptamine₃ or 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 subcutanous injection in combination with dexamethasone at least 30 minutes before the initiation of MEC or AC combination chemotherapy. It is administered on Day one of chemotherapy and not more frequently than once every seven 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 one of chemotherapy over a period of 30 minutes, given two hours prior to the initiation of chemotherapy. Rolapitant (Varubi®) is administered in a regimen with dexamethasone and a 5-HT₃antagonist.

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 11/2017. Available at: http://cinvanti.com/. Accessed November 19, 2018.

Elsevier’s Clinical Pharmacology Compendium. Aprepitant (Cinvanti™). [Clinical Key Web site].04/06/18. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed November 19, 2018.

Elsevier’s Clinical Pharmacology Compendium. Fosaprepitant dimeglumine (Emend®). [Clinical Key Web site].04/06/18. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed November 19, 2018.

Elsevier’s Clinical Pharmacology Compendium. Granisetron (Sustol®). [Clinical Key Web site].10/06/16. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed November 19, 2018.

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 November 19, 2018.

Emend® (fosaprepitant dimeglumine). [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2017. Available at: http://www.emend.com/. Accessed November 19, 2018.

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]. November 19, 2018.

Lexi-Drugs Compendium. Granisetron (Sustol®). [Lexicomp Online Web site]. 11/16/18. Available at: http://online.lexi.com/lco/action/home [via subscription only]. November 19, 2018.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Fosaprepitant dimeglumine (Emend®). [NCCN Web site]. 2018. Available at: https://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. November 19, 2018.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Granisetron (Sustol®). [NCCN Web site]. 2018. Available at: https://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed November 19, 2018.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Antiemesis. V.3.2018. [NCCN Web site]. 06/11/18. Available at: https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf [via free subscription]. Accessed November 19, 2018.

Sustol® (granisetron). [prescribing information] Redwood City, CA: Heron Therapeutics; updated 08/2016. Available at: http://sustol.com/hcp/healthcare-professionals. Accessed November 19, 2018.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Aprepitant (Cinvanti™). Greenwood Village, CO. [Micromedex® Solutions Web site]. Last modified: 11/06/18. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed November 19, 2018.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Fosaprepitant dimeglumine (Emend®). Greenwood Village, CO. [Micromedex® Solutions Web site]. Last modified: 11/06/18. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed November 19, 2018.

Truven Health Analytics. Micromedex® DrugDex® Compendium. granisetron (Sustol®). Greenwood Village, CO. [Micromedex® Solutions Web site]. Last modified:10/05/18. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed November 19, 2018.

Truven Health Analytics. Micromedex® DrugDex® Compendium. rolapitant (Varubi®). Greenwood Village, CO. [Micromedex® Solutions Web site]. Last modified:10/05/18. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed November 19, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Aprepitant (Cinvanti™) prescribing information and approval letter [FDA Web site]. updated 11/2017. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed November 19, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Fosaprepitant dimeglumine (Emend®) prescribing information and approval letter [FDA Web site]. Updated 04/2018. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed November 19, 2018.

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 November 19, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Rolapitant (Varubi®) prescribing information and approval letter [FDA Web site]. Updated 04/13/2018. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=208399. Accessed November 19, 2018.

Varubi® (Rolapitant). [prescribing information]. Waltham, MA: Tesaro, Inc.; updated 10/2017. Available at: http://www.varubirx.com/en. Accessed November 19, 2018.

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

J1456 Injection, fosaprepitant (teva), not therapeutically equivalent to j1453, 1 mg

J1627 Injection, granisetron, extended-release, 0.1 mg

J2797 Injection, rolapitant, 0.5 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Version Effective Date:

1/1/2023

Version Issued Date:

12/30/2022

Version Reissued Date: