Notification



Notification Issue Date:



Medical Policy Bulletin


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

Policy #:08.01.41c

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

MEDICALLY NECESSARY

Coverage is subject to the terms, conditions, and limitations of the member's contract.

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) 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 with or without olanzapine
    • Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC)
  • Intravenous aprepitant (Cinvanti) will be used in combination with dexamethasone and a 5-HT3 antagonist (e.g., granisetron [Kytril®], ondansetron [Zofran®], palonosetron [Aloxi®]) before intravenous anti cancer 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 six months of age or older when all of the following criteria are met:
  • The individual is taking fosaprepitant dimeglumine (Emend®) 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, with or without olanzapine
    • Prevention of nausea and vomiting associated with concurrent radiotherapy and cisplatin-based chemotherapy
    • Prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC)
  • Intravenous fosaprepitant dimeglumine (Emend®) will be used in combination with dexamethasone and a 5-HT3 antagonist (e.g., granisetron [Kytril®], ondansetron [Zofran®], palonosetron [Aloxi®]) in adult individuals, and with or without a corticosteroid on chemotherapy day one for pediatric individuals, 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 acute and delayed nausea and vomiting when all of the following criteria are met:
  • Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of high or moderately emetogenic chemotherapy or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens, whose appropriate regimen is also listed in Attachment A of this Policy*
    • The individual has a documented failure, contraindication, or intolerance to generic formulations of 5-HT3 antagonists (e.g., granisetron [Kytril®], ondansetron [Zofran®], palonosetron [Aloxi®])
    • 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 emetogenic cancer chemotherapy with or without olanzapine
    • Prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy
  • Intravenous rolapitant (Varubi®) will be used in combination with dexamethasone and a 5-HT3 antagonist (e.g., granisetron [Kytril®], ondansetron [Zofran®], palonosetron [Aloxi®]), unless the individual is intolerant of, or has a contraindication to, those drugs

* 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 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 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)

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 moderately emetogenic chemotherapy (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, highly emetogenic chemotherapy. 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-HT3 antagonist.

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-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 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 subcutaneous 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-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 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.

Lexi-Drugs Compendium. rolapitant (Varubi®). [Lexicomp Online Web site]. 11/16/18. Available at: http://online.lexi.com/lco/action/home [via subscription only]. November 28, 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

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


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


Cross References

Attachment A: Aprepitant (Cinvanti™), Fosaprepitant Dimeglumine (Emend®), Granisetron (Sustol®), and Rolapitant (Varubi®)
Description: Risk of Emesis Without Prophylaxis: Intravenous and Oral Antineoplastic Agents




Policy History

Revisions from 08.01.41c
03/11/2019This version of the policy will become effective 03/11/2019.

The following criteria have been added to this policy:
  • New FDA approval for pediatric individuals for fosaprepitant dimeglumine (Emend)
  • New age criteria added for Fosaprepitant.
  • Optional use of olanzapine based on NCCN recommendations.

Revisions from 08.01.41b
01/01/2019This policy has been identified for the HCPCS code update, effective 01/01/2019.

The following HCPCS codes have been added to this policy:

J0185 Injection, aprepitant, 1 mg
J2797 Injection, rolapitant, 0.5 mg

The following HCPCS codes have been termed from this policy:

C9463 Injection, aprepitant, 1 mg
C9464 Injection, rolapitant, 0.5 mg
----------------------------------------------------------------------------------------------------
On 1/9/2019 the following HCPCS code and header have been removed from this policy because the more specific code of J0185 is in effect:

THE FOLLOWING CODE IS USED TO REPRESENT APREPITANT [CINVANTI] AND ROLAPITANT [VARUBI®]:

J3490 Unclassified drugs

Revisions from 08.01.41a
04/01/2018This policy has been identified for the HCPCS code update, effective 04/01/2018.

The following HCPCS codes have been added to this policy:
C9463 Injection, aprepitant, 1 mg
C9464 Injection, rolapitant, 0.5 mg

The following HCPCS code has been removed from this policy:
C9486 Injection, granisetron extended release, 0.1

Revisions from 08.01.41
01/01/2018This version of the policy will become effective 01/01/2018.

The following new policy has been developed to communicate the Company’s coverage criteria for aprepitant (Cinvanti™), fosaprepitant dimeglumine (Emend), granisetron (Sustol), and rolapitant (Varubi®).

On 11/07/2017, the following Medical Necessity language was removed from the Policy Section for fosaprepitant dimeglumine (Emend) and rolapitant (Varubi®):
  • The individual has a documented failure, contraindication, or intolerance to oral aprepitant (Emend®), palonosetron (Aloxi®), or generic formulations of 5-HT3 antagonists (e.g., granisetron [Kytril®], ondansetron [Zofran®])


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 03/11/2019
Version Issued Date: 03/11/2019
Version Reissued Date: N/A

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