CurrentmhnPolicy CP.PMN.158

Netupitant and Palonosetron (Akynzeo), Fosnetupitant and Palonosetron (Akynzeo IV)

Defines medical necessity, prior authorization and coverage criteria for Akynzeo (oral and injectable) to prevent acute and delayed chemotherapy-induced nausea and vomiting in adults receiving moderately to highly emetogenic chemotherapy; applies to Centene-affiliated health plans.

Policy Summary

Payermhn

PolicyNetupitant and Palonosetron (Akynzeo), Fosnetupitant and Palonosetron (Akynzeo IV)

Policy CodePolicy CP.PMN.158

Change TypeNo material change

Effective DateSep 1, 2009

Next Review Date

Key ActionPrior authorization is required; submit documentation showing member meets all approval criteria including age ≥18, scheduled receipt of moderately to highly emetogenic chemotherapy, combination with dexamethasone, and dosing within per-cycle limits.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

≥18minimum age for coverage

1/cyclesingle dose limit

courseauthorization length

300/0.5oral strength

235/0.25injectable strength

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Coverage and Medical Necessity Criteria

inv-01: Initial Approval Criteria

Covered when ALL of the following are met

Initial Approval: Prevention of CINV: 1) Prescribed for the prevention of chemotherapy-induced nausea/vomiting; 2) Age ≥ 18 years; 3) Member is scheduled to receive moderately to highly emetogenic cancer chemotherapy (see Appendix D); 4) Prescribed in combination with dexamethasone; 5) Dose does not exceed one of the specified per-cycle limits: (a) Akynzeo capsules: netupitant 300 mg/palonosetron 0.5 mg (1 capsule) per chemotherapy cycle OR (b) Akynzeo for injection/Akynzeo injection: fosnetupitant 235 mg/palonosetron 0.25 mg (1 vial) per chemotherapy cycle; 6) Member meets one of the following: (a) prior failure of a 5-HT3 receptor antagonist (ondansetron preferred) at maximally indicated doses unless contraindicated AND prior failure of an NK1 antagonist (aprepitant preferred) at maximally indicated doses unless contraindicated (prior authorization required for aprepitant) OR (b) request is for treatment in a state with regulations against step therapy in certain oncology settings (see Appendix E).

Approval duration: Projected course of chemotherapy

inv-02: Continued Therapy Criteria

Covered when ALL of the following are met for continuation

Continued Therapy: Prevention of CINV: 1) Member meets one of the following: (a) currently receiving medication via Centene benefit or previously met initial approval criteria OR (b) member is currently receiving medication and is enrolled in a state/product with continuity of care regulations; 2) Member is responding positively to therapy; 3) Prescribed in combination with dexamethasone; 4) Member continues to receive moderately to highly emetogenic cancer chemotherapy (see Appendix D); 5) If request is for a dose increase, new dose does not exceed one of the per-cycle limits: (a) Akynzeo capsules: netupitant 300 mg/palonosetron 0.5 mg (1 capsule) per chemotherapy cycle OR (b) Akynzeo for injection/Akynzeo injection: fosnetupitant 235 mg/palonosetron 0.25 mg (1 vial) per chemotherapy cycle.

Approval duration: Projected course of chemotherapy

inv-03: Initial and continuation therapy

Covered when ALL of the following are met

Primary coverage criteria: 1) Member is scheduled to receive moderately to highly emetogenic cancer chemotherapy; 2) Netupitant/palonosetron (oral) or fosnetupitant/palonosetron (IV) will be used for prevention of chemotherapy-induced nausea and vomiting in combination with dexamethasone; 3) Dosing follows product administration timing: oral capsule given 1 hour prior to chemotherapy OR IV vial infused over 30 minutes starting 30 minutes before chemotherapy; 4) Continuation requires ongoing receipt of moderately to highly emetogenic chemotherapy.

Continuation requires ongoing receipt of moderately to highly emetogenic chemotherapy.

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the request includes sufficient documentation demonstrating efficacy and safety in accordance with applicable off‑label use policies (see CP.CPA.09 for commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or other accepted evidence of coverage.

For members enrolled in Medicaid, state Medicaid coverage provisions take precedence when they conflict with the provisions of this clinical policy. Refer to the applicable state Medicaid manual for specific coverage rules.

Uses of netupitant/palonosetron (Akynzeo) or fosnetupitant/palonosetron for non‑FDA approved indications that lack adequate off‑label justification or supporting evidence are considered not authorized under this policy.

Regimen	Recommended use / role
AKYNZEO (netupitant/palonosetron oral capsule or fosnetupitant/palonosetron IV) in combination with dexamethasone and generally with a 5-HT3 antagonist (palonosetron component)
Use as part of antiemetic prophylaxis for moderately to highly emetogenic chemotherapy per ASCO/NCCN guidance; NK1 antagonists (component of Akynzeo) are recommended for high emetic risk regimens and may be used for moderate emetic risk in combination with a 5-HT3 antagonist and dexamethasone.

Product Codes, Dosing and Billing

Product Availability / NDCsNDC

NDC not listed

Product availability lists capsule and vial strengths; no NDC codes provided in this document.

HCPCS CodesHCPCS

J1454	Injection, fosnetupitant 235 mg and palonosetron 0.25 mg.
J8655	Netupitant 300 mg and palonosetron 0.5 mg, oral.

Dose per chemotherapy cycle — One capsule (netupitant 300 mg/palonosetron 0.5 mg) OR one vial (fosnetupitant 235 mg/palonosetron 0.25 mg)

Per-cycle oral doseOne capsule: netupitant 300 mg / palonosetron 0.5 mg (1 capsule per chemotherapy cycle)

Per-cycle IV doseOne vial: fosnetupitant 235 mg / palonosetron 0.25 mg (1 vial per chemotherapy cycle)

Administration timing (oral)1 capsule PO given 1 hour prior to chemotherapy (Day 1)

Administration timing (IV)1 vial infused over 30 minutes starting 30 minutes before chemotherapy (Day 1)

Approval durationApproval duration: projected course of chemotherapy

Prior Authorization, Documentation, and Step Therapy

Prior Authorization

Prior Authorization Required

Prior authorization is required and approval is granted when all initial approval criteria are met. Requests lacking documentation that the member meets all approval criteria, or that the member is scheduled to receive moderately to highly emetogenic cancer chemotherapy, may be denied.

Prior authorization required for Akynzeo and related agents when used for prevention of chemotherapy-induced nausea/vomiting.
Requests must document that the member is scheduled to receive moderately to highly emetogenic cancer chemotherapy (see Appendix D).
Prior authorization requests that do not include required documentation may be denied.

Documentation Required

Required Documentation

Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that the member has met all applicable approval criteria. Documentation should include the chemotherapy regimen/emetogenicity, prior medication history per step therapy requirements (if applicable), and the planned dosing regimen for Akynzeo (oral or IV).

Intended Line of Therapy

inv-22: first-line

Indication: Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including highly emetogenic chemotherapy (per FDA labeling); injectable formulation has not been studied for anthracycline plus cyclophosphamide regimens.

inv-23: first-line

Line of therapy: Not restricted by specific line of therapy; indicated for prevention of CINV associated with moderately to highly emetogenic chemotherapy regardless of line, provided criteria are met.

Policy allows state-based step therapy bypasses per Appendix E.

Definitions and Formulations

Akynzeo / fosnetupitant/palonosetron — Fixed combination

Drug class / compositionFixed combination of netupitant (NK1 receptor antagonist) and palonosetron (5-HT3 receptor antagonist)

Brand nameAkynzeo (oral and injectable formulations)

Clinical usePrevention of acute and delayed chemotherapy-induced nausea and vomiting when used with dexamethasone

Emetogenic risk categories — Categories used to guide antiemetic prophylaxis

CategoriesMinimal, Low, Moderate, High emetogenic risk

High risk guidanceNK1 antagonists plus a 5-HT3 antagonist and dexamethasone are recommended

Background and Clinical Context

Akynzeo (netupitant/palonosetron) and the intravenous fosnetupitant/palonosetron formulation are fixed‑combination antiemetic products that pair an NK1 receptor antagonist (netupitant or the prodrug fosnetupitant) with the 5‑HT3 antagonist palonosetron to prevent acute and delayed chemotherapy‑induced nausea and vomiting (CINV). These combinations are intended for use with dexamethasone as part of guideline‑recommended prophylaxis for moderately to highly emetogenic chemotherapy regimens.

Policy Revision History

2023-09-01effective_date

Policy effective date updated to 2023-09-01 per document header and annual review noting continuation requirement updates in 3Q 2023.

2021-01-01annual_review

1Q 2021 annual review: no significant clinical changes; revised references to off-label policy HIM.PHAR.21 updated to HIM.PA.154 and added coding implications.

2006-09-01initial_effective_dateLatest