CurrentCentenePolicy CP PHAR.304

Irinotecan Liposome (Onivyde) coverage criteria

Defines medical necessity criteria, initial and continued therapy requirements, approved indications (FDA and select off-label), dosing limits, prescriber requirements, duration of approval, contraindications, coding (HCPCS J9205), and references for Onivyde for Centene lines of business (Medicaid, HIM).

Policy Summary

PayerCentene

PolicyIrinotecan Liposome (Onivyde) coverage criteria

Policy CodePolicy CP PHAR.304

Change TypeUpdates to indications, prescriber and off-label criteria (annual reviews)

Effective Date02.01.17

Next Review DateN/A

Key ActionProvider must submit documentation (office chart notes, lab results or other clinical information) supporting that member meets all approval criteria.

SourceLink

POLICY UPDATE CHANGES

Added oncologist prescriber requirement.

Clarified disease stage requirement and progression criteria per NCCN and FDA label.

Updated wording from FOLFIRINOX to fluoropyrimidine-based therapy without irinotecan; added NALIRIFOX component language.

Updated FDA approved indications section and added ampullary adenocarcinoma off-label criteria supported by NCCN compendium.

2FDA-approved indications listed

1Supported off‑label indications

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6/12Approval durations (init/cont)

Coverage Summary

This policy defines medical necessity and coverage criteria for Irinotecan liposome (Onivyde). Effective date: 02.01.17; last review/P&T approval: 11.24.24; status: CURRENT.

The policy covers FDA-approved indications (two listed): 1) as a component of the NALIRIFOX regimen (in combination with oxaliplatin, fluorouracil, and leucovorin) for first-line treatment of metastatic pancreatic adenocarcinoma, and 2) in combination with fluorouracil and leucovorin for treatment of metastatic pancreatic adenocarcinoma after disease progression following gemcitabine-based therapy. The policy also supports one specifically identified off-label indication: ampullary adenocarcinoma, when criteria and supporting evidence per NCCN compendium are met.

Threshold summary

Age≥ 18 years

Dose limit - NALIRIFOX regimen≤ 50 mg/m2 every 2 weeks

Dose limit - combination with fluorouracil and leucovorin≤ 70 mg/m2 every 2 weeks

Minimum treatment duration prior to continued therapy consideration≥ 30 days

Approval durationsInitial: 6 months; Continued: 12 months

Medical Necessity Criteria

Initial Approval Criteria

Onivyde is medically necessary when ALL of the following are met:

ALL of the following

Pancreatic Adenocarcinoma (must meet all)
- Diagnosis of locally advanced, metastatic, or recurrent pancreatic adenocarcinoma
- Prescriber: Prescribed by or in consultation with an oncologist
  Added 4Q2020
- Age ≥ 18 years≥ 18 years
- ONE of the following prescribing scenarios

Coding

Primary HCPCS code for drugHCPCSCovered

J9205

Injection, irinotecan liposome; 1 mg

Provider Actions & Billing

Prior Authorization

Documentation submission required

Provider must submit documentation supporting that the member meets all approval criteria. Acceptable documentation includes office chart notes, laboratory results, and other clinical information demonstrating diagnosis, prior therapies, dosing, and response.

Prior Authorization

Prescriber specialty requirement

Prescriptions must be written by or in consultation with an oncologist. (Requirement added in 4Q2020.)

Documentation Required

Support for off-label use

For off‑label indications, the prescriber must submit supporting evidence (practice guidelines or peer‑reviewed literature) demonstrating the regimen’s efficacy and safety to support coverage.

Background & Evidence

Onivyde is a topoisomerase inhibitor formulated as irinotecan liposome injection. The policy summarizes that Onivyde exerts cytotoxic effects consistent with its irinotecan class and is administered in combination regimens for pancreatic malignancies.

FDA approvals described in the policy include the newly added first-line NALIRIFOX use (liposomal irinotecan with oxaliplatin, fluorouracil, and leucovorin) for metastatic pancreatic adenocarcinoma and the previously approved use in combination with fluorouracil and leucovorin after progression on gemcitabine-based therapy. The policy aligns coverage with the FDA label and NCCN recommendations and references the NALIRIFOX definition in Appendix D.

For supported off-label use (for example, ampullary adenocarcinoma), the policy provides a pathway requiring that the prescribed regimen be recommended by NCCN or supported by practice guidelines or peer-reviewed literature, with the prescriber submitting supporting evidence. The policy also requires oncology specialty involvement (prescribed by or in consultation with an oncologist) and documents that provider submission of clinical documentation is required to demonstrate that approval criteria are met.

Evidence sources

Primary sourceOnivyde Prescribing Information, Merrimack Pharmaceuticals, Feb 2024

Guideline sourceNCCN Pancreatic Adenocarcinoma and Ampullary Adenocarcinoma compendia (2023-2024)

Revision History

4Q2020 (P&T Approval Date: 11.20.20)policy_change

Added oncologist prescriber requirement (4Q2020 annual review).

4Q2022 (P&T Approval Date: 11.22.22)policy_change

Clarified disease stage requirement to locally advanced, metastatic, or recurrent and added requirement for disease progression following gemcitabine-based therapy or FOLFIRINOX (per NCCN and FDA label).

4Q2023 (RT4 update; newly FDA-approved first-line use noted 02.29.24; P&T Approval Date: 11.23.23)policy_change

Policy Summary

PayerCentene

PolicyIrinotecan Liposome (Onivyde) coverage criteria

Policy CodePolicy CP PHAR.304

Change TypeUpdates to indications, prescriber and off-label criteria (annual reviews)

Effective Date02.01.17

Next Review DateN/A

Key ActionProvider must submit documentation (office chart notes, lab results or other clinical information) supporting that member meets all approval criteria.

SourceLink

On This Page

First-line: In combination with oxaliplatin, fluorouracil, and leucovorin as first-line therapy (component of NALIRIFOX regimen)
See Appendix D for NALIRIFOX
Post-gemcitabine or fluoropyrimidine without irinotecan: In combination with fluorouracil and leucovorin for disease progression following gemcitabine-based therapy or fluoropyrimidine-based therapy without irinotecan
Supported off-label: Prescribed regimen is supported by practice guidelines or peer-reviewed literature for relevant off-label use (prescriber must submit supporting evidence)

Dose limits depending on regimen

NALIRIFOX dose limit: Dose does not exceed 50 mg/m2 every 2 weeks when used as a component of the NALIRIFOX regimen≤ 50 mg/m2 every 2 weeks
Fluorouracil/leucovorin combination dose limit: Dose does not exceed 70 mg/m2 every 2 weeks when prescribed in combination with fluorouracil and leucovorin only≤ 70 mg/m2 every 2 weeks
FDA maximum or guideline-supported: Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines/peer-reviewed literature for off-label use (prescriber must submit supporting evidence)

Regimen requirement: Prescribed regimen must be FDA-approved or recommended by NCCN

Ampullary Adenocarcinoma (Off-label) - Initial Approval

Onivyde is medically necessary when ALL of the following are met:

Ampullary Adenocarcinoma (off-label) (must meet all)

Diagnosis of ampullary adenocarcinoma
Prescriber: Prescribed by or in consultation with an oncologist
Added 4Q2020
Age ≥ 18 years≥ 18 years
Prior therapy: Prior gemcitabine-based therapy
Prior therapy for disease progression
- Fluoropyrimidine without irinotecan: Prescribed in combination with fluorouracil and leucovorin for disease progression if previously treated with fluoropyrimidine-based therapy without irinotecan
- Oxaliplatin without irinotecan: Prescribed in combination with fluorouracil and leucovorin for disease progression if previously treated with oxaliplatin-based therapy without irinotecan
Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence)
Regimen requirement: Prescribed regimen must be FDA-approved or recommended by NCCN

Continued Therapy

Continued therapy is authorized when ALL of the following are met:

Current use: Member is currently receiving Onivyde via Centene benefit or documentation supports member has received Onivyde for a covered indication for at least 30 days≥ 30 days
All initial indications met: All indications in Section I are met
Response: Member is responding positively to therapy
Dose limits for continued therapy
- NALIRIFOX continued dose: New dose does not exceed 50 mg/m2 every 2 weeks as a component of the NALIRIFOX regimen≤ 50 mg/m2 every 2 weeks
  Appendix D defines NALIRIFOX
- Fluorouracil/leucovorin continued dose: New dose does not exceed 70 mg/m2 every 2 weeks in combination with fluorouracil and leucovorin only≤ 70 mg/m2 every 2 weeks

Other Diagnoses/Indications

Coverage for other uses is governed by formulary and off-label policies:

On formulary/PDL: If drug is on formulary/PDL: follow no coverage criteria policy HIM.PA.33 (marketplace) or CP.PMN.255 (Medicaid)
Not on formulary/PDL: If drug is not on formulary/PDL: follow non-formulary policy HIM.PA.103 (marketplace) or CP.PMN.16 (Medicaid)
Requests not listed: If requested use is not listed and initial criteria do not apply: refer to off-label use policy HIM.PA.154 (marketplace) or CP.PMN.53 (Medicaid)

Diagnoses/Indications Not Authorized

Diagnoses/Indications Not Authorized: Non-FDA approved indications not addressed in this policy are not authorized unless sufficient documentation of efficacy and safety is provided per off-label use policies CP.PMN.53 (Medicaid) and HIM.PA.154 (marketplace)

Billing Rule

Use appropriate HCPCS

Report Onivyde using the appropriate HCPCS code.

J9205

Prior Authorization

Approval durations

Initial approval duration is 6 months. Continued therapy approval duration is 12 months.

Definitions

NALIRIFOX definitionRegimen containing fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin

FDA maximum limit termMaximum dose per FDA-approved prescribing information for Onivyde

Updated wording from FOLFIRINOX to fluoropyrimidine-based therapy without irinotecan; added NALIRIFOX component language and RT4 noting newly FDA-approved first-line use in combination with oxaliplatin, fluorouracil, and leucovorin (02.29.24).

4Q2024 (P&T Approval Date: 11.24.24)policy_changeLatest

Updated FDA-approved indications section to align with prescriber information and added ampullary adenocarcinoma off-label criteria supported by the NCCN compendium (4Q2024 annual review).