ModifiedHealth NetPolicy CP PHAR.304

Clinical Policy: Irinotecan Liposome (Onivyde)

Defines medical necessity, prior authorization, dosing limits, and approved indications for irinotecan liposome (Onivyde) for Health Net lines of business (Medicaid, HIM). Affects prescribers and prior authorization reviewers.

Policy Summary

PayerHealth Net

PolicyClinical Policy: Irinotecan Liposome (Onivyde)

Policy CodePolicy CP PHAR.304

Change TypeMultiple material updates (prescriber requirement, prior-therapy clarification, FDA first-line addition)

Effective DateFeb 1, 2017

Next Review Date

Key ActionSubmit prior authorization with documentation showing oncologist prescriber status, indication, prior therapies, and regimen details.

SourceLink

POLICY UPDATE CHANGES

Added oncologist prescriber requirement.

Specified disease must be locally advanced, metastatic, or recurrent and require progression following gemcitabine-based therapy or FOLFIRINOX.

Updated prior-therapy language from FOLFIRINOX to fluoropyrimidine-based therapy without prior irinotecan and added examples in Appendix B.

Added newly FDA-approved first-line use in combination with oxaliplatin, fluorouracil, and leucovorin for metastatic disease.

Expanded continued therapy section to apply to all indications and added ampullary adenocarcinoma off-label criteria supported by NCCN.

6 monthsInitial approval duration

12 monthsContinued therapy approval duration

J9205HCPCS code

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Coverage Criteria

Initial Therapy (Pancreatic Adenocarcinoma)

Covered when ALL of the following are met for initial approval (Pancreatic Adenocarcinoma):

Initial Approval - Pancreatic Adenocarcinoma: 1. Diagnosis of locally advanced, metastatic, or recurrent pancreatic adenocarcinoma; 2. Prescribed by or in consultation with an oncologist; 3. Age >= 18 years; 4. Prescribed as one of the following: (a) in combination with oxaliplatin, fluorouracil, and leucovorin as a component of the NALIRIFOX regimen as first-line therapy (dose does not exceed 50 mg/m2 every 2 weeks); OR (b) in combination with fluorouracil and leucovorin for disease progression following gemcitabine-based therapy, or fluoropyrimidine-based therapy without irinotecan (dose does not exceed 70 mg/m2 every 2 weeks); OR (c) dose supported by practice guidelines or peer-reviewed literature for the relevant off-label use with prescriber-submitted supporting evidence; 5. Prescribed regimen must be FDA-approved or recommended by NCCN.

Initial Therapy (Ampullary Adenocarcinoma, off-label)

Covered when ALL of the following are met for off-label ampullary adenocarcinoma:

Initial Approval - Ampullary Adenocarcinoma (off-label): 1. Diagnosis of ampullary adenocarcinoma; 2. Prescribed by or in consultation with an oncologist; 3. Age >= 18 years; 4. Prior gemcitabine-based therapy; 5. Prescribed in combination with fluorouracil and leucovorin for disease progression if previously treated with fluoropyrimidine-based therapy without irinotecan or oxaliplatin-based therapy without irinotecan; 6. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence); 7. Prescribed regimen must be FDA-approved or recommended by NCCN.

Continuation Therapy

Criteria for continued therapy:

Continued Therapy: 1. Member is currently receiving medication via the benefit or documentation supports that the member has received Onivyde for at least 30 days; 2. All indications criteria from Section I continue to be met; 3. Member is responding positively to therapy; 4. New or continued dose does not exceed dosing limits: does not exceed 50 mg/m2 every 2 weeks when used as a component of the NALIRIFOX regimen, or does not exceed 70 mg/m2 every 2 weeks when used in combination with fluorouracil and leucovorin only; if a dose increase is requested, the request must meet these dosing constraints or be supported per policy.

Primary coverage criteria (summary)

Covered when meeting FDA/NCCN-aligned indication and prior-therapy requirements

General coverage prerequisites: 1. Prescribed by an oncologist; 2. Indication is for locally advanced, metastatic, or recurrent disease per label/NCCN; 3. Documentation of prior therapy history where required (for example, progression after gemcitabine-based therapy or appropriate fluoropyrimidine-based therapy without prior irinotecan) unless an FDA-approved first-line combination regimen is used;

Specifics and exceptions (for example, ampullary adenocarcinoma off-label NCCN-supported use) are addressed elsewhere in the policy.

Non–FDA approved indications that are not specifically addressed by this policy are excluded unless the provider submits sufficient documentation demonstrating efficacy and safety consistent with the applicable off‑label use policies. Supporting materials should follow the referenced off‑label use procedures (for example, CP.PMN.53 for Medicaid and HIM.PA.154 for the Health Insurance Marketplace) or other evidence of coverage documents to justify consideration.

The listing or omission of procedure or billing codes in this policy does not, by itself, guarantee payment or coverage. Providers must follow current professional coding guidance and submit claims using appropriate codes; incorrect or unsupported coding may lead to denial of reimbursement.

Per FDA labeling, Onivyde is not indicated as a single agent for the treatment of metastatic pancreatic adenocarcinoma. Requests for single‑agent use are not supported by the FDA indication and therefore are not covered under this policy.

Coding

HCPCS CodesHCPCS

J9205

Injection, irinotecan liposome; 1 mg

HCPCS CodesHCPCS

J9205

Injection, irinotecan liposome; 1 mg

Dose limits and UGT1A1 considerations (INV-10)

Liposomal irinotecan dose — NALIRIFOX50 mg/m2 IV every 2 weeks when used as part of the NALIRIFOX regimen

Liposomal irinotecan dose — with fluorouracil + leucovorin onlyUp to 70 mg/m2 IV every 2 weeks when used in combination with fluorouracil and leucovorin (not combined with oxaliplatin)

UGT1A1*28 homozygotesIf homozygous for UGT1A1*28 allele, use 50 mg/m2 IV every 2 weeks

Dose escalation guidanceIncrease dose to 70 mg/m2 as tolerated in subsequent cycles per dosing guidance

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit supporting clinical documentation (e.g., office chart notes, lab results, treatment history) demonstrating the member meets all approval criteria. Approval durations: initial approval = 6 months; continued therapy approvals per policy requirements.

Initial and continuation requests must document indication, prior therapies, regimen, and dosing.
Prescriber must be an oncologist or in consultation with an oncologist.
Approval durations: Initial = 6 months; continued therapy per policy.

Documentation Required

Required Clinical Documentation

Providers must document oncologist prescriber status, disease stage (locally advanced, metastatic, or recurrent), and prior therapy history including progression following gemcitabine‑based therapy or fluoropyrimidine‑based therapy without irinotecan when required by the criteria. If requesting an off‑label regimen, include supporting peer‑reviewed literature or guideline evidence.

Line of Therapy

first-line/second-line

First-line: Use in combination with oxaliplatin, fluorouracil, and leucovorin as NALIRIFOX for first-line treatment of metastatic pancreatic adenocarcinoma (dose <= 50 mg/m2 every 2 weeks).

Second-line: Use in combination with fluorouracil and leucovorin for treatment after disease progression following gemcitabine-based therapy (dose up to 70 mg/m2 every 2 weeks).

first-line | second-line

Line of therapy options: Approved as later-line therapy after specified prior therapies; RT4 adds newly FDA‑approved first‑line use in combination with oxaliplatin, fluorouracil, and leucovorin for metastatic disease.

Details of required prior regimens and sequencing are provided in other sections.

Covered Regimens & Dosing

Regimen	Components	Dose limit (liposomal irinotecan)	Coverage status
NALIRIFOX
Fluorouracil; leucovorin; liposomal irinotecan; oxaliplatin
50 mg/m2 IV every 2 weeks (liposomal irinotecan)
Covered when criteria met

Regimen	Components	Dose limit (liposomal irinotecan)	Coverage status
Onivyde + fluorouracil and leucovorin
Liposomal irinotecan (Onivyde); fluorouracil; leucovorin
Up to 70 mg/m2 IV every 2 weeks
Covered with criteria (post-gemcitabine progression)

Regimen	Components	Line of therapy / Note	Coverage status
Irinotecan liposome in combination with oxaliplatin, fluorouracil, and leucovorin
Liposomal irinotecan; oxaliplatin; fluorouracil; leucovorin
Newly FDA‑approved first‑line option for metastatic pancreatic adenocarcinoma
Covered when used per FDA label and policy criteria

Indication	Prior therapy requirement / Labeling detail	Dose considerations	Coverage status
Disease progressed after gemcitabine-based therapy or fluoropyrimidine-based therapy (as applicable)
Per FDA and NCCN labeling; where specified, no prior irinotecan exposure required
Dose per FDA/NCCN labeling; see regimen-specific dose limits (eg, up to 70 mg/m2 every 2 weeks or 50 mg/m2 in NALIRIFOX)
Covered with criteria when prior‑therapy requirements and other policy criteria are met

Definitions

NALIRIFOX regimen definition (INV-20)

Regimen nameNALIRIFOX (fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin)

Component — fluorouracilFluorouracil included as part of NALIRIFOX regimen

Component — leucovorinLeucovorin included as part of NALIRIFOX regimen

Component — liposomal irinotecanIrinotecan liposome (Onivyde) included as part of NALIRIFOX regimen

Component — oxaliplatinOxaliplatin included as part of NALIRIFOX regimen

First-line combined use with oxaliplatin, fluorouracil, and leucovorin (INV-21)

New FDA first-line approval (RT4)

Background

Irinotecan liposome (Onivyde) is a liposomal formulation of the topoisomerase‑I inhibitor irinotecan designed for intravenous administration. It is approved in combination regimens for metastatic pancreatic adenocarcinoma — specifically with oxaliplatin, fluorouracil, and leucovorin as a first‑line option and with fluorouracil and leucovorin for disease progressed after gemcitabine‑based therapy. The policy aligns use and dosing with FDA labeling and relevant practice guidelines, including combination regimens such as NALIRIFOX (fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin).

Revision History

2020-07-13policy_revision

Added requirement that prescriber be an oncologist (oncologist prescriber requirement).

2022-07-28policy_revision

Aligned to NCCN and FDA labeling by specifying disease must be locally advanced, metastatic, or recurrent and added requirement for progression following gemcitabine-based therapy or FOLFIRINOX (later clarified to fluoropyrimidine-based therapy without prior irinotecan).

2023-08-06policy_revision