Onivyde (irinotecan liposomal) — HCPCS J9205

About Onivyde (irinotecan liposomal) FDA verified May 2026

Pegylated liposomal topoisomerase I inhibitor for metastatic pancreatic adenocarcinoma. Originally approved 2015; expanded to 1L in 2024.

Onivyde is irinotecan hydrochloride trihydrate encapsulated inside a pegylated liposome (PEGylated nanoliposome delivery system, originally developed by Merrimack Pharmaceuticals; commercial rights acquired by Ipsen in 2017). The liposomal carrier prolongs circulation time and concentrates drug in tumor tissue via the enhanced permeability and retention effect, producing meaningfully different pharmacokinetics from conventional irinotecan: longer plasma half-life, slower clearance of the active SN-38 metabolite, and a distinct cumulative late-onset diarrhea profile.

Clinical use of Onivyde is currently limited to metastatic adenocarcinoma of the pancreas, in two specific chemotherapy regimens: NALIRIFOX (1L) and NAPOLI (post-gemcitabine 2L). Onivyde is not interchangeable with conventional irinotecan and cannot be substituted in FOLFIRI, FOLFIRINOX, or other irinotecan-containing regimens.

J9205 (Onivyde) vs J9206 (conventional irinotecan) CMS Q2 2026

Two HCPCS codes for two different drugs. Confusing them is a coding error AND a clinical error.

Conventional irinotecan was originally branded Camptosar (Pfizer/Pharmacia) and is now widely available as a generic injection. It is billed under HCPCS J9206 ("Inj irinotecan 20 mg") and is the irinotecan used in FOLFIRI and FOLFIRINOX regimens for colorectal, gastric, and other cancers.

Onivyde is a fundamentally different product: irinotecan hydrochloride encapsulated inside a pegylated liposome. It is billed under HCPCS J9205 ("Inj irinotecan liposome 1 mg") and is approved exclusively for metastatic pancreatic adenocarcinoma in NALIRIFOX or NAPOLI regimens.

Dosing & unit math FDA label 2024

All Onivyde doses are BSA-based. The 43 mg fixed-vial size means almost every dose produces partial-vial waste.

NALIRIFOX 1L pancreatic (FDA Feb 2024)

• Onivyde 50 mg/m² IV (free base; equivalent to 60 mg/m² as the salt form) Day 1
• Oxaliplatin 60 mg/m² IV Day 1 (after Onivyde)
• Leucovorin 400 mg/m² IV Day 1
• 5-FU 2,400 mg/m² IV over 46 hours (continuous infusion via portable pump) starting Day 1
• Cycle: every 14 days; continue until progression or unacceptable toxicity

NAPOLI 2L post-gemcitabine (FDA Oct 2015)

• Onivyde 70 mg/m² IV (free base; equivalent to 80 mg/m² as the salt form) Day 1
• Leucovorin 400 mg/m² IV Day 1
• 5-FU 2,400 mg/m² IV over 46 hours starting Day 1
• Cycle: every 14 days
• UGT1A1*28 homozygotes: starting dose 50 mg/m² (28% reduction)

UGT1A1 dose modification (both regimens)

• UGT1A1*28 homozygotes have impaired SN-38 glucuronidation and increased exposure to active metabolite
• NALIRIFOX 50 mg/m² → 36 mg/m² starting dose (28% reduction)
• NAPOLI 70 mg/m² → 50 mg/m² starting dose (28% reduction)
• Subsequent cycles: titrate up to standard dose if tolerated (no severe neutropenia or diarrhea cycle 1)
• See UGT1A1 testing detail

Worked example — NALIRIFOX dose for BSA 1.8 m²

Annualized dosing — NALIRIFOX patient, BSA 1.8 m²

Premedication

• Standard antiemetic regimen: 5-HT3 antagonist (ondansetron, palonosetron, granisetron) + dexamethasone — given 30 min before infusion
• Atropine 0.25–1 mg IV/SC available for early-onset cholinergic diarrhea (within 24 hr of infusion)
• Loperamide (high-dose protocol: 4 mg loading, 2 mg q2h until diarrhea-free for 12 hr) for late-onset diarrhea (days 3–10)
• NK1 antagonist optional (regimen is moderate-to-high emetogenic)

NALIRIFOX 1L pancreatic regimen detail NCCN + FDA verified 2026

FDA approved February 2024 based on the NAPOLI 3 trial (NCT04083235). Now an NCCN-preferred 1L option for metastatic pancreatic adenocarcinoma.

NALIRIFOX (also written NALIRIFOX or NAL-IRI-FOX) is a four-drug regimen given on Day 1 of each 14-day cycle. It supplanted Onivyde's prior label as a 2L-only option (NAPOLI) and put liposomal irinotecan into direct 1L competition with FOLFIRINOX (which uses conventional irinotecan) and gemcitabine + nab-paclitaxel.

NAPOLI 3 trial summary (informational)

• Phase 3, open-label, randomized 1:1 (NALIRIFOX vs gemcitabine + nab-paclitaxel)
• 770 patients with treatment-naïve metastatic pancreatic adenocarcinoma
• Primary endpoint: overall survival — NALIRIFOX 11.1 mo vs Gem/nab-pac 9.2 mo (HR 0.83, p = 0.04)
• FDA approved February 13, 2024 based on these data

NCCN preferred status

NCCN Pancreatic Adenocarcinoma Guidelines list NALIRIFOX as a Category 1 preferred regimen for 1L treatment of metastatic disease in patients with good performance status (ECOG 0–1). It sits alongside FOLFIRINOX and modified FOLFIRINOX (which use conventional irinotecan via J9206) and gemcitabine + nab-paclitaxel. Choice between regimens depends on toxicity tolerance, comorbidities, UGT1A1 status, and infusion logistics.

UGT1A1 testing & dose modification FDA label 2024

UGT1A1*28 homozygotes are at materially higher risk of severe neutropenia. The FDA label specifies a 28% starting dose reduction.

Irinotecan is converted to its active metabolite SN-38, which is then glucuronidated and inactivated by the UGT1A1 enzyme. Patients homozygous for the UGT1A1*28 allele (a TA repeat polymorphism in the gene promoter, also called Gilbert's syndrome variant) have markedly reduced UGT1A1 activity, resulting in higher SN-38 exposure and increased risk of severe neutropenia, severe diarrhea, and treatment-related death.

Testing logistics

• CPT 81350 — UGT1A1 (UDP glucuronosyltransferase family 1, polypeptide A1) gene analysis (common variants — e.g., *28, *6, *36, *37)
• Send-out lab (Mayo, Quest, LabCorp, or local molecular path) — 5–10 day turnaround typical
• Single-test result — valid for life (germline polymorphism)
• Document genotype in chart and PA submission

NDC reference FDA NDC Directory verified May 2026

Administration codes CPT verified May 2026

90-minute IV infusion crosses the 1-hour 96413 boundary, so 96415 (each additional hour) is required.

Modifiers CMS verified May 2026

JW — required on most claims (waste is the norm)

Onivyde comes only as 43 mg single-dose vials and is dosed by BSA, so almost every dose produces partial-vial waste. Bill the discarded portion with JW on a separate claim line. CMS reimburses both the administered units (drug line) and the waste units (JW line) for single-dose vial drugs. Do NOT round the dose up to the nearest vial multiple to avoid waste — the patient receives the labeled dose, and the waste is billed and reimbursed.

JZ — only when there is no waste

Effective July 1, 2023, CMS requires either JZ (no waste) or JW (waste reported) on every single-dose container claim. JZ applies to Onivyde only when the prescribed dose happens to be a clean multiple of 43 mg (uncommon). Most Onivyde claims will use JW; reserve JZ for the rare exact-multiple dose.

Modifier 25 — same-day E/M

Use modifier 25 on the E/M code when a significant, separately identifiable evaluation and management service is performed on the same day as the infusion. Routine pre-infusion clinical assessment is bundled.

340B modifiers (JG, TB)

For 340B-acquired Onivyde, follow your MAC's current 340B modifier policy. Ipsen's billing guide does not provide 340B-specific instructions.

ICD-10-CM by indication FY2026 verified May 2026

Onivyde is approved exclusively for metastatic pancreatic adenocarcinoma. Use the most specific C25 code supported by encounter documentation.

Site of care & place of service Verified May 2026

NALIRIFOX is a logistically demanding regimen: 90-min Onivyde + 2-hr oxaliplatin + 30-min leucovorin + 46-hr 5-FU pump start = roughly 4 hours of in-clinic chair time on Day 1, plus 5-FU pump disconnection on Day 3. Most administrations occur in physician oncology offices (POS 11) or ambulatory infusion centers (POS 49). Hospital outpatient (POS 22 / 19) is acceptable but increasingly disfavored by commercial UM.

Claim form field mapping Ipsen Cares 2026

Standard CMS-1500 / 837P fields. NDC qualifier and JW waste line are the high-value fields to verify.

Payer policy snapshot Reviewed May 2026

All major payers require PA, indication-specific documentation, and concurrent PA on combo agents.

Step therapy

For 1L NALIRIFOX, step therapy is generally NOT required — it is FDA-labeled 1L. For 2L NAPOLI, documentation of prior gemcitabine-based regimen failure or progression is required. Some plans require documentation that FOLFIRINOX was considered and rejected (typically based on UGT1A1*28 status, performance status, or comorbidity) before approving NALIRIFOX over modified FOLFIRINOX.

Medicare reimbursement CMS Q2 2026 (live)

Quarterly ASP from CMS Part B Drug Pricing File. Refreshes automatically each quarter.

Coverage

No NCD specific to Onivyde. Coverage falls under MAC LCDs for chemotherapy and the generic drug-coverage framework. All MACs cover J9205 for FDA-approved on-label indications (metastatic pancreatic adenocarcinoma, NALIRIFOX 1L or NAPOLI 2L) with appropriate ICD-10 documentation.

Code history

• J9205 — permanent code, "Inj irinotecan liposome 1 mg" — effective shortly after October 2015 FDA approval; pre-permanent-code period used unclassified J9999
• 2024 expansion (NALIRIFOX 1L) did not change the HCPCS code — same J9205 covers both regimens

Patient assistance — Ipsen Cares Ipsen verified May 2026

• Ipsen Cares (Onivyde Patient Support): 1-866-435-5677 / ipsencares.com — benefits investigation, prior authorization assistance, appeal support, copay assistance enrollment
• Onivyde Co-Pay Program: commercial copay support; eligible commercially-insured patients (excludes Medicare, Medicaid, federal program patients per IRA-era rules)
• Onivyde Patient Assistance Program (PAP): free product for uninsured / underinsured patients meeting income requirements
• Foundations: for Medicare patients, refer to PAN, HealthWell, CancerCare — verify open pancreatic cancer funds quarterly (oncology funds open and close based on disease-state donations)
• Web: ipsencares.com

Diarrhea management FDA label 2024

Onivyde causes two distinct diarrhea syndromes. Both can be severe and life-threatening. Atropine and loperamide must be available at every infusion.

Common denials & how to fix them

Frequently asked questions

What is the HCPCS code for Onivyde?

Onivyde (irinotecan liposomal, pegylated) is billed under HCPCS J9205 — "Inj irinotecan liposome 1 mg." Each milligram equals one billable unit. J9205 is NOT the same as J9206 (conventional irinotecan / Camptosar / generic). Different drug, different toxicity, ~860× cost differential per mg.

What is the difference between J9205 and J9206?

J9205 is Onivyde, the pegylated liposomal formulation of irinotecan, manufactured by Ipsen, used in NALIRIFOX / NAPOLI for metastatic pancreatic adenocarcinoma. Q2 2026 ASP+6%: $66.374/mg. J9206 is conventional irinotecan (Camptosar / generic), used in FOLFIRI / FOLFIRINOX for colorectal and other indications. Q2 2026 ASP+6%: $1.532 per 20 mg unit (~$0.077/mg). Onivyde costs approximately 860× more per mg.

How many units of Onivyde do I bill for a typical NALIRIFOX dose?

For a patient with BSA 1.8 m² receiving the 50 mg/m² NALIRIFOX dose: 90 units of J9205 administered + waste. Three 43 mg vials are needed (129 mg purchased) — bill 90 units administered and 39 units of waste (JW) on a separate line.

What is the NALIRIFOX regimen and when did it get FDA approval?

NALIRIFOX is the 1L combination regimen for metastatic pancreatic adenocarcinoma: liposomal irinotecan (Onivyde) 50 mg/m² + oxaliplatin 60 mg/m² + leucovorin 400 mg/m² + 5-FU 2,400 mg/m² (46-hour infusion), all on Day 1 every 14 days. FDA approved February 13, 2024 based on the NAPOLI 3 trial, which showed superior overall survival vs gemcitabine + nab-paclitaxel. NALIRIFOX is now an NCCN-preferred 1L option for fit patients with metastatic pancreatic adenocarcinoma.

Does Onivyde require UGT1A1 testing?

UGT1A1 genotyping is recommended pre-treatment by the FDA label and required by many payers in the PA submission. Patients homozygous for UGT1A1*28 have higher SN-38 exposure and increased risk of severe neutropenia. The label specifies a 28% starting dose reduction in *28 homozygotes: NALIRIFOX 50 → 36 mg/m²; NAPOLI 70 → 50 mg/m². UGT1A1 testing is billed under CPT 81350.

What administration CPT do I use for Onivyde?

CPT 96413 (chemo IV, up to 1 hour, initial) plus 96415 × 1 (each additional hour). Onivyde is a 90-minute infusion, so 96413 covers the first hour and one unit of 96415 covers the additional 30 min. In NALIRIFOX combo, add 96417 for each additional sequential drug (oxaliplatin, leucovorin) and 96416 for the 5-FU 46-hour pump start.

What is the Medicare reimbursement for J9205?

For Q2 2026, the Medicare Part B payment limit for J9205 is $66.374 per mg (ASP + 6%). For a patient with BSA 1.8 m² receiving the 50 mg/m² NALIRIFOX dose (90 mg), drug reimbursement is approximately $5,973.66 per dose for the administered units, plus ~$2,588 for the 39 mg waste from 3 × 43 mg vials (also reimbursable). Annualized drug-only Medicare cost (administered + waste, 26 q14d cycles): ~$222,617/year. Sequestration (~2%) reduces actual paid to roughly ASP + 4.3%.

How is Onivyde-related diarrhea managed?

Two distinct syndromes: early-onset (within 24 hr) is cholinergic — treat with atropine 0.25–1 mg IV/SC at infusion start or onset. Late-onset (days 3–10) is from SN-38 toxicity to gut epithelium — treat with high-dose loperamide (4 mg loading, 2 mg q2h until diarrhea-free for 12 hr), aggressive hydration, and electrolyte management. Severe (grade 3+) late-onset diarrhea requires hospitalization and a 25% dose reduction next cycle. Atropine and loperamide must be available at every infusion. See Diarrhea management.

Source documents

1. FDA — ONIVYDE (irinotecan liposome) Prescribing Information
   FDA-approved label, most recent revision (NALIRIFOX 1L 2024 expansion); BLA 207793
2. DailyMed — ONIVYDE (irinotecan liposome) label
3. FDA — February 2024 approval announcement, NALIRIFOX 1L pancreatic
   FDA Drug Approval Announcement, February 13, 2024 (NAPOLI 3 trial)
4. CMS — Medicare Part B Drug ASP Pricing File
   Q2 2026 quarterly file, effective April 1 – June 30, 2026 (J9205 and J9206 both verified)
5. NCCN Clinical Practice Guidelines in Oncology — Pancreatic Adenocarcinoma
   NALIRIFOX listed as Category 1 preferred 1L option (post-2024 update)
6. Ipsen Cares — Onivyde Patient Support
   Manufacturer access program: benefits investigation, copay assistance, PAP. 1-866-435-5677.
7. UnitedHealthcare — Oncology Medication Clinical Coverage Policy
8. SEER CanMED — HCPCS J9205 reference
9. SEER CanMED — HCPCS J9206 reference (conventional irinotecan, comparison)
10. FDA National Drug Code Directory
11. Wainberg ZA, et al. NAPOLI 3 trial (Lancet 2023; updated NEJM 2024)
    Phase 3 NALIRIFOX vs gemcitabine + nab-paclitaxel; OS 11.1 vs 9.2 mo, HR 0.83

Refresh cadence

Change log

• May 2, 2026 — Initial publication. ASP data: Q2 2026. Manufacturer source: Ipsen Cares 2026. FDA label: 2024 NALIRIFOX 1L expansion (BLA 207793). Includes formulation comparison vs J9206 conventional irinotecan, UGT1A1 testing protocol, NALIRIFOX 1L regimen detail, diarrhea management.