Onivyde (irinotecan liposome injection)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.


Approval Status:

Approved October 2015

Specific Treatments:

metastatic pancreatic cancer

Therapeutic Areas

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General Information

Onivyde (irinotecan liposome injection) is a topoisomerase inhibitor.

Onivyde is specifically indicated in combination with fluorouracil and leucovorin, for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. 

Onivyde is supplied as an injection for intravenous infusion. Administer Onivyde prior to leucovorin and fluorouracil. The recommended dose of Onivyde is 70 mg/m2 administered by intravenous infusion over 90 minutes every 2 weeks. Increase the dose of Onivyde to 70 mg/m2 as tolerated in subsequent cycles.

Please see drug label for dosing in specific populations and for dose modifications.

Clinical Results

FDA Approval

The FDA approval of Onivyde was based on a three-arm, randomized, open-label trial in 417 patients with metastatic pancreatic adenocarcinoma with documented disease progression, after gemcitabine or gemcitabine-based therapy. Subjects were were randomized to receive Onivyde plus fluorouracil/leucovorin (Onivyde/5-FU/LV), Onivyde, or fluorouracil/leucovorin (5-FU/LV). Randomization was stratified by ethnicity (White vs. East Asian vs. other), KPS (70-80 vs. 90-100), and baseline albumin level (≥ 4 g/dL vs. 3.0-3.9 g/dL). Patients randomized to Onivyde/5-FU/LV received Onivyde 70 mg/m2 as an intravenous infusion over 90 minutes, followed by leucovorin 400 mg/m2 intravenously over 30 minutes, followed by fluorouracil 2400 mg/m2 intravenously over 46 hours, every 2 weeks. The Onivyde dose of 70 mg/m2 is based on irinotecan free base (equivalent to 80 mg/m2 of irinotecan as the hydrochloride trihydrate). Patients randomized to Onivyde as a single agent received Onivyde 100 mg/m2 as an intravenous infusion over 90 minutes every 3 weeks. Patients randomized to 5-FU/LV received leucovorin 200 mg/m2 intravenously over 30 minutes, followed by fluorouracil 2000 mg/m2 intravenously over 24 hours, administered on Days 1, 8, 15 and 22 of a 6-week cycle. Patients homozygous for the UGT1A1*28 allele initiated Onivyde at a reduced dose (50 mg/m2 Onivyde if given with 5-FU/LV or 70 mg/m2 Onivyde as a single agent). The major efficacy outcome measure was overall survival (OS) with two pair-wise comparisons: Onivyde versus 5-FU/LV and Onivyde/5-FU/LV versus 5-FU/LV. The study showed a statistically significant improvement in overall survival for the Onivyde/5-FU/LV arm over the 5-FU/LV arm. There was no improvement in overall survival for the Onivyde arm over the 5-FU/LV arm.

Side Effects

Adverse effects associated with the use of Onivyde may include, but are not limited to, the following:

  • diarrhea
  • fatigue/asthenia
  • vomiting
  • nausea
  • decreased appetite
  • stomatitis
  • pyrexia
  • lymphopenia
  • neutropenia

Onivyde comes with a black box warning of the potential for severe neutropenia and severe diarrhea with the use of Onivyde.

Mechanism of Action

Onivyde (irinotecan liposome injection) is a topoisomerase inhibitor encapsulated in a lipid bilayer vesicle or liposome. Topoisomerase 1 relieves torsional strain in DNA by inducing single-strand breaks. Irinotecan and its active metabolite SN-38 bind reversibly to the topoisomerase 1-DNA complex and prevent re-ligation of the single-strand breaks, leading to exposure time-dependent double-strand DNA damage and cell death. In mice bearing human tumor xenografts, irinotecan liposome administered at irinotecan HCl-equivalent doses 5-fold lower than irinotecan HCl achieved similar intratumoral exposure of SN-38.

Additional Information

For additional information regarding Onivyde or hyperkalemia, please visit https://www.onivyde.com/