WELL-CHARACTERIZED SAFETY PROFILE1

NAPOLI-1: ADVERSE REACTIONS1

ADVERSE REACTIONS OCCURRING AT A HIGHER INCIDENCE IN THE ONIVYDE + 5-FU/LV ARM THAN IN THE 5-FU/LV ARM (BETWEEN-ARM DIFFERENCE OF 5% [GRADES 1-4]* OR 2% [GRADES 3 AND 4])

 

  • Discontinuation rate due to adverse reactions was 11%1
  • There were no overall differences in safety observed between younger (<65 years) and older patients (65 years)1
  • The most common serious adverse reactions (2%) of ONIVYDE, alone or in combination, were diarrhea, vomiting, neutropenic fever or neutropenic sepsis, nausea, pyrexia, sepsis, dehydration, septic shock, pneumonia, acute renal failure, and thrombocytopenia1

*National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 used for grading.
Early diarrhea: onset ≤24 hours after ONIVYDE administration.
Late diarrhea: onset >1 day after ONIVYDE administration.
§Includes stomatitis, aphthous stomatitis, mouth ulceration, mucosal inflammation.
||Includes febrile neutropenia.

NAPOLI-1: LABORATORY ABNORMALITIES1

LABORATORY ABNORMALITIES OCCURRING AT A HIGHER INCIDENCE IN THE ONIVYDE + 5-FU/LV ARM THAN IN THE 5-FU/LV ARM (BETWEEN-ARM DIFFERENCE OF 5% [GRADES 1-4] OR 2% [GRADES 3 AND 4])

 

PLEASE SEE DOSE MODIFICATIONS DESIGNED TO SUPPORT ACTIVE MANAGEMENT OF CERTAIN GRADE 3 OR 4 ADVERSE REACTIONS AND GRADE 2–4 DIARRHEA

National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 used for grading.

Indication and Important Safety Information, incl. Boxed Warning

INDICATION

ONIVYDE® (irinotecan liposome injection) is indicated, in combination with fluorouracil (5-FU) and leucovorin (LV), for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy.

Limitation of Use: ONIVYDE is not indicated as a single agent for the treatment of patients with metastatic adenocarcinoma of the pancreas.

WARNING: SEVERE NEUTROPENIA and SEVERE DIARRHEA

  • Fatal neutropenic sepsis occurred in 0.8% of patients receiving ONIVYDE. Severe or life-threatening neutropenic fever or sepsis occurred in 3% and severe or life-threatening neutropenia occurred in 20% of patients receiving ONIVYDE in combination with 5-FU and LV. Withhold ONIVYDE for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment
  • Severe diarrhea occurred in 13% of patients receiving ONIVYDE in combination with 5-FU/LV. Do not administer ONIVYDE to patients with bowel obstruction. Withhold ONIVYDE for diarrhea of Grade 2–4 severity. Administer loperamide for late diarrhea of any severity. Administer atropine, if not contraindicated, for early diarrhea of any severity
CONTRAINDICATION
  • ONIVYDE is contraindicated in patients who have experienced a severe hypersensitivity reaction to ONIVYDE or irinotecan HCl
WARNINGS AND PRECAUTIONS
  • Severe Neutropenia: See Boxed WARNING. In patients receiving ONIVYDE/5-FU/LV, the incidence of Grade 3/4 neutropenia was higher among Asian (18/33 [55%]) vs White patients (13/73 [18%]). Neutropenic fever/neutropenic sepsis was reported in 6% of Asian vs 1% of White patients
  • Severe Diarrhea: See Boxed WARNING. Severe and life-threatening late-onset (onset >24 hours after chemotherapy [9%]) and early-onset diarrhea (onset ≤24 hours after chemotherapy [3%], sometimes with other symptoms of cholinergic reaction) were observed
  • Interstitial Lung Disease (ILD): Irinotecan HCl can cause severe and fatal ILD. Withhold ONIVYDE in patients with new or progressive dyspnea, cough, and fever, pending diagnostic evaluation. Discontinue ONIVYDE in patients with a confirmed diagnosis of ILD
  • Severe Hypersensitivity Reactions: Irinotecan HCl can cause severe hypersensitivity reactions, including anaphylactic reactions. Permanently discontinue ONIVYDE in patients who experience a severe hypersensitivity reaction
  • Embryo-Fetal Toxicity: ONIVYDE can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during and for 1 month after ONIVYDE treatment
ADVERSE REACTIONS
  • The most common adverse reactions (≥20%) were diarrhea (59%), fatigue/asthenia (56%), vomiting (52%), nausea (51%), decreased appetite (44%), stomatitis (32%), and pyrexia (23%)
  • The most common Grade 3/4 adverse reactions (≥10%) were diarrhea (13%), fatigue/asthenia (21%), and vomiting (11%)
  • Adverse reactions led to permanent discontinuation of ONIVYDE in 11% of patients receiving ONIVYDE/5-FU/LV; The most frequent adverse reactions resulting in discontinuation of ONIVYDE were diarrhea, vomiting, and sepsis
  • Dose reductions of ONIVYDE for adverse reactions occurred in 33% of patients receiving ONIVYDE/5-FU/LV; the most frequent adverse reactions requiring dose reductions were neutropenia, diarrhea, nausea, and anemia
  • ONIVYDE was withheld or delayed for adverse reactions in 62% of patients receiving ONIVYDE/5-FU/LV; the most frequent adverse reactions requiring interruption or delays were neutropenia, diarrhea, fatigue, vomiting, and thrombocytopenia
  • The most common laboratory abnormalities (≥20%) were anemia (97%), lymphopenia (81%), neutropenia (52%), increased ALT (51%), hypoalbuminemia (43%), thrombocytopenia (41%), hypomagnesemia (35%), hypokalemia (32%), hypocalcemia (32%), hypophosphatemia (29%), and hyponatremia (27%)
DRUG INTERACTIONS
  • Avoid the use of strong CYP3A4 inducers, if possible, and substitute non-enzyme inducing therapies ≥2 weeks prior to initiation of ONIVYDE
  • Avoid the use of strong CYP3A4 or UGT1A1 inhibitors, if possible, and discontinue strong CYP3A4 inhibitors ≥1 week prior to starting therapy
USE IN SPECIFIC POPULATIONS
  • Pregnancy and Reproductive Potential: See WARNINGS & PRECAUTIONS. Advise males with female partners of reproductive potential to use condoms during and for 4 months after ONIVYDE treatment
  • Lactation: Advise nursing women not to breastfeed during and for 1 month after ONIVYDE treatment

Please see full Prescribing Information, including Boxed WARNING.

References: 1. ONIVYDE [package insert]. Basking Ridge, NJ. Ipsen Biopharmaceuticals, Inc.; 2017. 2. Wang-Gillam A, Li C-P, Bodoky G, et al. Lancet. 2016;387:545-557. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pancreatic Adenocarcinoma V.1.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed May 9, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org. 4. Data on file #1. Basking Ridge, NJ. Ipsen Biopharmaceuticals, Inc.; 2015. 5. Zhang H. Onco Targets Ther. 2016;9:3001-3007. 6. Kalra AV, Kim J, Klinz G, et al. Cancer Res. 2014;74:7003-7013. 7. Data on file #3. Basking Ridge, NJ. Ipsen Biopharmaceuticals, Inc.; 2015.

©2019 Ipsen Biopharmaceuticals, Inc. All rights reserved. March 2019 ONV-US-001533

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