Managing CERTAIN adverse reactions with dose modifications

NAPOLI-1: Dose reduction, delay, and discontinuation1

Toxicity NCI
CTCAE v4.0*
DirectionsONIVYDE® adjustment in patients receiving 70 mg/m2Patients homozygous for UGT1A1*28 (who are currently receiving 50 mg/m2)
Grade 2 DiarrheaWithhold ONIVYDE®. Administer loperamide for late diarrhea of any severity. Administer atropine, if not contraindicated, for early diarrhea of any severityN/AN/A
Grade 3 or 4 DiarrheaWithhold ONIVYDE®. Initiate loperamide for late-onset diarrhea of any severity. Administer intravenous or subcutaneous atropine 0.25 to 1 mg (unless clinically contraindicated) for early-onset diarrhea of any severity. Upon recovery to Grade 1, resume ONIVYDE® at a modified doseFIRST OCCURRENCE
50 mg/m243 mg/m2
SECOND OCCURRENCE
43 mg/m235 mg/m2
THIRD OCCURRENCE
Discontinue ONIVYDE®
Grade 3 or 4 Adverse ReactionsWithhold ONIVYDE®. Upon recovery to Grade 1, resume ONIVYDE® at a modified doseFIRST OCCURRENCE
50 mg/m243 mg/m2
SECOND OCCURRENCE
43 mg/m235 mg/m2
THIRD OCCURRENCE
Discontinue ONIVYDE®
Interstitial Lung DiseaseFIRST OCCURRENCE
Discontinue ONIVYDE®
Anaphylactic ReactionFIRST OCCURRENCE
Discontinue ONIVYDE®

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

When ONIVYDE® was withheld or discontinued for adverse reactions, 5-FU was also withheld or discontinued.1

When the dose of ONIVYDE® was reduced for adverse reactions, the dose of 5-FU was reduced by 25%.1

  • 62% of patients withheld or delayed1
    • Adverse reactions leading to withholding or delaying ONIVYDE® + 5-FU/LV were neutropenia, diarrhea, fatigue, vomiting, and thrombocytopenia1
  • 33% of patients dose reduced1
    • Adverse reactions leading to dose reductions of ONIVYDE® + 5-FU/LV were neutropenia, diarrhea, nausea, and anemia1
  • 11% of patients discontinued1
    • Adverse reactions leading to permanent discontinuation of ONIVYDE® + 5-FU/LV included diarrhea, vomiting, and sepsis1
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Management of severe neutropenia1

  • Monitor complete blood cell counts on Days 1 and 8 of every cycle and more frequently if clinically indicated
  • Withhold ONIVYDE® for absolute neutrophil count below 1500/mm3 or neutropenic fever
  • Upon recovery to ANC 1500/mm3, reduce ONIVYDE® dose for Grade 3–4 neutropenia or neutropenic fever
  • Special considerations:
    • Grade 3 or 4 neutropenia was higher among Asian patients (18 of 33 [55%]) compared to White patients (13 of 73 [18%]). Neutropenic fever/neutropenic sepsis was reported in 6% of Asian patients compared to 1% of White patients
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Management of severe diarrhea1

  • Severe or life-threatening diarrhea followed one of two patterns:
    • Late-onset diarrhea (onset more than 24 hours following chemotherapy); and
    • Early-onset diarrhea (onset within 24 hours of chemotherapy, sometimes occurring with other symptoms of cholinergic reaction)
    • An individual patient may experience both early- and late-onset diarrhea
  • Withhold ONIVYDE® for diarrhea of Grade 2–4 severity
  • Administer loperamide for late diarrhea of any severity; 34% of patients received loperamide for late-onset diarrhea
  • Administer atropine for early diarrhea of any severity; 26% of patients received atropine for early-onset diarrhea
  • Following recovery to Grade 1 diarrhea, resume ONIVYDE® at a reduced dose