onivyde

Important safety information

Interstitial lung disease (ILD): Fatal ILD has occurred in patients receiving irinotecan including ONIVYDE. Discontinue ONIVYDE if ILD is diagnosed. ( 5.3 ) Severe hypersensitivity reaction: Permanently discontinue ONIVYDE for severe hypersensitivity reactions. ( 5.4 , 4 ) Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.5 , 8.1 , 8.3 ) 5.1 Severe Neutropenia ONIVYDE can cause severe or life-threatening neutropenia and fatal neutropenic sepsis. In NAPOLI 3, Grade 3 and 4 neutropenia occurred in 26% of patients receiving ONIVYDE in combination with oxaliplatin, fluorouracil, and leucovorin (NALIRIFOX) and fatal neutropenic fever in 0.3% of patients [see Adverse Reactions (6.1) ]. In NAPOLI-1, Grade 3 and 4 neutropenia occurred in 20% of patients receiving ONIVYDE in combination with fluorouracil and leucovorin (ONIVYDE/FU/LV). Neutropenic sepsis occurred in 3% and fatal neutropenic sepsis in 0.8% [see Adverse Reactions (6.1) ]. In NAPOLI 3, the incidence of Grade 3 or 4 neutropenia was similar among Asian patients [6 of 20 (30%)] compared to White patients [76 of 289 (26%)] receiving ONIVYDE in combination with oxaliplatin, fluorouracil, and leucovorin. Neutropenic fever was reported in 5% of Asian patients (1 of 20) compared to 2.3% of White patients (7 of 306). In NAPOLI-1, the incidence of Grade 3 or 4 neutropenia was higher among Asian patients [18 of 33 (55%)] compared to White patients [13 of 73 (18%)] receiving ONIVYDE/FU/LV. Neutropenic fever/neutropenic sepsis was reported in 6% of Asian patients compared to 1% of White patients [see Clinical Pharmacology (12.3) ]. Monitor complete blood cell counts on Days 1 and 8 of every cycle and more frequently if clinically indicated. Withhold ONIVYDE if the absolute neutrophil count (ANC) is below 1500/mm 3 or if neutropenic fever occurs. Resume ONIVYDE when the ANC is 1500/mm 3 or above. Reduce ONIVYDE dose for Grade 3-4 neutropenia or neutropenic fever following recovery in subsequent cycles [see Dosage and Administration (2.2) ] . 5.2 Severe Diarrhea ONIVYDE can cause severe and life-threatening diarrhea. Do not administer ONIVYDE to patients with a bowel obstruction. Severe or life-threatening diarrhea can follow 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) [see Adverse Reactions (6.1) ] . An individual patient may experience both early and late-onset diarrhea. In NAPOLI 3, Grade 3 and 4 diarrhea (early and late-onset) occurred in 20% receiving ONIVYDE in combination with oxaliplatin, fluorouracil, and leucovorin (NALIRIFOX). In NAPOLI-1, Grade 3 or 4 diarrhea occurred in 13% receiving ONIVYDE/FU/LV. The incidence of Grade 3 or 4 late onset diarrhea was 9% in patients receiving ONIVYDE/FU/LV. The incidence of Grade 3 or 4 early onset diarrhea was 3% in patients receiving ONIVYDE/FU/LV. Of patients receiving ONIVYDE/FU/LV in NAPOLI-1, 34% received loperamide for late-onset diarrhea and 26% received atropine for early-onset diarrhea. To reduce the risk of severe diarrhea, patients should stop lactose-containing products, eat a low-fat diet and maintain hydration during treatment with ONIVYDE. Withhold ONIVYDE for Grade 2-4 diarrhea. Administer intravenous or subcutaneous atropine 0.25 to 1 mg (unless clinically contraindicated) for early onset diarrhea of any severity. Initiate loperamide for late onset diarrhea of any severity. Local institutional guidelines should be followed for the treatment of diarrhea that does not improve within 48 hours and may include the addition of diphenoxylate hydrochloride plus atropine sulfate or octreotide. Following recovery to Grade 1 diarrhea, resume ONIVYDE at a reduced dose [see Dosage and Administration (2.3) ] . 5.3 Interstitial Lung Disease ONIVYDE can cause severe and fatal interstitial lung disease (ILD), including pneumonitis. Postmarketing cases of severe and fatal ILD have been reported with ONIVYDE. Risk factors include pre-existing lung disease, use of pneumotoxic medicinal products, colony stimulating factors or having previously received radiation therapy. Patients with risk factors should be closely monitored for respiratory symptoms before and during ONIVYDE therapy. 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. 5.4 Severe Hypersensitivity Reaction Irinotecan including ONIVYDE can cause severe hypersensitivity reactions, including anaphylactic reactions. Permanently discontinue ONIVYDE in patients who experience a severe hypersensitivity reaction [see Contraindications (4) , Adverse reactions (6.2) ]. 5.5 Embryo-Fetal Toxicity Based on animal data with irinotecan HCl and the mechanism of action of ONIVYDE, ONIVYDE can cause fetal harm when administered to a pregnant woman. Embryotoxicity and teratogenicity were observed following treatment with irinotecan HCl, at doses resulting in irinotecan exposures lower than those achieved with ONIVYDE 70 mg/m 2 in humans, administered to pregnant rats and rabbits during organogenesis. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ONIVYDE and for seven months following the last dose [see Use in Specific Populations (8.1 , 8.3) , Clinical Pharmacology (12.1) ] .