Onivyde

In combination w/ oxaliplatin, 5-fluorouracil (5-FU) & leucovorin (LV) for the 1st-line treatment of adults w/ metastatic adenocarcinoma of the pancreas. In combination w/ 5-FU & LV for the treatment of metastatic adenocarcinoma of the pancreas in adults who have progressed following gemcitabine-based therapy.

In combination w/ oxaliplatin, 5-FU & LV Onivyde 50 mg/m² intravenously over 90 min, followed by oxaliplatin 60 mg/m² intravenously over 120 min, followed by LV 400 mg/m² intravenously over 30 min, followed by 5-FU 2,400 mg/m² intravenously over 46 hr. Administer every 2 wk. Discontinue oxaliplatin if not well tolerated & continue treatment w/ Onivyde + 5-FU/LV. Patient known to be homozygous for UGT1A1*28 allele Onivyde starting dose remains 50 mg/m² intravenously over 90 min. In combination w/ 5-FU & LV Onivyde 70 mg/m² intravenously over 90 min, followed by LV 400 mg/m² intravenously over 30 min, followed by 5-FU 2,400 mg/m² intravenously over 46 hr. Administer every 2 wk. Patient known to be homozygous for UGT1A1*28 allele Consider reduced Onivyde starting dose of 50 mg/m², then consider dose increase to 70 mg/m² if tolerated in subsequent cycles.

History of severe hypersensitivity. Lactation.

Not equiv to non-lipos irinotecan formulations & should not be interchanged. Do not administer as a single agent. Pre-medicate w/ standard doses of dexamethasone (or equiv corticosteroid) together w/ 5-HT₃ antagonist (or other antiemetic) at least 30 min prior to Onivyde infusion. CBC monitoring is recommended during treatment. Risk of sepsis w/ neutropenic fever & consequent septic shock w/ fatal outcome. Should not be used to treat patients w/ severe bone marrow failure. Increased risk of severe neutropenia & febrile neutropenia in patients w/ history of prior abdominal radiation. Caution in patients receiving concurrent administration w/ irradiation. Greater risk of myelosuppression in patients w/ deficient glucuronidation of bilirubin (eg, Gilbert's syndrome). Can cause severe & life-threatening diarrhoea. Must not be administered to patients w/ bowel obstruction & chronic inflammatory bowel disease. Diarrhoea can occur early (onset in ≤24 hr after starting treatment) or late (>24 hr). A new cycle of therapy should not begin until diarrhoea resolves to grade ≤1 (2-3 stools/day more than pre-treatment frequency). Reduce subsequent dose following grade 3 or 4 diarrhoea. Early onset diarrhoea may be accompanied by cholinergic symptoms. Hypersensitivity reactions, including acute infusion-related reaction, anaphylactic/anaphylactoid reaction & angioedema may occur. Discontinue treatment in case of severe hypersensitivity reactions. Higher risk of serious infections in patients w/ history of Whipple procedure following Onivyde in combination w/ 5-FU & LV. Associated w/ thromboembolic events eg, pulmonary embolism, venous thrombosis & arterial thromboembolism. Patients w/ risk factors for pulmonary toxicity should be closely monitored for resp symptoms before & during therapy. New or progressive dyspnoea, cough, & fever should prompt treatment interruption, pending diagnostic evaluation. Discontinue treatment in patients w/ confirmed ILD diagnosis. Avoid vaccination w/ live or live-attenuated vaccines. Killed or inactivated vaccines may be administered, however, response to such vaccines may be diminished. Do not administer w/ strong CYP3A4 inducers; strong CYP3A4 inhibitors; strong UGT1A1 inhibitors. Contains 33.1 mg Na per vial, equiv to 1.65% of WHO-recommended max daily intake of 2 g Na for an adult. Moderate influence on the ability to drive & use machines. Avoid use in patients w/ bilirubin >2 mg/dL, or AST & ALT >2.5x ULN or >5x ULN if liver metastasis is present. Caution when given in combination w/ other hepatotoxic medicinal products, especially in patients w/ pre-existing hepatic impairment. Not recommended for use in patients w/ severe renal impairment (CrCl <30 mL/min). Women of childbearing potential should use effective contraception during treatment & 7 mth thereafter. Males should use condoms during treatment & 4 mth thereafter. Can cause foetal harm when administered to pregnant woman. Should not be used during pregnancy unless clearly necessary. Patients should not breast-feed until 1 mth after the last dose. Patients should consider preservation of gametes prior to starting administration of Onivyde. Safety & efficacy in childn & adolescents ≤18 yr have not yet been established. Caution in patients w/ BMI <18.5 kg/m².

In combination w/ oxaliplatin, 5-FU & LV: Diarrhoea, nausea, vomiting, decreased appetite, fatigue, asthenia, neutropenia, decreased neutrophil count, anaemia. In combination w/ 5-FU & LV: Diarrhoea, nausea, vomiting, decreased appetite, neutropenia, fatigue, asthenia, anaemia, stomatitis, pyrexia.

Reduced systemic exposure w/ CYP3A4 inducers (eg, phenytoin, phenobarb, carbamazepine, rifampin, rifabutin, St. John's wort). Increased systemic exposure w/ CYP3A4 inhibitors (eg, grapefruit juice, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole); UGT1A1 inhibitors (eg, atazanavir, gemfibrozil, indinavir, regorafenib). Adverse effects of irinotecan (eg, myelosuppression) may be exacerbated by other antineoplastic agents (including flucytosine as a prodrug for 5-FU) having a similar adverse-effect profile.

Cytotoxic Chemotherapy

L01CE02 - irinotecan ; Belongs to the class of Topoisomerase 1 (TOP1) inhibitors. Used in the treatment of cancer.

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