Onivyde

Irinotecan

In combination w/ oxaliplatin, 5-fluorouracil (5-FU) & leucovorin (LV) for 1st-line treatment of adult patients w/ metastatic pancreatic adenocarcinoma; w/ 5-FU & LV for metastatic pancreatic adenocarcinoma in adult patients who have progressed following gemcitabine-based therapy & w/ Eastern Co-operation Oncology Group performance status 0-2.

Premed w/ dexamethasone (or an equiv corticosteroid) + 5-HT₃ antagonist (or other antiemetic) at least 30 min prior to lipos infusion. IV In combination w/ oxaliplatin, 5-FU & LV 50 mg/m² over 90 min, followed by oxaliplatin 60 mg/m² over 120 min, followed by LV 400 mg/m² over 30 min & 5-FU 2,400 mg/m² over 46 hr every 2 wk. In combination w/ 5-FU & LV 70 mg/m² over 90 min, followed by LV 400 mg/m² over 30 min & 5-FU 2,400 mg/m² over 46 hr every 2 wk. Patient known to be UGT1A1*28 allele homozygous Reduce starting dose to 50 mg/m², may be increased to 70 mg/m² if tolerated in subsequent cycles. Patient who start treatment w/ 50 mg/m² 1st dose reduction: 43 mg/m² & 2nd dose reduction: 35 mg/m².

History of severe hypersensitivity. Lactation.

Hypersensitivity reactions including acute infusion reaction, anaphylactic/anaphylactoid reaction & angioedema. Discontinue treatment in case of hypersensitivity reactions; confirmed diagnosis of ILD. Interrupt treatment in pending diagnostic evaluation of new or progressive dyspnoea, cough & fever. Reduce dose or discontinue treatment in severe haematological events. Not to be used in patients w/ severe bone marrow failure; bowel obstruction & chronic inflammatory bowel disease. Not to be interchanged w/ other non-lipos irinotecan formulations. Consider use of myeloid growth factors in patients w/ history of abdominal radiation. Early (≤24 hr) or late (>24 hr) onset of diarrhoea; delay new cycle of treatment until diarrhoea resolves to Grade 1 (2-3 stools/day more than pre-treatment frequency). Reduce dose following Grade 3 or 4 diarrhoea. Early onset diarrhoea accompanied by cholinergic symptoms eg, rhinitis, increased salivation, flushing, diaphoresis, bradycardia, miosis & hyperperistalsis. Sepsis w/ neutropenic fever & consequent septic shock; thromboembolic events eg, pulmonary embolism, venous thrombosis & arterial thromboembolism; ILD. History of Whipple procedure. Pre-existing lung disease, use of pneumotoxic medicinal products, colony stimulating factors or previous RT. Patients w/ deficient glucuronidation of bilirubin eg, those w/ Gilbert's syndrome; receiving concomitant irradiation therapy. Underwt patients w/ BMI <18.5 kg/m². Asian patients. Monitor CBC during treatment; signs of infection. Closely monitor for resp symptoms before & during therapy in patients w/ risk factors of ILD. Monitor & replace fluid electrolytes, stop loperamide, & continue antibiotic support if diarrhoea persists >48 hr. Not to be administered w/ strong CYP3A4 inducers eg, anticonvulsants (phenytoin, phenobarb, carbamazepine), rifampin, rifabutin & St. John's wort; CYP3A4 inhibitors (eg, grapefruit juice, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole); UGT1A1 inhibitors (eg, atazanavir, gemfibrozil, indinavir). Avoid administration of live or live-attenuated vaccines in immunocompromised by chemotherapeutic medicinal products. Contains Na. May affect ability to drive & use machines. Not recommended in severe renal impairment (CrCl <30 mL/min). Pre-existing hepatic impairment (bilirubin >2x ULN; transaminases >5x ULN). Males should use effective contraception during treatment & 4 mth thereafter. Women of childbearing potential should use effective contraception during treatment & 7 mth thereafter. Pregnancy. Not to breastfeed until 1 mth after last dose. Childn & adolescents ≤18 yr.

Anaemia, neutropenia, thrombocytopenia, febrile neutropenia, leukopenia, lymphopenia; hypokalaemia, decreased appetite, hypomagnesaemia, dehydration; diarrhoea, nausea, vomiting, abdominal pain, stomatitis; alopecia; asthenia, mucosal inflammation; decreased wt. Sepsis; hypophosphataemia, hypoalbuminaemia; cholinergic syndrome, dysgeusia, dizziness; hypotension, thomboembolic events, pulmonary embolism, dyspnoea; colitis, haemorrhoids; pyrexia, oedema; increased transaminases (ALT & AST); infusion related reaction. In combination w/ oxaliplatin/5-FU/LV: Peripheral neuropathy, paraesthesia, abdominal discomfort. UTI, candida infection, nasopharyngitis; hypocalcaemia; tremor, neurotoxicity, dysaesthesia, headache; blurred vision; tachycardia; hiccups, epistaxis; enterocolitis, constipation, dry mouth, flatulence, abdominal distension, dyspepsia, GERD, dysphagia; hyperbilirubinaemia; dry skin, palmar-plantar erythrodysaesthesia syndrome, rash, skin hyperpigmentation; muscular weakness, myalgia, muscle spasms; acute kidney injury; chills; increased blood alkaline phosphatase, γ-glutamyltransferase & blood creatinine. In combination w/ 5-FU & LV: Peripheral oedema; septic shock, pneumonia, gastroenteritis, oral candidiasis; hypoglycaemia; insomnia; dysphonia; pruritus; acute renal failure; increased bilirubin, increased INR.

Reduced systemic exposure w/ strong CYP3A4 inducers eg, anticonvulsants (phenytoin, phenobarb or carbamazepine), St. John's wort. Increased systemic exposure w/ strong CYP3A4 (eg, grapefruit juice, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) & UGT1A1 (eg, atazanavir, gemfibrozil, indinavir, regorafenib) inhibitors. Exacerbated adverse effects by other antineoplastics including flucytosine.

Cytotoxic Chemotherapy

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

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