Onivyde Dosage/Direction for Use

ONIVYDE pegylated liposomal must only be prescribed and administered to patients by healthcare professionals experienced in the use of anti-cancer therapies.
ONIVYDE pegylated liposomal is not equivalent to non-liposomal irinotecan formulations and should not be interchanged.
Posology: ONIVYDE pegylated liposomal should not be administered as a single agent and should be continued until disease progression or no longer tolerated by the patient.
ONIVYDE pegylated liposomal in combination with oxaliplatin, 5-fluorouracil and leucovorin: ONIVYDE pegylated liposomal, oxaliplatin, LV and 5-FU should be administered sequentially. The recommended dose of ONIVYDE pegylated liposomal is 50 mg/m² intravenously over 90 minutes, followed by oxaliplatin 60 mg/m² intravenously over 120 minutes, followed by LV 400 mg/m² intravenously over 30 minutes, followed by 5-FU 2,400 mg/m² intravenously over 46 hours. This regimen should be administered every 2 weeks.
Oxaliplatin may be discontinued if not well tolerated and treatment with ONIVYDE pegylated liposomal + 5-FU/LV can continue.
The recommended starting dose of ONIVYDE pegylated liposomal in patients known to be homozygous for UGT1A1*28 allele is unchanged and remains 50 mg/m² administered intravenously over 90 minutes (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
ONIVYDE pegylated liposomal in combination with 5-fluorouracil and leucovorin: ONIVYDE pegylated liposomal, leucovorin and 5-fluorouracil should be administered sequentially. The recommended dose and regimen of ONIVYDE pegylated liposomal is 70 mg/m² intravenously over 90 minutes, followed by LV 400 mg/m² intravenously over 30 minutes, followed by 5-FU 2,400 mg/m² intravenously over 46 hours, administered every 2 weeks.
A reduced starting dose of ONIVYDE pegylated liposomal of 50 mg/m² should be considered for patients known to be homozygous for the UGT1A1*28 allele (see Adverse Reactions and Pharmacology: Pharmacodynamics under Actions). A dose increase of ONIVYDE pegylated liposomal to 70 mg/m² should be considered if tolerated in subsequent cycles.
Pre-medication: It is recommended that patients receive pre-medication with standard doses of dexamethasone (or an equivalent corticosteroid) together with a 5-HT₃ antagonist (or other antiemetic) at least 30 minutes prior to ONIVYDE pegylated liposomal infusion.
Dose adjustments: All dose modifications should be based on the worst preceding toxicity. The LV dose does not require adjustment.
ONIVYDE pegylated liposomal in combination with oxaliplatin, 5-fluorouracil and leucovorin: (See Table 4.)

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Patients homozygous for the UGT1A1*28 allele should initiate ONIVYDE pegylated liposomal at the same dose and the same dose reduction requirements should apply.
ONIVYDE pegylated liposomal in combination with 5-fluorouracil and leucovorin: For patients who start treatment with 50 mg/m² ONIVYDE pegylated liposomal and do not dose escalate to 70 mg/m², the recommended first dose reduction is to 43 mg/m² and the second dose reduction is to 35 mg/m². Patients who require further dose reduction should discontinue treatment.
Patients who are known to be homozygous for UGT1A1*28 and without drug related toxicities during the first cycle of therapy (reduced dose of 50 mg/m²) may have the dose of ONIVYDE pegylated liposomal increased to a total dose of 70 mg/m² in subsequent cycles based on individual patient tolerance. (See Tables 5 and 6.)

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Click on icon to see table/diagram/image

Special populations: Hepatic impairment: No dedicated hepatic impairment study has been conducted with ONIVYDE pegylated liposomal. The use of ONIVYDE pegylated liposomal should be avoided in patients with bilirubin >2.0 mg/dl, or aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.5 times upper limit of normal (ULN) or >5 times ULN if liver metastasis is present (see Precautions).
Renal impairment: No dedicated renal impairment study has been conducted with ONIVYDE pegylated liposomal. No dose adjustment is recommended in patients with mild to moderate renal impairment (see Precautions and Pharmacology: Pharmacokinetics under Actions). ONIVYDE pegylated liposomal is not recommended for use in patients with severe renal impairment (CLcr <30 ml/min).
Elderly: Forty-nine percent (49.6%) in NAPOLI-3 and forty-one percent (41%) in NAPOLI-1 of patients treated with ONIVYDE pegylated liposomal were ≥65 years. No dose adjustment is recommended.
Paediatric population: The safety and efficacy of ONIVYDE pegylated liposomal in children and adolescents aged ≤18 years have not yet been established. No data are available.
Method of administration: ONIVYDE pegylated liposomal is for intravenous use. The concentrate must be diluted prior to administration and given as single intravenous infusion over 90 minutes. For more details, see Special precautions for disposal and other handling under Cautions for Usage.
Precautions to be taken before handling or administering the medicinal product: ONIVYDE pegylated liposomal is a cytotoxic medicinal product. The use of gloves, goggles and protective clothing when handling or administering ONIVYDE pegylated liposomal is recommended. Pregnant staff should not handle ONIVYDE pegylated liposomal.