ONIVYDE PEGYLATED LIPOSOMAL (IRINOTECAN) CONCENTRATE FOR DISPERSION FOR INFUSION 4.3 mg/mL

SERVIER (S) PTE LTD

SERVIER (S) PTE LTD

Therapeutic

Prescription Only

INFUSION, SOLUTION CONCENTRATE

**13 DOSAGE AND ADMINISTRATION** **13.1 Important Use Information** **DO NOT SUBSTITUTE** ONIVYDE pegylated liposomal for other drugs containing irinotecan HCl. **13.2 Recommended Use** Administer ONIVYDE pegylated liposomal prior to leucovorin and fluorouracil _\[see Clinical Studies (5)_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_ _\]_. - The recommended dose of ONIVYDE pegylated liposomal is 70 mg/m2 administered by intravenous infusion over 90 minutes every 2 weeks. - A reduced starting dose of ONIVYDE pegylated liposomal of 50 mg/m2 should be considered in patients known to be homozygous for the UGT1A1\*28 allele. A dose increase of ONIVYDE pegylated liposomal to 70 mg/m2 should be considered if tolerated in subsequent cycles. - There is no recommended dose of ONIVYDE pegylated liposomal for patients with serum bilirubin above the upper limit of normal _\[see Adverse Reactions (9.1) and Clinical Studies (5)_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_ _\]_. Premedication Administer a corticosteroid and an anti-emetic 30 minutes prior to ONIVYDE pegylated liposomal infusion. **13.3 Dose Modifications for Adverse Reactions** All dose modifications should be based on the worst preceding toxicity. LV dose does not require adjustment. For Grade 1 and 2 toxicities, there are no dose modifications recommended. Dose adjustments, as summarized in Table 5 and Table 6, are recommended to manage Grade 3 or 4 toxicities related to ONIVYDE pegylated liposomal. 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.   For recommended dose modifications of fluorouracil (5-FU) or leucovorin (LV), refer to the Full Prescribing Information; refer to Clinical Studies (5) – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_. **13.4 Preparation and Administration** ONIVYDE pegylated liposomal is a cytotoxic drug. Follow applicable special handling and disposal procedures.1 Preparation - Withdraw the calculated volume of ONIVYDE pegylated liposomal from the vial using a needle not larger than 21 gauge. Dilute ONIVYDE pegylated liposomal in 500 mL 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP and mix diluted dispersion by gentle inversion. - Protect diluted dispersion from light. - Chemical and physical stability for the diluted dispersion for infusion has been demonstrated at 15°C to 25°C for up to 4 hours or in the refrigerator (2°C to 8°C) for not more than 24 hours. Allow diluted dispersion to come to room temperature prior to administration. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user. - Do NOT freeze. Administration - Infuse diluted dispersion intravenously over 90 minutes. Do not use in-line filters. Discard unused portion. * * * **16 REFERENCES** 1. OSHA Hazardous Drugs. _OSHA._ http://www.osha.gov/SLTC/hazardousdrugs/index.html