BLINCYTO

Aseptic preparation Aseptic handling must be ensured when preparing the infusion.‍‍‍‍‍‍​​​‍​​​​​​ Preparation of BLINCYTO should be: - performed under aseptic conditions by trained personnel in accordance with good practice rules especially with respect to the aseptic preparation of parenteral products. - prepared in a laminar flow hood or biological safety cabinet using standard precautions for the safe handling of intravenous agents. It is very important that the instructions for preparation and administration provided in this section are strictly followed to minimise medication errors (including underdose and overdose). Other instructions • BLINCYTO is compatible with polyolefin, PVC non-di-ethylhexylphthalate (non‑DEHP), or ethyl vinyl acetate (EVA) infusion bags/pump cassettes. • At the end of infusion, any unused medicinal product or waste material should be disposed of in accordance with local requirements. Preparation of the solution for infusion These supplies are also required, but not included in the package • Sterile single-use disposable syringes • 21‑23 gauge needle(s) (recommended) • Water for injections • Infusion bag with 250 mL sodium chloride 9 mg/mL (0.9%) solution for injection; o To minimise the number of aseptic transfers, use a 250 mL pre-filled infusion bag. BLINCYTO dose calculations are based on a usual overfill volume of 265 to 275 mL sodium chloride 9 mg/mL (0.9%) solution for injection. o Use only polyolefin, PVC non-di-ethylhexylphthalate (non‑DEHP), or ethyl vinyl acetate (EVA) infusion bags/pump cassettes. • Polyolefin, PVC non‑DEHP, or EVA intravenous tubing with a sterile, non-pyrogenic, low protein-binding 0.2 micrometre in-line filter. o Ensure that the tubing is compatible with the infusion pump. Reconstitute BLINCYTO with water for injections. Do not reconstitute BLINCYTO vials with the solution (stabiliser). To prime the intravenous tubing, use only the solution in the bag containing the FINAL prepared BLINCYTO solution for infusion. Do not prime with sodium chloride 9 mg/mL (0.9%) solution for injection. Reconstitution of BLINCYTO 1. Determine the number of BLINCYTO vials needed for a dose and infusion duration. 2. Using a syringe, reconstitute each vial of BLINCYTO powder for concentrate using 3 mL of water for injections. Direct the water along the walls of the BLINCYTO vial and not directly on the lyophilized powder. • Do not reconstitute BLINCYTO powder for concentrate with the solution (stabiliser). • The addition of water for injections to the powder for concentrate results in a total volume of 3.08 mL for a final BLINCYTO concentration of 12.5 mcg/mL. 3. Gently swirl contents to avoid excess foaming. • Do not shake. 4. Visually inspect the reconstituted solution for particulate matter and discolouration during reconstitution and prior to preparing infusion bag. The resulting solution should be clear to slightly opalescent, colourless-to-slightly yellow. • Do not use if the solution is cloudy or has precipitated. Preparation of BLINCYTO infusion bag Verify the prescribed dose and infusion duration for each BLINCYTO infusion bag. To minimise errors, use the specific volumes described in Tables 19 and 20 to prepare the BLINCYTO infusion bag . • Table 20 for patients weighing greater than or equal to 45 kg • Table 21 for patients weighing less than 45 kg 1. Use an infusion bag pre-filled with 250 mL sodium chloride 9 mg/mL (0.9%) solution for injection that usually contains a total volume of 265 to 275 mL. 2. To coat the infusion bag, using a syringe, aseptically transfer 5.5 mL of the solution (stabiliser) to the infusion bag. Gently mix the contents of the bag to avoid foaming. Discard the remaining solution (stabiliser) 3. Using a syringe, aseptically transfer the required volume of reconstituted BLINCYTO solution into the infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for injection and the solution (stabiliser). Gently mix the contents of the bag to avoid foaming. • Refer to table 20 for patients weighing greater than or equal to 45 kg for the specific volume of reconstituted BLINCYTO. • Refer to table 21 for patients weighing less than 45 kg (dose based on BSA) for the specific volume of reconstituted BLINCYTO. • Discard the vial containing any unused BLINCYTO reconstituted solution 4. Remove air from the infusion bag . This is particularly important for use with an ambulatory infusion pump. 5. Under aseptic conditions, attach the intravenous tubing to the infusion bag with the sterile 0.2 micron in-line filter. Ensure that the intravenous tubing is compatible with the infusion pump. 6. Prime the intravenous infusion line only with the solution in the bag containing the FINAL prepared BLINCYTO solution for infusion. 7. Store at refrigerated 2°C ‑ 8°C if not used immediately. Table 20. For patients weighing greater than or equal to 45 kg: volumes of sodium chloride 9 mg/mL (0.9%) solution for injection, solution (stabiliser), and reconstituted BLINCYTO to add to infusion bag Sodium chloride 9 mg/mL (0.9%) solution for injection (starting volume) 250 mL (usual overfill volume of 265 to 275 mL) Solution (stabiliser) (fixed volume for 24, 48, 72, and 96‑hour infusion durations) 5.5 mL Infusion duration Dose Infusion rate Reconstituted BLINCYTO Volume Vials 24 hours 9 mcg/day 10 mL/hour 0.83 mL 1 28 mcg/day 10 mL/hour 2.6 mL 1 48 hours 9 mcg/day 5 mL/hour 1.7 mL 1 28 mcg/day 5 mL/hour 5.2 mL 2 72 hours 9 mcg/day 3.3 mL/hour 2.5 mL 1 28 mcg/day 3.3 mL/hour 8 mL 3 96 hours 9 mcg/day 2.5 mL/hour 3.3 mL 2 28 mcg/day 2.5 mL/hour 10.7 mL 4 Table 21. For patients weighing less than 45 kg: volumes of sodium chloride 9 mg/mL (0.9%) solution for injection, solution (stabiliser), and reconstituted BLINCYTO to add to infusion bag Sodium chloride 9 mg/mL (0.9%) solution for injection (starting volume) 250 mL (usual overfill volume of 265 to 275 mL) Solution (stabiliser) (fixed volume for 24, 48, 72, and 96‑hour infusion durations) 5.5 mL Infusion duration Dose Infusion rate BSA* (m 2 ) Reconstituted BLINCYTO Volume Vials 24 hours 5 mcg/m 2 /day 10 mL/hour 1.5 – 1.59 0.7 mL 1 1.4 – 1.49 0.66 mL 1 1.3 – 1.39 0.61 mL 1 1.2 – 1.29 0.56 mL 1 1.1 – 1.19 0.52 mL 1 1 – 1.09 0.47 mL 1 0.9 – 0.99 0.43 mL 1 0.8 – 0.89 0.38 mL 1 0.7 – 0.79 0.33 mL 1 0.6 – 0.69 0.29 mL 1 0.5 – 0.59 0.24 mL 1 0.4 – 0.49 0.2 mL 1 24 hours 15 mcg/m 2 /day 10 mL/hour 1.5 – 1.59 2.1 mL 1 1.4 – 1.49 2 mL 1 1.3 – 1.39 1.8 mL 1 1.2 – 1.29 1.7 mL 1 1.1 – 1.19 1.6 mL 1 1 – 1.09 1.4 mL 1 0.9 – 0.99 1.3 mL 1 0.8 – 0.89 1.1 mL 1 0.7 – 0.79 1 mL 1 0.6 – 0.69 0.86 mL 1 0.5 – 0.59 0.72 mL 1 0.4 – 0.49 0.59 mL 1 48 hours 5 mcg/m 2 /day 5 mL/hour 1.5 – 1.59 1.4 mL 1 1.4 – 1.49 1.3 mL 1 1.3 – 1.39 1.2 mL 1 1.2 – 1.29 1.1 mL 1 1.1 – 1.19 1 mL 1 1 – 1.09 0.94 mL 1 0.9 – 0.99 0.85 mL 1 0.8 – 0.89 0.76 mL 1 0.7 – 0.79 0.67 mL 1 0.6 – 0.69 0.57 mL 1 0.5 – 0.59 0.48 mL 1 0.4 – 0.49 0.39 mL 1 48 hours 15 mcg/m 2 /day 5 mL/hour 1.5 – 1.59 4.2 mL 2 1.4 – 1.49 3.9 mL 2 1.3 – 1.39 3.7 mL 2 1.2 – 1.29 3.4 mL 2 1.1 – 1.19 3.1 mL 2 1 – 1.09 2.8 mL 1 0.9 – 0.99 2.6 mL 1 0.8 – 0.89 2.3 mL 1 0.7 – 0.79 2 mL 1 0.6 – 0.69 1.7 mL 1 0.5 – 0.59 1.4 mL 1 0.4 – 0.49 1.2 mL 1 72 hours 5 mcg/m 2 /day 3.3 mL/hour 1.5 – 1.59 2.1 mL 1 1.4 – 1.49 2 mL 1 1.3 – 1.39 1.8 mL 1 1.2 – 1.29 1.7 mL 1 1.1 – 1.19 1.6 mL 1 1 – 1.09 1.4 mL 1 0.9 – 0.99 1.3 mL 1 0.8 – 0.89 1.1 mL 1 0.7 – 0.79 1 mL 1 0.6 – 0.69 0.86 mL 1 0.5 – 0.59 0.72 mL 1 0.4 – 0.49 0.59 mL 1 72 hours 15 mcg/m 2 /day 3.3 mL/hour 1.5 – 1.59 6.3 mL 3 1.4 – 1.49 5.9 mL 3 1.3 – 1.39 5.5 mL 2 1.2 – 1.29 5.1 mL 2 1.1 – 1.19 4.7 mL 2 1 – 1.09 4.2 mL 2 0.9 – 0.99 3.8 mL 2 0.8 – 0.89 3.4 mL 2 0.7 – 0.79 3 mL 2 0.6 – 0.69 2.6 mL 1 0.5 – 0.59 2.2 mL 1 0.4 – 0.49 1.8 mL 1 96 hours 5 mcg/m 2 /day 2.5 mL/hour 1.5 – 1.59 2.8 mL 1 1.4 – 1.49 2.6 mL 1 1.3 – 1.39 2.4 mL 1 1.2 – 1.29 2.3 mL 1 1.1 – 1.19 2.1 mL 1 1 – 1.09 1.9 mL 1 0.9 – 0.99 1.7 mL 1 0.8 – 0.89 1.5 mL 1 0.7 – 0.79 1.3 mL 1 0.6 – 0.69 1.2 mL 1 0.5 – 0.59 0.97 mL 1 0.4 – 0.49 0.78 mL 1 96 hours 15 mcg/m 2 /day 2.5 mL/hour 1.5 – 1.59 8.4 mL 3 1.4 – 1.49 7.9 mL 3 1.3 – 1.39 7.3 mL 3 1.2 – 1.29 6.8 mL 3 1.1 – 1.19 6.2 mL 3 1 – 1.09 5.7 mL 3 0.9 – 0.99 5.1 mL 2 0.8 – 0.89 4.6 mL 2 0.7 – 0.79 4 mL 2 0.6 – 0.69 3.4 mL 2 0.5 – 0.59 2.9 mL 2 0.4 – 0.49 2.3 mL 1 BSA = body surface area *The safety of the administration of BLINCYTO for BSA of less than 0.4 m 2 has not been established.