Olipudase alfa

Dosage and Administration Modifications and Monitoring In the event of a severe hypersensitivity reaction (e.g., anaphylaxis) or a severe infusion-associated reaction (IAR), immediately discontinue XENPOZYME administration and initiate appropriate medical treatment [see Warnings and Precautions (5.1 , 5.2) ] . In the event of a mild to moderate hypersensitivity reaction or a mild to moderate IAR, consider temporarily holding or slowing the infusion rate, and/or reducing the XENPOZYME dose.

If dose is reduced, re-escalate following dose escalation described in Tables 1 and 2 for adult and pediatric patients, respectively [see Warnings and Precautions (5.1 , 5.2) ] . If transaminase levels are elevated above baseline and >2 times the ULN prior to the next scheduled administration, the XENPOZYME dose can be adjusted (prior dose repeated or reduced) or treatment can be temporarily withheld until the liver transaminases return to the patient's baseline value [see Warnings and Precautions ] .

Preparation Instructions Use aseptic technique during preparation. Reconstitute and dilute XENPOZYME in the following manner: Reconstitution and Dilution Instructions 1. Determine the number of XENPOZYME vials to be reconstituted based on the calculated dose [see Dosage and Administration (2.2 , 2.3) ] . 2. Remove XENPOZYME vials from refrigeration and set aside for approximately 20 to 30 minutes to allow vials to reach room temperature. 3.

Reconstitute each vial with: 1.1 mL of Sterile Water for Injection, USP into the 4 mg vial 5.1 mL of Sterile Water for Injection, USP into the 20 mg vial by directing the diluent flow to the inside wall of the vial to avoid foaming. 4. Gently roll and tilt vial(s) to reconstitute XENPOZYME and avoid foaming. Each reconstituted vial will yield a 4 mg/mL clear, colorless solution. 5.

Visually inspect the reconstituted solution in the vials for particulate matter and discoloration. The solution should be clear and colorless. Discard if the solution is discolored or if visible particulate matter is present. 6. Withdraw the required volume of XENPOZYME from the vial(s) and dilute the XENPOZYME solution for infusion with 0.9% Sodium Chloride Injection, USP in a syringe or infusion bag depending on the volume of infusion (see Table 4 ).

For patients who weigh less than 10 kg receiving 0.03 mg/kg and 0.1 mg/kg and patients who weigh between 10 to 20 kg receiving 0.03 mg/kg dose, the volume of infusion will vary to achieve a fixed final concentration of 0.1 mg/mL (see Table 4 ). Prepare the required dose diluted to a final concentration of 0.1 mg/mL in a syringe for infusion.

For all other patient weights and doses, the final concentration will vary to achieve a fixed total volume (see Table 4 ). - For total volume less than or equal to 20 mL prepare a syringe for infusion: Inject the required volume of the reconstituted XENPOZYME solution (4 mg/mL) from step 3 slowly down the inside wall of the syringe.

Add slowly the quantity sufficient of 0.9% Sodium Chloride Injection, USP to obtain the required total infusion volume (avoid foaming within the syringe). - For a total volume of greater than or equal to 50 mL prepare an infusion bag : Add slowly the required volume of the reconstituted XENPOZYME solution (4 mg/mL) from step 3 into the appropriate size 0.9% Sodium Chloride Injection, USP infusion bag (avoid foaming within the bag) to achieve a fixed total volume per Table 4. 7.

Gently invert the syringe or the infusion bag to mix. Do not shake. Because this is a protein solution, slight flocculation (described as thin translucent fibers) occurs occasionally after dilution. 8. Vials are for single dose only. Discard any unused solution. Storage and Handling of the Reconstituted and Diluted Solutions If the reconstituted XENPOZYME vials are not used immediately, store refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours or at controlled room temperature at 20°C to 25°C (68°F to 77°F) for up to 6 hours.

Discard the unused XENPOZYME reconstituted solution after 24 hours if stored refrigerated or 6 hours if stored at controlled room temperature. If the diluted solution is not used immediately, refrigerate the diluted solution at 2°C to 8°C (36°F to 46°F) for up to 24 hours or store at room temperature at 20°C to 25°C (68°F to 77°F) for up to 12 hours (inclusive of infusion time), or discard.

Do not freeze. [See table below.] 0.6 mg/kg 10 mL 20 mL 50 mL 100 mL 1 mg/kg 20 mL 50 mL 100 mL 100 mL 2 mg/kg 50 mL 75 mL 200 mL 100 mL 3 mg/kg 50 mL 100 mL 250 mL 100 mL

Administration Instructions Prior to administration, inspect the syringe or infusion bag for foaming. If foaming is present, let foam dissipate before administering XENPOZYME. Use a low-protein binding, 0.2 micron, in-line filter during administration. The following materials can be used: polyolefin or polyvinylchloride (PVC) with DEHP for infusion bags, polypropylene for syringes, polyurethane or PVC DEHP-free for infusion sets and polyethersulfone or polytetrafluoroethylene for in-line filters.

Infuse XENPOZYME using the infusion rates described in Table 5 and Table 6. In absence of infusion-associated reactions, increase infusion rate per the steps of infusion as indicated (+/- 5 minutes). Each step of infusion will last for 20 minutes with the exception of the final step which should last until completion of the infusion volume.

At the end of the infusion, flush the infusion line with 0.9% Sodium Chloride Injection, USP using the same infusion rate as the one used for the last part of the infusion. Do not infuse XENPOZYME in the same intravenous line with other products. [See table below.] [See table below.] 0.1 mg/kg/hour for the full length of the infusion NA NA NA 0.1 mg/kg 0.1 mg/kg/hour 0.3 mg/kg/hour NA NA 0.3 mg/kg 0.1 mg/kg/hour 0.3 mg/kg/hour 0.6 mg/kg/hour NA 0.6 mg/kg 0.1 mg/kg/hour 0.3 mg/kg/hour 0.6 mg/kg/hour 1 mg/kg/hour 1 mg/kg 2 mg/kg 3 mg/kg Home Infusion Home administration under the supervision of a healthcare provider may be considered for patients on maintenance dose [see Dosage and Administration (2.2 , 2.3) ] and who are tolerating their infusion well.

The decision to have patients moved to home infusion should be made after evaluation and recommendation by a physician. The dose and infusion rate used in the home setting should remain the same as were used in the supervised clinical setting and should not be changed without supervision of a physician. In case of missed dose(s) or delayed infusion, contact a physician as subsequent infusions may occur in a supervised clinical setting.