2 DOSAGE AND ADMINISTRATION See Full Prescribing Information for important recommendations prior to XENPOZYME treatment initiation. 1 mg/kg administered as an intravenous infusion. 03 mg/kg administered as an intravenous infusion. 3 ) See Full Prescribing Information for the recommended dose escalation and maintenance dosage, dosage modifications to reduce the risk of adverse reactions, and preparation and administration instructions.
1 Important Recommendations Prior to XENPOZYME Treatment Initiation Therapy with XENPOZYME should be directed in consultation with physicians knowledgeable in the management of ASMD. In order to avoid dosing errors including overdosage [see Overdosage (10) ] , follow all instructions for dosage and administration.
3) ] . 3) ] . 2) ] . 1) ] . 3) ] are based on body weight as follows for patients with a body mass index (BMI): Less than or equal to 30, the dosage is based on actual body weight (kg) Greater than 30, the dosage is based on adjusted body weight (kg).
1 mg/kg. 3) ] . Administer XENPOZYME via intravenous infusion every 2 weeks.
Table 1:
XENPOZYME Dose Escalation Regimen for Adult Patients Use actual body weight for patients with a BMI less than or equal to 30. 1) ] . 6 mg/kg Sixth dose (Week 10) 1 mg/kg Seventh dose (Week 12) 2 mg/kg Eighth dose (Week 14) The dose escalation phase includes the first 3 mg/kg dose.
3 mg/kg (recommended maintenance dose) Maintenance Phase The recommended maintenance dosage of XENPOZYME in adults is 3 mg/kg via intravenous infusion every 2 weeks. 03 mg/kg. 3) ] . Administer XENPOZYME via intravenous infusion every 2 weeks.
Table 2:
XENPOZYME Dose Escalation Regimen for Pediatric Patients Use actual body weight for patients with a BMI less than or equal to 30. 1) ] . 6 mg/kg Seventh dose (Week 12) 1 mg/kg Eighth dose (Week 14) 2 mg/kg Ninth dose (Week 16) The dose escalation phase includes the first 3 mg/kg dose.
3 mg/kg (recommended maintenance dose) Maintenance Phase The recommended maintenance dosage of XENPOZYME in pediatric patients is 3 mg/kg via intravenous infusion every 2 weeks. 4 Missed Doses A dose is considered missed when it is not administered within 3 days of the scheduled date.
When a dose of XENPOZYME is missed, refer to Table 3. Follow the instructions in the "Escalation Phase" or "Maintenance Phase" depending on which phase the patient misses the dose. 6 mg/kg, administer that dose twice as per Table 1 and 2.
1 mg/kg and follow Table 1. 03 mg/kg and follow Table 2. 3 mg/kg and follow Table 1 for adult patients or Table 2 for pediatric patients. 1 mg/kg and dose escalate according to Table 1. 03 mg/kg and dose escalate according to Table 2. 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. 2) ] . 3) ] . 6 Preparation Instructions Use aseptic technique during preparation.
Reconstitute and dilute XENPOZYME in the following manner:
Reconstitution and Dilution Instructions 1. 3) ] . 2. Remove XENPOZYME vials from refrigeration and set aside for approximately 20 to 30 minutes to allow vials to reach room temperature. 3. 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. 9% Sodium Chloride Injection, USP in a syringe or infusion bag depending on the volume of infusion (see Table 4 ).
1 mg/mL (see Table 4 ). 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.
9% Sodium Chloride Injection, USP to obtain the required total infusion volume (avoid foaming within the syringe). 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.
Table 4:
XENPOZYME Infusion Volumes for Pediatric and Adult Patients Based on Body Weight Use actual or adjusted body weight per patient BMI. Refer to section 2. 3) ] . 7 Administration Instructions Prior to administration, inspect the syringe or infusion bag for foaming.
If foaming is present, let foam dissipate before administering XENPOZYME. 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.
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.
Table 5:
XENPOZYME Infusion Rates for Adult Patients Dose Infusion Rate step 1 step 2 step 3 step 4 NA: Not applicable. Start infusion at step 1 and in absence of infusion-associated reaction increase infusion rate sequentially per the steps of infusion.
33 mL/hour Table 6: XENPOZYME Infusion Rates for Pediatric Patients Dose Infusion rate step 1 step 2 step 3 step 4 NA: Not applicable. Start infusion at step 1 and in absence of infusion-associated reactions increase infusion rate sequentially per the steps of infusion.
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.