Drug Detail:Xenpozyme (Olipudase alfa-rpcp)
Generic Name: OLIPUDASE ALFA 20mg in 5.1mL
Dosage Form: injection, powder, lyophilized, for solution
Drug Class: Lysosomal enzymes
Important Recommendations
Laboratory Testing
Before initiating XENPOZYME:
- Obtain baseline transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) levels in all patients within 1 month prior to treatment initiation [see Warnings and Precautions (5.3)].
- Verify pregnancy status in females of reproductive potential [see Use in Specific Populations (8.1, 8.3)].
Pretreatment Recommendations
Prior to XENPOZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids [see Warnings and Precautions (5.1, 5.2)].
Weight-Based Dosing Information
The recommended adult and pediatric dosages of XENPOZYME for the dose escalation and maintenance phases [see Dosage and Administration (2.2, 2.3)] 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). Calculate an adjusted body weight (kg) based on height in meters as described below:
- Adjusted body weight (kg) = (actual height in m)2 × 30
Dosing
Treatment with Xenpozyme should always be initiated via a dose escalation regimen followed by a maintenance dose. For missed doses, see Missed Doses (2.4).
In order to avoid dosing errors including overdose [see Overdosage (10)], follow all instructions for dosage and administration, including for preparation and handling, below.
Recommended Dosage in Adult Patients
Dose Escalation Phase
The recommended starting dose of XENPOZYME in adults is 0.1 mg/kg.
In order to reduce the risk of hypersensitivity and infusion-associated reactions or elevated transaminase levels, follow the dose escalation regimen in Table 1 [see Warnings and Precautions (5.1, 5.2, 5.3)].
Administer XENPOZYME via intravenous infusion every 2 weeks.
| Adult Patients (18 years and older) | |
|---|---|
|
|
| First dose (Day 1/Week 0) | 0.1 mg/kg |
| Second dose (Week 2) | 0.3 mg/kg |
| Third dose (Week 4) | 0.3 mg/kg |
| Fourth dose (Week 6) | 0.6 mg/kg |
| Fifth dose (Week 8) | 0.6 mg/kg |
| Sixth dose (Week 10) | 1 mg/kg |
| Seventh dose (Week 12) | 2 mg/kg |
| Eighth dose (Week 14)† | 3 mg/kg (recommended maintenance dose) |
Recommended Dosage in Pediatric Patients
Dose Escalation Phase
The recommended starting dose of XENPOZYME in pediatric patients is 0.03 mg/kg.
In order to reduce the risk of hypersensitivity and infusion-associated reactions or elevated liver enzyme elevations, follow the dose escalation regimen in Table 2 [see Warnings and Precautions (5.1, 5.2, 5.3)].
Administer XENPOZYME via intravenous infusion every 2 weeks.
| Pediatric Patients (0 to 17 years) | |
|---|---|
|
|
| First dose (Day 1/Week 0) | 0.03 mg/kg |
| Second dose (Week 2) | 0.1 mg/kg |
| Third dose (Week 4) | 0.3 mg/kg |
| Fourth dose (Week 6) | 0.3 mg/kg |
| Fifth dose (Week 8) | 0.6 mg/kg |
| Sixth dose (Week 10) | 0.6 mg/kg |
| Seventh dose (Week 12) | 1 mg/kg |
| Eighth dose (Week 14) | 2 mg/kg |
| Ninth dose (Week 16)† | 3 mg/kg (recommended maintenance dose) |
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.
| Consecutive Missed Doses In: | Escalation Phase | Maintenance Phase |
|---|---|---|
|
||
| 1 missed dose |
|
First and subsequent doses after missed dose: Administer maintenance dose |
| 2 consecutive missed doses |
|
|
| 3 or more consecutive missed doses | First and subsequent doses after missed doses: Resume dose escalation at 0.3 mg/kg and follow Table 1 for adults or Table 2 for pediatric patients | First and subsequent doses after missed doses: Restart dosing at 0.3 mg/kg and follow Table 1 for adult patients or Table 2 for pediatric patients |
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 (5.3)].
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 room temperature at 20°C to 25°C (68°F to 77°F) for up to 6 hours.
- If the diluted solution is not administered immediately, store refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours or at room temperature at 20°C to 25°C (68°F to 77°F) for up to 12 hours (including infusion time).
- Do not freeze.
| Pediatric Patients (0 to 17 years) | Adult patients (18 years and older) | |||
|---|---|---|---|---|
| Body Weight ≥2 kg and <10 kg) |
Body Weight ≥10 kg and <20 kg) |
Body Weight ≥20 kg |
Body Weight ≥20 kg |
|
| XENPOZYME Dose | Total Infusion Volume | |||
|
||||
| 0.03 mg/kg | Actual volume will vary† (0.6 mL to 3 mL) |
Actual volume will vary† (3 mL to 6 mL) |
5 mL | NA |
| 0.1 mg/kg | Actual volume will vary† (2 mL to 10 mL) |
5 mL | 10 mL | 20 mL |
| 0.3 mg/kg | 5 mL | 10 mL | 20 mL | 100 mL |
| 0.6 mg/kg | 10 mL | 20 mL | 50 mL | 100 mL |
| 1.0 mg/kg | 20 mL | 50 mL | 100 mL | 100 mL |
| 2.0 mg/kg | 50 mL | 75 mL | 200 mL | 100 mL |
| 3.0 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 an in-line low protein-binding 0.2 micron 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.
| 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. | ||||
| 0.1 mg/kg | 20 mL/hour | 60 mL/hour | NA | NA |
| 0.3 to 3 mg/kg | 3.33 mL/hour | 10 mL/hour | 20 mL/hour | 33.33 mL/hour |
| 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. | ||||
| 0.03 mg/kg | 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.
Dose and infusion rates should remain constant for home administration and cannot be changed without supervision of a physician. In case of missed doses or delayed infusion, a physician should be contacted.
