Xenpozyme Dosage

Generic name: OLIPUDASE ALFA 20mg in 5.1mL
Dosage form: injection, powder, lyophilized, for solution
Drug class: Lysosomal enzymes

Medically reviewed by Drugs.com. Last updated on Dec 12, 2023.

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.

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)].

Premedication

Prior to XENPOZYME administration, consider premedicating with antihistamines, antipyretics, and/or corticosteroids [see Warnings and Precautions (5.1, 5.2)].

Medical Support

Appropriate medical support measures including cardiopulmonary resuscitation equipment should be readily available during XENPOZYME administration [see Warnings and Precautions (5.1)].

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

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 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.

Table 1: XENPOZYME Dose Escalation Regimen for Adult Patients*
Adult Patients (18 years and older)
* Use actual body weight for patients with a BMI less than or equal to 30. For patients with a BMI greater than 30, calculate adjusted body weight (kg) = (actual height in m)2 × 30 [see Dosage and Administration (2.1)]. † The dose escalation phase includes the first 3 mg/kg dose.
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)

Maintenance Phase

The recommended maintenance dosage of XENPOZYME in adults is 3 mg/kg via intravenous infusion every 2 weeks.

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.

Table 2: XENPOZYME Dose Escalation Regimen for Pediatric Patients*
Pediatric Patients (0 to 17 years)
* Use actual body weight for patients with a BMI less than or equal to 30. For patients with a BMI greater than 30, calculate adjusted body weight (kg) = (actual height in m)2 × 30 [see Dosage and Administration (2.1)]. † The dose escalation phase includes the first 3 mg/kg dose.
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)

Maintenance Phase

The recommended maintenance dosage of XENPOZYME in pediatric patients is 3 mg/kg via intravenous infusion every 2 weeks.

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.

Table 3: Dosing Recommendations for XENPOZYME Missed Doses*
Consecutive Missed Doses In:	Escalation Phase	Maintenance Phase
* At scheduled infusion after a missed dose, if the dose administered is 0.3 or 0.6 mg/kg, administer that dose twice as per Table 1 and 2.
1 missed dose	First dose after a missed dose: Administer last tolerated dose Second and subsequent doses after missed dose: Resume dose escalation at next infusion according to Table 1 for adult patients or Table 2 for pediatric patients	First and subsequent doses after missed dose: Administer maintenance dose
2 consecutive missed doses	First dose after missed dose: Administer 1 dose below last tolerated dose Second and subsequent doses after missed dose: Resume dose escalation according to Table 1 for adults or Table 2 for pediatric patients	First dose after missed dose: Administer 1 dose below the maintenance dose Second and subsequent doses after missed dose: Resume the maintenance dose
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 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*
	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
* Use actual or adjusted body weight per patient BMI. Refer to section 2. [see Dosage and Administration (2.2, 2.3)]. † Volume will vary to achieve a final concentration of 0.1 mg/mL
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 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.

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.
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

Table 6: XENPOZYME Infusion Rates for Pediatric Patients
Dose	Infusion rate
Dose	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.