Acid Sphingomyelinase Deficiency (ASMD) in patients with type A/B or type B

The rapid metabolism of accumulated sphingomyelin (SM) by olipudase alfa generates pro-inflammatory breakdown products, which may induce infusion-associated reactions and/or transient liver enzyme elevations. A dose escalation regimen can minimise the majority of these adverse events.

Olipudase alfa dose is based on the actual body weight for patient with a body mass index (BMI) ≤30 or an optimal body weight for patient with a BMI >30 (see section for patients with a BMI >30).

Dose escalation phase

he recommended starting dose of olipudase alfa is 0.03 mg/kg* for paediatric patients, and the dose should be subsequently increased according to the dose escalation regimen presented in Table 2.

Table 2. Dose escalation regimen in paediatric patients:

^* Actual body weight will be used for patients with a BMI ≤30. For patients with a BMI >30, an optimal body weight will be used as described below.

Maintenance phase

The recommended maintenance dose of olipudase alfa is 3 mg/kg* every 2 weeks.

^* Actual body weight will be used for patients with a BMI ≤30. For patients with a BMI >30, an optimal body weight will be used as described below.

Patients with BMI >30

In paediatric patients with a body mass index (BMI) >30, the body weight that is used to calculate the dose of olipudase alfa is estimated via the following method (for dose escalation and maintenance phases).

Body weight (kg) to be used for dose calculation = 30 × (actual height in m²)

Example:

For a patient with:

BMI of 38
body weight of 110 kg
height of 1.7 m.

The dose to be administered will be calculated using a body weight of 30 × 1.72 = 86.7 kg.

Missed doses

A dose is considered missed when not administered within 3 days of the scheduled date. When a dose of olipudase alfa is missed, the next dose should be administered as described below as soon as possible. Thereafter, administrations should be scheduled every 2 weeks from the date of the last administration.

During the dose escalation phase:

• If 1 infusion is missed: the last tolerated dose should be administered, before resuming dose escalation according to the regimen in paediatric patients (Table 2).
• If 2 consecutive infusions are missed: 1 dose level lower than the last tolerated dose (using a minimal dose of 0.3 mg/kg) should be administered, before resuming dose escalation according to Table 2.
• If 3 or more consecutive infusions are missed: dose escalation should be resumed at 0.3 mg/kg according to Table 2. At the next scheduled infusion after a missed dose, if the dose administered is 0.3 or 0.6 mg/kg, that dose should be administered twice as per Table 2.

During the maintenance phase:

• If 1 maintenance infusion is missed: the maintenance dose should be administered and the treatment schedule adjusted accordingly.
• If 2 consecutive maintenance infusions are missed: 1 dose below the maintenance dose (i.e. 2 mg/kg) should be administered. Then for subsequent infusions, the maintenance dose (3 mg/kg) every 2 weeks should be administered.
• If 3 or more consecutive maintenance infusions are missed: dose escalation should be resumed at 0.3 mg/kg according to Table 2.

Olipudase alfa is for intravenous use only. Infusions should be administered in a stepwise manner preferably using an infusion pump.

After reconstitution and dilution, the solution is administered as an intravenous infusion. The infusion rates must be incrementally increased during the infusion only in the absence of infusion-associated reactions. The infusion rate and duration of infusion (+/- 5 min) for each step of infusion are detailed in the following table.

Infusion rates and duration of infusion in paediatric patients:

hr: hour; min: minute; NA: Not applicable

Signs and symptoms of infusion-associated reactions (IARs), such as headache, urticaria, pyrexia, nausea and vomiting, and other signs or symptoms of hypersensitivity should be monitored during the infusion. Depending on the symptom severity, the infusion may be slowed, paused or discontinued and appropriate medical treatment initiated as needed.

In case of severe hypersensitivity and/or anaphylactic reaction, treatment with olipudase alfa should be discontinued immediately.

At the end of infusion (once the syringe or infusion bag is empty), the infusion line should be flushed with sodium chloride 9 mg/mL (0.9%) solution for injection using the same infusion rate as the one used for the last part of the infusion.