2.1 Recommendations Prior to ELFABRIO Treatment

Pretreatment

• In enzyme replacement therapy (ERT)-experienced patients, if pretreatment with antihistamines, antipyretics, and/or corticosteroids was used prior to ERT administration, consider similar pretreatment with these medications before the first several ELFABRIO infusions. After 4 to 6 ELFABRIO infusions, a stepwise decrease in the pretreatment medication dose(s) and/or discontinuation of the pretreatment medication(s) may be considered if treatment with ELFABRIO was tolerated.
  
• In ERT-naïve patients, prior to ELFABRIO administration, pre-treating with antihistamines, antipyretics, and/or corticosteroids may be considered [see Warnings and Precautions (5.1, 5.2)].

Medical Support

Appropriate medical support measures including cardiopulmonary resuscitation equipment should be readily available during ELFABRIO administration.

2.2 Recommended Dosage and Administration

The recommended dosage of ELFABRIO, based on actual body weight, is 1 mg/kg administered by intravenous infusion every 2 weeks.

The initial recommended ELFABRIO infusion rates for ERT-experienced or ERT-naïve patients are based on actual body weight [see Tables 1 and 2].

If one or more doses are missed, restart ELFABRIO treatment as soon as possible, maintaining the 2 week interval between infusions thereafter. Do not double a dose to compensate for a missed dose.

2.3 Administration Modifications Due to Hypersensitivity Reactions and/or Infusion-Associated Reactions

In the event of a severe hypersensitivity reaction (e.g., anaphylaxis) or severe infusion-associated reaction (IAR), immediately discontinue ELFABRIO administration and initiate appropriate medical treatment. For additional recommendations in the event of a severe hypersensitivity reaction or IAR, 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 the infusion for 15 to 30 minutes or slowing the infusion rate by 25% to 50% [see Dosage and Administration (2.6)], and initiating appropriate medical treatment [see Warnings and Precautions (5.1, 5.2)].

• If symptoms persist despite holding or slowing the infusion, stop the infusion and monitor the patient. Consider re-initiating the infusion within 7 to 14 days at 25% to 50% of the rate at which the reaction occurred with appropriate pretreatment.
  
• If symptoms subside after holding the infusion, resume infusion at a 25% to 50% reduced rate as tolerated. Alternatively, if symptoms subside after slowing the infusion, complete infusion at the reduced rate as tolerated.
  
• Starting with the next infusion, increase the infusion rate by increments of 25% every third infusion as tolerated until the infusion rate at which the reaction occurred is reached. Closely monitor the patient.

2.4 Preparation Instructions

Use aseptic technique during preparation. Dilute ELFABRIO in the following manner:

• Determine the number of ELFABRIO vials to be diluted based on actual body weight in kg and the recommended dose [see Dosage and Administration (2.2) and Dosage Forms and Strengths (3)]. Round the number of vials up to the next whole number.
  
• Remove the appropriate number of ELFABRIO vials from the refrigerator and allow the vials to sit for 15-30 minutes at room temperature 20°C to 25°C (68°F to 77°F) before use. Do not use an external heat source to heat the product because heat may damage the product.
  
• Visually inspect the 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.
  
• Dilute the supplied ELFABRIO solution required for a dose in 0.9% Sodium Chloride Injection to a total volume based on actual body weight specified in Tables 1 and 2 below.
  
• Prior to adding the volume of ELFABRIO required for the dose, remove the equal volume of 0.9% Sodium Chloride Injection from the infusion bag.
  
• Withdraw the volume of ELFABRIO required for the dose from the vials (discard any unused solution remaining in the vial).
  
• Inject the ELFABRIO solution directly into the 0.9% Sodium Chloride Injection solution through the port of the infusion bag. Do not inject in the airspace within the infusion bag.
  
• Gently invert infusion bag to mix the solution. Avoid vigorous shaking or agitation.

2.5 Storage of the Diluted Solution

• If the diluted ELFABRIO 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. The solution must be infused within 8 hours after removal from the refrigerator, inclusive of the total infusion time, or discarded.
  ○ Store the diluted solution at room temperature at 20°C to 25°C (68°F to 77°F) for up to 8 hours. The solution must be used within 8 hours, inclusive of infusion time, or discarded.
  
• Do not freeze or shake.

2.6 Administration Instructions

Administer ELFABRIO as follows:

• Use an in-line low protein-binding, 0.2 micron, in-line filter during administration.
  
• For the initial 4-6 infusions, infuse ELFABRIO using the infusion rates described in Table 1 for ERT-experienced patients and Table 2 for ERT-naïve patients.
  
• If a patient tolerates the initial 4-6 ELFABRIO infusions, the duration of every third infusion may be decreased in decrements of 30 minutes as tolerated. The minimum recommended infusion duration is 1.5 hours.
  
• At the end of the infusion, flush the line with 0.9% Sodium Chloride Injection using the same infusion rate as the one used for the last part of the ELFABRIO infusion.
  
• Do not infuse ELFABRIO in the same intravenous line with other products.

Table 1 presents the recommended infusion rates for the initial 4-6 ELFABRIO infusions based on actual body weight for ERT-experienced patients.

1 Infusion rate may be increased if the patient tolerates the initial 4-6 infusions (see above). Infusion rate may be slowed in case of a hypersensitivity reaction or an IAR [see Dosage and Administration (2.3)].

Table 2 presents the recommended infusion rates for the initial 4-6 ELFABRIO infusions based on actual body weight for ERT-naïve patients.

1 Infusion rate may be increased if the patient tolerates the initial 4-6 infusions (see above). Infusion rate may be slowed in case of a hypersensitivity reaction or an IAR [see Dosage and Administration (2.3)].

Administration of ELFABRIO to Patients Previously Treated with ERT with an Infusion Duration Over 3 Hours

In patients previously treated with an ERT with an infusion duration over 3 hours:

• Use the same infusion rate for the ELFABRIO infusion.
  
• May decrease the duration of every third infusion after the initial 4-6 ELFABRIO infusions in decrements of 30 minutes as tolerated. The recommended minimum infusion duration of the maintenance infusion is 1.5 hours.

Home Infusion

Home administration under the supervision of a healthcare provider may be considered for patients who have reached an infusion duration that is tolerated well [see Dosage and Administration (2.1, 2.3)]. The decision to have a patient move to home infusion should be made after evaluation and recommendation by a healthcare provider.

The infusion duration should remain constant for home administration and the duration should only be decreased in a healthcare facility. In case of a missed dose or delayed infusion, a healthcare provider should be contacted.