AVLAYAH Powder for solution for injection Ref.[116748] Active ingredients: Tividenofusp alfa

Source: FDA, National Drug Code (US)  Revision Year: 2026 

1. Indications and Usage

AVLAYAH is indicated for the treatment of neurologic manifestations of Hunter syndrome (Mucopolysaccharidosis type II, MPS II) when initiated in presymptomatic or symptomatic pediatric patients weighing at least 5 kg prior to advanced neurologic impairment.

This indication is approved under accelerated approval based on the reduction of cerebrospinal fluid heparan sulfate [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Limitations of Use:

AVLAYAH is not recommended for use in combination with other enzyme replacement therapies for the treatment of Hunter syndrome.

2. Dosage and Administration

2.1 Important Recommendations Prior to AVLAYAH Treatment Initiation

Administer AVLAYAH under the supervision of a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis [see Warnings and Precautions (5.1)].

Initiate AVLAYAH in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment [see Warnings and Precautions (5.1)].

Consider pretreatment with antihistamines, antipyretics, and/or corticosteroids [see Warnings and Precautions (5.1, 5.2)].

Obtain a baseline hemoglobin value in all patients [see Warnings and Precautions (5.3)].

2.2 Recommended Dosage

The recommended starting dosage of AVLAYAH for pediatric patients weighing at least 5 kg is 3 mg/kg administered once weekly via intravenous infusion.

To reduce the risk of infusion-associated reactions (IARs), follow the dose escalation regimen in Table 1 [see Warnings and Precautions (5.2)]. Administer each dosage level for at least 4 weeks before escalating to the next dosage level.

The recommended maintenance dosage of AVLAYAH for pediatric patients who weigh at least 5 kg is 15 mg/kg administered once weekly via intravenous infusion.

Table 1. Recommended AVLAYAH Dosage for Pediatric Patients Weighing ≥5 kga:

Dosing WeekDosage Level
Week 1 to Week 43 mg/kg once weekly
Week 5 to Week 87.5 mg/kg once weekly
Week 9 and beyond15 mg/kg once weekly
(maintenance dosage)

a Do not escalate the dosage level if the current dosage level is not tolerated [see Dosage and Administration (2.3)].

2.3 Dosage and Administration Modifications and Monitoring

In the event of a severe hypersensitivity reaction (e.g., anaphylaxis) or a severe IAR, discontinue AVLAYAH and immediately initiate appropriate medical treatment. Consider the risks and benefits of re-administering AVLAYAH following a severe reaction. If the decision is made to re-administer AVLAYAH, re-evaluate pre-treatment medications, slow the infusion rate, and/or reduce the AVLAYAH dose. Monitor patients closely upon re-administration of AVLAYAH [see Warnings and Precautions (5.1, 5.2)].

In the event of a mild to moderate hypersensitivity reaction or a mild to moderate IAR, temporarily hold the infusion and/or reduce the infusion rate by at least 50% from the current rate, then titrate up to the recommended infusion rate as tolerated (see Table 3) [see Warnings and Precautions (5.1, 5.2)].

If the dose has been decreased due to an adverse reaction, evaluate when it is appropriate to increase the dose and follow the recommended dose escalation regimen to achieve the maintenance dosage of 15 mg/kg once weekly [see Dosage and Administration (2.2)].

2.4 Preparation Instructions

Prepare AVLAYAH using polypropylene syringes and infusion bags composed of polyvinylchloride (PVC) or polyolefins (PO) such as polyethylene (PE) and polypropylene (PP); infusion sets composed of PVC or PE; and filter membranes composed of polyethersulfone (PES).

Use aseptic technique during preparation. Reconstitute and dilute AVLAYAH in the following manner:

Reconstitution Instructions

  • Determine the number of AVLAYAH vials to be reconstituted based on the patient's weight in kg and the recommended dosage [see Dosage and Administration (2.2)]. Round the number of vials up to the next whole number.
  • Remove the required number of AVLAYAH vials from the refrigerator and set aside for 15 to 30 minutes to allow vials to reach room temperature 20°C to 25°C (68°F to 77°F). Do not use an external heat source.
  • Reconstitute each vial with 5.2 mL of Sterile Water for Injection by slowly injecting the diluent onto the inside wall of each vial to avoid foaming. Do not inject forcefully or directly onto the lyophilized powder.
  • Gently swirl each vial to completely dissolve the lyophilized powder. Do not invert or shake the vial. Each reconstituted vial will yield a concentration of 30 mg/mL of tividenofusp alfa-eknm.
  • Visually inspect the reconstituted solution in the vial(s) for particulate matter and discoloration. The solution should be clear to slightly opalescent and colorless to slightly brown/yellow, and free of visible particles. Discard the reconstituted AVLAYAH solution if it is discolored, cloudy, or contains visible particulates.

Dilution Instructions

Dilute the reconstituted AVLAYAH solution with 0.9% Sodium Chloride Injection to a final concentration between 0.6 mg/mL and 15 mg/mL [see Dosage and Administration (2.6)] in an infusion bag as follows:

  • Determine the appropriate volume of the infusion bag based on patient weight (see Table 2) and determine the volume of reconstituted AVLAYAH solution required for the calculated dose.
  • Prepare the infusion bag:
    • Remove any airspace within the infusion bag.
    • Withdraw a volume of 0.9% Sodium Chloride Injection from the infusion bag equivalent to the volume of AVLAYAH to be added.
  • Slowly withdraw the required volume of reconstituted solution from the AVLAYAH vial(s). Discard unused portion after each use; do not administer more than one dose from the vial.
  • Slowly inject AVLAYAH into the infusion bag of 0.9% Sodium Chloride Injection. Avoid introducing air into the infusion bag.
  • Gently invert the infusion bag to mix the solution. Do not shake.

Table 2. Recommended Total Infusion Volumes for AVLAYAH Based on Patient Weight and Dose:

Patient Weight RangeAVLAYAH Dose
3 mg/kg7.5 mg/kg15 mg/kg
Recommended Total Infusion Volumesa
5 kg to less than 10 kg25 mL25 mL or 50 mL25 mL or 50 mL
10 kg to less than 20 kg25 mL or 50 mL25 mL, 50 mL, or 100 mL25 mL, 50 mL, or 100 mL
20 kg to less than 25 kg25 mL, 50 mL, or 100 mL25 mL, 50 mL, or 100 mL25 mL, 50 mL, or 100 mL
25 kg to less than 50 kg25 mL, 50 mL, or 100 mL25 mL, 50 mL, or 100 mL50 mL or 100 mL
50 kg to less than 60 kg50 mL or 100 mL50 mL or 100 mL100 mL
60 kg to less than 100 kg50 mL, 100 mL, or 250 mL50 mL, 100 mL, or 250 mL100 mL or 250 mL
100 kg or greater100 mL or 250 mL100 mL or 250 mL250 mL

a Ensure the final concentration of the diluted AVLAYAH solution is between 0.6 mg/mL and 15 mg/mL.

2.5 Storage Instructions for the Reconstituted and Diluted Solutions

Reconstituted Solution:

Do not shake. Do not freeze.

If the reconstituted AVLAYAH vials are not diluted immediately, store at controlled room temperature between 20°C to 25°C (68°F to 77°F) for up to 4 hours.

Diluted Solution:

If the diluted AVLAYAH solution is not used immediately, store refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours.

After removal of the diluted solution from the refrigerator:

  • Completely infuse within 10 hours.
  • Do not store back into the refrigerator.

Discard the diluted solution if refrigerated more than 24 hours or if the diluted solution cannot be completely infused within 10 hours after removal from the refrigerator.

Do not shake. Do not freeze.

2.6 Administration Instructions

1) Administer AVLAYAH without delay as an intravenous infusion using only infusion sets composed of PVC or PE and filter membranes composed of PES.

2) If the diluted solution was refrigerated, allow solution to equilibrate to room temperature prior to infusion.

3) Use a dedicated infusion line equipped with a sterile, non-pyrogenic, low protein-binding, 0.2 micron, in-line filter to administer AVLAYAH.

4) Infuse AVLAYAH over approximately 4 hours per the recommended infusion rates in Table 3. Increase the initial infusion rate to the subsequent infusion rate every hour based on patient tolerance. Total infusion time should not exceed 8 hours.

5) In the absence of hypersensitivity reactions and IARs, AVLAYAH infusion rate can be gradually increased to complete the infusion in a minimum infusion duration of 3 hours based on patient tolerance.

Table 3. AVLAYAH Infusion Rate Based on Total Infusion Volume:

Total Infusion VolumeInfusion Duration
First hourSecond hourThird hour to completion
Infusion Rate (mL/hour)
25 mL2.5 mL/hour5 mL/hour10 mL/hour
50 mL5 mL/hour10 mL/hour20 mL/hour
100 mL10 mL/hour20 mL/hour40 mL/hour
250 mL25 mL/hour50 mL/hour100 mL/hour

6) At the end of the infusion, flush the infusion line with 0.9% Sodium Chloride Injection using the final infusion rate that was used to administer AVLAYAH.

7) Do not infuse AVLAYAH in the same intravenous infusion line with other products.

Home Infusion:

If a patient reaches and tolerates the maintenance AVLAYAH dosage, the patient may receive home infusion under the supervision of a healthcare provider [see Dosage and Administration (2.1, 2.7)]. The decision to have patients move to home infusion should be made after evaluation and recommendation by a healthcare provider.

In case of a missed dose or an IAR, contact a healthcare provider.

2.7 Missed Dose

If an AVLAYAH dose is missed, skip the missed dose. Do not double a dose to compensate for a missed dose. Restart AVLAYAH treatment as soon as possible, maintaining the one-week interval between infusions thereafter. Resume dosing at the last administered dosage following the recommended infusion rate [see Dosage and Administration (2.6)].

16.2. Storage and Handling

Store refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Do not shake.

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