Drug Detail:Nexviazyme (Avalglucosidase alfa [ ay-val-gloo-koe-si-dase-al-fa ])
Generic Name: AVALGLUCOSIDASE ALFA 100mg in 10mL
Dosage Form: injection, powder, lyophilized, for solution
Drug Class: Lysosomal enzymes
Recommended Dosage and Administration
- Prior to NEXVIAZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids [see Warnings and Precautions (5.1)].
- NEXVIAZYME must be reconstituted and diluted prior to use [see Dosage and Administration (2.3)].
- NEXVIAZYME is administered as intravenous infusion. For patients weighing:
- ≥30 kg, the recommended dosage is 20 mg/kg (of actual body weight) every two weeks [see Dosage and Administration (2.4)]
- <30 kg, the recommended dosage is 40 mg/kg (of actual body weight) every two weeks [see Dosage and Administration (2.4)]
- The initial recommended infusion rate is 1 mg/kg/hour. Gradually increase the infusion rate every 30 minutes if there are no signs of infusion-associated reactions (IARs) [see Dosage and Administration (2.4)].
Dosage and Administration Modifications Due to Hypersensitivity Reactions and/or Infusion-Associated Reactions
- In the event of a severe hypersensitivity reaction (including anaphylaxis) or a severe infusion-associated reaction (IAR), immediately discontinue NEXVIAZYME administration and initiate appropriate medical treatment [see Warnings and Precautions (5.1)].
- In the event of a mild to moderate hypersensitivity reaction or a moderate IAR, consider temporarily holding or slowing the infusion rate and initiating appropriate medical treatment [see Warnings and Precautions (5.1, 5.2)]. If symptoms:
- Persist despite temporarily holding the infusion, wait at least 30 minutes for symptoms to resolve before deciding to stop the infusion for the day.
- Subside, resume the infusion for 30 minutes at half the rate at which the reaction occurred, and subsequently increase the infusion rate by 50% for 15 minutes to 30 minutes. If symptoms do not recur, increase the infusion rate to the rate at which the reaction occurred and consider continuing to increase the rate in a stepwise manner.
Reconstitution and Dilution Instructions
Reconstitute and dilute NEXVIAZYME in the following manner. Use aseptic technique during preparation.
Reconstitute the Lyophilized Powder
- Determine the number of vials to be reconstituted based on individual patient's weight and the recommended dose [see Dosage and Administration (2.1)].
- Remove the required number of vials needed for the infusion from the refrigerator and set aside for approximately 30 minutes to allow them to reach room temperature.
- Reconstitute each vial by injecting 10 mL of Sterile Water for Injection, USP, into each vial by a slow drop-wise addition of the diluent down the inside of the vial and not directly onto the lyophilized powder. Tilt and roll each vial gently. Avoid forceful impact of the diluent on the lyophilized powder and avoid foaming. Do not invert, swirl, or shake. Allow the solution to become dissolved. After reconstitution, each vial will yield 100 mg/10 mL (10 mg/mL) of avalglucosidase alfa-ngpt.
- Perform an immediate visual inspection of the reconstituted solution in vials for particulate matter and discoloration. The reconstituted solution is clear, colorless to pale-yellow. If upon immediate inspection, particles are observed or if the solution is discolored, do not use.
Storage of the Reconstituted Solution
Dilute the reconstituted solution without delay. If immediate use is not possible, the reconstituted solution can be stored up to 24 hours in a refrigerator, 36°F to 46°F (2°C to 8°C). Do not freeze.
Dilute the Reconstituted Solution
- Slowly withdraw the volume of reconstituted solution from each vial (calculated according to patient's weight).
- Add the reconstituted solution slowly and directly into 5% Dextrose Injection. See Table 1 for the recommended total infusion volume based on the patient's weight. Avoid foaming or agitation of the infusion bag and avoid air introduction into the infusion bag. Discard any unused reconstituted solution remaining in the vial.
- Mix the contents of the infusion bag by gently inverting or massaging the infusion bag. Do not shake. After dilution, the solution will have a final concentration of 0.5 to 4 mg/mL of avalglucosidase alfa-ngpt.
- Administer the diluted solution without delay. The recommended infusion duration is between 4 to 7 hours [see Dosage and Administration (2.4)]. Discard any unused diluted solution after 9 hours.
Storage of the Diluted Solution
- If the diluted solution is not used immediately, refrigerate at 36°F to 46°F (2°C to 8°C) for up to 24 hours. Do not freeze.
- Completely infuse the diluted solution within 9 hours after removal from the refrigerator.
- If the diluted solution is removed from the refrigerator, it must not be restored in the refrigerator.
- Discard the diluted solution if refrigerated more than 24 hours or if the diluted solution is not able to be completely infused within 9 hours after removal from the refrigerator.
| Patient Weight Range (kg) |
Total Infusion Volume (mL) for 20 mg/kg | Total Infusion Volume (mL) for 40 mg/kg |
|---|---|---|
| 5 to 9.9 | N/A | 100 |
| 10 to 19.9 | N/A | 200 |
| 20 to 29.9 | N/A | 300 |
| 30 to 34.9 | 200 | N/A |
| 35 to 49.9 | 250 | N/A |
| 50 to 59.9 | 300 | N/A |
| 60 to 99.9 | 500 | N/A |
| 100 to 119.9 | 600 | N/A |
| 120 to 140 | 700 | N/A |
Administration Instructions
- It is recommended to use an in-line, low protein binding, 0.2 micrometer filter to administer NEXVIAZYME.
- Administer the infusion incrementally, as determined by the patient's response and comfort.
When the recommended dose is 20 mg/kg- Initial and Subsequent Infusions: The recommended starting infusion rate is 1 mg/kg/hour. If there are no signs of infusion-associated reactions (IARs), gradually increase the infusion rate every 30 minutes in each of the following three steps: 3 mg/kg/hour, 5 mg/kg/hour, and then 7 mg/kg/hour; then, maintain the infusion rate at 7 mg/kg/hour until the infusion is complete. The approximate total infusion duration is 4 hours to 5 hours.
When the recommended dose is 40 mg/kg- Initial Infusion: The recommended starting infusion rate is 1 mg/kg/hour. If there are no signs of IARs, gradually increase the infusion rate every 30 minutes in each of the following three steps: 3 mg/kg/hour, 5 mg/kg/hour, and then 7 mg/kg/hour; then, maintain the infusion rate at 7 mg/kg/hour until the infusion is complete (4-step process). The approximate total infusion duration is 7 hours.
- Subsequent Infusions: The recommended starting infusion rate is 1 mg/kg/hour, with gradual increase in infusion rate every 30 minutes if there are no signs of IARs. The process may use either the above 4-step process or the following 5-step process: 3 mg/kg/hour, 6 mg/kg/hour, 8 mg/kg/hour, and then 10 mg/kg/hour; then, maintain the infusion rate at 10 mg/kg/hour until the infusion is complete. The approximate total 5-step infusion duration is 5 hours.
- After the infusion is complete, flush the intravenous line with 5% Dextrose Injection.
- Discard any unused diluted product after 9 hours.
- Do not infuse NEXVIAZYME in the same intravenous line with other products.
