Avalglucosidase alfa
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: SEVERE HYPERSENSITIVITY REACTIONS, INFUSION-ASSOCIATED REACTIONS, and RISK OF ACUTE CARDIORESPIRATORY FAILURE IN SUSCEPTIBLE PATIENTS WARNING: SEVERE HYPERSENSITIVITY REACTIONS, INFUSION-ASSOCIATED REACTIONS, and RISK OF ACUTE CARDIORESPIRATORY FAILURE IN SUSCEPTIBLE PATIENTS See full prescribing information for complete boxed warning. Hypersensitivity Reactions Including Anaphylaxis Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available. If a severe hypersensitivity reaction occurs, discontinue NEXVIAZYME immediately and initiate appropriate medical treatment.
( 5.1 ) Infusion-Associated Reactions (IARs) If severe IARs occur, consider immediate discontinuation and initiation of appropriate medical treatment. ( 5.2 ) Risk of Acute Cardiorespiratory Failure in Susceptible Patients Patients susceptible to fluid volume overload, or those with acute underlying respiratory illness or compromised cardiac or respiratory function, may be at risk of serious exacerbation of their cardiac or respiratory status during NEXVIAZYME infusion. ( 5.3 ) Hypersensitivity Reactions Including Anaphylaxis Patients treated with NEXVIAZYME have experienced life-threatening hypersensitivity reactions, including anaphylaxis.
Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available during NEXVIAZYME administration. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue NEXVIAZYME immediately and initiate appropriate medical treatment. In patients with severe hypersensitivity reactions, a desensitization procedure to NEXVIAZYME may be considered [see Warnings and Precautions (5.1) ] . Infusion-Associated Reactions (IARs) Patients treated with NEXVIAZYME have experienced severe IARs.
If severe IARs occur, consider immediate discontinuation of NEXVIAZYME, initiation of appropriate medical treatment, and the benefits and risks of readministering NEXVIAZYME following severe IARs. Patients with an acute underlying illness at the time of NEXVIAZYME infusion may be at greater risk for IARs. Patients with advanced Pompe disease may have compromised cardiac and respiratory function, which may predispose them to a higher risk of severe complications from IARs [see Warnings and Precautions (5.2) ] .
Risk of Acute Cardiorespiratory Failure in Susceptible Patients Patients susceptible to fluid volume overload, or those with acute underlying respiratory illness or compromised cardiac or respiratory function for…
Hydrolytic Lysosomal Glycogen-specific Enzyme
Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Preparation and administration
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Recommendations Prior to NEXVIAZYME Treatment Prior to NEXVIAZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids [see Warnings and Precautions (5.1 , 5.2) ] . NEXVIAZYME must be reconstituted and diluted prior to use [see Dosage and Administration ] . Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available during NEXVIAZYME administration.
Recommended Dosage and Administration NEXVIAZYME is administered as intravenous infusion. For patients weighing: 30 kg or more- the recommended dosage is 20 mg/kg (of actual body weight) every two weeks [see Dosage and Administration ] Less than 30 kg- the recommended dosage is 40 mg/kg (of actual body weight) every two weeks [see Dosage and Administration ] 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 ] . If one or more doses are missed, restart NEXVIAZYME treatment as soon as possible, maintaining the 2 week interval between infusions thereafter.
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 NEXVIAZYME 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 30 minutes or slowing the infusion rate by 50% [see Dosage and Administration ] and initiating appropriate medical treatment [see Warnings and Precautions (5.1 , 5.2) ] . If symptoms persist for longer than 30 minutes despite holding or slowing the infusion, stop the infusion and monitor the patient.
Consider re-initiating the infusion on the same day when symptoms subside at 50% of the rate at which the reaction occurred with appropriate pretreatment. If symptoms subside after holding the infusion, resume infusion at 50% of the rate at which the reaction occurred, and subsequently increase the infusion rate every 15 to 30 minutes by 50% as tolerated.
Alternatively, if symptoms subside after slowing the infusion, complete the infusion at the reduced rate as tolerated. Starting with the next infusion, increase the infusion rate until the infusion rate at which the reaction occurred is reached. Consider continuing to increase the infusion rate in a stepwise manner until reaching the recommended infusion rate.
Closely monitor the patient.
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 NEXVIAZYME vials to be reconstituted based on actual body weight in kg and the recommended dose [see Dosage and Administration ] .
Round the number of vials up to the next whole number. Remove the required number of NEXVIAZYME vials from the refrigerator and allow the vials to sit for 30 minutes at room temperature 20°C to 25°C (68°F to 77°F) before use. Reconstitute each vial by injecting 10 mL of Sterile Water for Injection, down the inside wall of each vial.
Avoid adding the Sterile Water for Injection to the vial forcefully or directly onto the lyophilized powder to minimize foaming. Gently tilt and roll each vial to enhance the dissolution process. Do not invert, swirl, or shake the vial. Allow the solution to become dissolved. Each vial will yield a concentration of 100 mg/10 mL (10 mg/mL) of avalglucosidase alfa-ngpt.
Visually inspect the reconstituted solution in the vials for particulate matter and discoloration. The reconstituted solution should be clear, colorless to pale-yellow. Discard if particles are present or the solution is discolored. Dilute the Reconstituted Solution Select an appropriate size 5% Dextrose Injection infusion bag and prepare by removing a volume equal to the required NEXVIAZYME volume and any overfill to achieve a fixed total volume per Table 1 based on actual body weight.
Slowly withdraw the required volume of reconstituted solution from the NEXVIAZYME vial(s). Discard any unused reconstituted solution remaining in the vial. Gently inject the NEXVIAZYME reconstituted solution into the port of the 5% Dextrose Injection bag. Avoid foaming or agitation of the infusion bag and avoid introducing air into the infusion bag.
Gently invert the infusion bag to mix the solution. 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 ] . Discard any unused diluted solution after 9 hours. [See table below.] 100 mL 10 to 19.9 kg N/A 200 mL 20 to 29.9 kg N/A 300 mL 30 to 34.9 kg 200 mL N/A 35 to 49.9 kg 250 mL N/A 50 to 59.9 kg 300 mL N/A 60 to 99.9 kg 500 mL N/A 100 to 119.9 kg 600 mL N/A 120 to 140 kg 700 mL N/A
Storage Instructions for the Reconstituted and Diluted Product Storage of the Reconstituted Solution Dilute the reconstituted solution without delay. If the reconstituted solution is not diluted immediately, refrigerate at 2°C to 8°C (36°F to 46°F) for up to 24 hours. Do not freeze. Storage of the Diluted Solution 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.
The diluted solution must be infused within 9 hours after removal from the refrigerator, inclusive of infusion time, or discarded. Once the diluted solution is removed from the refrigerator, it must not be restored back into the refrigerator. Do not freeze.
| Patient Actual Body Weight Range (kg) | Total Infusion Volume (mL) for 20 mg/kg | Total Infusion Volume (mL) for 40 mg/kg |
|---|---|---|
| 5 to 9.9 kg | N/A | 100 mL |
| 10 to 19.9 kg | N/A | 200 mL |
| 20 to 29.9 kg | N/A | 300 mL |
| 30 to 34.9 kg | 200 mL | N/A |
| 35 to 49.9 kg | 250 mL | N/A |
| 50 to 59.9 kg | 300 mL | N/A |
| 60 to 99.9 kg | 500 mL | N/A |
| 100 to 119.9 kg | 600 mL | N/A |
| 120 to 140 kg | 700 mL | N/A |
| Dose | Step 1 | Step 2 | Step 3 | Step 4 | Step 5 |
|---|---|---|---|---|---|
| Start infusion at step 1 and in absence of infusion-associated reaction increase infusion rate sequentially per the steps of infusion every 30 minutes until completion (total time approximately 4 to 5 hours). | |||||
| 20 mg/kg | 1 mg/kg/hour | 3 mg/kg/hour | 5 mg/kg/hour | 7 mg/kg/hour | Continue 7 mg/kg/hour |
| Dose | Step 1 | Step 2 | Step 3 | Step 4 | Step 5 | |
|---|---|---|---|---|---|---|
| Start infusion at step 1 and in absence of infusion-associated reaction increase infusion rate sequentially per the steps of infusion every 30 minutes until completion. Total time for initial infusion approximately 7 hours and can optionally increase rate of subsequent infusions to decrease total duration to 5 hours. | ||||||
| 40 mg/kg | Initial infusion rate | 1 mg/kg/hour | 3 mg/kg/hour | 5 mg/kg/hour | 7 mg/kg/hour | Continue 7 mg/kg/hour |
| Subsequent infusions (optional) | 1 mg/kg/hour | 3 mg/kg/hour | 6 mg/kg/hour | 8 mg/kg/hour | Continue 10 mg/kg/hour | |
Contraindications
None. None. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for avalglucosidase alfa. Check the label's hepatic warnings.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Available data from case reports of NEXVIAZYME use in pregnant women are insufficient to evaluate for a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, available data from postmarketing reports and published case reports on alglucosidase alfa (another hydrolytic lysosomal glycogen-specific enzyme replacement therapy) use in pregnant women have not identified a drug-associated risk of adverse pregnancy outcomes. The continuation of treatment for Pompe disease during pregnancy should be individualized to the pregnant woman.
Untreated Pompe disease may result in worsening disease symptoms in pregnant women (see Clinical Considerations ) . Embryo-fetal toxicity studies performed in pregnant mice resulted in maternal toxicity related to an immunologic response (including an anaphylactoid response) and embryo-fetal loss at 17 times the human steady-state AUC at the recommended biweekly dose of 20 mg/kg for LOPD patients weighing ≥30 kg or 10 times the human steady-state AUC at the recommended biweekly dose of 40 mg/kg for LOPD patients weighing <30 kg. Avalglucosidase alfa-ngpt did not cross the placenta in mice, therefore, the adverse effects were likely related to the immunologic response in the mothers.
Embryo-fetal toxicity studies performed in pregnant rabbits showed no adverse effects on the fetuses at exposure up to 91 times the human steady-state AUC at the recommended biweekly dosage of 20 mg/kg for LOPD patients weighing ≥30 kg or 50 times the human steady-state AUC at the recommended biweekly dose of 40 mg/kg for LOPD patients weighing <30 kg (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriage, or other adverse outcomes. In the U.S.
general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Pregnant women exposed to NEXVIAZYME, or their healthcare providers, should report NEXVIAZYME exposure by calling 1-800-633-1610, option 1. Clinical Considerations Disease-associated maternal and/or embryo-fetal risk Untreated Pompe disease has been associated with worsening respiratory and musculoskeletal symptoms in some pregnant women. Data Animal data The majority of reproductive toxicity studies in mice included the pretreatment with diphenhydramine (DPH) to prevent or minimize hypersensitivity reactions.
The effects of NEXVIAZYME were evaluated…
Breastfeeding (LactMed)
Information available on the clinical use of avalglucosidase during breastfeeding indicates that it does not increase the alphaglucosidase activity of infants breastfed by mothers taking the drug. Two infants breastfed during maternal avalglucosidase therapy had no apparent adverse effects and were developing normally. No special precaution appear to be necessary.
- Alglucerase
- Imiglucerase
- Taliglucerase Alfa
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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