Version May 2024
Patients treated with avalglucosidase alfa have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available during avalglucosidase alfa administration. If a severe hypersensitivity reaction (eg, anaphylaxis) occurs, discontinue avalglucosidase alfa immediately and initiate appropriate medical treatment. In patients with severe hypersensitivity reactions, a desensitization procedure to avalglucosidase alfa may be considered.
Patients treated with avalglucosidase alfa have experienced severe infusion-associated reactions (IARs). If severe IARs occur, consider immediate discontinuation of avalglucosidase alfa, initiation of appropriate medical treatment, and the benefits and risks of readministering avalglucosidase alfa following severe IARs. Patients with an acute underlying illness at the time of avalglucosidase alfa 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.
Patients susceptible to fluid volume overload, or those with acute underlying respiratory illness or compromised cardiac or respiratory function for whom fluid restriction is indicated may be at risk of serious exacerbation of their cardiac or respiratory status during avalglucosidase alfa infusion. More frequent monitoring of vitals should be performed during avalglucosidase alfa infusion in such patients.
Note: Consider pretreatment with antihistamines, antipyretics, and/or corticosteroids to reduce the risk of infusion-associated reactions.
Pompe disease, late onset:
Actual body weight <30 kg: IV: 40 mg/kg every 2 weeks.
Actual body weight ≥30 kg: IV: 20 mg/kg every 2 weeks.
Missed dose: If ≥1 dose is missed, restart treatment as soon as possible while maintaining the 2-week interval between infusions thereafter.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Hypersensitivity:
Mild or moderate: Temporarily hold avalglucosidase alfa infusion for 30 minutes or decrease infusion rate by 50% and initiate appropriate medical management.
If symptoms persist for >30 minutes despite temporarily holding or decreasing the infusion rate: Stop the infusion and monitor the patient; may consider reinitiating the infusion on the same day symptoms subsided at 50% of the rate at which the symptoms occurred with appropriate pretreatment.
If symptoms subside after holding the infusion: Resume infusion at 50% of the rate at which the symptoms occurred and then increase the infusion rate every 15 to 30 minutes by 50% as tolerated. Alternatively, if symptoms subside after decreasing the infusion rate, complete the infusion at the reduced rate as tolerated.
Subsequent infusions: Starting with the next infusion, increase the infusion rate until the infusion rate at which the symptoms occurred is reached; consider continuing to increase the infusion rate in a stepwise manner until reaching the recommended infusion rate while monitoring the patient closely.
Severe hypersensitivity or anaphylaxis: Discontinue avalglucosidase alfa immediately and begin appropriate medical management. Some patients have been rechallenged using decreased infusion rates and lower than approved doses. In patients with a severe hypersensitivity reaction, may consider a desensitization procedure. If tolerated, the infusion rate and dose may be increased to reach the usual recommended dose.
Infusion-associated reaction:
Mild or moderate: Temporarily hold avalglucosidase alfa infusion for 30 minutes or decrease infusion rate by 50% and initiate appropriate medical management.
If symptoms persist for >30 minutes despite temporarily holding or decreasing the infusion rate: Stop the infusion and monitor the patient; may consider reinitiating the infusion on the same day symptoms subsided at 50% of the rate at which the symptoms occurred with appropriate pretreatment.
If symptoms subside after holding the infusion: Resume infusion at 50% of the rate at which the symptoms occurred and then increase the infusion rate every 15 to 30 minutes by 50% as tolerated. Alternatively, if symptoms subside after decreasing the infusion rate, complete the infusion at the reduced rate as tolerated.
Subsequent infusions: Starting with the next infusion, increase the infusion rate until the infusion rate at which the symptoms occurred is reached; consider continuing to increase the infusion rate in a stepwise manner until reaching the recommended infusion rate while monitoring the patient closely.
Severe: Discontinue avalglucosidase alfa immediately and begin appropriate medical management. Some patients have been rechallenged using decreased infusion rates and lower than approved doses. If tolerated, the dose may be increased to reach the usual recommended dose.
Refer to adult dosing.
(For additional information see "Avalglucosidase alfa: Pediatric drug information")
Note: Pretreatment with antihistamines, antipyretics, and/or corticosteroids can be considered to reduce risk of infusion reactions. Calculate avalglucosidase alfa dose based on actual body weight.
Pompe disease, late onset:
Children and Adolescents:
<30 kg: IV: 40 mg/kg/dose every 2 weeks.
≥30 kg: IV: 20 mg/kg/dose every 2 weeks.
Canadian labeling: Infants >6 months, Children, and Adolescents: IV: 20 mg/kg/dose every 2 weeks.
Dosage adjustment for toxicity:
Children and Adolescents:
Hypersensitivity:
Mild or moderate: Decrease infusion rate or temporarily discontinue avalglucosidase alfa. If symptoms persist despite temporarily stopping the infusion, wait ≥30 minutes for symptoms to resolve (before deciding to stop infusion for the day). If symptoms subside, may resume the infusion at one-half of the infusion rate at which reaction occurred for 30 minutes, then increase the infusion rate by 50% for 15 to 30 minutes. If symptoms do not recur, increase the infusion rate to the rate at which the reaction occurred and continue to increase rate in a stepwise manner.
Severe hypersensitivity or anaphylaxis: Discontinue avalglucosidase alfa immediately and begin appropriate medical management. Some patients have been rechallenged using decreased infusion rates and lower than approved doses. In patients with a severe hypersensitivity reaction, may consider a desensitization procedure. If tolerated, the infusion rate and dose may be increased to reach the usual recommended dose.
Infusion-associated reaction:
Mild or moderate: Consider temporarily stopping avalglucosidase alfa infusion or decreasing the infusion rate, and begin appropriate medical management. If symptoms persist despite temporarily stopping the infusion, wait at least 30 minutes for symptoms to resolve (before deciding to stop infusion for the day). If symptoms subside, may resume the infusion at one-half of the infusion rate at which reaction occurred for 30 minutes, then increase the infusion rate by 50% for 15 to 30 minutes. If symptoms do not recur, increase the infusion rate to the rate at which the reaction occurred and continue to increase rate in a stepwise manner.
Severe: Discontinue avalglucosidase alfa immediately and begin appropriate medical management. Some patients have been rechallenged using decreased infusion rates and lower than approved doses. If tolerated, the dose may be increased to reach the usual recommended dose.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Patients treated with avalglucosidase alfa have commonly experienced hypersensitivity reaction, including life-threatening severe hypersensitivity reaction and anaphylaxis.
Mechanism: Non–dose-related; immediate hypersensitivity reactions are considered IgE mediated (Ref).
Risk factors:
• Higher anti-avalglucosidase alfa-ngpt antibody titers (antidrug antibodies [ADA])
• Higher infusion rates
Infusion-related reactions, including chest discomfort, diarrhea, dizziness, dysphagia, edema, erythema of skin, headache, hypertension, hypotension, hypoxia, flu-like symptoms, nausea, respiratory distress, and tongue edema have been reported with avalglucosidase alfa; reactions can be severe.
Mechanism: Non–dose-related; immunologic.
Onset: Rapid; occurred at the time of infusion and/or within a few hours after completion of the infusion.
Risk factors:
• Acute underlying illness at the time of avalglucosidase alfa infusion
• Advanced Pompe disease with compromised cardiac and respiratory function
• Higher infusion rates
• High anti-avalglucosidase alfa-ngpt antibody titers (antidrug antibodies [ADA]) (peak titer ≥12,800)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adolescents and adults from late-onset Pompe disease trials and may include infantile-onset Pompe disease data (off-label indication) in children.
>10%:
Gastrointestinal: Diarrhea, nausea
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis [2%] and severe hypersensitivity reaction [4%]), infusion-related reaction (25% to 34%; severe [4%]) (table 1)
|
Drug (Avalglucosidase Alfa) |
Comparator (Alglucosidase Alfa) |
Population |
Dose |
Number of Patients (Avalglucosidase Alfa) |
Number of Patients (Alglucosidase Alfa) |
|---|---|---|---|---|---|
|
34% |
N/A |
N/A |
N/A |
N/A |
N/A |
|
25% |
33% |
Adolescents and adults |
20 mg/kg given every other week for 49 weeks |
51 |
49 |
Immunologic: Antibody development (including neutralizing antibodies)
Nervous system: Fatigue, headache
1% to 10%:
Cardiovascular: Flushing, hypertension, hypotension
Dermatologic: Erythema of skin, pruritus, skin rash, urticaria
Gastrointestinal: Abdominal pain, vomiting
Nervous system: Chills, dizziness, paresthesia
Neuromuscular & skeletal: Arthralgia, myalgia
Respiratory: Dyspnea
Miscellaneous: Fever
Frequency not defined: Respiratory: Respiratory distress
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Life-threatening hypersensitivity to avalglucosidase alfa or any component of the formulation when rechallenge was unsuccessful.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Nexviazyme: Avalglucosidase alfa-ngpt 100 mg (1 ea) [contains polysorbate 80]
No
Solution (reconstituted) (Nexviazyme Intravenous)
100 mg (per each): $2,225.60
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Nexviazyme: Avalglucosidase alfa-ngpt 100 mg (1 ea) [contains polysorbate 80]
IV: If diluted solution was refrigerated, allow solution to reach room temperature (30 minutes) prior to infusion. Infuse through a separate line via an inline, low-protein-binding, 0.2-micron filter.
Discontinue immediately and initiate appropriate medical treatment for severe hypersensitivity (including anaphylaxis) or severe infusion reaction; decrease infusion rate or temporarily hold avalglucosidase alfa for mild to moderate hypersensitivity or infusion reaction.
Diluted solution for infusion must be used within 9 hours after preparation or within 9 hours after removal from refrigerator (if stored); discard any unused portion.
Actual body weight <30 kg (40 mg/kg/dose):
Initial infusion: Initiate IV infusion at 1 mg/kg/hour. If tolerated, gradually increase the infusion rate every 30 minutes as follows: 3 mg/kg/hour, then 5 mg/kg/hour, then 7 mg/kg/hour. Then, maintain infusion rate at 7 mg/kg/hour until the infusion is complete (total IV infusion duration: ~7 hours).
Subsequent infusions: Initiate IV infusion at 1 mg/kg/hour. If tolerated, gradually increase infusion rate as described under the initial infusion protocol above (total IV infusion duration: ~7 hours); alternatively, may gradually increase the infusion rate every 30 minutes as follows: 3 mg/kg/hour, then 6 mg/kg/hour, then 8 mg/kg/hour, then 10 mg/kg/hour. Then, maintain the infusion rate at 10 mg/kg/hour until the infusion is complete (total IV infusion duration: ~5 hours).
Actual body weight ≥30 kg (20 mg/kg/dose): Initiate IV infusion at 1 mg/kg/hour. If tolerated, gradually increase the infusion rate every 30 minutes as follows: 3 mg/kg/hour, then 5 mg/kg/hour, then 7 mg/kg/hour. Then, maintain infusion rate at 7 mg/kg/hour until the infusion is complete (total IV infusion duration: ~4 to 5 hours).
Parenteral: IV infusion: Infuse through a separate line via an in-line, low-protein-binding, 0.2 micron filter. Administer the infusion incrementally according to patient weight and as determined by the patient's response and comfort. Infusion time varies (~4 to 7 hours), but infusion must be completed within 9 hours of dilution or if refrigerated, within 9 hours after removal from refrigerator. Infusion rate calculations based on patient actual body weight.
Children and Adolescents:
Patient weight <30 kg (40 mg/kg/dose):
Initial infusion: Initiate infusion at 1 mg/kg/hour. If tolerated and no signs of infusion-related reactions are seen, gradually increase the infusion rate every 30 minutes as follows: 3 mg/kg/hour, 5 mg/kg/hour, then 7 mg/kg/hour. Maintain infusion rate at 7 mg/kg/hour until the infusion is complete (~7 hours). After infusion is complete, flush line with D5W.
Subsequent infusions:
7-hour infusion (4-step): May administer following same as initial infusion above (~7 hours).
5-hour infusion (5-step): Initiate infusion at 1 mg/kg/hour. If tolerated and no signs of infusion-related reactions are seen, gradually increase the infusion rate every 30 minutes as follows: 3 mg/kg/hour, 6 mg/kg/hour, 8 mg/kg/hour, then 10 mg/kg/hour. Maintain the infusion rate at 10 mg/kg/hour until the infusion is complete (~5 hours). After infusion is complete, flush line with D5W.
Patient weight ≥30 kg (20 mg/kg/dose):
Initial infusion and subsequent infusions: Initiate infusion at 1 mg/kg/hour. If tolerated and no signs of infusion-related reactions are observed, gradually increase the infusion rate every 30 minutes as follows: 3 mg/kg/hour, 5 mg/kg/hour, then 7 mg/kg/hour. Maintain infusion rate at 7 mg/kg/hour until the infusion is complete (~4 to 5 hours). After infusion is complete, flush line with D5W.
Canadian labeling: Infants >6 months, Children, and Adolescents (20 mg/kg/dose regardless of weight): Initial infusion and subsequent infusions: Initiate infusion at 1 mg/kg/hour. If tolerated and no signs of infusion-related reactions are seen, gradually increase the infusion rate every 30 minutes as follows: 3 mg/kg/hour, 5 mg/kg/hour, then 7 mg/kg/hour. Maintain infusion rate at 7 mg/kg/hour until the infusion is complete. After infusion is complete, flush line with D5W (Ref).
Hypersensitivity and/or infusion-related reaction modifications:
Mild to moderate hypersensitivity or moderate infusion-related reactions: Decrease infusion rate or temporarily hold infusion. If symptoms persist despite temporarily holding the infusion, wait ≥30 minutes for symptoms to resolve before deciding to stop infusion for the day. If symptoms subside, may re-initiate infusion at 50% of rate at which reaction occurred for 30 minutes; if patient remains without symptoms, increase infusion rate by 50% for 15 to 30 minutes; if symptoms do not recur, increase to rate at which reaction occurred and consider continuing to increase rate in a stepwise manner.
Severe hypersensitivity or infusion-related reaction: Discontinue treatment and initiate appropriate medical treatment.
Pompe disease, late onset: Treatment of late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) in patients ≥1 year of age.
Avalglucosidase alfa may be confused with agalsidase alfa, agalsidase beta, alglucosidase alfa, andexanet alfa, or asfotase alfa.
None known.
There are no known significant interactions.
In a phase I safety trial, patients who could become pregnant were required to use effective contraception.
Information related to the treatment of Pompe disease during pregnancy is limited; when use of enzyme replacement therapy is noted, available reports use alglucosidase alfa (refer to the Alglucosidase Alfa monograph for additional information).
Adverse events, such as worsening muscle weakness or decreased respiratory function, may be exacerbated by pregnancy and/or Pompe disease (Karabul 2014). The continuation of enzyme replacement therapy during pregnancy may be considered (van der Ploeg 2017).
A registry has been established for patients diagnosed with Pompe disease; pregnant patients are encouraged to enroll in the registry (1-800-745-4447, extension 15500).
It is not known if avalglucosidase alfa is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
A registry has been established for patients diagnosed with Pompe disease; patients who are breastfeeding are encouraged to enroll in the registry (1-800-745-4447, extension 15500).
Vital signs during (prior to each infusion rate increase) and following infusion (increase monitoring in patients susceptible to volume overload/cardiorespiratory decompensation). Monitor for hypersensitivity and infusion-associated reactions.
Avalglucosidase alfa is an exogenous source of the enzyme acid alpha-glucosidase (GAA), which is required for glycogen cleavage. Due to an inherited GAA deficiency or absence, glycogen accumulates in the tissues of patients with Pompe disease. Mannose-6-phosphate (M6P) on avalglucosidase alfa mediates binding to M6P receptors on the cell surface with high affinity. After binding, it is internalized and transported to lysosomes where it is activated for increased enzymatic glycogen cleavage.
Distribution: Vd: 3.4 L.
Metabolism: Expected to be metabolized into small peptides and amino acids via catabolic pathways.
Half-life elimination: 1.6 hours.
Excretion: Clearance: 0.9 L/hour.
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