RyR1 Structural Alterations Explain Statin-Associated Muscle Dysfunction
December 16, 2025
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Brand Name :
avalglucosidase alfa-ngpt,nexviazyme
Synonyms :
avalglucosidase alfa
Class :
Lysosomal enymes
Brand Name :
avalglucosidase alfa-ngpt,nexviazyme
Synonyms :
avalglucosidase alfa
Class :
Lysosomal enymes
Dosage Forms & Strengths
Lyophilized powder for reconstitution injection
100mg/vial
Type II Glycogen Storage Disease (Pompe Disease)Â
Indicated for late-onset Pompe disease:
≥30kg: 20mg/kg intravenous every two weeks
Dose Adjustments
Hypersensitivity reactions
Severe hypersensitivity (including anaphylaxis) or severe infusion-associated reaction (IAR): Immediately discontinue and implement appropriate medical treatment
Mild-to-moderate
• Consider temporarily holding or slowing the infusion rate and initiating appropriate medical treatment as follows
• If symptoms persist, wait at least 30 minutes for symptoms to resolve before stopping infusion for the day
• If symptoms subside, resume infusion for 30 minutes by decreasing the rate to 50% at which the reaction occurred, and subsequently increase the infusion rate by 50% for 15-30 minutes; if symptoms do not recur, increase infusion rate to rate at which the reaction occurred and consider continuing to increase in a stepwise manner
• This information pertains to managing mild-to-moderate and severe hypersensitivity or severe infusion-associated reactions (IAR) to a medication administered through an infusion
• In case of a severe hypersensitivity reaction (including anaphylaxis) or severe IAR, the infusion should be immediately discontinued, and appropriate medical treatment should be initiated
In mild-to-moderate reactions, the infusion rate should be temporarily held or slowed down, and appropriate medical treatment should be initiated. If symptoms persist, the infusion should be stopped for the day and resumed the next day after a waiting period of at least 30 minutes. If symptoms subside, the infusion rate should be gradually increased stepwise, starting with a 50% reduction in the rate at which the reaction occurred. If symptoms do not recur, the infusion rate can be gradually increased until it reaches the rate at which the reaction occurred
Lyophilized powder for reconstitution injection
100mg/vial
Type II Glycogen Storage Disease (Pompe Disease)Â
Indicated for late-onset Pompe disease
:
<30kg: 40mg/kg intravenous every two weeks
≥30kg: 20mg/kg intravenous every 2 weeks
Dose Adjustments
Hypersensitivity reactions
In case of severe hypersensitivity or severe infusion-associated reaction, the infusion should be immediately discontinued, and appropriate medical treatment should be initiated. Consider temporarily holding or slowing the infusion rate and initiating appropriate medical treatment for mild to moderate reactions. If symptoms persist, wait for at least 30 minutes for symptoms to resolve before discontinuing the infusion for the day. If symptoms subside, the infusion rate can be resumed, decreased by 50%, and then gradually increased over time to monitor for the recurrence of symptoms
Refer adult dosing
Mechanism of action
The mechanism of action of avalglucosidase alfa is to replace the deficient enzyme in patients with Pompe disease, which leads to the breakdown of glycogen. This complex carbohydrate accumulates in cells and causes cellular damage, particularly in the muscles
Spectrum
The spectrum of activity of avalglucosidase alfa is limited to Pompe disease, and it is ineffective in treating other lysosomal storage disorders. Its efficacy has been demonstrated in clinical trials, showing improved muscle strength and function in patients with Pompe disease
Frequency defined:
>10%
Infusion-related infections
Fatigue
Nausea
Hypersensitivity reactions
Headache
Diarrhea
Antidrug antibodies
Treatment experienced
ADAs after treatment
NAb inhibition of enzyme activity
ADAs baseline
NAb inhibition of enzyme cellular uptake
NaĂŻve treatment
ADAs after treatment
NAb inhibition of enzyme cellular uptake
ADAs baseline
NAb inhibition of enzyme activity
1-10%
Dizziness
Pruritis
Dyspnea
Paresthesia
Severe hypersensitivity reactions
Arthralgia
Myalgia
Vomiting
Erythema
Urticaria
Anaphylaxis
Black box warning
avalglucosidase alfa has a black box warning regarding the risk of severe hypersensitivity reactions, including anaphylaxis, during administration. This warning highlights the need for proper monitoring and pre-treatment of patients with antihistamines and corticosteroids before each infusion.
Patients who experience a severe hypersensitivity reaction during an infusion should discontinue avalglucosidase alfa and receive appropriate medical treatment
Contraindications
It is contraindicated in patients with a known hypersensitivity to avalglucosidase alfa or any of its excipients. This includes patients with a severe hypersensitivity reaction, such as anaphylaxis, during previous treatment with avalglucosidase alfa
Additionally, avalglucosidase alfa is not indicated for use in patients with other lysosomal storage disorders, as its efficacy has only been established in patients with Pompe disease
Caution
It should be used cautiously in patients with severe hypersensitivity reactions, including anaphylaxis, during previous infusions. In such patients, careful monitoring and pre-treatment with antihistamines and corticosteroids may be necessary before each infusion.
In addition, healthcare providers should be aware of the risk of neutralizing antibodies, which can develop in some patients and reduce the efficacy of avalglucosidase alfa. Regular monitoring for the development of neutralizing antibodies is recommended, and alternative treatment options should be considered if neutralizing antibodies are detected
Pregnancy consideration: Insufficient data available
Lactation: Excretion of the drug in human breast milk is unknown
Pregnancy category:
Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.
Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.
Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.
Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.
Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.
Category N: There is no data available for the drug under this category
Pharmacology
Recombinant acid alpha-glucosidase (GAA) is the active ingredient in avalglucosidase alfa (brand name: Myozyme). The carbohydrate groups on the GAA molecule bind to mannose-6-phosphate receptors, which allows the molecule to be transported into cells, where it undergoes proteolytic cleavage. This results in increased enzymatic activity and the ability of GAA to cleave glycogen, which is essential for normal muscle development and function.
In patients with Pompe disease, a genetic disorder caused by a deficiency of the acid alpha-glucosidase enzyme, the administration of avalglucosidase alfa provides the missing enzyme. It helps to break down glycogen, reducing the accumulation of glycogen in cells and improving muscle function.
Pharmacodynamics
The pharmacodynamics of aval glucosidase alfa involves binding the carbohydrate groups on the GAA molecule to mannose-6-phosphate receptors, which allows the molecule to be transported into cells where it undergoes proteolytic cleavage and increases its enzymatic activity. This results in the cleavage of glycogen, reducing its accumulation in cells and improving muscle function.
The efficacy of avalglucosidase alfa in treating Pompe disease has been demonstrated in clinical trials, where it was shown to improve muscle strength and function, reduce the size of the liver, and slow the progression of the disease. However, it is essential to note that individual responses to avalglucosidase alfa may vary, and regular monitoring is necessary to ensure that the desired therapeutic effect is achieved
Pharmacokinetics
Absorption:
The peak plasma concentration of avalglucosidase alfa is ≥259 mcg/mL after the first week of administration and decreases to ≥242 mcg/mL after the second week. The area under the curve (AUC) is ≥1290 mcgh/mL after the first week of administration and decreases to ≥1250 mcgh/mL after 49 weeks
Distribution:
The distribution volume of avalglucosidase alfa is estimated to be 3.4 L
Metabolism:
The metabolism of avalglucosidase alfa is not well characterized, but it is expected to be metabolized into small peptides and amino acids via catabolic pathways
Elimination/excretion:
The elimination/excretion half-life of avalglucosidase alfa is approximately 1.6 hours, and its clearance is estimated to be 0.9 L/hr. The drug is primarily eliminated through the kidneys, with a small fraction eliminated in the feces
Administration
avalglucosidase alfa is administered intravenously (IV) by a healthcare provider in a clinical setting. The recommended dose and infusion rate will vary based on the patient’s weight, age, and medical history. The dose is usually expressed in units per kilogram of body weight, and the infusion time can range from 60 minutes to several hours, depending on the individual patient.
It is essential to follow the recommended administration guidelines and to monitor the patient closely during and after the infusion for any adverse reactions. If an adverse reaction occurs, the infusion should be temporarily stopped or slowed, and appropriate medical treatment should be initiated as needed
Patient information leaflet
Generic Name: avalglucosidase alfa
Pronounced: [ AY-val-gloo-KOE-si-dase-AL-fa ]
Why do we use avalglucosidase alfa?
avalglucosidase alfa is a prescription medication used to treat patients with Pompe disease, also known as glycogen storage disease type II. Pompe disease is a rare, inherited disorder that affects the muscles and causes progressive weakness, breathing problems, and heart failure
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