alglucosidase alfa

Action and Spectrum

Actions and Spectrum: 

Actions: 

In patients with Pompe disease (acid α-glucosidase (GAA) deficiency), it is a medicine that restores a missing or deficient enzyme. A substitute enzyme might be required because individuals with Pompe illness do not generate enough of the GAA enzyme on their own. The purpose of the genetically modified enzyme is to function similarly to the naturally occurring GAA that is typically produced by human cells. 

Spectrum: 

Alglucosidase alfa, a recombinant enzyme replacement therapy, functions as a therapeutic intervention for Pompe disease, a rare lysosomal storage disorder. It addresses the deficiency of acid alpha-glucosidase, the primary cause of the condition, which results in the accumulation of glycogen in tissues. Through its interaction with mannose-6-phosphate receptors, alglucosidase alfa enters cells and undergoes proteolytic cleavage. This process amplifies the enzymatic cleavage of glycogen, alleviating the abnormal buildup of glycogen. This enzyme replacement therapy serves as a crucial and enduring treatment for individuals diagnosed with Pompe disease, ultimately enhancing their overall well-being and quality of life. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Respiratory distress (33%) 

Infusion reactions (51%) 

Constipation (23%) 

Diaper dermatitis (46%) 

Otitis media (44%) 

Pharyngitis (36%) 

Rash (54%) 

Tachycardia (23%) 

Catheter-related infection (28%) 

Rhinorrhea (28%) 

GERD (26%) 

Pneumonia (46%) 

Tachypnea (23%) 

Tremor (46%) 

Post-procedural pain (26%) 

Oral candidiasis (31%) 

Diarrhea (62%) 

Cough (46%) 

Urticaria (21%) 

Nasopharyngitis (23%) 

Bronchiolitis (23%) 

Pyrexia (92%) 

Flushing (21%) 

Respiratory failure (31%) 

Vomiting (49%) 

Gastroenteritis (41%) 

Anemia (31%) 

URI (44%) 

Bradycardia (21%) 

Gastritis (21%) 

O2 saturation decreased (41%) 

Frequency not defined 

Blurred vision 

Cyanosis 

Insomnia 

Abdominal pain 

Facial Erythema 

Coronary artery disease 

Restlessness 

Agitation 

Dyspnea 

Tremor 

Bronchospasm 

Pallor 

Vertigo 

Hypokalemia 

Irritability 

Conjunctivitis 

Postmarketing Reports 

Anaphylactic shock, respiratory arrest, hypoxia, cardiac arrest, respiratory failure, convulsions, dyspnea, peripheral coldness, wheezing, restlessness, back pain, pharyngeal edema, nervousness, muscle spasm, abdominal pain, hyperparathyroidism, apnea, stridor, conjunctivitis,  

Nephrotic syndrome and proteinuria secondary to membranous glomerulonephritis and necrotizing skin lesions were reported. 

Black Box Warning

Black Box Warning: 

Following IV infusions of the drug, reports of severe hypersensitivity events, including potentially fatal anaphylactic reactions and anaphylaxis, have been made. There have also been reports of immune-mediated reactions, including necrotizing skin lesions, nephrotic syndrome, and proteinuria. Healthcare professionals must be ready to handle anaphylactic and hypersensitivity responses, and they must closely monitor patients both during and after administration. The warning signs and symptoms of these responses should be shared with patients and carers, who should also be advised to seek emergency medical attention if any appear. Fluid overload may provide a risk of serious acute aggravation for individuals with infantile-onset Pompe disease who have reduced cardiac or pulmonary function, requiring further monitoring in these circumstances. 

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• Hypersensitivity 

Cautions 

• Patients receiving alglucosidase alfa may experience anaphylaxis and hypersensitivity reactions, with some reactions being life-threatening. These reactions include anaphylactic shock, respiratory arrest, cardiac arrest, respiratory distress, and various other symptoms. Immediate management involves infusion interruption and administration of antihistamines, fluids, corticosteroids, and oxygen. Epinephrine may be administered, and appropriate medical support, including resuscitation equipment, should be readily available. Consideration of re-administration should weigh risks and benefits, with close monitoring and resuscitation measures if re-administration is chosen. 
• Nephrotic syndrome has been observed in some patients with persistently positive antibodies, necessitating periodic urinalysis. Those with acute respiratory or cardiac issues may face exacerbation during infusions. General anesthesia should be approached with caution, particularly in patients with cardiac hypertrophy. Immunogenicity is a potential concern; monitor IgG antibodies regularly and test if hypersensitivity reactions occur. Immune tolerance induction may aid tolerability, especially in CRIM-negative patients, and should be managed by a specialist. CRIM status correlates with immunogenicity and treatment response in pediatric Pompe disease. 
• Pregnancy 
• Breastfeeding 
• Drug interactions 
• Geriatrics 
• Renal impairment 
• Hepatic impairment 

Pregnancy / Lactation

Pregnancy consideration:  

Pregnancy category: B 

Reproduction studies in mice and rabbits showed no evidence of harm or impaired fertility at doses up to 40 mg/kg/day. However, as there are no adequate studies in pregnant women, alglucosidase alfa should be used during pregnancy only if clearly needed, considering potential benefits and risks. 

Breastfeeding warnings:  

No data is available regarding the excretion of drug in breast milk. 

Pregnancy category: B 

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 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: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

Recombinant acid alpha-glucosidase (GAA) works by having carbohydrate groups on its molecule bind to mannose-6-phosphate receptors. This binding allows GAA to be transported into the cell. Once inside the cell, GAA undergoes proteolytic cleavage, leading to an increase in its ability to break down glycogen enzymatically. 

Pharmacodynamics: 

Limited data is available 

Pharmacokinetics: 

Absorption 

The time to achieve peak effect is 3-4 hours 

Peak plasma concentration is 131-193 mcg/m 

Distribution 

The volume of distribution is 80-110 L/kg 

AUC is 670-952 mcg-hour/mL 

Elimination and Excretion 

The half-life is 2-3 hours 

Clearance is 20-30 mL per hour per kg 

Adminstartion

Administration: 

It is indicated for long-term enzyme replacement therapy in confirmed Pompe disease patients. A physician experienced in managing such conditions should supervise treatment. The recommended dose is 20 mg/kg, administered intravenously every two weeks. Reconstitute Myozyme with water for injections, dilute with sodium chloride 9 mg/ml solution and administer via intravenous infusion using aseptic techniques. A 0.2-micron low protein binding in-line filter is recommended, with incremental administration starting at 1 mg/kg/h and increasing gradually up to a maximum rate of 7 mg/kg/h if no infusion reactions occur. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: alglucosidase alfa 

Pronounced: al-gloo-KOS-i-dase AL-fa 

Why do we use alglucosidase alfa? 

Alglucosidase alfa is employed to treat Pompe disease, an uncommon hereditary lysosomal storage disorder. Pompe disease results from a shortage of the enzyme acid alpha-glucosidase (GAA), causing glycogen accumulation, especially in muscles. Serving as an enzyme replacement therapy, alglucosidase alfa substitutes the deficient GAA enzyme, diminishing glycogen buildup and relieving symptoms related to Pompe disease. The goal of the therapy is to improve muscle function and the general quality of life for those who have this genetic condition.