Replagal Agalsidase Alfa Concentrated Solution for Infusion

1. Indications and Usage
Fabry Disease:
Indicated for long-term enzyme replacement therapy in patients with confirmed Fabry disease (alpha-galactosidase A deficiency) to clear globotriaosylceramide (GL-3) from vascular endothelial cells and other cell types.
2. Dosage and Administration
Route of Administration:
For Intravenous (IV) Infusion ONLY. Must be administered by a healthcare professional.
Recommended Dosage:
The recommended dose is 0.2 mg/kg body weight administered every other week.
Administration Instructions:
Preparation: The concentrated solution must be diluted with 0.9% Sodium Chloride Injection, USP prior to administration. Do not mix with other medications in the same infusion line.
Infusion Rate: Administer as an IV infusion over approximately 40 minutes.
Premedication: Antipyretics or antihistamines may be considered prior to infusion to reduce the risk of hypersensitivity reactions.
Missed Dose: If a dose is missed, administer as soon as possible. Subsequent doses should be scheduled at 2-week intervals from the date of the last administered dose.
3. Mechanism of Action
Enzyme Replacement Therapy:
Agalsidase alfa is a purified form of the lysosomal enzyme alpha-galactosidase A. In patients with Fabry disease, this enzyme is deficient, leading to the accumulation of glycosphingolipids, primarily globotriaosylceramide (GL-3), in various tissues.
Substrate Clearance:
Exogenously administered agalsidase alfa is taken up into cellular lysosomes via mannose receptors, where it catalyzes the hydrolysis of GL-3 into lactosylceramide and galactose, thereby reducing GL-3 storage.
4. Safety and Warnings
Hypersensitivity Reactions (Including Anaphylaxis):
Severe hypersensitivity reactions, including anaphylaxis, have been reported during or shortly after infusion. Patients should be closely monitored during and after administration. Appropriate medical support must be readily available.
Antibody Formation:
Patients may develop IgG antibodies against agalsidase alfa. Antibody formation may be associated with hypersensitivity reactions and potentially reduced clinical efficacy.
Acute Renal Failure:
Cases of acute renal failure have been reported in patients receiving agalsidase alfa. Monitor renal function periodically.
Infusion-Associated Reactions:
Fever, chills, nausea, vomiting, headache, and fatigue are common during infusion. Slowing the infusion rate or temporarily stopping the infusion may alleviate symptoms.
5. Adverse Reactions
Most Common:
Chills, fever, headache, nausea, vomiting, fatigue, paresthesia, and pruritus. These events typically occur during or within hours of the infusion.
Other Reported Reactions:
Hypersensitivity reactions (rash, urticaria, dyspnea, hypotension, angioedema), elevated liver enzymes, and injection site reactions.
6. Drug Interactions
No formal drug-drug interaction studies have been conducted with agalsidase alfa. Because it is an enzyme replacement therapy, it is not expected to interact with drugs metabolized by hepatic cytochrome P450 enzymes. However, caution is advised when co-administering with nephrotoxic agents due to the underlying risk of renal impairment in Fabry disease.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Agalsidase alfa (recombinant human alpha-galactosidase A produced in human fibroblast cells).
Available Strengths: Vials containing 3.5 mg/3.5 mL (1 mg/mL) of agalsidase alfa.
Excipients: Polysorbate 20, sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate dihydrate, and water for injections.
Storage:
Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.