Fabrazyme (agalsidase beta) Injection, powder, lyophilized for solution for intravenous use
Fabry disease is an X-linked genetic disorder of glycosphingolipid metabolism. Deficiency of the lysosomal enzyme α-galactosidase A leads to progressive accumulation of glycosphingolipids, predominantly GL-3, in many body tissues, starting early in life and continuing over decades. Clinical manifestations of Fabry disease include renal failure, cardiomyopathy, and cerebrovascular accidents.
Fabry disease is an X-linked genetic disorder of glycosphingolipid metabolism. Deficiency of the lysosomal enzyme α-galactosidase A leads to progressive accumulation of glycosphingolipids, predominantly GL-3, in many body tissues, starting early in life and continuing over decades. Clinical manifestations of Fabry disease include renal failure, cardiomyopathy, and cerebrovascular accidents.
Accumulation of GL-3 in renal endothelial cells may play a role in renal failure. Fabrazyme® (agalsidase beta) is intended to provide an exogenous source of α-galactosidase A in Fabry disease patients. Nonclinical and clinical studies evaluating a limited number of cell types indicate that Fabrazyme will catalyze the hydrolysis of glycosphingolipids, including GL-3.
Initial U.S. Approval: 2003
Initial U.S. Approval: 2003
RECENT MAJOR CHANGES
Warnings and Precautions, Anaphylaxis and Allergic Reactions 2008
INDICATIONS AND USAGE
Fabrazyme is indicated for use in patients with Fabry disease. Fabrazyme reduces globotriaosylceramide (GL-3) deposition in capillary endothelium of the kidney and certain other cell types
DOSAGE AND ADMINISTRATION
1 mg/kg body weight given every two weeks as an IV infusion. Patients should receive antipyretics prior to infusion.
DOSAGE FORMS AND STRENGTHS
Lyophilized powder for reconstitution with Sterile Water for Injection, USP to yield 5 mg/mL. Available as 35 mg or 5 mg single-use vials.
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
- Life-threatening anaphylactic and severe allergic reactions have been observed in some patients during Fabrazyme infusions. If severe allergic or anaphylactic reactions occur, immediately discontinue administration of Fabrazyme and provide necessary emergency treatment. Appropriate medical support measures should be readily available when Fabrazyme is administered because of the potential for severe infusion reactions. Infusion reactions occurred in approximately 50 to 55% of patients during Fabrazyme administration in clinical trials. Some reactions were severe. In patients experiencing infusion reactions, pretreatment with an antipyretic and antihistamine is recommended. If an infusion reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administrating additional antipyretics, antihistamines, and/or steroids may ameliorate the symptoms.
- If severe infusion reactions occur, immediate discontinuation of the administration of Fabrazyme should be considered, and appropriate medical treatment should be initiated. Severe reactions are generally managed with administration of antihistamines, corticosteroids, IV fluids and/or oxygen as clinically indicated.
- Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from infusion reactions, and these patients should be monitored closely during Fabrazyme administration
- Re-administration of Fabrazyme to patients who have previously experienced severe or serious allergic reactions to Fabrazyme should be done only after careful consideration of the risks and benefits of continued treatment, and only under the direct supervision of qualified personnel and with appropriate medical support measures readily available.
ADVERSE REACTIONS
The most common adverse reactions reported are infusion reactions. Serious and/or frequently occurring (≥ 5% incidence) related adverse reactions, including infusion reactions, consisted of one or more of the following: chills, fever, feeling hot or cold, dyspnea, nausea, flushing, headache, vomiting, paresthesia, fatigue, pruritus, pain in extremity, hypertension, chest pain, throat tightness, abdominal pain, dizziness, tachycardia, nasal congestion, diarrhea, edema peripheral, myalgia, back pain, pallor, bradycardia, urticaria, hypotension, face edema, rash, and somnolence
DRUG INTERACTIONS
- No drug interaction studies were performed
- No in vitro metabolism studies were performed