Agalsidase beta

U.S. BRAND NAMES — Fabrazyme®
PHARMACOLOGIC CATEGORY Enzyme
DOSING: ADULTS — Fabry disease: I.V.: 1 mg/kg every 2 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment required.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 5 mg [contains mannitol 33 mg; derived from Chinese hamster cells]; 35 mg [contains mannitol 222 mg/vial; derived from Chinese hamster cells]
DOSAGE FORMS: CONCISE Injection, powder for reconstitution: Fabrazyme®: 5 mg, 35 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Antipyretics should be administered prior to infusion. Initial infusion rate should not exceed 0.25 mg/minute (15 mg/hour). Decrease rate in the event of an infusion reaction. After patient tolerance to the infusion is established, rate may be increased in increments of 0.05-0.08 mg/minute (3-5 mg/hour) with each subsequent infusion. A 0.2 micron low protein-binding filter may be used.
COMPATIBILITY — Stable in NS.
Compatibility when admixed: Do not mix with other products.
USE — Replacement therapy for Fabry disease
ADVERSE REACTIONS SIGNIFICANT — Note: The most common and serious adverse reactions are infusion reactions (symptoms may include fever, tachycardia, hypertension, throat tightness, dyspnea, chills, abdominal pain, pruritus, urticaria, vomiting).
>10%: Cardiovascular: Edema (21%), chest pain (17%), hypotension (14%) Central nervous system: Fever (48%), headache (45%), anxiety (28%), pain (21%), dizziness (14%), paresthesia (14%) Dermatologic: Pallor (14%) Gastrointestinal: Nausea (28%) Neuromuscular & skeletal: Rigors (52%), skeletal pain (21%) Respiratory: Rhinitis (38%), pharyngitis (28%) Miscellaneous: Infusion reactions (alteration of temperature sensation 17%)
1% to 10%: Cardiovascular: Cardiomegaly (10%), hypertension (10%) Central nervous system: Depression (10%) Gastrointestinal: Dyspepsia (10%) Genitourinary: Testicular pain (7%) Neuromuscular & skeletal: Arthrosis (10%) Respiratory: Bronchitis (10%), bronchospasm (7%), laryngitis (7%), sinusitis (7%)
Other reported severe reactions (frequency not established): Arrhythmia, ataxia, bradycardia, cardiac arrest, cardiac output decreased, nephritic syndrome, stroke, vertigo
CONTRAINDICATIONS — No known contraindications
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Infusion reactions: Are common, and may be severe; pretreatment with antipyretics is advised.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease; risk related infusion reactions may be increased.
Special populations: Pediatrics: Safety and efficacy have not been established in children (studies limited to patients 16 years of age).
Other warnings/precautions: Registry: A registry has been created to monitor therapeutic responses and adverse effects during long-term treatment; patients should be encouraged to register (www.fabryregistry.com or 1-800-745-4447).
DRUG INTERACTIONS — No formal drug interaction studies have been conducted.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential are encouraged to enroll in Fabry registry.
LACTATION — Excretion in breast milk unknown/use caution
BREAST-FEEDING CONSIDERATIONS — Nursing mothers are encouraged to enroll in Fabry registry.
MONITORING PARAMETERS — Development of IgG or IgE antibodies in patients with suspected allergic reactions (test available from manufacturer).
CANADIAN BRAND NAMES — Fabrazyme®
INTERNATIONAL BRAND NAMES — Fabrazyme (AT, BE, BG, CA, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IL, IT, NL, NO, PL, PT, RU, SE, TR)
MECHANISM OF ACTION — Agalsidase beta is a recombinant form of the enzyme alpha-galactosidase-A, which is required for the hydrolysis of GL-3 and other glycosphingolipids. The compounds may accumulate (over many years) within the tissues of patients with Fabry disease, leading to renal and cardiovascular complications. In clinical trials of limited duration, agalsidase been noted to reduce tissue inclusions of a key sphingolipid (GL-3). It is believed that long-term enzyme replacement may reduce clinical manifestations of renal failure, cardiomyopathy, and stroke. However, the relationship to a reduction in clinical manifestations has not been established.
PHARMACODYNAMICS / KINETICS — Half-life elimination: 42-102 minutes (nonlinear)