Agalsidase bet

U.S. BRAND NAMES — Fabrazyme®
CANADIAN BRAND NAMES — Fabrazyme®
SYNONYMS — Fabrase; Recombinant Human Alpha-Galactosidase A
THERAPEUTIC CATEGORY Enzyme, alpha-galactosidase AFabry's Disease, Treatment Agent
DOSING — I.V.: Children and Adults: 1 mg/kg/dose every two weeks
(For additional information see "Agalsidase beta: Drug information")
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]
GENERIC AVAILABLE — No
ADMINISTRATION — I.V.: Reconstitute vial with 7.2 mL SWI to result in 5 mg/mL concentration; swirl to dissolve; do not shake; further dilute dosage in 500 mL NS*. Initial infusion not to exceed 15 mg/hour (0.25 mg/minute); after patient tolerance to initial infusion rate is established, the infusion rate may be increased in increments of 3-5 mg/hour (0.05-0.08 mg/minute) with subsequent infusions. In clinical studies, patients have tolerated infusion rates 33 mg/hour. Pretreatment with acetaminophen and an antihistamine is recommended to reduce infusion related side effects (See Warnings)
*Agalsidase beta stability when diluted in NS at a concentration of 2.55 mg/mL has been demonstrated by the manufacturer. Infusion volumes as low as 100 mL were used in phase I/II clinical trials. (Personal communication, Genzyme Corporation, 2003)
USE — Treatment of Fabry's disease
ADVERSE REACTIONS Cardiovascular: Tachycardia, hypertension, hypotension, chest pain, chest tightness, bradycardia, arrhythmias, cardiac arrest, edema, pallor
Central nervous system: Headache, dizziness, fever, anxiety, depression, chills, rigors, vertigo
Dermatologic: Pruritus, urticaria
Gastrointestinal: Dyspepsia, nausea, abdominal pain, vomiting
Genitourinary: Testicular pain
Neuromuscular & skeletal: Arthrosis, skeletal pain, myalgia
Otic: Hypoacousia
Respiratory: Bronchitis, bronchospasm, laryngitis, pharyngitis, sinusitis, rhinitis, dyspnea
Miscellaneous: Hypersensitivity reactions
CONTRAINDICATIONS — Hypersensitivity to agalsidase beta or any component
PRECAUTIONS — Use with caution in patients with compromised cardiac function (seen in advanced Fabry's disease) due to an increased potential for severe infusion related reactions; monitor these patients closely; patients may develop IgG antibodies to agalsidase beta
WARNINGS — Infusion-related reactions (ranging from mild to severe) including fever, rigors, chest tightness, hypertension, hypotension, pruritus, myalgia, dyspnea, urticaria, abdominal pain, and headache have been reported; these reactions may be minimized by pretreatment with acetaminophen and an antihistamine; if an infusion related reaction occurs, regardless of pretreatment, decreasing the infusion rate, temporarily stopping the infusion, and/or additional administration of analgesics, antihistamines, or corticosteroids may ameliorate the reaction.
DRUG INTERACTIONS — None as yet have been identified
PREGNANCY RISK FACTOR — B (show table)
MONITORING PARAMETERS — Vital signs during infusion; globotriaosylceramide (GL3) plasma levels; improvement in symptomatology
REFERENCE RANGE — Normal endogenous activity of alpha-galactosidase A in plasma is approximately 170 nmol/hour/mL; in patients with Fabry's disease this activity is <1.5 nmol/hour/mL
Normal (goal) globotriaosylceramide (GL3) <1.2 ng/microliter
STABILITY — Store in refrigerator 2ºC to 8ºC (36ºF to 46ºF); reconstituted solution is stable for 24 hours refrigerated
MECHANISM OF ACTION — Agalsidase beta is a recombinant human alpha-galactosidase A enzyme with the same amino acid sequence as the naturally-occurring enzyme. Fabry's disease is an X-linked genetic disorder occurring in 1 in 50,000 male births, which results in a deficiency of alpha-galactosidase A. Lack of this enzyme leads to a progressive accumulation of glycosphingolipids, predominantly GL-3, in the vascular endothelium, leading to ischemia and infarction, especially in the kidney, heart, and brain. Clinical manifestations of Fabry's disease in childhood include intermittent severe pain in the extremities, characteristic vascular skin lesions (angiokeratomas), corneal and lenticular opacities that do not affect vision, decreased ability to sweat, intolerance to heat, cold, and exercise, mild proteinuria, and GI problems. By adulthood, this progresses to renal failure, cardiomyopathy, and cerebrovascular accidents.
PHARMACOKINETICS Distribution: Vd: Adults: 80-330 mL/kg
Half-life: Adults: 45-102 minutes (dose dependent)
ADDITIONAL INFORMATION — Agalsidase beta is an orphan drug; a Fabry Patient Support Group (800-745-4447) is available to assist patients in obtaining reimbursement from private insurers, Medicare, and Medicaid, and a Charitable Access Program sponsored by Genzyme provides the drug gratis to those patients in need. Detailed information regarding organizations and websites is also available in the Expert Panel Recommendations (Desnick, 2003)