Agalsidase beta

EDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Agalsidase beta may be confused with agalsidase alfa, alglucerase, alglucosidase alfa

International issues:
Agalsidase beta may be confused with agalsidase alfa, which is available in international markets

U.S. BRAND NAMES — Fabrazyme®

PHARMACOLOGIC CATEGORY
Enzyme

DOSING: ADULTS — Fabry disease: I.V.: 1 mg/kg every 2 weeks

DOSING: PEDIATRIC

(For additional information see "Agalsidase beta: Pediatric drug information")
Fabry disease: Children ≥ 8 years: I.V.: 1 mg/kg every 2 weeks

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT — No dosage adjustment required.

DOSING: ADJUSTMENT FOR TOXICITY — Patient with IgE antibodies to agalsidase beta (rechallenge): 0.5 mg/kg every 2 weeks at an initial maximum infusion rate of 0.01 mg/minute; may gradually escalate dose (to maximum of 1 mg/kg every 2 weeks) and/or infusion rate (doubling the infusion rate every 30 minutes to a maximum rate of 0.25 mg/minute) as tolerated.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution:
Fabrazyme®: 5 mg [contains mannitol 33 mg; derived from Chinese hamster cells]; 35 mg [contains mannitol 222 mg; 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). Interrupt or decrease rate in the event of an infusion reaction; may be restarted after resolution of symptoms and/or after administration of antipyretics, antihistamines, and/or steroids. 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. Maximum infusion rate: Patients <30 kg: 0.25 mg/minute; patients ≥ 30 kg: Infuse over at least 1.5 hours. An initial maximum infusion rate of 0.01 mg/minute should be used for rechallenge in patients with IgE antibodies; may increase infusion rate (doubling the infusion rate every 30 minutes) to a maximum rate of 0.25 mg/minute as tolerated. A 0.2 micron low protein-binding filter may be used during administration.

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: Peripheral edema (21%)
Central nervous system: Chills (43%), headache (39%), fever (6% to 36%), fatigue (25%), dizziness (21%), pain (16%)
Gastrointestinal: Vomiting (24%)
Hematologic: Anemia (14%)
Neuromuscular & skeletal: Paresthesia (31%), limb pain (19%), back pain (16%)
Respiratory: Cough (33%), nasopharyngitis (28%), nasal congestion (19%), upper respiratory tract infection (19%), pharyngolaryngeal pain (16%), lower respiratory infection (11%)
Miscellaneous: IgG antibody formation (69% to 79%)

1% to 10%:
Cardiovascular: Hypertension (5% to 10%), chest discomfort (5%), tachycardia (5%), ventricular wall thickening (5%)
Central nervous system: Hypoesthesia (9%), insomnia (9%), anxiety (8%), depression (6%)
Dermatologic: Rash (10%), excoriation (9%), pruritus (8%), contact dermatitis (5%)
Endocrine & metabolic: Bicarbonate decreased (9%)
Gastrointestinal: Abdominal discomfort (6%), toothache (6%)
Neuromuscular & skeletal: Myalgia (8%), burning sensation (6%), muscle spasms (5%), neck pain (5%)
Otic: Tinnitus (8%), hearing impairment (5%)
Renal: Creatinine increased (9%), proteinuria (5%)
Respiratory: Sinusitis (9%), bronchitis (8%), congestion (8%), dyspnea (8%), pharyngitis (6%), wheezing (6%)
Miscellaneous: Feeling cold (10%), viral infection (5% to 6%), fungal infection (5%), infusion reactions (≥ 5%)

Other reported severe reactions (frequency not established): Abdominal pain, arrhythmia, ataxia, bradycardia, cardiac arrest, cardiac output decreased, chest pain, face edema, flushing, hypotension, nausea, nephrotic syndrome, pallor, stroke, throat tightness, urticaria, vertigo

CONTRAINDICATIONS — Hypersensitivity to agalsidase beta or any component of the formulation

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Antibody formation: Development of IgG antibodies is common, however some patients may also develop IgE antibodies; consider IgE testing in patients with allergic reaction. Rechallenge of patients with IgE-mediated reaction may be done with caution. Infusion reactions: Infusion-related reactions are common, and may be severe; pretreatment with antipyretics is advised. Medication for the treatment of reactions should be readily available.

Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease; may have increased risk of complications from infusion reactions; monitor closely.

Special populations: Pediatrics: Safety and efficacy have not been established in children <8 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 — There are no known significant interactions.

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — Animal reproduction studies have not demonstrated adverse effects. 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). Monitor for infusion-related reactions.

CANADIAN BRAND NAMES — Fabrazyme®

INTERNATIONAL BRAND NAMES — Fabrazyme (AT, AU, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IL, IT, KP, NL, NO, NZ, PL, PT, RU, SE, TR, TW)

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
Distribution: Vdss: Children: 247-1097 mL/kg; Adults: 112-570 mL/kg

Half-life elimination: Children: 86-151 minutes; Adults: 45-119 minutes