|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Pronunciation
(aye GAL si days BAY ta)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Replacement therapy for Fabry disease
Pregnancy Risk Factor
B
Pregnancy Considerations
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 (www.fabryregistry.com or 1-800-745-4447).
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
Nursing mothers are encouraged to enroll in Fabry registry.
Contraindications
There are no contraindications listed within the manufacturers labeling.
Warnings/Precautions
Concerns related to adverse effects:
• Anaphylaxis/allergic reactions: Life-threatening anaphylactic and severe allergic reactions have been reported. Reactions may include angioedema, bronchospasm, chest discomfort, dysphagia, dyspnea, flushing, hypotension, nasal congestion, pruritus, rash, and urticaria. Stop infusion if severe reactions occur; immediate medical support should be readily available.
• Antibody formation: Development of IgG antibodies is common and has been observed within 3 months from the onset of therapy. 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 (chills, vomiting, hypotension, paresthesia); pretreatment with antipyretics and antihistamines is advised. Decrease infusion rate, temporarily discontinue infusion, and/or administer additional antipyretics, antihistamines, and/or steroids to manage infusion reactions. Immediate discontinuation of infusion should be considered for severe reactions. Appropriate medical support for the management of infusion reactions should be readily available. Infusion reactions have occurred despite premedication. Use with caution when readministering to patients with history of infusion reactions.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with cardiovascular disease; may have increased risk of complications from infusion reactions; monitor closely.
Other warnings/precautions:
• Registry: A registry has been created to monitor therapeutic responses and adverse effects during long-term treatment, as well as effects on pregnant and breast-feeding women and their offspring; should be encouraged to register (www.fabryregistry.com or 1-800-745-4447).
Adverse Reactions
Note: The most common and serious adverse reactions are infusion reactions (symptoms may include fever, tachycardia, hyper-/hypotension, throat tightness, dyspnea, chills, abdominal pain, paresthesia, pruritus, urticaria, vomiting).
>10%:
Cardiovascular: Peripheral edema (21%)
Central nervous system: Chills (43%), fever (39%), headache (39%), fatigue (24%), dizziness (21%), pain (16%)
Local: Infusion site reactions (50% to 55%; severe: ≥5%), procedural pain (25%)
Neuromuscular & skeletal: Paresthesia (31%), pain in extremity (19%), back pain (16%)
Respiratory: Upper respiratory tract infection (44%), cough (33%), nasal congestion (19%), lower respiratory infection (18%)
Miscellaneous: IgG antibody formation (69% to 79%), feeling cold (11%)
1% to 10%:
Cardiovascular: Hypertension (14%), tachycardia (9%), bradycardia (≥5%), chest pain/discomfort (≥5%), facial edema (≥5%), flushing (≥5%), hypotension (≥5%), pallor (≥5%), ventricular wall thickening (5%)
Central nervous system: Hypoesthesia (9%), anxiety (6%), depression (6%)
Dermatologic: Rash (20%), pruritus (10%), excoriation (9%), urticaria (≥5%), bruising (4%)
Gastrointestinal: Toothache (6%), abdominal pain (≥5%), diarrhea (≥5%), nausea (≥5%), vomiting (≥5%), xerostomia (4%)
Local: Postprocedural complication (10%), thermal burn (4%)
Neuromuscular & skeletal: Myalgia (14%), burning sensation (6%), fall (6%), muscle spasms (5%)
Otic: Tinnitus (8%), hearing impairment (5%)
Renal: Creatinine increased (9%)
Respiratory: Sinusitis (9%), congestion (8%), dyspnea (8%), pharyngitis (6%), wheezing (6%), throat tightness (≥5%)
Miscellaneous: Viral infection (5%), fungal infection (5%)
Other reported severe reactions (frequency not established): Anaphylaxis, allergic reactions, arrhythmia, ataxia, cardiac arrest, cardiac output decreased, nephrotic syndrome, stroke, vertigo
<1%, postmarketing, and/or case reports: Anaphylactic shock, angioedema (including dysphagia, edema of ears, edema of eye, edema of lips, edema of tongue, pharyngeal edema), arthralgia, bronchospasm, cerebrovascular accident, erythema, heart failure, hypoxia, hyperhidrosis, lacrimation increased, leukocytoclastic vasculitis, lymphadenopathy, MI, oxygen saturation decreased, palpitation, pneumonia, renal failure, respiratory failure, rhinorrhea, sepsis, weakness
Metabolism/Transport Effects
None known.
Drug Interactions
Amiodarone: May diminish the therapeutic effect of Agalsidase Beta. Risk X: Avoid combination
Chloroquine: May diminish the therapeutic effect of Agalsidase Beta. Risk X: Avoid combination
Gentamicin: May diminish the therapeutic effect of Agalsidase Beta. Risk X: Avoid combination
Gentamicin (Systemic): May diminish the therapeutic effect of Agalsidase Beta. Risk X: Avoid combination
Storage
Store intact vials between 2°C and 8°C (36°F and 46°F); do not freeze.
Reconstitution
Allow vials and diluent to reach room temperature prior to reconstitution (~30 minutes). Each 35 mg vial should be reconstituted with 7.2 mL SWFI; reconstitute 5 mg vials with 1.1 mL SWFI; inject down internal side wall of vial; roll and tilt gently. Resulting solution contains 5 mg/mL. Do not use filter needle to prepare. To make final infusion, add the desired amount of reconstituted solution to make a final volume based on patient weight. The minimum total volume will range from 50 mL in patients ≤35 kg to 500 mL in patients >100 kg. Avoid vigorous shaking or agitation.
Compatibility
Stable in NS.
Compatibility when admixed: Do not mix with other products.
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: 81-570 mL/kg
Half-life elimination: Children: 86-151 minutes; Adults: 45-119 minutes
Dosage
I.V.: Children ≥8 years and Adults: 1 mg/kg every 2 weeks
Dosage adjustment in 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 adjustment in renal impairment: No dosage adjustment required
Administration: I.V.
Antipyretics should be administered prior to infusion.
Administration: I.V. Detail
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.
Monitoring Parameters
Development of IgG or IgE antibodies in patients with suspected allergic reactions (test available from manufacturer). Monitor for infusion-related reactions.
Patient Education
This medication can only be administered by infusion; you will be closely monitored during infusion. Report immediately difficulty breathing or chest tightness, vomiting, difficulty swallowing, itching or rash, or swelling. Between treatments, maintain adequate nutrition and hydration, unless instructed to restrict fluid intake. You may experience abdominal discomfort or vomiting, headache, fatigue, dizziness, or muscle pain. Report chest pain, palpitations, severe headache, signs of infection or rash, swelling of limbs or significant weight increase, difficulty breathing, persistent gastrointestinal discomfort, or numbness in extremities.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Anxiety and dizziness are common; may cause depression
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Assess patient for previous experience with enzyme replacement therapy prior to beginning treatment. Premedication with antipyretics is recommended. Patient must be monitored closely for infusion reactions (fever, chills, dyspnea, tachycardia, hypertension, pruritus, vomiting) during and following infusion; medication/equipment for treating reactions should be readily available. Encourage patients to enroll in Fabry registry.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Fabrazyme®: 5 mg [contains mannitol; derived from or manufactured using Chinese hamster ovary cells]
Fabrazyme®: 35 mg [contains mannitol; derived from or manufactured using Chinese hamster ovary cells]
References
Banikazemi M, Bultas J, Waldek S, et al, “Agalsidase-Beta Therapy for Advanced Fabry Disease: a Randomized Trial,” Ann Intern Med, 2007, 146(2):77-86.
Eng C, Guffton N, Wilcox WR, et al, “Safety and Efficacy of Recombinant Human Alpha-Galactosidase A Replacement Therapy in Fabry's Disease,” N Engl J Med, 2001, 345(1):9-16.
Lidove O, Joly D, Barbey, F, et al, “Clinical Results of Enzyme Replacement Therapy in Fabry Disease: A Comprehensive Review of Literature,” Int J Clin Pract, 2007, 61(2):293-302.
International Brand Names
Lexi-Comp.com
Last full review/revision October 2011
Content last modified October 2011
| 
