Version July 2025
Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement and after extended duration of therapy. Initiate agalsidase beta in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (eg, anaphylaxis) occurs, discontinue agalsidase beta and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur.
Dosage guidance:
Safety: Consider pretreatment with antihistamines, antipyretics, and/or corticosteroids. Initiate in a health care setting that includes cardiopulmonary monitoring and can provide resuscitation if necessary.
Fabry disease: Children ≥2 years and Adolescents: IV: 1 mg/kg/dose every 2 weeks (Ref).
Patients with IgE antibodies or a positive skin test to agalsidase beta (rechallenge): Children ≥2 years and Adolescents: IV: 0.5 mg/kg/dose every 2 weeks.
There are no dosage adjustments provided in the manufacturer's labeling; however, dose adjustment is unlikely to be necessary as agalsidase beta is used to reduce complications of Fabry disease (which includes kidney impairment) (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Agalsidase beta: Drug information")
Dosage guidance:
Clinical considerations: Consider pretreatment with antihistamines, antipyretics, and/or corticosteroids prior to agalsidase beta administration. Initiate in a health care setting with appropriate medical monitoring and support measures, including CPR equipment, readily available during administration.
Fabry disease: IV: 1 mg/kg every 2 weeks. Initial infusion rate should not exceed 0.25 mg/minute (15 mg/hour); rate may be increased in increments of 0.05 to 0.08 mg/minute (3 to 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.
No dosage adjustment required.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Hypertension (14%), peripheral edema (21%)
Dermatologic: Skin rash (20%)
Gastrointestinal: Abdominal pain, diarrhea, nausea, vomiting
Immunologic: Antibody development (69% to 83%)
Local: Infusion site reaction (59%; severe infusion related reaction: 5%)
Nervous system: Chills (49%), dizziness (21%), fatigue (24%), headache (39%), pain (16%), paresthesia (31%)
Neuromuscular & skeletal: Arthralgia, back pain (16%), limb pain (19%), myalgia (18%)
Respiratory: Cough (33%), lower respiratory tract infection (18%), pharyngitis, rhinitis, upper respiratory tract infection (53%)
Miscellaneous: Fever (39%)
1% to 10%:
Cardiovascular: Chest discomfort (5%), tachycardia (9%)
Dermatologic: Excoriation of skin (9%), pruritus (10%)
Endocrine & metabolic: Hot flash (5%)
Hypersensitivity: Anaphylaxis (≤1%), hypersensitivity reaction (≤1%, including severe hypersensitivity reaction)
Infection: Fungal infection (5%), viral infection (5%)
Nervous system: Anxiety (6%), burning sensation (6%), depression (6%), falling (6%)
Otic: Hypoacusis (5%), tinnitus (8%)
Renal: Increased serum creatinine (9%)
Respiratory: Dyspnea (8%), wheezing (6%)
Frequency not defined:
Cardiovascular: Bradycardia, chest pain, facial edema, flushing, hypotension
Dermatologic: Urticaria
Nervous system: Drowsiness, sensation of cold
Respiratory: Nasal congestion, pharyngeal edema
Postmarketing:
Cardiovascular: Acute myocardial infarction, cardiac failure, cerebrovascular accident, hypersensitivity angiitis, palpitations
Dermatologic: Hyperhidrosis
Gastrointestinal: Dysphagia, oral hypoesthesia
Hematologic & oncologic: Lymphadenopathy
Hypersensitivity: Angioedema
Nervous system: Hypoesthesia
Neuromuscular & skeletal: Asthenia
Renal: Renal failure syndrome
Respiratory: Bronchospasm, hypoxia, respiratory failure
There are no contraindications listed within the US labeling.
Canadian labeling: Anaphylaxis to agalsidase beta or any component of the formulation.
Concerns related to adverse effects:
• 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 or skin test reactivity; consider IgE testing in patients with allergic reaction. Rechallenge of patients with IgE-mediated reaction or who have had a positive skin test may be done with caution.
• Hypersensitivity: Agalsidase alfa may cause severe hypersensitivity reactions, including anaphylaxis (sometimes life-threatening). The most common hypersensitivity reactions reported in clinical trials include angioedema, bronchospasm, chest discomfort, dysphagia, dyspnea, flushing, hypotension, nasal congestion, pruritus, rash, and urticaria. Patients who develop IgE antibodies may be at a higher risk for hypersensitivity reactions. Management strategies of more severe reactions include symptomatic treatment, pretreatment with antihistamines, antipyretics, and/or corticosteroids, and slowing of the infusion rate. Treatment should be discontinued if anaphylaxis or other acute reactions occur.
• Infusion reactions: Infusion-related reactions are common, and may be severe (chills, vomiting, hypotension, paresthesia); consider pretreatment with antipyretics, antihistamines, and/or corticosteroids. Patients who were positive for anti-Fabrazyme antibodies had an increased incidence of infusion-related reactions. 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 compromised cardiac function; may have increased risk of complications from infusion reactions.
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; patients should be encouraged to register (www.registrynxt.com or 1-800-745-4447).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Fabrazyme: 5 mg (1 ea); 35 mg (1 ea) [contains mouse (murine) and/or hamster protein]
No
Solution (reconstituted) (Fabrazyme Intravenous)
5 mg (per each): $1,341.62
35 mg (per each): $9,392.96
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Fabrazyme: 5 mg (1 ea); 35 mg (1 ea)
Note: Initiate infusion in a health care setting that includes cardiopulmonary monitoring and can provide resuscitation if necessary. Consider pretreatment with antihistamines, antipyretics, and/or corticosteroids.
Parenteral: IV infusion: Administer using 0.2 micron low protein-binding filter. Infusion rate, titration, and maximum infusion rate determined based on weight and presence of antibodies or positive skin test.
Patient weight <30 kg: Initiate at 15 mg/hour (0.25 mg/minute); no further titration recommended; maximum infusion rate: 15 mg/hour (0.25 mg/minute).
Patient weight ≥30 kg: Initiate at 15 mg/hour (0.25 mg/minute); after tolerance to initial infusion rate is established, the infusion rate may be increased in increments of 3 to 5 mg/hour (0.05 to 0.08 mg/minute) with each subsequent infusions. Administration duration: ≥1.5 hours (based upon individual tolerability).
Rechallenge in patients with IgE antibodies or who have had a positive skin test to agalsidase beta: Administer using a lower initial infusion rate of 0.6 mg/hour (0.01 mg/minute); after the infusion is tolerated, slowly increase the infusion by doubling the infusion rate every 30 minutes as tolerated to a maximum rate of 15 mg/hour (0.25 mg/minute).
Rate adjustment for infusion-related reactions or hypersensitivity:
Mild to moderate infusion-related reactions: Consider slowing infusion rate, temporary interruption of the infusion, and/or dose reduction.
Anaphylaxis or severe hypersensitivity or infusion-related reaction: Discontinue therapy immediately and initiate appropriate medical treatment. If the decision is made to readminister following a risk versus benefit assessment, appropriately trained personnel and emergency medications should be immediately available and patients monitored closely for recurrence.
IV: Consider administering antihistamines, antipyretics, and/or corticosteroids prior to infusion; have appropriate medical monitoring and support measures, including CPR equipment, readily available during administration. Infuse through a low protein binding 0.2 micron in-line filter. 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 to 0.08 mg/minute (3 to 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 (0.6 mg/hour) should be used for rechallenge in patients with IgE antibodies or who have had a positive skin test to agalsidase beta; may increase infusion rate (doubling the infusion rate every 30 minutes) to a maximum rate of 0.25 mg/minute as tolerated.
Store intact vials between 2°C and 8°C (36°F and 46°F). Product is preservative free; use reconstituted and solutions diluted in NS immediately. If not used immediately, reconstituted and diluted solutions are stable for 24 hours at 2°C and 8°C (36°F and 46°F).
Treatment of confirmed Fabry disease (FDA approved in ages ≥2 years and adults).
Agalsidase beta may be confused with agalsidase alfa, alglucerase, alglucosidase alfa
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Amiodarone: May decrease therapeutic effects of Agalsidase Beta. Management: Avoid concomitant use of amiodarone with agalsidase beta when possible as amiodarone could antagonize intracellular alpha-galactosidase activity. Risk D: Consider Therapy Modification
Chloroquine: May decrease therapeutic effects of Agalsidase Beta. Management: Avoid concomitant use of chloroquine with agalsidase beta when possible as chloroquine could antagonize intracellular alpha-galactosidase activity. Risk D: Consider Therapy Modification
Gentamicin (Systemic): May decrease therapeutic effects of Agalsidase Beta. Management: Avoid concomitant use of gentamicin with agalsidase beta when possible as gentamicin could antagonize intracellular alpha-galactosidase activity. Risk D: Consider Therapy Modification
Hydroxychloroquine: May decrease therapeutic effects of Agalsidase Beta. Risk C: Monitor
Outcome data related to the use of agalsidase beta in pregnancy are limited (Germain 2010; Madsen 2019; Politei 2010; Senocak Tasci 2015).
Data collection to monitor pregnancy and infant outcomes following exposure to Fabrazyme is ongoing. Patients may enroll in the Fabry registry by calling 1-800-745-4447 extension 15500 (http://www.registrynxt.com). Pregnant patients or their health care providers may also call 1-800-633-1610, option 1.
Signs/symptoms of hypersensitivity (including anaphylaxis); infusion-related reactions (chills, vomiting, hypotension, paresthesia); vital signs during infusion; infusion-related reactions; globotriasylceramide (GL3) plasma concentrations; development of IgG or IgE antibodies in patients with suspected allergic reactions (test available from manufacturer).
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.
Distribution: Vdss: Mean range: Children: 247 to 1,097 mL/kg; Adults: 81 to 570 mL/kg.
Half-life elimination (dose-dependent): Mean range: Children: 86 to 151 minutes; Adults: 45 to 119 minutes.
Clearance: Children: Mean range: 1.1 to 5.8 mL/minute/kg; Adults: 0.8 to 4.9 mL/minute/kg.
