Version May 2024
Fabry disease: IV: 1 mg/kg every 2 weeks.
No dosage adjustment required.
There are no dosage adjustments provided in the manufacturer's labeling.
Patient with IgE antibodies or a positive skin test to agalsidase beta (rechallenge): IV: 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.
Refer to adult dosing.
(For additional information see "Agalsidase beta: Pediatric drug information")
Note: Pretreat with antipyretics (eg, acetaminophen) prior to infusion; patients with prior infusion-related reactions should also receive antihistamines.
Fabry disease: Children ≥2 years and Adolescents: IV: 1 mg/kg/dose every 2 weeks (Ref).
Dosing adjustment for toxicity: 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 at an initial maximum infusion rate of 0.01 mg/minute; once tolerated, may gradually escalate dose (to maximum of 1 mg/kg/dose 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.
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.
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: Life-threatening anaphylactic reactions and severe hypersensitivity reactions (eg, angioedema, bronchospasm, chest discomfort, dysphagia, dyspnea, flushing, hypotension, nasal congestion, pruritus, rash, urticaria) have been reported. Patients who develop IgE antibodies may be at a higher risk for hypersensitivity reactions. Stop infusion if severe reactions occur; immediate medical support should be readily available. Consider risks/benefits of readministration following an anaphylactic or severe allergic reaction; some patients have been rechallenged under close clinical supervision; appropriate emergency medications should be immediately available.
• Infusion reactions: Infusion-related reactions are common, and may be severe (chills, vomiting, hypotension, paresthesia); pretreatment with antipyretics and antihistamines is advised. Patients who were positive for anti-Fabrazyme antibodies had an increased incidence of infusion-related reactions. 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 compromised cardiac function; 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; 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): $1,277.74
35 mg (per each): $8,945.68
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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)
IV: Antipyretics should be administered prior to infusion. 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 0.05-0.08 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 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.
IV: Pretreatment with acetaminophen and an antihistamine is recommended to reduce infusion-related reactions. 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 <30 kg: Infusion should be initiated at a rate of 15 mg/hour (0.25 mg/minute); no further titration recommended; maximum infusion rate: 15 mg/hour (0.25 mg/minute).
Patient ≥30 kg: Infusion should be initiated at a rate of 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: Patients with IgE antibodies or who have had a positive skin test to agalsidase beta: Patients being rechallenged should receive 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).
Fabry disease: Treatment of Fabry disease in adults and pediatric patients ≥2 years of age.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Amiodarone: May diminish the therapeutic effect 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 diminish the therapeutic effect 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 diminish the therapeutic effect 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 diminish the therapeutic effect of Agalsidase Beta. Risk C: Monitor therapy
Data collection to monitor pregnancy and infant outcomes following exposure to Fabrazyme is ongoing. Females of childbearing potential may enroll in the Fabry registry by calling 1-(800)-745-4447 extension 15500 (www.registrynxt.com).
Information related to the use of agalsidase beta in pregnancy is limited (Germain 2010; Madsen 2019; Politei 2010; Senocak Tasci 2015).
Data collection to monitor pregnancy and infant outcomes following exposure to Fabrazyme is ongoing. Pregnant females may enroll in the Fabry registry by calling 1-(800)-745-4447 extension 15500 (www.registrynxt.com).
It is not known if agalsidase beta is present in breast milk.
According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risks of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Data collection to monitor pregnancy and infant outcomes following exposure to Fabrazyme is ongoing. Lactating women may enroll in the Fabry registry by calling 1-(800)-745-4447 extension 15500 (www.registrynxt.com).
Development of IgG or IgE antibodies in patients with suspected allergic reactions (test available from manufacturer). Monitor for infusion-related reactions.
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.
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