Version May 2024
Note: Premedication with an antipyretic (eg, acetaminophen), antihistamines, and/or corticosteroids should be considered; premedication is typically given 1 to 24 hours (prior to subsequent infusions in patients with a history of infusion-related reactions requiring symptomatic treatment (Ref).
Fabry disease: IV: 0.2 mg/kg every 2 weeks.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
There are no dosage adjustments provided in the manufacturer’s labeling; has not been studied
No data available. Safety and efficacy have not been established.
Note: Premedication with oral antihistamines and corticosteroids may alleviate infusion-related reactions associated with agalsidase alfa.
Fabry disease: Children ≥7 years and Adolescents: IV: Refer to adult dosing.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Chest pain (27%), flushing (12%), palpitations (15%), peripheral edema (24%)
Dermatologic: Skin rash (16%)
Gastrointestinal: Abdominal pain (26%), diarrhea (42%), nausea (42%), vomiting (40%)
Immunologic: Antibody development (9% to 17%)
Nervous system: Dizziness (33%), fatigue (31%; fatigue aggravated: 16%), headache (63%), hypoesthesia (15%), neuralgia (27%), pain (25%), paresthesia (30%), rigors (28%)
Neuromuscular & skeletal: Arthralgia (33%), asthenia (21%), back pain (32%), limb pain (40%), myalgia (20%), swelling of extremities (11%), tremor (11%)
Otic: Tinnitus (14%; tinnitus aggravated: 11%)
Respiratory: Cough (40%), dyspnea (18%), nasopharyngitis (50%), pharyngitis (29%)
Miscellaneous: Fever (38%), infusion related reaction (14%; more common in children & adolescents)
1% to 10%:
Cardiovascular: Atrial fibrillation (2%), chest tightness (7%), hypertension (8%), hypotension (5%), livedo reticularis (1%), tachycardia (3%)
Dermatologic: Acne vulgaris (7%), erythema of skin (6%), pruritus (6%), rash at injection site (1%), urticaria (1%)
Gastrointestinal: Abdominal distress (2%), dysgeusia (3%)
Hypersensitivity: Hypersensitivity reactions (5%)
Nervous system: Feeling hot (5%), hypersomnia (2%), local discomfort (2%), malaise (8%), sensation of cold (4%)
Neuromuscular & skeletal: Joint swelling (8%), musculoskeletal pain (discomfort: 3%)
Ophthalmic: Increased lacrimation (2%), reduced blinking (1%)
Respiratory: Flu-like symptoms (10%), hoarseness (3%), increased bronchial secretions (1%), pharyngeal edema (6%), rhinorrhea (6%)
Frequency not defined:
Cardiovascular: Heart failure, ischemic heart disease, oxygen saturation decreased, tachyarrhythmia, ventricular premature contractions
Dermatologic: Hyperhidrosis
Hypersensitivity: Anaphylaxis, angioedema
Nervous system: Altered sense of smell, feeling of heaviness
Postmarketing: Hypersensitivity: Severe infusion related reaction
Severe hypersensitivity to agalsidase alfa or any component of the formulation
Concerns related to adverse effects:
• Antibody formation: The development of antidrug antibodies to recombinant agalsidase alfa is common, including patients naive to agalsidase alfa and those who previously received other enzyme replacement therapy (eg, agalsidase beta). In many of the patients with antidrug antibodies, presence of neutralizing antibodies was also detected on at least one occasion in an open-label safety study. Antidrug antibodies, including neutralizing antibodies, may be transient or persistent (Khan 2021). The presence of antidrug antibodies is usually observed following approximately 6 to 12 months of therapy. Further studies are needed to determine the clinical significance, if any, of antidrug antibodies (neutralizing and nonneutralizing) (Lenders 2018a; Lenders 2018b; Mauhin 2018; Mehta 2022).
• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, have been reported with agalsidase alfa use. Discontinue therapy immediately for hypersensitivity reaction and treat appropriately.
• Infusion reactions: Infusion reactions are common. Typically, infusion-related reactions are mild and characterized by fever, rigors, headache, dyspnea, nausea/vomiting, flushing, and fatigue. However, severe infusion reactions may occur, including angioedema, severe dyspnea with bronchospasm, throat tightness, urticaria, and cardiac events (tachycardia, hypo-/hypertension). Reactions generally occur within 2 to 4 months after therapy initiation although a later onset (ie, after 1 year) has also been observed. Infusion-related reactions usually diminish in frequency over time and can be attenuated with premedication. Depending on the severity of the reaction, the infusion may be temporarily interrupted (5 to 10 minutes) until the acute reaction subsides, or corticosteroids should be considered, particularly to prevent subsequent reactions in patients with a history of reactions. If severe allergic or anaphylactic-type reactions occur, immediate discontinuation is recommended (Khan 2021; Mehta 2022; Nicholls 2012).
Disease-related concerns:
• Renal impairment: Patients with Fabry disease are at risk for progressive kidney failure due to the natural progression of the untreated disease; however, enzyme replacement therapy (eg, agalsidase alfa, agalsidase beta) may lessen the decline of kidney function (Feriozzi 2012; Khan 2021). Dosage adjustment is not necessary in patients with kidney impairment. According to the manufacturer’s labeling, impaired kidney function (eGFR <60 mL/minute) may limit the renal response to enzyme replacement therapy potentially due to irreversible pathological changes.
Not available in the US
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Concentrate, Intravenous:
Replagal: 1 mg/mL (3.5 mL)
IV: Must be diluted further prior to infusion; do not administer undiluted. Infuse IV over 40 minutes using a dedicated IV line with filter. Do not infuse other agents through same IV line. Interrupt infusion in the presence of infusion-related reactions; infusion may be restarted after 5 to 10 minutes if symptoms are mild and subside.
IV: Must be diluted further prior to infusion; do not administer undiluted. Infuse IV over 40 minutes using a dedicated IV line with filter. Do not infuse other agents through same IV line. Interrupt infusion in the presence of infusion-related reactions; infusion may be restarted after 5 to 10 minutes if symptoms are mild and subside.
Note: Not approved in the US.
Fabry disease: Enzyme replacement therapy for Fabry disease (alpha-galactosidase A deficiency; Anderson-Fabry disease).
Agalsidase alfa may be confused with agalsidase beta, 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 Alfa. Risk X: Avoid combination
Chloroquine: May diminish the therapeutic effect of Agalsidase Alfa. Risk X: Avoid combination
Gentamicin (Systemic): May diminish the therapeutic effect of Agalsidase Alfa. Risk X: Avoid combination
Hydroxychloroquine: May diminish the therapeutic effect of Agalsidase Alfa. Risk C: Monitor therapy
Adverse events were not observed in animal reproduction studies. Information related to use in pregnancy is limited (Kalkum 2009; Senocak Tasci 2015).
It is not known if agalsidase alfa is excreted into breast milk. The manufacturer recommends using with caution in breastfeeding women.
Monitor for signs/symptoms of infusion-related reactions (eg, fever, rigors, tachycardia, hyper-/hypotension, dyspnea).
Agalsidase alfa is a recombinant form of the enzyme alpha-galactosidase-A, which catalyzes the hydrolysis of globotriaosylceramide (Gb-3), cleaving a terminal galactose residue from the molecule. Accumulation of globotriaosylceramide (Gb-3) may occur within the tissues of patients with Fabry disease. Agalsidase has been noted to reduce cellular levels of Gb-3 in many cell types including endothelial and parenchymal.
Distribution: Vd: In a study of 17 adult males, median Vd was 203 mL/kg (range: 89 to 6,778 mL/kg); in 14 pediatric patients, mean Vd was 128 mL/kg
Metabolism: Plasma; via peptide hydrolysis
Half-life elimination: In a study of 17 adult males, median half-life was 54.7 minutes (range: 28.5 to 654.2 minutes); in 14 pediatric patients, mean half-life was 32 minutes
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