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Agalsidase Beta

Pronunciation

(aye GAL si days BAY ta)

Index Terms

  • Alpha-Galactosidase-A (Recombinant)
  • r-h α-GAL

Dosage Forms

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) [contains mouse protein (murine) (hamster)]

Brand Names: U.S.

  • Fabrazyme

Pharmacologic Category

  • Enzyme

Pharmacology

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: Children: 247 to 1097 mL/kg; Adults: 81 to 570 mL/kg

Excretion

Clearance: Children: 1.1 to 5.8 mL/minute/kg; Adults: 0.8 to 4.9 mL/minute/kg

Half-Life Elimination

Dose dependent: Children: 86 to 151 minutes; Adults: 45 to 119 minutes

Use: Labeled Indications

Replacement therapy for Fabry disease

Contraindications

There are no contraindications listed within the manufacturer's labeling.

Dosage

IV: 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.

Dosage adjustment in hepatic impairment: No dosage adjustment provided in manufacturer's labeling.

Reconstitution

IV: 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; do not shake. Resulting solution contains 5 mg/mL. Do not use filter needle to prepare. To make final infusion solution, add the desired amount of reconstituted solution to NS to make a final volume based on patient weight (see table for dilution volumes). Prior to adding the volume of agalsidase beta dose to the NS, remove an equal volume of NS. Avoid vigorous shaking or agitation.

Recommended Minimum Volumes for Dilution

Patient Weight

(kg)

Minimum Total Volume

(mL)

≤35

50

35.1 - 70

100

70.1 - 100

250

>100

500

Table has been converted to the following text:

Recommended minimum total volume for dilution

Patient weight ≤35 kg: 50 mL

Patient weight 35.1 - 70 kg: 100 mL

Patient weight 70.1 - 100 kg: 250 mL

Patient weight >100 kg: 500 mL

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.

Storage

Store intact vials between 2°C and 8°C (36°F and 46°F); do not freeze. Reconstituted solution is stable for 24 hours refrigerated.

Drug Interactions

Amiodarone: May diminish the therapeutic effect of Agalsidase Beta. Avoid combination

Chloroquine: May diminish the therapeutic effect of Agalsidase Beta. Avoid combination

Gentamicin (Systemic): May diminish the therapeutic effect of Agalsidase Beta. Avoid combination

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% (Limited to important or life-threatening): 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

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).

Monitoring Parameters

Development of IgG or IgE antibodies in patients with suspected allergic reactions (test available from manufacturer). Monitor for infusion-related reactions.

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).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience rhinorrhea or back pain. Have patient report immediately to prescriber signs of depression (ie, suicidal ideation, anxiety, emotional instability, illogical thinking), hearing impairment, tinnitus, severe dizziness, syncope, dysphagia, or signs of infusion-related reactions (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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