Agalsidase Beta

Trade Names:Fabrazyme- Powder for injection, lyophilized 5.5 mg (5 mg/mL when reconstituted)- Powder for injection, lyophilized 37 mg (5 mg/mL when reconstituted)

Pharmacology

Provides exogenous source of α-galactosidase A.

Pharmacokinetics

Elimination

Terminal t _½ ranges from 45 to 102 min.

Indications and Usage

Treatment of Fabry disease.

Contraindications

Standard considerations.

Dosage and Administration

IV 1 mg/kg infused every 2 wk.

General Advice

• Allow vials of powder for injection and diluent to reach room temperature before reconstitution.
• Reconstitute 35 mg vial with 7.2 mL sterile water for injection. Slowly inject diluent down inside wall of vial then roll and tilt vial gently until powder has dissolved. Final concentration of reconstituted solution is 5 mg/mL.
• Reconstitute 5 mg vial with 1.1 mL sterile water for injection. Slowly inject diluent down inside wall of vial then roll and tilt vial gently until powder has dissolved. Final concentration of reconstituted solution is 5 mg/mL.
• Do not shake or agitate vials during reconstitution or dilution. Do not use filter needles during preparation of infusion.
• Further dilute reconstituted solution with sodium chloride 0.9% injection to a final volume of 500 mL by removing equal volume of sodium chloride injection before adding prescribed volume of reconstituted solution.
• When adding reconstituted solution to normal saline injection, inject reconstituted solution directly into saline solution and gently invert infusion bag to mix the solution. Do not inject reconstituted solution into the airspace within the infusion bag or vigorously shake or agitate the infusion bag to mix solution.
• Inspect solution visually before administration. Do not administer if solution is cloudy, discolored, or contains particulate matter.
• Discard any unused product. Vials are for single-use only. Do not save medication for future use.
• Initial IV infusion rate should be no more that 0.25 mg/min (15 mg/h). After patient tolerance to the infusion has been established each subsequent infusion may be increased in increments of 0.05 to 0.08 mg/min (3 to 5 mg/h).
• Infusion may be filtered through in-line low protein-binding 0.2 mcm filter during administration.
• Do not administer in same IV line with other products.

Storage/Stability

Store unopened vials in refrigerator (36° to 46°F). Use reconstituted and diluted solutions immediately. If immediate use is not possible, store the reconstituted and diluted solutions for up to 24 h in refrigerator.

Drug Interactions

None well documented.

Incompatibility

Do not infuse in the same IV line with other products.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Dependent edema (21%); hypotension (14%); cardiomegaly, hypertension (10%); bradycardia, cardiac arrest, cardiac arrhythmia, decreased cardiac output, stroke.

CNS

Headache (45%); anxiety (28%); dizziness, paresthesia (14%); ataxia, depression, vertigo.

EENT

Pharyngitis (28%); laryngitis (7%); hypoacousia.

GI

Nausea (28%); dyspepsia (10%).

Genitourinary

Nephrotic syndrome, testicular pain (7%).

Respiratory

Rhinitis (38%); bronchitis (10%); bronchospasm, sinusitis (7%).

Miscellaneous

Rigors (52%); infusion reactions (eg, tachycardia, hypertension, throat tightness, chest pain/tightness, dyspnea), fever (48%); pain, skeletal pain (21%); chest pain, sensations of temperature change (17%); pallor (14%); arthrosis (10%); abdominal pain, chills/rigors, lip or ear edema, nausea, pruritus, rash, urticaria, vomiting.

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Undetermined.

Antibodies

Most patients develop IgG antibodies and some develop IgE antibodies to treatment. Consider testing for IgE if a suspected allergic reaction develops.

Cardiac Function

Patients with advanced Fabry disease may have compromised cardiac function, that may predispose them to higher risk of severe complications from infusion reactions. Monitor cardiac function closely in patients with compromised cardiac function.

Infusion Reactions

Infusion-related hypersensitivity reactions may occur. Some reactions may be severe. Reactions may include fever, chills, rigors, throat and chest tightness, chest pain, rash, pruritus, hives, myalgia, dyspnea, abdominal pain, headache, hypotension, and hypertension. Prior to infusion, patients should receive antipyretics. If an infusion reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of additional antipyretics, antihistamines, and/or steroids may ameliorate the symptoms.

Patient Information

• Advise patient, family, or caregiver that medication will be prepared and administered by a health care provider in a health care setting and that medication will not be administered at home.
• Advise patient, family, or caregiver that an antipyretic (eg, acetaminophen), an antihistamine (eg, diphenhydramine), and possibly a corticosteroid (eg, prednisone), will be administered before each treatment to prevent or reduce severity of infusion reactions.
• Advise patient, family, or caregiver to immediately report any signs or symptoms of infusion reaction (eg, fever, chills, or rigors; throat tightness; chest pain or tightness; rash; itching; hives; muscle aches; difficulty breathing; stomach pain; headache).
• Encourage patient to enroll and participate in the Fabry Registry as noted in the manufacturer's product information.

Copyright © 2009 Wolters Kluwer Health.