Fabrazyme

Dosage Forms & Strengths

powder for injection

• 5mg/vial
• 35mg/vial

Fabry Disease

1 mg/kg IV infusion q2Weeks 

Infuse initial infusion over 4-6 hours; subsequent infusions may be administered at 3-5 mg/min

Dosage Forms & Strengths

powder for injection

• 5mg/vial
• 35mg/vial

Fabry Disease

<8 years: Safety & efficacy not established

≥8 years: As adult; 1 mg/kg IV infusion q2Weeks 

IV Incompatibilities

Should not be infused in the same intravenous line with other products.

IV Preparation

Reconstitute 35 mg vial by injecting 7.2 mL of SWI & 5 mg vial by injecting 1.1 mL SWI to yield a 5 mg/mL clear, colorless solution

Visually inspect the reconstituted vials for particulate matter & discoloration

Do not use the reconstituted solution if there is particulate matter or if it is discolored

The reconstituted solution should be further diluted with NS to a final total volume of 50-500 mL based on dosage

Remove dose amount of NS from infusion bag & replace w/ drug solution

IV Administration

Reconstituted & diluted solns should be used immediately (drug contains no preservatives); however may be stored in fridge for up to 24 hr

Initial infusion rate

• Not to exceed 0.25 mg/min (15 mg/hr); may incr by 0.05-0.08 mg/min (3-5 mg/hr) for on each subsequent infusion
• <30 kg: not to exceed 0.25 mg/min
• >30 kg: infuse over at least 1.5 hr

Do not shake or agitate product

Do not use filter needles during the preparation of the infusion

Storage

Refrigerate

Contraindications

• No known contraindications.1

Warnings/Precautions

Warnings

Potentially severe infusion reactions (e.g., chills, fever, dyspnea, nausea, vomiting, hypotension, paresthesia, flushing, headache, fatigue, pruritus, pain in extremity, hypertension, chest pain, throat tightness, abdominal pain, dizziness, tachycardia, nasal congestion, diarrhea, peripheral edema) reported.a Infusion reactions may occur in patients pretreated with acetaminophen and in patients pretreated with antipyretics, an antihistamine, and an oral corticosteroid.1

Administer antipyretics prior to infusion.a If an infusion reaction occurs, decrease infusion rate or interrupt infusion; institute appropriate supportive treatment (i.e., additional antipyretics, antihistamines, and/or corticosteroids) as indicated.a

Incidence of infusion reactions decreases with continued infusions; however, such reactions may occur even with extended duration of therapy.a

Sensitivity Reactions

Development of IgG antibodies to agalsidase beta reported in most patients, usually within the first 3 months of therapy; however, antibodies did not appear to affect efficacy and did not have a neutralizing effect.1 2 3 5

Possible development of IgE antibodies or skin test reactivity to agalsidase beta.a Consider testing for IgE antibodies if allergic reaction is suspected; consider risks and benefits of continued treatment in patients with evidence of IgE antibody development.1

Following discontinuance of therapy because of development of positive skin test or IgE antibodies to agalsidase beta, therapy may be reinitiated using a rechallenge protocol.a (See Dosage under Dosage and Administration.)

General Precautions

Increased risk of severe complications from infusion reactions in patients with compromised cardiac function; monitor such patients closely.1 (See Infusion Reactions under Cautions.)

A registry has been established to monitor the variability and progression of Fabry’s disease, to monitor and evaluate the long-term treatment effects of agalsidase beta, to monitor the effect of agalsidase beta on pregnant women and their developing fetuses, and to determine whether the drug is distributed into breast milk.1 Information is available at and 800-745-4447.a

Specific Populations

Category B.a Pregnancy registry at 800-745-4447. 1

Not known whether agalsidase beta is distributed into milk.a Caution if used in nursing women.1

Safety and efficacy not established in children <8 years of age;a however, experts recommend initiation of enzyme replacement therapy in children with clinical manifestations of Fabry’s disease.3 5

IgG seroconversion in pediatric patients associated with increased half-life and plasma agalsidase beta concentrations; this phenomenon is rarely observed in adult patients.a (See Immunologic Reactions and Antibody Formation under Cautions.)

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1

Response in females does not appear to differ from that in males.a

Common Adverse Effects

Infusion reactions (e.g., vomiting, chills, fever, fatigue, feeling cold, hypertension), anemia, peripheral edema, pain, respiratory tract infection, nasopharyngitis, procedural pain.a

Absorption

AUC does not increase proportionately with increased dose.a

Elimination

Half-life

82–199 minutes.1

Special Populations

Half-life is increased in pediatric patients who develop IgG antibodies.a

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Fabrazyme® (agalsidase beta) is indicated for use in patients with Fabry disease.  Fabrazyme reduces globotriaosylceramide (GL‑3) deposition in capillary endothelium of the kidney and certain other cell types.

Fabrazyme is supplied as a sterile, nonpyrogenic, white to off-white, lyophilized cake or powder for reconstitution with Sterile Water for Injection, USP to yield a concentration of 5 mg/mL; and then further diluted with 0.9% Sodium Chloride Injection, USP for intravenous infusion.

Single-use vials are available in 35 mg and 5 mg dosages.

None.

Anaphylaxis and Allergic Reactions

Life-threatening anaphylactic and severe allergic reactions have been observed in patients during Fabrazyme infusions. Reactions have included localized angioedema (including swelling of the face, mouth, and throat), bronchospasm, hypotension, generalized urticaria, dysphagia, rash, dyspnea, flushing, chest discomfort, pruritus, and nasal congestion. Interventions have included cardiopulmonary resuscitation, oxygen supplementation, IV fluids, hospitalization, and treatment with inhaled beta-adrenergic agonists, epinephrine, and IV corticosteroids.

In clinical trials and postmarketing safety experience with Fabrazyme, approximately 1% of patients developed anaphylactic or severe allergic reactions during Fabrazyme infusion. 

If anaphylactic or severe allergic reactions occur, immediately discontinue the administration of Fabrazyme and initiate necessary emergency treatment. Because of the potential for severe allergic reactions, appropriate medical support measures should be readily available when Fabrazyme is administered.

The risks and benefits of re-administering Fabrazyme following an anaphylactic or severe allergic reaction should be considered. Extreme care should be exercised, with appropriate medical support measures readily available, if the decision is made to re-administer the product [see Warnings and Precautions (5.4) and Clinical Studies (14)].

Infusion Reactions

In clinical trials with Fabrazyme, approximately 50-55% of patients experienced infusion reactions during Fabrazyme administration, some of which were severe [see Warnings and Precautions (5.1)].  Severe infusion reactions experienced by more than one patient in clinical studies with Fabrazyme included chills, vomiting, hypotension, and paresthesia.  Other infusion reactions included pyrexia, feeling hot or cold, dyspnea, nausea, flushing, headache, fatigue, pruritus, pain in extremity, hypertension, chest pain, throat tightness, abdominal pain, dizziness, tachycardia, nasal congestion, diarrhea, edema peripheral, myalgia, urticaria, bradycardia, and somnolence. 

Most patients in clinical trials were pretreated with acetaminophen.  In patients experiencing infusion reactions, pretreatment with an antipyretic and antihistamine is recommended.  Infusion reactions occurred in some patients after receiving pretreatment with antipyretics, antihistamines, and oral steroids.  Infusion reactions tended to decline in frequency with continued use of Fabrazyme.  However, infusion reactions may still occur despite extended duration of Fabrazyme treatment.  If an infusion reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administrating additional antipyretics, antihistamines, and/or steroids may ameliorate the symptoms.  If severe infusion reactions occur, immediate discontinuation of the administration of Fabrazyme should be considered, and appropriate medical treatment should be initiated.  Severe reactions are generally managed with administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated.  Because of the potential for severe infusion reactions, appropriate medical support measures should be readily available when Fabrazyme is administered.  Patients who have experienced infusion reactions should be treated with caution when re-administering Fabrazyme. 

Compromised Cardiac Function

Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from infusion reactions [see Warnings and Precautions (5.1) and (5.2)]. Patients with compromised cardiac function should be monitored closely if the decision is made to administer Fabrazyme.

Immunogenicity and Re-challenge

In clinical trials with Fabrazyme, a few patients developed IgE antibodies or skin test reactivity specific to Fabrazyme.  Two of six patients in the re-challenge study discontinued treatment with Fabrazyme prematurely due to recurrent infusion reactions. Four serious infusion reactions occurred in three patients during Fabrazyme infusions, including bronchospasm, urticaria, hypotension, and development of Fabrazyme-specific antibodies.  Other infusion-related reactions occurring in more than one patient during the study included rigors, hypertension, nausea, vomiting, and pruritus.  Physicians should consider testing for IgE antibodies in patients who experienced suspected allergic reactions and consider the risks and benefits of continued treatment in patients with anti-Fabrazyme IgE antibodies [see Warnings and Precautions (5.1) and Dosage and Administration (2)].

Patients who have had a positive skin test to Fabrazyme or who have tested positive for Fabrazyme-specific IgE antibody have been re-challenged with Fabrazyme using a re-challenge protocol [see Clinical Studies (14)].  Re-challenge of these patients should only occur under the direct supervision of qualified personnel, with appropriate medical support measures readily available.

Monitoring: Laboratory Tests

There are no marketed tests for antibodies against Fabrazyme.  If testing is warranted, contact your local Genzyme representative or Genzyme Corporation at (800) 745-4447.

Interference with Other Drugs

No drug interaction studies were performed.

No in vitro metabolism studies were performed.

Interference with Laboratory Tests

There is no known interference by Fabrazyme with laboratory tests.  Antibody samples should be collected prior to Fabrazyme infusions.

Fabrazyme (agalsidase beta) is a recombinant human α-galactosidase A enzyme with the same amino acid sequence as the native enzyme. Purified agalsidase beta is a homodimeric glycoprotein with a molecular weight of approximately 100 kD. The mature protein is comprised of two subunits of 398 amino acids (approximately 51 kD), each of which contains three N-linked glycosylation sites. α‑galactosidase A catalyzes the hydrolysis of globotriaosylceramide (GL-3) and other α‑galactyl-terminated neutral glycosphingolipids, such as galabiosylceramide and blood group B substances to ceramide dihexoside and galactose. The specific activity of Fabrazyme is approximately 70 U/mg (one unit is defined as the amount of activity that results in the hydrolysis of 1 µmole of a synthetic substrate, p-nitrophenyl-α-D-galactopyranoside, per minute under the assay conditions).

Fabrazyme is produced by recombinant DNA technology in a Chinese Hamster Ovary mammalian cell expression system.

Fabrazyme is intended for intravenous infusion. It is supplied as a sterile, nonpyrogenic, white to off-white, lyophilized cake or powder for reconstitution with Sterile Water for Injection, USP. Each 35 mg vial contains 37 mg of agalsidase beta, as well as 222 mg mannitol, 20.4 mg sodium phosphate monobasic monohydrate, and 59.2 mg sodium phosphate dibasic heptahydrate. Following reconstitution as directed, 35 mg of agalsidase beta (7 mL) may be extracted from each 35 mg vial.

Each 5 mg vial contains 5.5 mg of agalsidase beta, as well as 33.0 mg mannitol, 3.0 mg sodium phosphate monobasic monohydrate, and 8.8 mg sodium phosphate dibasic heptahydrate. Following reconstitution as directed, 5 mg of agalsidase beta (1 mL) may be extracted from each 5 mg vial.

Fabrazyme (agalsidase beta) is a man-made form of the naturally-occurring alpha-galactosidase A enzyme. A deficiency of this enzyme is called Fabry disease. Agalsidase beta reduces deposits of globotriaosylceramide (GL-3) in the kidneys and certain other cells in the body.

Fabrazyme is used in the treatment of Fabry disease.

Fabrazyme may also be used for purposes other than those listed here.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.