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Overview
Agalsidase beta is a Endocrine-Metabolic Agent that is FDA approved for the treatment of Fabry disease. Common adverse reactions include infusion reactions.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
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.
Recommended Dose
The recommended dosage of Fabrazyme is 1 mg/kg body weight infused every two weeks as an intravenous (IV) infusion. Patients should receive antipyretics prior to infusion [see WARNINGS AND PRECAUTIONS (5.2)].
The initial IV infusion rate should be no more than 0.25 mg/min (15 mg/hr). The infusion rate may be slowed in the event of infusion reactions. After patient tolerance to the infusion is well established, the infusion rate may be increased in increments of 0.05 to 0.08 mg/min (increments of 3 to 5 mg/hr) with each subsequent infusion. For patients weighing < 30 kg, the maximum infusion rate should remain at 0.25 mg/min (15 mg/hr). For patients weighing ≥ 30 kg, the administration duration should not be less than 1.5 hours (based on individual patient tolerability).
Patients who have had a positive skin test to Fabrazyme or who have tested positive for anti-Fabrazyme IgE may be successfully re-challenged with Fabrazyme. The initial re-challenge administration should be a low dose at a lower infusion rate, e.g., 1/2 the therapeutic dose (0.5 mg/kg) at 1/25 the initial standard recommended rate (0.01 mg/min). Once a patient tolerates the infusion, the dose may be increased to reach the approved dose of 1 mg/kg and the infusion rate may be increased by slowly titrating upwards (doubled every 30 minutes up to a maximum rate of 0.25 mg/min), as tolerated.
3 DOSAGE FORMS AND STRENGTHS
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.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Agalsidase beta in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Agalsidase beta in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Agalsidase beta in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Agalsidase beta in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Agalsidase beta in pediatric patients.
Contraindications
None
Warnings
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)].
5.2 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.
5.3 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.
5.4 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.
5.5 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.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Agalsidase beta in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Agalsidase beta in the drug label.
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Agalsidase beta in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Agalsidase beta during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Agalsidase beta with respect to nursing mothers.
Pediatric Use
There is no FDA guidance on the use of Agalsidase beta with respect to pediatric patients.
Geriatic Use
There is no FDA guidance on the use of Agalsidase beta with respect to geriatric patients.
Gender
There is no FDA guidance on the use of Agalsidase beta with respect to specific gender populations.
Race
There is no FDA guidance on the use of Agalsidase beta with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Agalsidase beta in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Agalsidase beta in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Agalsidase beta in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Agalsidase beta in patients who are immunocompromised.
Administration and Monitoring
Administration
Instructions for Use
Fabrazyme does not contain any preservatives. Vials are for single use only. Discard any unused product.
Avoid shaking or agitating this product. Do not use filter needles during the preparation of the infusion.
Reconstitution and Dilution (using Aseptic Technique)
Allow Fabrazyme vials and diluent to reach room temperature prior to reconstitution (approximately 30 minutes). The number of 35 mg and 5 mg vials needed is based on the patient’s body weight (kg) and the recommended dose of 1 mg/kg.
Select a combination of 35 mg and 5 mg vials so that the total number of mg is equal to or greater than the patient’s number of kg of body weight.
Reconstitute each 35 mg vial of Fabrazyme by slowly injecting 7.2 mL of Sterile Water for Injection, USP down the inside wall of each vial. Roll and tilt each vial gently. Each vial will yield a 5 mg/mL clear, colorless solution (total extractable amount per vial is 35 mg, 7 mL).
Reconstitute each 5 mg vial of Fabrazyme by slowly injecting 1.1 mL of Sterile Water for Injection, USP down the inside wall of each vial. Roll and tilt each vial gently. Each vial will yield a 5 mg/mL clear, colorless solution (total extractable amount per vial is 5 mg, 1 mL).
Visually inspect the reconstituted vials for particulate matter and 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 0.9% Sodium Chloride Injection, USP to a total volume based on patient weight specified in TABLE 1 below. Prior to adding the volume of reconstituted Fabrazyme required for the patient dose, remove an equal volume of 0.9% Sodium Chloride Injection, USP from the infusion bag.
Patient dose (in mg) ÷ 5 mg/mL = Number of mL of reconstituted Fabrazyme required for patient dose
Example: Patient dose = 80 mg
80 mg ÷ 5 mg/mL = 16 mL of Fabrazyme
Slowly withdraw the reconstituted solution from each vial up to the total volume required for the patient dose. Inject the reconstituted Fabrazyme solution directly into the Sodium Chloride solution. Do not inject in the airspace within the infusion bag. Discard any vial with unused reconstituted solution.
Gently invert infusion bag to mix the solution, avoiding vigorous shaking and agitation.
Do not infuse Fabrazyme in the same intravenous line with other products.
Administer FABRAZYME using an in-line low protein binding 0.2 µm filter.
Monitoring
There is limited information regarding Monitoring of Agalsidase beta in the drug label.
Description
IV Compatibility
There is limited information regarding IV Compatibility of Agalsidase beta in the drug label.
Overdosage
Acute Overdose
Signs and Symptoms
Description
Management
Description
Chronic Overdose
There is limited information regarding Chronic Overdose of Agalsidase beta in the drug label.
Pharmacology
There is limited information regarding Agalsidase beta Pharmacology in the drug label.
