Administration

Fabrazyme® (agalsidase beta) is indicated for use in patients with Fabry disease. Fabrazyme reduces globotriaosylceramide (GL-3) deposition in the capillary endothelium of the kidney and certain other cell types. Fabrazyme can be administered at an infusion center, a physician's office or at home. Appropriate medical support measures should be readily available when Fabrazyme is administered.

DOSAGE AND ADMINISTRATION

  • The recommended dosage of Fabrazyme is 1 mg/kg body weight infused every two weeks as an intravenous infusion. The initial intravenous infusion rate is no more than 0.25 mg/min (15 mg/hour). Slow the infusion rate in the event of infusion-associated reactions.
  • Administer antipyretics prior to infusion of Fabrazyme.
  • After patient tolerance to the infusion is well established, increase the infusion rate in increments of 0.05 to 0.08 mg/min (increments of 3 to 5 mg/hour) with each subsequent infusion.
  • The maximum infusion rate for patients weighing less than 30 kg, is 0.25 mg/minute (15 mg/hour).
  • For patients weighing 30 kg or greater, the minimum infusion duration is 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 rechallenged with Fabrazyme. Providing Fabrazyme to patients who have experienced severe or serious allergic reactions to Fabrazyme should only be done after carefully considering the risks and benefits of continuing the treatment, and only under the direct supervision of a qualified healthcare professional and with appropriate medical support readily available. The initial rechallenge 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 1.0 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.

HOW SUPPLIED/STORAGE AND HANDLING

Fabrazyme is supplied as a sterile, nonpyrogenic, white to off-white lyophilized cake or powder. Fabrazyme 35 mg vials are supplied in single-use, clear Type I glass 20 mL (cc) vials. The closure consists of a siliconized butyl stopper and an aluminum seal with a plastic purple flip-off cap. Fabrazyme 5 mg vials are supplied in single-use, clear Type I glass 5 mL (cc) vials. The closure consists of a siliconized butyl stopper and an aluminum seal with a plastic gray flip-off cap.

35 mg vial: NDC 58468-0040-1
5 mg vial: NDC 58468-0041-1

Refrigerate vials of Fabrazyme at 2° to 8°C (36° to 46°F). DO NOT USE Fabrazyme after the expiration date on the vial. Reconstituted and diluted solutions of Fabrazyme should be used immediately. This product contains no preservatives. If immediate use is not possible, the reconstituted and diluted solution may be stored for up to 24 hours at 2° to 8°C (36° to 46°F).

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. The diluted solution may be filtered through an in-line low protein-binding 0.2 μm filter during administration. DO NOT USE Fabrazyme after the expiration date on the vial.

Reconstitution and Dilution (using Aseptic Technique)

  1. 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.

    To calculate:
    • Patient’s weight (in kg) = Patient dose (in mg)
    • Patient dose (in mg) ÷ 5 mg/mL = Number of mL of reconstituted Fabrazyme required for patient dose
    • Based on the patient dose in mL, determine the number of 35 mg (7 mL extractable volume) and 5 mg (1 mL extractable volume) vials needed
    • Example: Patient weight (80 kg) = Patient dose (80 mg)
      80 mg ÷ 5 mg/mL = 16 mL, therefore, two 35 mg vials and two 5 mg vials should be reconstituted.
  2. 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 dose 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).

  3. 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. Instead, report it to Sanofi Genzyme Medical Information at 800-745-4447 (option 2).

  4. The reconstituted solution should be further diluted with 0.9% Sodium Chloride Injection, USP to total volume based on patient weight specified in the table 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 Weight (kg)   Minimum Total Volume (mL)
    ≤ 35     50
    35.1 – 70       100
    70.1 – 100   250
    >100                      500

    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.

  5. Gently invert infusion bag to mix the solution, avoiding vigorous shaking and agitation.

  6. Do not infuse Fabrazyme in the same intravenous line with other products.

  7. Administer Fabrazyme using an in-line low protein binding 0.2 µm filter.

Indication and Usage

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.

The reduction of GL-3 inclusions suggests that Fabrazyme may ameliorate disease expression; however, the relationship of GL-3 inclusion reduction to specific clinical manifestations of Fabry disease has not been established.

Important Safety Information

Warnings and Precautions
Anaphylaxis and Allergic Reactions: Life-threatening anaphylactic and severe allergic reactions have been observed in patients during Fabrazyme infusions. In clinical trials and postmarketing safety experience, approximately 1% of patients developed anaphylactic or severe allergic reactions 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, antihistamines, epinephrine, and IV corticosteroids.
  • If severe allergic or anaphylactic reactions occur, immediately discontinue administration of Fabrazyme and provide necessary emergency treatment. Because of the potential for severe allergic reactions, appropriate medical support measures should be readily available when Fabrazyme is administered.

Infusion-Associated Reactions: In clinical trials with Fabrazyme, 59% of patients experienced infusion-associated reactions, some of which were severe.

  • In patients experiencing infusion-associated reactions, pretreatment with an antipyretic and antihistamine is recommended. Infusion-associated reactions occurred in some patients after receiving pretreatment.
  • If an infusion-associated 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-associated 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-associated reactions, appropriate medical support measures should be readily available when Fabrazyme is administered.

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-associated reactions. Patients with compromised cardiac function should be monitored closely if the decision is made to administer Fabrazyme.

Immunogenicity and Rechallenge: In clinical trials, a few patients developed IgE or skin test reactivity specific to Fabrazyme. Physicians should consider testing for IgE in patients who experienced suspected allergic reactions. Re-administration of Fabrazyme to patients who have previously experienced severe or serious allergic reactions to Fabrazyme should be done only after careful consideration of the risks and benefits of continued treatment, and only under the direct supervision of qualified personnel and with appropriate medical support measures readily available.

Adverse Reactions

  • Common adverse reactions reported (≥20% and >2.5% compared to placebo) were upper respiratory tract infection (44% vs 30%), headache (39% vs 28%), cough (33% vs 25%), paresthesia (31% vs 18%), fatigue (24% vs 17%), dizziness (21% vs 8%), peripheral edema (21% vs 7%), and rash (20% vs 10%).
  • Serious and/or frequently occurring (≥ 5% incidence) related adverse reactions based on a pooled analysis of 150 patients treated with Fabrazyme in double-blind and open-label clinical studies consisted of one or more of the following: chills, fever, feeling hot or cold, dyspnea, nausea, flushing, headache, vomiting, paresthesia, fatigue, pruritus, pain in extremity, hypertension, chest pain, throat tightness, abdominal pain, dizziness, tachycardia, nasal congestion, diarrhea, edema peripheral, myalgia, back pain, pallor, bradycardia, urticaria, hypotension, face edema, rash, and somnolence.
  • Other serious adverse events reported in clinical studies included stroke, pain, ataxia, bradycardia, cardiac arrhythmia, cardiac arrest, decreased cardiac output, vertigo, and nephrotic syndrome. These adverse events also occur as manifestations of Fabry disease; an alteration in frequency or severity cannot be determined from the small numbers of patients studied.
  • Adverse reactions (regardless of relationship) resulting in death reported in the postmarketing setting with Fabrazyme treatment included cardiorespiratory arrest, respiratory failure, cardiac failure, sepsis, cerebrovascular accident, myocardial infarction, renal failure, and pneumonia. Some of these reactions were reported in Fabry disease patients with significant underlying disease.

The safety and efficacy of Fabrazyme in patients younger than 8 years of age have not been evaluated.

Please see full prescribing information for Fabrazyme.