Fabrazyme (Agalsidase Beta)

FABRAZYME^® is indicated for the treatment of adult and pediatric patients 2 years of age and older with confirmed Fabry disease.

• Administration of FABRAZYME should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. (
  2.1 Recommendations Prior to FABRAZYME Treatment

  • Administration of FABRAZYME should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis

    [see Warnings and Precautions (5.1)].
  • Initiate FABRAZYME in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment

    [see Warnings and Precautions (5.1)].
  • Prior to FABRAZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids
    [see Warnings and Precautions (5.1, 5.2)]
    .
  • FABRAZYME must be reconstituted and diluted prior to use
    [see Dosage and Administration (2.4)]
  )
• The recommended dosage is 1 mg/kg body weight given every two weeks as an intravenous infusion. (
  2.2 Recommended Dosage and Administration

  • The recommended dosage of FABRAZYME is 1 mg/kg body weight infused every two weeks as an intravenous infusion.
  • The initial recommended infusion rate is 0.25 mg/min (15 mg/hour)
    [see Dosage and Administration (2.6)]
    .
  )
• See the full prescribing information for rechallenge, preparation, storage, and administration instructions. (
  2.3 Rechallenge Instructions

  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. The initial rechallenge administration should be a low dose at a lower infusion rate, e.g., one-half the therapeutic dose (0.5 mg/kg) at 1/25^thof the initial standard recommended rate (0.01 mg/min or 0.6 mg/hr). 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/minute), as tolerated

  [see Adverse Reactions (6.2)]

  .
  ,
  2.4 Preparation Instructions

  Use aseptic technique during preparation. Reconstitute and dilute FABRAZYME in the following manner:

  Reconstitution Instructions

  • 1.000000000000000e+00Determine the number of 35 mg and 5 mg FABRAZYME vials to be reconstituted based on actual body weight (kg) and the recommended dose
    [see Dosage and Administration (2.2)]
    .
  • 2.000000000000000e+00Remove the required number of 35 mg and 5 mg FABRAZYME vials from the refrigerator and allow the vials to sit for approximately 30 minutes at room temperature 20°C to 25°C (68°F to 77°F) before use.
  • 3.000000000000000e+00Reconstitute each vial by directing the diluent down the inside wall of each vial then gently tilt and roll each vial. Use the following volumes for reconstitution:
    • 7.2 mL of FABRAZYME Sterile Water for Injection into the 35 mg vial. Total extractable amount per vial is 35 mg, 7 mL.
    • 1.1 mL of Sterile Water for Injection into the 5 mg vial. Total extractable amount per vial is 5 mg, 1 mL.
  • 4.000000000000000e+00Each reconstituted vial will yield a concentration of 5 mg/mL of agalsidase beta.
  • 5.000000000000000e+00Do not shake or agitate the product.
  • 6.000000000000000e+00Visually inspect the reconstituted solution in the vials for particulate matter and discoloration. The reconstituted solution should be clear and colorless. Discard if visible particulate matter is present or the solution is discolored.

  Dilution Instructions

  • 7.000000000000000e+00Select an appropriate size 0.9% Sodium Chloride Injection infusion bag and prepare by removing a volume equal to the required FABRAZYME volume to achieve a total volume per Table 1.
  • 8.000000000000000e+00Slowly withdraw the required volume of reconstituted solution from the FABRAZYME vial(s). Discard any unused reconstituted solution remaining in the vial.

    Table 1: Total Infusion Volume Based on Patient Weight

    Patient Weight (kg)	Total Volume (mL)
    ≤35	50
    35.1 to 70	100
    70.1 to 100	250
    >100	500

  • 9.000000000000000e+00Gently inject the FABRAZYME reconstituted solution into the port of the 0.9% Sodium Chloride Injection infusion bag. Do not inject into the airspace within the infusion bag.
  • 1.000000000000000e+01Gently invert the infusion bag to mix the solution. Do not shake or agitate the product. After dilution, the solution will have a final concentration of 0.2 to 0.7 mg/mL of agalsidase beta.
  ,
  2.5 Storage Instructions for the Reconstituted and Diluted Product

  • Dilute the reconstituted solution without delay and use immediately. If immediate use is not possible, the reconstituted and diluted solution may be stored at 2°C to 8°C (36°F to 46°F) for up to 24 hours.
  ,
  2.6 Administration Instructions

  • The initial recommended infusion rate is 0.25 mg/min (15 mg/hour). For patients weighing:
    • 30 kg or more, in the absence of hypersensitivity and/or infusion-associated reactions (IARs), increase the infusion rate in increments of 0.05 to 0.08 mg/min (3 to 5 mg/hour) with each subsequent infusion. The minimum infusion duration is 1.5 hours (based on individual patient tolerability)
      [see Dosage and Administration (2.6)]
      .
    • Less than 30 kg, the maximum infusion rate is 0.25 mg/minute (15 mg/hour)
      [see Dosage and Administration (2.6)]
      .
  • 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.
  )

For injection: 5 mg or 35 mg of agalsidase beta as a white to off-white, lyophilized cake or powder in a single-dose vial for reconstitution.

Available data from a pregnancy sub-study within the Fabry Disease registry, post-marketing case reports, and case series with FABRAZYME use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.