Agalsidase beta

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

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 ]

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 ] .

Preparation Instructions Use aseptic technique during preparation. Reconstitute and dilute FABRAZYME in the following manner: Reconstitution Instructions 1. Determine 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.

Remove 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. Reconstitute 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. Each reconstituted vial will yield a concentration of 5 mg/mL of agalsidase beta. 5. Do not shake or agitate the product. 6. Visually 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. Select 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.

Slowly withdraw the required volume of reconstituted solution from the FABRAZYME vial(s). Discard any unused reconstituted solution remaining in the vial. [See table below.] 9. Gently 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. 10.

Gently 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.

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.

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 ] . Less than 30 kg, the maximum infusion rate is 0.25 mg/minute (15 mg/hour) [see Dosage and Administration ] . 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.