Imiglucerase

Recommended Dosage and Administration Ensure physicians knowledgeable in the management of patients with Gaucher disease direct therapy with CEREZYME. The recommended dosage of CEREZYME is 2.5 units/kg three times a week to 60 units/kg once every two weeks administered intravenously. Titrate the dosage based on disease severity and therapeutic goals for the patient.

For adults and pediatric patients weighing greater than 20 kg, infuse the diluted CEREZYME solution over 1 to 2 hours [see Dosage and Administration ] . For pediatric patients weighing 20 kg or less, infuse the diluted CEREZYME solution over 2 hours [see Dosage and Administration ] .

Dosage and Administration Modifications Due to Hypersensitivity Reactions and/or Infusion-Associated Reactions If a severe hypersensitivity reaction (e.g., anaphylaxis) or a severe infusion-associated reaction (IAR) occurs, discontinue CEREZYME and immediately initiate appropriate medical treatment [see Warnings and Precautions (5.1 , 5.2) ].

If a mild or moderate hypersensitivity reaction or a mild or moderate IAR occurs, consider decreasing the infusion rate, temporarily stopping the infusion, and/or administering antihistamines, antipyretics, and/or corticosteroids [ see Warnings and Precautions (5.1 , 5.2) ].

Preparation Instructions Use aseptic technique during preparation. Reconstitution 1. Determine the number of CEREZYME vials to be reconstituted based on the individual patient's dosage regimen and remove vial(s) from the refrigerator [see Dosage and Administration ] . 2. Reconstitute each vial of CEREZYME by slowly injecting 10.2 mL of Sterile Water for Injection, down the inside wall of each vial. 3.

Roll and tilt the vial to allow the powder to dissolve completely. Visually inspect the reconstituted solution for particulate matter and discoloration. Discard if opaque particles or discoloration are observed. After reconstitution, each vial will yield CEREZYME at a concentration of 40 units/mL. 4. Withdraw the required volume of CEREZYME from the vial(s).

Dilution Dilute the CEREZYME solution for infusion promptly with 0.9% Sodium Chloride Injection to a final volume that is calculated based on prescribed dose. For CEREZYME administered at a dose of 60 units/kg, use the following final volumes (see Table 1 ). For patients weighing between 1.5 kg and less than 6 kg, dilute CEREZYME to a final volume of 12 mL in a syringe for infusion.

For patients weighing between 6 kg and less than 13 kg, dilute CEREZYME to a final volume of 26 mL in a syringe for infusion. For patients weighing between 13 kg and less than or equal to 20 kg, dilute CEREZYME to a final volume of 100 mL in an infusion bag. For patients weighing greater than 20 kg and less than or equal to 100 kg, dilute CEREZYME to a final volume of 200 mL in an infusion bag.

For patients weighing greater than 100 kg, dilute CEREZYME to a final volume of 400 mL in an infusion bag. If CEREZYME is prescribed at a dose lower than 60 units/kg, dilute the required total units of reconstituted CEREZYME (at a concentration of 40 units/mL) with 0.9% Sodium Chloride Injection to a final concentration between 6 units/mL and 30 units/mL inclusive.

If the determined dose of CEREZYME translates into a total volume of 26 mL or less, administer using a syringe for infusion via a syringe pump. For accuracy of dilution, if less than 2 mL of reconstituted CEREZYME (40 units/mL) is needed for the preparation of the determined dose, prepare a larger final volume of CEREZYME for infusion initially maintaining the final concentration of the diluted CEREZYME solution between 6 units/mL to 30 units/mL.

Subsequently, discard the excess volume and administer only the volume of CEREZYME solution corresponding to the prescribed dose. Gently invert the syringe for infusion or the infusion bag to mix the solution. Throughout CEREZYME preparation, avoid vigorous shaking, agitation and foaming. Vials are for single dose only.

Discard any unused solution.

Administration Instructions Visually inspect the diluted solution prior to administration of the final product for particulate matter and discoloration. Slight flocculation of protein particles (described as thin translucent fibers) may occur after dilution and does not affect the quality of the product. Administer CEREZYME as an intravenous infusion with a 0.2 micron in-line low protein-binding filter. [See table below.]

Storage and Handling If the reconstituted CEREZYME vial is not used immediately: Refrigerate the reconstituted solution at 2°C to 8°C (36°F to 46°F) or store at room temperature at 20°C to 25°C (68°F to 77°F) for up to 12 hours. Refrigerate the diluted solution at 2°C to 8°C (36°F to 46°F) for up to 24 hours.