Lumizyme

WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS, IMMUNE-MEDIATED REACTIONS, and RISK OF ACUTE CARDIORESPIRATORY FAILURE

LUMIZYME^® is a hydrolytic lysosomal glycogen-specific enzyme indicated for patients with Pompe disease (acid α-glucosidase [GAA] deficiency).

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

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

    [see Warnings and Precautions (5.1)]

    .
  • Initiate LUMIZYME 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 LUMIZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids

    [see Warnings and Precautions (5.1, 5.2)]

    .
  • LUMIZYME must be reconstituted and diluted prior to
    use [see Dosage and Administration (2.3)]
    .
  • Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available during LUMIZYME administration
    [see Warnings and Precautions (5.1)]
    .
  )
• Recommended dosage is 20 mg/per kg body weight administered every 2 weeks as an intravenous infusion. The initial infusion rate should be no more than 1 mg/kg/hour (
  2.2 Recommended Dosage and Administration

  • The recommended dosage of LUMIZYME is 20 mg/kg body weight administered every 2 weeks as an intravenous infusion. The initial infusion rate should be no more than 1 mg/kg/hour
    [see Dosage and Administration (2.5)]
    .

  Missed Dose

  If one or more doses are missed, restart LUMIZYME treatment as soon as possible, maintaining the 2-week interval between infusions thereafter.
  )
• Reconstitute and dilute LUMIZYME prior to use. (
  2.3 Reconstitution and Dilution Instructions

  Reconstitute and dilute LUMIZYME in the following manner.

  Use aseptic technique during preparation. Do not use filter needles during preparation.

  Reconstitute the Lyophilized Powder

  • Determine the number of LUMIZYME vials to be reconstituted based on the actual body weight in kg and the recommended dose of 20 mg/kg. Round the number of vials up to the next whole number.
  • Remove the required number of LUMIZYME 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) prior to reconstitution.
  • Reconstitute each vial by slowly injecting 10.3 mL of Sterile Water for Injection, down the inside wall of each vial. Avoid adding the Sterile Water for Injection to the vial forcefully or directly onto the lyophilized powder to minimize foaming.
  • Gently tilt and roll each vial. Do not invert, swirl, or shake the vial. Each vial will yield a concentration of 5 mg/mL of LUMIZYME. The total extractable dose per vial is 50 mg per 10 mL.
  • Visually inspect the reconstituted solution in the vials for particulate matter and discoloration. Discard if particles are present or the solution is discolored. The reconstituted solution may occasionally contain some LUMIZYME particles (typically less than 10 in a vial) in the form of thin white strands or translucent fibers subsequent to the initial inspection. This may also happen following dilution for infusion. These particles have been shown to contain LUMIZYME and may appear after the initial reconstitution step and increase over time. Studies have shown that these particles are removed via in-line filtration without having a detectable effect on the purity or strength.

  Dilute the Reconstituted Solution

  • Select and prepare an appropriate size 0.9% Sodium Chloride for Injection infusion bag with quantity sufficient of 0.9% Sodium Chloride for Injection to obtain the recommended total infusion volume per table 1 based on patient weight and dilute.
  • Slowly withdraw the required volume of reconstituted solution from the LUMIZYME vial(s). Avoid foaming in the syringe. Discard any unused reconstituted solution remaining in the vial.
  • Remove airspace from the prepared 0.9% Sodium Chloride for Injection infusion bag to minimize particle formation due to the sensitivity of LUMIZYME to air-liquid interfaces.
  • Inject the LUMIZYME reconstituted solution slowly and directly into the port of the prepared 0.9% Sodium Chloride for Injection infusion bag. Avoid foaming and introducing air in the infusion bag.
  • Gently invert or massage the infusion bag to mix the solution. Do not shake. After dilution, the solution will have a final concentration of 0.5 to 4 mg/mL of LUMIZYME.
  )
• See full prescribing information for storage of the reconstituted and diluted product and administration instructions (
  2.4 Storage Instructions for the Reconstituted and Diluted Product

  • The reconstituted and diluted solution should be administered without delay. Storage of the reconstituted solution at room temperature is not recommended.
  • If immediate use is not possible, the reconstituted and diluted solution is stable for up to 24 hours refrigerated at 2°C to 8°C (36°F to 46°F).
  • The reconstituted and diluted LUMIZYME solution should be protected from light.
  • Do not freeze or shake.
  ,
  2.5 Administration Instructions

  • The total volume of infusion is determined by the patient's body weight and should be administered over approximately 4 hours.
  • Administer LUMIZYME using an in-line low protein binding 0.2-micron filter.
  • Infusions should be administered in a step-wise manner using an infusion pump. The initial infusion rate should be no more than 1 mg/kg/hr. The infusion rate may be increased by 2 mg/kg/hr every 30 minutes, after patient tolerance to the infusion rate is established, until a maximum rate of 7 mg/kg/hr is reached.
  • Vital signs should be obtained at the end of each step. If the patient is stable, LUMIZYME may be administered at the maximum rate of 7 mg/kg/hr until the infusion is completed.
  • The infusion rate may be slowed or temporarily stopped in the event of mild to moderate hypersensitivity reactions. In the event of anaphylaxis or severe hypersensitivity reaction, immediately discontinue administration of LUMIZYME and initiate appropriate medical treatment. See Table 1below for the rate of infusion at each step, expressed as mL/hr based on the recommended infusion volume by patient weight.
  • Do not infuse LUMIZYME in the same intravenous line with other products. Discard any unused product.

  Table 1: Recommended LUMIZYME Infusion Volumes and Incremental Rate Steps by Patient Weight

  Patient Weight Range	Total infusion volume	Step 1 1 mg/kg/hr	Step 2 3 mg/kg/hr	Step 3 5 mg/kg/hr	Step 4 7 mg/kg/hr
  		Infusion Rate in mL/hr
  1.25 to 2.5 kg	25 mL	1.25	3.75	6.25	6.6
  2.6 to 10 kg	50 mL	3	8	13	18
  10.1 to 20 kg	100 mL	5	15	25	35
  20.1 to 30 kg	150 mL	8	23	38	53
  30.1 to 35 kg	200 mL	10	30	50	70
  35.1 to 50 kg	250 mL	13	38	63	88
  50.1 to 60 kg	300 mL	15	45	75	105
  60.1 to 100 kg	500 mL	25	75	125	175
  100.1 to 120 kg	600 mL	30	90	150	210
  120.1 to 140 kg	700 mL	35	105	175	245
  140.1 to 160 kg	800 mL	40	120	200	280
  160.1 to 180 kg	900 mL	45	135	225	315
  180.1 to 200 kg	1,000 mL	50	150	250	350
  )

For injection: 50 mg of LUMIZYME is supplied as a sterile, nonpyrogenic, white to off-white, lyophilized cake or powder in a single-dose vial for reconstitution. After reconstitution, the resultant solution concentration is 5 mg/mL.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to LUMIZYME during pregnancy. Pregnant women and women of reproductive potential should be encouraged to enroll in the Pompe patient registry. The registry will monitor the effect of LUMIZYME on pregnant women and their offspring. For more information, visit www.registrynxt.com or call 1-800-745-4447, extension 15500.