Lamzede

LAMZEDE is indicated for the treatment of non-central nervous system manifestations of alpha-mannosidosis in adult and pediatric patients.

• For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment. (
  2.1

  Important Recommendations Prior to LAMZEDE Treatment Initiation

  For females of reproductive potential, verify that the patient is not pregnant

  [see Use in Specific Populations (

  8.1

  ,

  8.3

  )]

  .
  )
  
  
• Consider pretreating with antihistamines, antipyretics, and/or corticosteroids prior to LAMZEDE administration. (
  2.2

  Recommended Dosage and Administration

  Prior to LAMZEDE administration, consider pre-treating with antihistamines, antipyretics, and/or corticosteroids

  [see Warnings and Precautions (

  5.1

  ,

  5.2

  )]

  .

  The recommended dosage of LAMZEDE is 1 mg/kg (actual body weight) administered once every week as an intravenous infusion.

  The total volume of infusion is determined by the patient’s actual body weight and should be administered over a minimum of 60 minutes for patients weighing up to 49 kg. Patients weighing 50 kg and greater should be infused at a maximum infusion rate of 25 mL/hour to control the protein load

  [

  s

  ee

  Dosage and Administration (

  2.4

  )]

  .

  If one or more doses are missed, restart the treatment as soon as possible, as long as it is at least 3 days from the next scheduled dose. If it is within 3 days from the next scheduled dose, give only the next dose per schedule.
  )
  
  
• Recommended LAMZEDE dosage is 1 mg/kg (actual body weight) administered once every week as an intravenous infusion. (
  2.2

  Recommended Dosage and Administration

  Prior to LAMZEDE administration, consider pre-treating with antihistamines, antipyretics, and/or corticosteroids

  [see Warnings and Precautions (

  5.1

  ,

  5.2

  )]

  .

  The recommended dosage of LAMZEDE is 1 mg/kg (actual body weight) administered once every week as an intravenous infusion.

  The total volume of infusion is determined by the patient’s actual body weight and should be administered over a minimum of 60 minutes for patients weighing up to 49 kg. Patients weighing 50 kg and greater should be infused at a maximum infusion rate of 25 mL/hour to control the protein load

  [

  s

  ee

  Dosage and Administration (

  2.4

  )]

  .

  If one or more doses are missed, restart the treatment as soon as possible, as long as it is at least 3 days from the next scheduled dose. If it is within 3 days from the next scheduled dose, give only the next dose per schedule.
  )
  
  
• See the full prescribing information for dosage modifications due to hypersensitivity reactions or IARs. (
  2.000000000000000e+00

  3

  Dosage and Administration Modifications Due to Hypersensitivity Reactions

  and/or Infusion-Associated Reactions

  In the event of a

  severe

  hypersensitivity reaction (including anaphylaxis) or

  severe

  infusion-associated reaction (IAR), immediately discontinue LAMZEDE administration and initiate appropriate medical treatment. For additional recommendations in the event of a

  severe

  hypersensitivity reaction or IAR,

  see Warnings and Precautions (

  5.1

  ,

  5.2

  ).

  In the event of a

  mild

  to

  moderate

  hypersensitivity reaction or a

  mild

  to

  moderate

  IAR, consider temporarily holding the infusion for 15 to 30 minutes, slowing the infusion rate to 25% to 50% of the recommended rate, and initiating appropriate medical treatment

  [see Warnings and Precautions (

  5.1

  ,

  5.2

  )]

  .

  If symptoms:

  • Persist despite temporarily holding or slowing the infusion, stop the infusion and monitor the patient. If symptoms continue to persist, discontinue the infusion, and consider re-initiating the infusion within 7 to 14 days at 25% to 50% of the recommended rate with appropriate pretreatment.
    
    
  • Subside following holding or slowing the infusion, resume infusion at 25% to 50% the recommended rate. If tolerated, increase the infusion rate by increments of 25% of the recommended rate until the recommended infusion rate is reached. Closely monitor the patient.
  )
  
  
• See the full prescribing information for reconstitution and administration instructions. (
  2.000000000000000e+00

  4

  Reconstitution

  Instructions

  Use aseptic technique during preparation. Reconstitute LAMZEDE in the following manner:

  • Determine the number of LAMZEDE vials to be reconstituted based on the patient’s weight in kg and the recommended dose
    [see
    Dosage and Administration (
    2.2
    )
    ]
    . Round the number of vials up to the next whole number.
    
    
  • Remove vials from the refrigerator and set aside for approximately 30 minutes to allow vials to come to room temperature.
    
    
  • Reconstitute each vial by slowly injecting 5 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.
    
    
  • Allow the reconstituted vials to stand on the table for 5 – 15 minutes. Then gently tilt and roll each vial for 15 – 20 seconds to enhance the dissolution process. Each vial will yield a concentration of 2 mg/mL. Do not invert, swirl, or shake the vials.
    
    
  • Visually inspect the reconstituted solution in the vials for particulate matter and discoloration. The solution should be clear to slightly opalescent. Due to the nature of LAMZEDE, the solution may occasionally contain some proteinaceous particles in the form of thin white strands or translucent fibers which will be removed by the in line filter during infusion. Discard if opaque particles are present or the solution is discolored.
    
    
  • Slowly withdraw the required volume from the vials with caution to avoid foaming in the syringe. If the volume of the solution exceeds one syringe capacity, prepare the required number of syringes in order to replace the syringe quickly during the infusion. Discard unused portion remaining in the vials.

  Storage of the Reconstituted Solution

  • If the reconstituted LAMZEDE vial is not used immediately, store the vial refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours inclusive of infusion time. Protect from light during refrigeration. Do not freeze.
    
    
  • Reconstituted LAMZEDE vial must be infused within 10 hours after removal from the refrigerator, inclusive of total infusion time. Discard if not used within 10 hours.
    
    
  • Infuse reconstituted solution within 24 hours from the time of preparation, which includes the storage time in the refrigerator, the time at room temperature, and the duration of the infusion.
  ,
  2.000000000000000e+00

  5

  Administration Instructions

  • Use an infusion set equipped with a pump and a low protein binding, 0.2-micron, in-line filter to administer LAMZEDE. Do not shake the syringe.
    
    
  • The total volume of infusion is determined by the patient’s actual body weight and should be administered over a minimum of
    60
    minutes for patients weighing up to 49 kg. Patients weighing 50 kg and greater should be infused at a maximum infusion rate of 25 mL/hour to control the protein load.
    
    
  • When the last syringe is empty, replace the dosage syringe with a 20 mL syringe filled with 0.9% Sodium Chloride Injection, and then continue to infuse an additional 10 mL of 0.9% Sodium Chloride Injection through the infusion system to infuse the remaining fraction of LAMZEDE in the line to the patient.
  )

For injection: 10 mg of velmanase alfa-tycv as a white to off-white lyophilized powder with a cake-like appearance in a single-dose vial for reconstitution.

Based on findings from animal reproduction studies, LAMZEDE may cause embryo-fetal harm when administered to a pregnant female. In animal reproduction studies, major visceral malformations were observed in rats and rabbits when velmanase alfa-tycv was administered in pregnant rats and rabbits during the period of organogenesis. These malformations were observed in rats at the highest dose level, at exposures that were approximately 7-fold the recommended dose in patients of 1 mg/kg. Malformations occurred at all dose levels in rabbits with the highest dose exposures approximately 2.5-fold the recommended patient dose of 1 mg/kg

There are no available data on LAMZEDE use in pregnant females to evaluate a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Advise the pregnant female of the potential risk to the fetus. The decision to continue or discontinue LAMZEDE treatment during pregnancy should consider the female’s need for LAMZEDE, the potential drug-related risks to the fetus, and the potential adverse outcomes from untreated maternal disease.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, 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.

In an embryo-fetal development study in the rat, velmanase alfa-tycv was administered during the period of organogenesis from gestation day (GD) 6 to GD 17. Major malformations and variations were observed at exposures that were approximately 7-fold greater than the recommended dose of 1 mg/kg. Treatment-related major malformations included cleft palate, cleft palatine skull, severely bent pelvic girdle, and duplicated sternebrae.

In an embryofetal development study in the rabbit, administration of velmanase alfa-tycv from GDs 6 through 18 was associated with skeletal and/or visceral malformations, which occurred at exposures that were approximately 2.5-fold greater than those observed in patients treated at the 1 mg/kg dose level. Major malformations observed in rabbits included incomplete intraventricular septum; severely reduced size of one or more lung lobe; unilateral renal agenesis; unilateral ureter; diaphraghmatic hernia involving one or more lobe of the liver; hydrocephaly; single olfactory lobe; cystic dilatation of the cerebellum; malformed cervical, thoracic, caudal, and/or sacral vertebrae; and fused, absent, or vestigial ribs.

In the pre- and post-natal development study in rats, velmanase alfa-tycv was administered intravenously every 3 days at 0, 3.3, 10, and 30 mg/kg from GD 6 to lactation day 20. Velmanase alfa-tycv did not induce effects on maternal reproductive function or on developmental and reproductive parameters of male and female offspring; thus, the maternal and developmental NOAELs were 30 mg/kg. Exposures at this dose, based on the embryo-fetal development study, were estimated to be approximately 10-fold greater than the 1 mg/kg dose of velmanase alfa-tycv.