LAMZEDE Powder for solution for infusion Ref.[7641] Active ingredients: Velmanase alfa

The treatment should be supervised by a physician experienced in the management of patients with alpha-mannosidosis or in the administration of other enzyme replacement therapies (ERT) for lysosomal storage disorder. Administration of Lamzede should be carried out by a healthcare professional with the ability to manage ERT and medical emergencies.

Posology

The recommended dose regimen is 1 mg/kg of body weight administered once every week by intravenous infusion at a controlled speed. For infusion rate see section "Method of administration".

Special populations

Renal or hepatic impairment

No dose adjustment is necessary for patients with renal or hepatic impairment.

Elderly

No data are available and no relevant use in elderly patients is described.

Paediatric population

No dose adjustment is necessary for the paediatric population.

Method of administration

For intravenous infusion use only.

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

The reconstituted solution of Lamzede should be administered using an infusion set equipped with a pump and an in-line low protein-binding 0.22 µm filter. The infusion duration should be calculated individually considering a maximum infusion rate of 25 mL/hour to control the protein load. The infusion duration should be a minimum of 50 minutes. A slower infusion rate may be prescribed when clinically appropriate according to the physician's judgment, for example at the beginning of the treatment or in case of previous infusion-related reactions (IRRs). For the calculation of the infusion rate and the infusion time based on body weight see the table in section 6.6.

The patient should be observed for IRRs for at least one hour after the infusion according to clinical conditions and the physician's judgment. For further instructions, see section 4.4.

There is no experience with overdose of velmanase alfa. The maximum dose of velmanase alfa in clinical studies was a single administration of 100 units/kg (approximately corresponding to 3.2 mg/kg). During the infusion with this higher dose, fever of mild intensity and short duration (5 hours) was observed in one patient. No treatment was administered.

For the management of adverse reactions, see sections 4.4 and 4.8.

3 years.

Reconstituted solution for infusion:

Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C-8°C. From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C.

Store and transport refrigerated (2°C-8°C).

Store in the original package in order to protect from light.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

10 mL vial (Type I glass) with a bromobutyl rubber stopper, an aluminium seal and a polypropylene flip off cap.

Each vial contains 10 mg of velmanase alfa.

Pack sizes of 1, 5 or 10 vials per carton.

Not all pack sizes may be marketed.

Lamzede requires reconstitution and is intended for intravenous infusion only. Each vial is for single use only.

Instructions for reconstitution and administration

Lamzede should be reconstituted and administrated by a healthcare professional.

Aseptic technique is to be used during preparation. Filter needles must not be used during preparation.

a) The number of vials to be used should be calculated based on the individual patient's weight.

The recommended dose of 1 mg/kg is determined using the following calculation:

• Patient's weight (kg) × dose (mg/kg) = Patient dose (in mg)
• Patient dose (in mg) divided by 10 mg/vial (content of one vial) = number of vials to reconstitute. If the number of calculated vials includes a fraction, it should be rounded up to the next whole number.
• Approximately 30 minutes prior to reconstitution, the required number of vials should be removed from the refrigerator. The vials should reach ambient temperature (between 15°C and 25°C) prior to reconstitution.

Each vial is reconstituted by slowly injecting 5 mL of water for injections to the inside of the wall of each vial. Each mL of reconstituted solution contains 2 mg of velmanase alfa. Only the volume corresponding to the recommended dose should be administered.

Example:

• Patient's weight (44 kg) × dose (1 mg/kg) = Patient dose (44 mg)
• 44 mg divided by 10 mg/vial = 4.4 vials, therefore, 5 vials should be reconstituted.
• From the total reconstituted volume, only 22 mL (corresponding to 44 mg) should be administered.

b) The powder should be reconstituted in the vial by a slow drop-wise addition of the water for injections down the inside of the vial and not directly onto the lyophilised powder. Forcefully ejecting the water for injections from the syringe onto the powder should be avoided to minimise foaming. The reconstituted vials should stand on the table for about 5-10 minutes. Thereafter each vial should be tilted and rolled gently for 15-20 seconds to enhance the dissolution process. The vial should not be inverted, swirled, or shaken.

c) An immediate visual inspection of the solution for particulate matter and discoloration should be performed after reconstitution. The solution should be clear and not used if opaque particles are observed or if the solution is discoloured. Due to the nature of the medicinal product, the reconstituted solution may occasionally contain some proteinaceous particles in form of thin white strands or translucent fibers which will be removed by the in-line filter during infusion (see point e).

d) The reconstituted solution is to be slowly withdrawn from each vial with caution to avoid foaming in the syringe. If the volume of the solution exceeds one syringe capacity, the required number of syringes should be prepared in order to replace the syringe quickly during the infusion.

e) The reconstituted solution should be administered using an infusion set equipped with a pump and an in-line low protein-binding 0.22 μm filter. The total volume of infusion is determined by the patient's weight and should be administrated over a minimum of 50 minutes. For patients weighing less than 18 kg, and receiving less than 9 mL reconstituted solution, the infusion rate should be calculated so that the infusion time is ≥50 minutes. The maximum infusion rate is 25 mL/hour (see section 4.2). The infusion time can be calculated from the following table:

f) When the last syringe is empty, the dosage syringe is replaced with a 20 mL syringe filled with sodium chloride 9 mg/mL (0.9%) solution for injection. A volume of 10 mL sodium chloride solution should be administered through the infusion system to infuse the remaining fraction of Lamzede in the line to the patient.

Disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.