view any new information which may become available everyyear and this SmPC will be updated as necessary.
5.2 Pharmacokinetic properties
There were no apparent pharmacokinetic gender differences in patients with alpha-mannosidosisdisease.
Absorption
Lamzede is administered through intravenous infusion. At steady-state after weekly infusion
administration of 1 mg/kg of velmanase alfa, the mean maximum plasma concentration was about
8 µg/mL and was reached at 1.8 hours after the start of administration corresponding to the meaninfusion duration time.
Distribution
As expected for a protein of this size, the steady-state volume of distribution was low (0.27 L/kg),
indicating distribution confined to plasma. The clearance of velmanase alfa from plasma (mean6.7 mL/h/kg) is consistent with a rapid cellular uptake of velmanase alfa via mannose receptors.
Biotransformation
The metabolic pathway of velmanase alfa is predicted to be similar to other natural occurring proteinsthat degrade into small peptides and finally into amino acids.
Elimination
After the end of the infusion, velmanase alfa plasma concentrations fell in a biphasic fashion with amean terminal elimination half-life of about 30 hours.
Linearity/(Non)linearityVelmanase alfa exhibited a linear (i.e. first-order) pharmacokinetic profile, and Cmax and AUCincreased proportionally to the dose with doses ranging from 0.8 to 3.2 mg/kg (corresponding to 25and 100 units/kg).
Special populations
Velmanase alfa is a protein and is predicted to be metabolically degraded into amino acids. Proteinslarger than 50,000 Da, such as velmanase alfa, are not eliminated renally. Consequently hepatic andrenal impairment are not expected to affect the pharmacokinetic of velmanase alfa. As no patientsolder than 41 years have been identified across Europe, no relevant use in elderly patients is expected.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safetypharmacology, repeated dose toxicity, juvenile toxicity and toxicity to reproduction and development.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Disodium phosphate dihydrate
Sodium dihydrogen phosphate dihydrateMannitolGlycine
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
6.3 Shelf life
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 usedimmediately, in-use storage times and conditions prior to use are the responsibility of the user andwould normally not be longer than 24 hours at 2°C to 8°C.
6.4 Special precautions for storage
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.
6.5 Nature and contents of container
10 mL vial (Type I glass) with a bromobutyl rubber stopper, analuminiumsealandapolypropylene
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.
6.6 Special precautions for disposal and other handling
Lamzede requires reconstitution and is intended for intr |
