Lamzede

/ Kamada

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. The administration of this medicinal product should be carried out by a healthcare professional with the ability to manage ERT and medical emergencies.
The recommended dose regimen is 1 mg/kg of body weight administered once every week by intravenous infusion at a controlled speed. See prescribing information for full details.
Method of administration:
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 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).
The patient should be observed for IRRs for at least one hour after the infusion according to clinical conditions and the physician’s judgment. See prescribing information for full details.
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.

Enzyme replacement therapy for the treatment of non-neurological manifestations in patients with mild to moderate alpha-mannosidosis.

Severe allergic reaction to the active substance or to any of the excipients.

The effects of treatment with velmanase alfa should be periodically evaluated and discontinuation of treatment considered in cases where no clear benefits could be observed.
As the accumulation of end organ damage progresses over time, it is more difficult for the treatment to reverse the damage or to show improvements. As with other enzyme replacement therapies, velmanase alfa does not cross the blood-brain-barrier. It should be considered by the treating physician that the administration of velmanase alfa does not affect the irreversible complications (i.e. skeletal deformities, disostosis multiplex, neurological manifestations and impaired cognitive function).
Renal function:
In clinical studies, one patient experienced acute renal failure, therefore periodic monitoring of renal function is required.
Hypersensitivity:
Hypersensitivity reactions have been reported in patients in clinical studies. Appropriate medical support should be readily available when velmanase alfa is administered. If severe allergic or anaphylactic-type reactions occur, immediate discontinuation of velmanase alfa is recommended and current medical standards for emergency treatment are to be followed.
Infusion-related reaction:
Administration of velmanase alfa may result in an IRR, including anaphylactoid reaction. The IRRs observed in clinical studies of velmanase alfa were characterised by a rapid onset of symptoms and were of mild to moderate severity.
The management of IRRs should be based on the severity of the reaction and includes slowing the infusion rate, treatment with medicinal products such as antihistamines, antipyretics and/or corticosteroids, and/or stopping and resuming treatment with increased infusion time. Pre-treatment with antihistamines and/or corticosteroids may prevent subsequent reactions in those cases where symptomatic treatment was required. Patients were not routinely pre-medicated prior to infusion of velmanase alfa during clinical studies.
In case symptoms such as angioedema (tongue or throat swelling), upper airway obstruction or hypotension occur during or immediately after infusion, anaphylaxis or an anaphylactoid reaction should be suspected. In such a case, treatment with an antihistamine and corticosteroids should be considered as being appropriate. In the most severe cases, the current medical standards for emergency treatment are to be observed.
The patient should be kept under observation for IRRs for one hour or longer after the infusion, according to the treating physician’s judgement.
Immunogenicity:
Antibodies may play a role in treatment-related reactions observed with the use of velmanase alfa. To further evaluate the relationship, in instances of development of severe IRRs or lack or loss of treatment effect, patients should be tested for the presence of anti-velmanase alfa antibodies. In case the patient’s condition deteriorates during ERT, cessation of treatment should be considered.
There is a potential for immunogenicity. In the clinical studies at any time under treatment, 8 patients out of 33 (24%) developed IgG-class antibodies to velmanase alfa. No clear correlation was found between antibody titres (velmanase alfa IgG antibody level) and reduction in efficacy or occurrence of anaphylaxis or other hypersensitivity reactions.
The development of antibodies has not been shown to affect clinical efficacy or safety.
Sodium content:
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

The most common adverse reactions observed were weight increase, IRRs, diarrhoea , headache, arthralgia, increased appetite, and pain in extremity. See prescribing information for full details.

No interaction studies have been performed.

Pregnancy:
There are no data from the use of velmanase alfa in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. As velmanase alfa aims at normalizing alpha-mannosidase in alpha-mannosidosis patients, this medicinal product should be used during pregnancy only when strictly needed.
Breast-feeding:
It is unknown whether velmanase alfa or its metabolites are excreted in human milk. Nevertheless, the absorption of any ingested milk-containing velmanase alfa in the breastfed child is considered to be minimal and no untoward effects are therefore anticipated. This medicinal product can be used during breastfeeding.
Fertility:
There are no clinical data on the effects of velmanase alfa on fertility. Animal studies do not show evidence of impaired fertility.

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. See prescribing information for full details.

Store and transport refrigerated (2°C – 8°C).
Store in the original package in order to protect from light.