Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

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.

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

General consideration on the treatment

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 (see section 4.8). 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. Most of the 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 exploratory and pivotal clinical studies at any time under treatment, 8 patients out of 33 (24%) developed IgG-class antibodies to velmanase alfa.
In a paediatric clinical study in patients below 6 years, 4 patients out of 5 (80%) developed IgG-class antibodies to velmanase alfa. In this study, the immunogenicity test was performed with a different and more sensitive method and therefore the incidence of patients developing IgG-class antibodies to velmanase alfa was higher but not comparable to data of the previous studies.
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’.

Effects on Driving

4.7    Effects on ability to drive and use machines

Lamzede has no or negligible influence on the ability to drive and use machines.