ormities, disostosis multiplex, neurological manifestations and impaired cognitive function).
Hypersensitivity
Hypersensitivity reactions have been reported in patients in clinical studies. Appropriate medicalsupport should be readily available when velmanase alfa is administered. If severe allergic oranaphylactic-type reactions occur, immediate discontinuation of velmanase alfa is recommended andcurrent medical standards for emergency treatment are to be followed.
Infusion-related reactionAdministration of velmanase alfa may result in an IRR, including anaphylactoid reaction (seesection 4.8). The IRRs observed in clinical studies of velmanase alfa were characterised by a rapidonset 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 theinfusion rate, treatment with medicinal products such as antihistamines, antipyretics and/orcorticosteroids, and/or stopping and resuming treatment with increased infusion time. Pre-treatmentwith antihistamines and/or corticosteroids may prevent subsequent reactions in those cases wheresymptomatic treatment was required. Patients were not routinely pre-medicated prior to infusion ofvelmanase 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 reactionshould 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 emergencytreatment 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.
ImmunogenicityAntibodies may play a role in treatment-related reactions observed with the use of velmanase alfa.
Tofurther eva luate the relationship, in instances of development of severe IRRs or lack or loss oftreatment effect, patients should be tested for the presence of anti-velmanase alfa antibodies.
In casethe 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 patientsout of 33 (24%) developed IgG-class antibodies to velmanase alfa. No clear correlation was foundbetween antibody titres (velmanase alfa IgG antibody level) and reduction in efficacy or occurrence ofanaphylaxis or other hypersensitivity reactions.
The development of antibodies has not been shown to affect clinical efficacy or safety.
Sodium contentThis medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially‘sodium-free’.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
4.6 Fertility, pregnancy and lactation
PregnancyThere are no data from the use of velmanase alfa in pregnant women. Animal studies do not indicatedirect or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturitionor postnatal development (see section 5.3). As velmanase alfa aims at normalizing alpha-mannosidasein alpha-mannosidosis patients, Lamzede should be used during pregnancy only when strictly needed.
Breast-feeding
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