Velmanase alfa interacts in the following cases:
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.
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.
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, velmanase alfa should be used during pregnancy only when strictly needed.
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. Velmanase alfa can be used during breastfeeding.
There are no clinical data on the effects of velmanase alfa on fertility. Animal studies do not show evidence of impaired fertility.
Velmanase alfa has no or negligible influence on the ability to drive and use machines.
The most common adverse reactions observed were weight increase (18%), IRRs (9%), diarrhoea (12%), headache (9%), arthralgia (9%), increased appetite (6%) and pain in extremity (6%). All of these adverse reactions were non-serious. IRRs include hypersensitivity in 3 patients and anaphylactoid reaction in 1 patient. These reactions were non-serious and mild to moderate in intensity.
A total of 2 serious adverse reactions (loss of consciousness in 1 patient and acute renal failure in 1 patient) were observed. In both cases the patients recovered without sequelae.
The adverse reactions reflecting exposure of 33 patients treated with velmanase alfa in clinical studies are listed below. Adverse reactions are classified by system organ class and preferred term according to the MedDRA frequency convention. Frequency is defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) or not known (cannot be estimated from the available data).
Adverse reactions reported in clinical studies in patients with alpha-mannosidosis treated with velmanase alfa:
Common: Hypersensitivity1, Anaphylactoid reaction1
Common: Increased appetite
Common: Psychotic behaviour, Initial insomnia
Common: Confusional state, Loss of consciousness2, Syncope, Tremor, Dizziness, Headache
Common: Eye irritation, Eyelid oedema, Ocular hyperaemia
Common: Bradycardia
Common: Epistaxis
Very common: Diarrhoea
Common: Abdominal pain, Abdominal pain upper, Nausea1, Vomiting1, Reflux gastritis
Common: Urticaria1, Hyperhidrosis1
Common: Arthralgia, Back pain, Joint stiffness, Myalgia, Pain in extremity
Common: Renal failure acute2
Very common: Pyrexia1
Common: Catheter site pain, Chills1, Feeling hot1, Fatigue, Malaise1
Very common: Weight increase
Common: Procedural headache
1 Preferred terms considered as IRR as described in the section below.
2 Selected adverse reaction as described in the section below.
IRRs (including hypersensitivity, nausea, vomiting, pyrexia, chills, feeling hot, malaise, urticaria, anaphylactoid reaction and hyperhidrosis) were reported in 9% of the patients (3 out of 33 patients) in clinical studies. All were mild or moderate in severity and none were reported as a serious adverse event. All patients who experienced IRRs recovered.
In the clinical studies, one patient experienced acute renal failure considered possibly related to the study treatment. Acute renal failure was of moderate severity leading to temporary discontinuation of the study treatment and fully resolved within 3 months. Concomitant long-term treatment with high doses of ibuprofen was noted as a potentially causative contributor to the occurrence of the event.
In one patient, loss of consciousness considered related to the study treatment with recovery after a few seconds was reported. The patient received saline infusion in a hospital setting and was then discharged after 6-hour observation. The patient later experienced epileptic seizures that were considered not related.
The safety profile of velmanase alfa in clinical studies involving children and adolescents was similar to that observed in adult patients. Overall, 58% of patients (19 out of 33) with alpha-mannosidosis receiving velmanase alfa in clinical studies were aged 6 to 17 years at the start of the study.
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