Vestronidase alfa interacts in the following cases:
Serious hypersensitivity reactions, including anaphylaxis, have been reported with vestronidase alfa; therefore, appropriate medical support should be readily available when vestronidase alfa is administered.
Infusion should be avoided if the patient has an acute febrile or respiratory illness at the time.
It is recommended that premedication with non-sedating antihistamines with or without antipyretics be administered 30-60 minutes prior to the start of the infusion.
It is important to administer vestronidase alfa according to the recommended infusion rate schedule.
If severe hypersensitivity reactions occur, immediately stop the infusion of vestronidase alfa and initiate appropriate treatment. Management of hypersensitivity reactions should be based on the severity of the reaction and include temporary interruption or discontinuation of the infusion and/or administration of additional antihistamines, antipyretics, and/or corticosteroids for mild to moderate reactions. Consider rapid sodium chloride 9 mg/mL (0.9%) solution for infusion for decreased blood pressure and oxygen for hypoxia. Patients should be observed for a minimum of 60 minutes after completing the infusion of vestronidase alfa.
Patients should be informed of the signs and symptoms of hypersensitivity reactions and instructed to seek immediate medical care should such signs and symptoms occur. The risks and benefits of readministering vestronidase alfa should be considered following a severe hypersensitivity reaction.
There are no data on the use of vetronidase alfa in pregnant women. Animal studies with vestronidase alfa do not indicate direct or indirect harmful effects with respect to pregnancy or embryo-foetal development.
As a precautionary measure, it is preferable to avoid the use of vestronidase alfa during pregnancy, unless the potential benefit to the mother outweighs the potential theoretical risks to the foetus.
There are no data from studies in breast-feeding women. It is not known whether vestronidase alfa is excreted in human milk, but systemic exposure via breast-milk is not expected. Due to lack of human data, vestronidase alfa should only be administered to a breast-feeding woman if the potential benefit of vestronidase alfa to the mother and the benefit of breast-feeding to the infant outweighs the potential theoretical risks to the infant.
No human data are available on the effect of vestronidase alfa on fertility. Animal studies with vestronidase alfa do not indicate any impact on male or female fertility.
Vestronidase alfa has no or negligible influence on the ability to drive and use machines.
The assessment of adverse reactions was based on the exposure of 23 patients from 4 clinical trials, aged 5 months to 25 years, who received vestronidase alfa at doses up to 4 mg/kg once every two weeks for up to 132 weeks. Nineteen patients were younger than 18 years of age.
The most common adverse reactions from 4 clinical trials in 23 patients treated with vestronidase alfa were anaphylactoid reaction (13%), urticaria (13%), infusion site swelling (13%), infusion site extravasation (8.7%), pruritus (8.7%), diarrhoea (8.7%) and rash (8.7%). Most adverse reactions were mild to moderate in severity. There was a single adverse reaction of febrile convulsion observed in one patient (4.3%); the patient recovered without sequelae.
Listed below are the adverse reactions reported from 4 clinical trials in 23 patients treated with vestronidase alfa. Adverse reactions are presented by System Organ Class and frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1,000), and very rare (<1/10,000).
Very common: Anaphylactoid reaction
Common: Febrile convulsion*
Common: Diarrhoea
Very common: Urticaria
Common: Rash, Pruritus
Very common: Infusion site swelling**
Common: Infusion site extravasation
* Refer to description of selected adverse reactions for details on the febrile convulsion reported in 1 of 23 trial patients.
** One adverse reaction of Peripheral swelling is included within the frequency of Infusion site swelling as the event is classified as intravenous catheter issue.
One patient receiving a vestronidase alfa dose of 4 mg/kg experienced a febrile convulsion during treatment at the week 66, within 3 days of diphtheria, tetanus, pertussis vaccination. The infusion was stopped, the patient received anticonvulsants, antipyretics and antibiotics, and the febrile convulsion resolved. The patient subsequently was re-challenged without recurrence and continued on vestronidase alfa treatment. This event was assessed as possibly related to vestronidase alfa due to the temporal association with the infusion.
Sixteen out of 23 patients (70%) from 4 clinical trials developed anti-recombinant human betaglucuronidase (rhGUS) antibodies (ADA), nine of whom further developed neutralizing antibodies (NAb) on at least one occasion, but not consistently over time. There is no definitive correlation between the antibody titre and neutralizing antibody development. In most patients, a pattern of attenuated immunogenicity with chronic exposure was suggested by declining antibody titres over time on continuous treatment. The presence of ADA (non-NAb and NAb) does not appear to affect reduction in the pharmacodynamic marker, urinary glycosaminoglycans (uGAGs).
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