Cerliponase alfa interacts in the following cases:
Anaphylactic reactions have been reported with cerliponase alfa. As a precautionary measure, appropriate medical support should be readily available when cerliponase alfa is administered. If anaphylactic reactions occur, immediately discontinue the infusion and initiate appropriate medical treatment. Observe patients closely during and after the infusion. If anaphylaxis occurs, caution should be exercised upon re-administration.
There are no data on the use of cerliponase alfa in pregnant women. Animal reproduction studies have not been conducted using cerliponase alfa. It is not known whether cerliponase alfa can cause foetal harm when administered to a pregnant woman or can affect reproductive capacity. Cerliponase alfa should be given to a pregnant woman only if clearly needed.
There are no data on the presence of cerliponase alfa in human milk, the effects of cerliponase alfa on the breastfed child, or the effects of cerliponase alfa on milk production. Breastfeeding should be discontinued during treatment with cerliponase alfa.
No fertility studies with cerliponase alfa have been conducted in animals or humans.
No studies on the effect of cerliponase alfa on the ability to drive or use machines have been performed.
The adverse reactions described in this section were evaluated in 24 patients with CLN2 disease who received at least one dose of Cerliponase alfa in clinical studies of up to 141 weeks or in post-marketing experience. The most frequent (>20%) adverse reactions observed during Cerliponase alfa clinical trials include pyrexia, low CSF protein, ECG abnormalities, vomiting, upper respiratory tract infections, and hypersensitivity. No patients had to have their treatment discontinued due to adverse events.
Adverse reactions observed are listed below, by system organ class and frequency, following the MedDRA frequency convention 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), not known (cannot be estimated from the available data). Adverse reactions are presented in order of decreasing seriousness.
Frequency of adverse reactions with Cerliponase alfa:
Very common: Upper respiratory tract infection
Common: Conjunctivitis, Device-related infectiona
Not known: Meningitis
Very common: Hypersensitivity
Common: Anaphylactic reaction
Very common: Irritability
Common: Bradycardia
Very common: Convulsion eventsb, Headache, CSF Pleocytosis
Common: Dropped head syndrome
Very common: Vomiting
Common: Abdominal pain, Oral mucosal blistering, Tongue blistering, Gastrointestinal disorder
Common: Rash, Urticaria
Very common: Pyrexiac
Common: Feeling jittery, Pain
Very common: CSF protein increased, ECG abnormalities, CSF protein decreased
Device issue:
Common: Device leakage, Device occlusiond
Not known: Device dislocatione
Very common: Needle issuef
a Propionibacterium acnes, staphylococcus epidermis
b Atonic seizures, clonic convulsion, drop attacks, epilepsy, generalised tonic-clonic seizure, myoclonic epilepsy, partial seizures, petit mal epilepsy, seizure, seizure cluster, and status epilepticus
c Pyrexia includes combined preferred terms “Pyrexia” and "Increased body temperature"
d Catheter flow obstruction
e Device dislocation did not occur in clinical trials
f Dislodgement of infusion needle
Convulsions are a common manifestation of CLN2 disease and are expected to occur in this population. Overall, 23 (96%) subjects who received cerliponase alfa experienced an event that mapped to the Convulsions Standardized MedDRA Query. The most commonly reported convulsion events include seizure, epilepsy and generalized tonic-clonic seizure. Total convulsion events with a temporal relationship to cerliponase alfa administration was 17% and were mild to moderate, grade 1 to 2 in severity. Overall, 6% of all convulsion events were considered related to cerliponase alfa and ranged from mild to severe, CTCAE grade 1-4. Convulsions resolved with standard anti-convulsive therapies, and did not result in discontinuation of Cerliponase alfa treatment.
Hypersensitivity reactions were reported in 14 out of 24 patients (58%) treated with Cerliponase alfa. Severe (Common Terminology Criteria for Adverse Events (CTCAE) grade 3) hypersensitivity reactions occurred in three patients and no patients discontinued treatment. The most common manifestations included pyrexia with vomiting, pleocytosis, or irritability, which are inconsistent with classic immune mediated hypersensitivity. These adverse reactions were observed during or within 24 hours after completion of the Cerliponase alfa infusion and did not interfere with treatment. Symptoms resolved over time or with administration of antipyretics, antihistamines and/or glucocorticosteroids.
Anti-drug antibodies (ADAs) were detected in both serum and CSF in 79% and 21%, respectively, of patients treated with cerliponase alfa for up to 107 weeks. Drug-specific neutralizing antibodies (NAb) capable of inhibiting receptor-mediated cellular uptake of cerliponase alfa were not detected in the CSF. No association was found between serum or CSF ADA titres and incidence or severity of hypersensitivity. Patients who experienced moderate hypersensitivity adverse events were tested for drug-specific IgE and found to be negative. No correlations were found between higher ADA titres and reductions in efficacy measurements. There was no apparent effect of serum or CSF ADA on the plasma or CSF pharmacokinetics, respectively.
An ongoing study provides experience with two patients aged 2 years of age treated with Cerliponase alfa at 300 mg every other week. Both patients have received 8 infusions and the overall safety profile of Cerliponase alfa in these younger patients appears consistent with the safety profile observed in older children. Currently no clinical experience of Cerliponase alfa in children below 2 years of age is available.
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