Adverse Reaction
Patients Treated with Brineura
n=24 (%)
Pyrexia* 17 (71)
ECG abnormalities† 17 (71)
Decreased CSF protein 17 (71)
Vomiting 15 (63)
Seizures‡ 12 (50)
Hypersensitvity§ 11 (46)
Increased CSF protein 5 (21)
Hematoma 5 (21)
Headache 4 (17)
Irritability 4 (17)
Pleocytosis 4 (17)
Device-related infection¶ 2 (8)
Bradycardia 2 (8)
Feeling jittery 2 (8)
Hypotension 2 (8)
*Pyrexia includes: pyrexia and increased body temperature
†ECG abnormalities include: non-specific repolarization abnormality, notched QRS, ST segment elevation, biphasic T wave abnormality, supraventricular extrasystoles, braycardia, sinus tachycardia, and intraventricular conduction delay
‡Seizures include: atonic, generalized tonic-clonic, focal, and absence.
§Hypersensitivity includes: immune reactions and signs and symptoms observed concomitantly with hypersensitivity reactions including pyrexia, vomiting, pleocytosis or irritability
¶Device-related infections include: Propionibacterium acnes and Staphylococcus epidermidis
Description of Selected Adverse Reactions
Seizures
Seizures were reported in 12 of 24 (50%) patients. The seizure types reported include atonic, generalized tonic-clonic, focal, and absence. Seizures were managed with standard anti-convulsive therapies and did not result in discontinuation of Brineura treatment.
Device-Related Complications
Adverse reactions related to the device were observed in 12 of 24 (50%) of patients. Device-related adverse reactions include infection, delivery system-related complications, and pleocytosis. Nine of these patients (38%) experienced adverse reactions, which involved complications of the non-implanted delivery system components. Four patients (16%) had device-related adverse reactions, which required medical intervention, including two patients (8%) with intraventricular access device-related CNS infections, and one patient (4%) each with leakage of the intraventricular access device and pleocytosis. Device-related infections were diagnosed by increased CSF pleocytosis and microbiology culture and organism identification, without accompanying signs and symptoms of meningitis. Intraventricular access devices were replaced and infections were treated with antibiotics. Device-related complications did not result in discontinuation of Brineura treatment [see Warnings and Precautions (5.1)].
Hematoma
Hematoma adverse reactions were reported in 5 (21%) patients treated with Brineura and presented as hematoma, post procedural hematoma, traumatic hematoma and subdural hematoma. Hematomas did not require treatment and did not interfere with Brineura infusion.
Hypersensitivity
Hypersensitivity reactions were reported in 11 out of 24 patients (46%) treated with Brineura during or within 24 hours after completion of the Brineura infusion, despite pre-medication with antihistamines with or without antipyretics or corticosteroids [see Warnings and Precautions (5.1)]. The most common manifestations observed concomitantly with hypersensitivity included pyrexia with vomiting, pleocytos |
