ing Abnormal* 15 (14) 6 (5)
Nervous System
Convulsion 21 (19) 21 (19)
Hemiplegia 21 (19) 22 (20)
Headache 16 (15) 14 (13)
Somnolence 15 (14) 12 (11)
Confusion 11 (10) 9 (8)
Aphasia 10 (9) 12 (11)
Stupor 7 (6) 7 (6)
Brain Edema 4 (4) 1 (1)
Intracranial Hypertension 4 (4) 7 (6)
Meningitis or Abscess 4 (4) 1 (1)
Skin and Appendages
Rash 6 (5) 4 (4)
Urogenital System
Urinary Tract Infection 23 (21) 19 (17)
Post-marketing experience includes spontaneous reports of cyst formation after Gliadel® wafer implantation. These occurred at varying time intervals post-implantation. Cyst formation has also been reported in patients following resection of malignant glioma who have not had Gliadel® implanted.
The following four categories of adverse events are possibly related to treatment with Gliadel® Wafer. The frequency with which they occurred in the randomized trials along with descriptive detail is provided below.
1. Seizures: In the initial surgery trial, the incidence of seizures was 33.3% in patients receiving Gliadel® Wafer and 37.5% in patients receiving placebo. Grand mal seizures occurred in 5% of Gliadel® Wafer-treated patients and 4.2% of placebo treated patients. The incidence of seizures within the first 5 days after wafer implantation was 2.5% in the Gliadel® Wafer group and 4.2% in the placebo group. The time from surgery to the onset of the first post-operative seizure did not differ between the Gliadel® Wafer and placebo treated patients.
In the surgery for recurrent disease trial, the incidence of post-operative seizures was 19% in both patients receiving Gliadel® Wafer and placebo. In this study, 12/22 (54%) of patients treated with Gliadel® Wafer and 2/22 (9%) of placebo patients experienced the first new or worsened seizure within the first five post-operative days. The median time to onset of the first new or worsened post-operative seizure was 3.5 days in patients treated with Gliadel® Wafer and 61 days in placebo patients.
2. Brain Edema: In the initial surgery trial, brain edema was noted in 22.5% of patients treated with Gliadel® Wafer and in 19.2% of patients treated with placebo. Development of brain edema with mass effect (due to tumor recurrence, intracranial infection, or necrosis) may necessitate re-operation and, in some cases, removal of Gliadel® Wafer or its remnants.
3. Healing Abnormalities: The following healing abnormalities have been reported in clinical trials of Gliadel® Wafer: wound dehiscence, delayed wound healing, subdural, subgaleal or wound effusions, and cerebrospinal fluid leak. In the initial surgery trial, healing abnormalities occurred in 15.8% of Gliadel® Wafer treated patients and in 11.7% of placebo recipients. Cerebrospinal fluid leaks occurred in 5% of Gliadel® Wafer recipients and 0.8% of those given placebo. During surgery, a water-tight dural closure should be obtained to minimize the risk of cerebrospinal fluid leak.
In the surgery for recurrent disease trial, the incidence of healing abnormalities was 14% in Gliadel® Wafer treated patients and 5% in patients receiving placebo wafers.
4. Intracranial Infection: In the initial surgery trial, the incidence of brain abscess or meningitis was 5% in patients treated with Gliad |
