SIDE EFFECTS

Adverse reactions for the trials are described in the tables below.

Primary Surgery

The following data are the most frequently occurring adverse events observed in 5% or more of the newly-diagnosed malignant glioma patients during the trial.

COMMON ADVERSE EVENTS OBSERVED IN ≥ 5% OF PATIENTS RECEIVING GLIADEL® WAFER (polifeprosan 20 with carmustine) AT INITIAL SURGERY

Surgery for Recurrent Disease

The following post-operative adverse events were observed in 4% or more of the patients receiving GLIADEL® Wafer (polifeprosan 20 with carmustine) at recurrent surgery. Except for nervous system effects, where there is a possibility that the placebo wafers could have been responsible, only events more common in the GLIADEL® Wafer (polifeprosan 20 with carmustine) group are listed. These adverse events were either not present pre-operatively or worsened post-operatively during the follow-up period. The follow-up period was up to 71 months.

COMMON ADVERSE EVENTS OBSERVED IN ≥ 4% OF PATIENTS RECEIVING GLIADEL® WAFER (polifeprosan 20 with carmustine) AT SURGERY FOR RECURRENT DISEASE

Post-marketing experience includes spontaneous reports of cyst formation after GLIADEL® Wafer (polifeprosan 20 with carmustine) 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 (polifeprosan 20 with carmustine) implanted.

The following four categories of adverse events are possibly related to treatment with GLIADEL® Wafer (polifeprosan 20 with carmustine) . 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 (polifeprosan 20 with carmustine) and 37.5% in patients receiving placebo. Grand mal seizures occurred in 5% of GLIADEL® Wafer (polifeprosan 20 with carmustine) -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 (polifeprosan 20 with carmustine) 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 (polifeprosan 20 with carmustine) 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 (polifeprosan 20 with carmustine) and placebo. In this study, 12/22 (54%) of patients treated with GLIADEL® Wafer (polifeprosan 20 with carmustine) 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 (polifeprosan 20 with carmustine) 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 (polifeprosan 20 with carmustine) 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 (polifeprosan 20 with carmustine) or its remnants.
3. Healing Abnormalities: The following healing abnormalities have been reported in clinical trials of GLIADEL® Wafer (polifeprosan 20 with carmustine) : 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 (polifeprosan 20 with carmustine) treated patients and in 11.7% of placebo recipients. Cerebrospinal fluid leaks occurred in 5% of GLIADEL® Wafer (polifeprosan 20 with carmustine) 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 (polifeprosan 20 with carmustine) 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 GLIADEL (polifeprosan 20 with carmustine) ® Wafer and 6% in patients receiving placebo. In the recurrent setting, the incidence of brain abscess or meningitis was 4% in patients treated with GLIADEL (polifeprosan 20 with carmustine) ® Wafer and 1% in patients receiving placebo.

The following adverse events, not listed in the table above, were reported in less than 4% but at least 1% of patients treated with GLIADEL® Wafer (polifeprosan 20 with carmustine) in all studies. The events listed were either not present pre-operatively or worsened post-operatively. Whether GLIADEL® Wafer (polifeprosan 20 with carmustine) caused these events cannot be determined.

Body as a Whole: peripheral edema (2%); neck pain (2%); accidental injury (1%); back pain (1%); allergic reaction (1%); asthenia (1%); chest pain (1%); sepsis (1%)

Cardiovascular System: hypertension (3%); hypotension (1%)

Digestive System: diarrhea (2%); constipation (2%); dysphagia (1%); gastrointestinal hemorrhage (1%); fecal incontinence (1%)

Hemic and Lymphatic System: thrombocytopenia (1%); leukocytosis (1%)

Metabolic and Nutritional Disorders: hyponatremia (3%); hyperglycemia (3%); hypokalemia (1%)

Musculoskeletal System: infection (1%)

Nervous System: hydrocephalus (3%); depression (3%); abnormal thinking (2%); ataxia (2%); dizziness (2%); insomnia (2%); monoplegia (2%); coma (1%); amnesia (1%); diplopia (1%); paranoid reaction (1%). In addition, cerebral hemorrhage and cerebral infarct were each reported in less than 1% of patients treated with GLIADEL® Wafer (polifeprosan 20 with carmustine) .

Respiratory System: infection (2%); aspiration pneumonia (1%)

Skin and Appendages: rash (2%)

Special Senses: visual field defect (2%); eye pain (1%)

Urogenital System: urinary incontinence (2%)

Read the entire FDA prescribing information for Gliadel (Polifeprosan 20 with Carmustine) »