GLIADEL® Wafer (polifeprosan 20 with carmustine implant) is indicated
in patients with newly diagnosed high-grade malignant glioma as an adjunct to surgery
GLIADEL Wafer is also indicated in patients with recurrent glioblastoma multiforme
as an adjunct to surgery.
Important Safety Information
GLIADEL® Wafer (polifeprosan 20 with carmustine implant) should not
be given to patients who have demonstrated a previous hypersensitivity to carmustine
or any of the components of GLIADEL Wafer.
Patients undergoing craniotomy for malignant glioma and implantation of GLIADEL
Wafer should be monitored closely for known complications of craniotomy, including
seizures, intracranial infections, abnormal wound healing, and brain edema. Cases
of intracerebral mass effect unresponsive to corticosteroids have been described
in patients treated with GLIADEL Wafer, including 1 case leading to brain herniation.
Carmustine, the active component of GLIADEL Wafer, can cause fetal harm when administered
to a pregnant woman. It is recommended that patients receiving GLIADEL Wafer discontinue
Communication between the surgical resection cavity and the ventricular system should
be avoided to prevent the wafers from migrating into the ventricular system and
causing obstructive hydrocephalus. If a communication larger than the diameter of
a wafer exists, it should be closed prior to wafer implantation.
CT and MRI of the head may demonstrate enhancement in the brain tissue surrounding
the resection cavity after implantation of GLIADEL Wafer. This enhancement may represent
edema and inflammation caused by GLIADEL Wafer or tumor progression.
The short-term and long-term toxicity profiles of GLIADEL Wafer when given in conjunction
with chemotherapy have not been fully explored.
The following 4 categories of adverse events are possibly related to treatment with
- 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.
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 5 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.
- 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 recurrences, intracranial
infection, or necrosis) may necessitate re-operation and, in some cases, removal
of GLIADEL Wafer or its remnants.
- Healing Abnormalities: The following healing abnormalities have been reported
in GLIADEL Wafer clinical trials: 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.
- Intracranial Infection: In the initial surgery trial, the incidence of brain
abscess or meningitis was 5% in patients treated with GLIADEL Wafer and 6% in patients
receiving placebo. In the recurrent setting, the incidence of brain abscess or meningitis
was 4% in GLIADEL Wafer patients and 1% in patients receiving placebo.
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Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
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