IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Seizures: Seizures occurred in 37% of patients treated with GLIADEL Wafers for
recurrent glioma in the
recurrent high-grade glioma trial. New or worsening (treatment emergent) seizures occurred in 20% of
patients; 54% of treatment emergent seizures occurred within the first 5 post-operative days. The
median time to onset of the first new or worsened post-operative seizure was four days. Institute
optimal anti-seizure therapy prior to surgery. Monitor patients for seizures postoperatively.
Intracranial Hypertension: Brain edema occurred in 23% of patients with newly
treated with GLIADEL Wafers in the newly-diagnosed high-grade glioma trial. Additionally, one GLIADEL-treated
patient experienced intracerebral mass effect unresponsive to corticosteroids which led to brain
herniation. Monitor patients closely for intracranial hypertension related to brain edema, inflammation,
or necrosis of the brain tissue surrounding the resection. In refractory cases, consider re-operation and
removal of GLIADEL Wafers or Wafer remnants.
Impaired Neurosurgical Wound Healing: Impaired neurosurgical wound healing including
dehiscence, delayed wound healing, and subdural, subgaleal, or wound effusions occur with GLIADEL
Wafer treatment. In the newly-diagnosed high-grade glioma trial, 16% of GLIADEL Wafer-treated
patients with newly diagnosed glioma experienced impaired intracranial wound healing and 5% had
cerebrospinal fluid leaks. In the recurrent high-grade glioma trial, 14% of GLIADEL Wafer-treated
patients with recurrent high-grade glioma experienced wound healing abnormalities. Monitor patients
post-operatively for impaired neurosurgical wound healing.
Meningitis: Meningitis occurred in 4% of patients with recurrent glioma receiving
GLIADEL Wafers in the
recurrent high-grade glioma trial. Two cases of meningitis were bacterial; one patient required removal
of the Wafers four days after implantation; the other developed meningitis following reoperation for
recurrent tumor. One case was diagnosed as chemical meningitis and resolved following steroid
treatment. In one case the cause was unspecified, but meningitis resolved following antibiotic
treatment. Monitor postoperatively for signs of meningitis and central nervous system infection.
Wafer Migration: GLIADEL Wafer migration can occur. To reduce the risk of
due to wafer migration into the ventricular system, close any communication larger than the diameter
of a Wafer between the surgical resection cavity and the ventricular system prior to Wafer implantation.
Monitor patients for signs of obstructive hydrocephalus.
Embryo-Fetal Toxicity: GLIADEL Wafers can cause fetal harm when administered to a
Carmustine, the active component of GLIADEL Wafer, is embryotoxic and teratogenic in rats at
exposures less than the exposure at the recommended human dose based on body surface area (BSA)
and embryotoxic in rabbits at exposures similar to the exposure at the recommended human dose
based on BSA. Advise patients of the potential risk to a fetus. Advise females of reproductive potential
to use effective contraception for 6 months after implantation of GLIADEL Wafer. Advise males with
female partners of reproductive potential to use effective contraception for 3 months following
implantation of Gliadel Wafers.
The most common adverse reactions in newly-diagnosed high-grade glioma patients (incidence >10%
and between arm difference ≥4%) are cerebral edema, asthenia, nausea, vomiting, constipation, wound
healing abnormalities and depression.
The most common adverse reactions in recurrent high-grade glioma patients (incidence >10% and
between arm difference ≥4%) are urinary tract infection, wound healing abnormalities and fever.
For additional safety information, please consult the GLIADEL full Prescribing
You are encouraged to report side effects of prescription drugs to Arbor Pharmaceuticals, LLC Medical
Information at 1-866-516-4950 or to the FDA at www.fda.gov/medwatch or call 1-800-FDA-1088.
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