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Drug Details
Gliadel 7.7mg Implant
- Presentation
Implant Off-white to pale yellow flat discoid implant. - Description
Each implant contains 7.7 mg of carmustine. - Indications
GLIADEL Implant is indicated in newly-diagnosed high-grade malignant glioma patients as an adjunct to surgery and radiation.
GLIADEL Implant is indicated for use as an adjunct to surgery in patients with recurrent histologically proved glioblastoma multiforme for whom surgical resection is indicated.
- Adult Dosage
For intralesional use in adults only.
Each GLIADEL Implant contains 7.7 mg of carmustine, resulting in a dose of 61.6 mg when eight implants are placed in the tumour resection cavity.
It is recommended that a maximum of eight implants be placed if the size and shape of the resection cavity allows it. Implants broken in half may be used, but implants broken in more than two pieces should be discarded in the dedicated biohazard waste containers.
It is recommended that the placement of the implants should be directly from the product's inner sterile packaging into the resection cavity. Oxidised regenerated cellulose may be placed over the implants to secure them to the cavity surface .
- Contra Indications
Hypersensitivity to the active substance carmustine or to any of the excipients of GLIADEL Implant.
- Special Precautions
Patients undergoing craniotomy for glioblastoma and implantation of GLIADEL Implant should be monitored closely in view of known complications of craniotomy which includes convulsions, intracranial infections, abnormal wound healing, and brain oedema. Cases of intracerebral mass effect unresponsive to corticosteroids have been described in patients treated with GLIADEL Implant, including one case leading to brain herniation. Careful monitoring of GLIADEL Implant-treated patients for cerebral oedema/intracranial hypertension with consequent steroid use is warranted. CSF leak was more common in GLIADEL Implant-treated patients. Attention to a water-tight dural closure and local wound care is indicated.
Development of brain oedema with mass effect (due to tumour recurrence, intracranial infection, or necrosis) may necessitate re-operation and, in some cases, removal of GLIADEL Implant or its remnants.
Communication between the surgical resection cavity and the ventricular system should be avoided to prevent the implants from migrating into the ventricular system and possibly causing obstructive hydrocephalus. If a communication larger than the diameter of the implant exists, it should be closed prior to GLIADEL Implant implantation.
Computed tomography and magnetic resonance imaging may demonstrate enhancement in the brain tissue surrounding the resection cavity after placement of GLIADEL Implants. This enhancement may represent oedema and inflammation caused by GLIADEL Implants or tumour progression.
- Interactions
Interactions of GLIADEL Implant with other drugs or chemotherapy have not been formally evaluated.
- Adverse Drug Reactions
The spectrum of undesirable effects observed in patients with newly-diagnosed high-grade malignant glioma and recurrent malignant gliomas was generally consistent with that encountered in patients undergoing craniotomy for malignant gliomas.
Very common (
1/10), common ( 1/100 to < 1/10) and uncommon ( 1/1,000 to < 1/100) adverse reactions reported in patients receiving GLIADEL Implant during the clinical trials are listed below.Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Primary Surgery
The following data are the most frequently occurring adverse events observed in 5% or more of the 120 newly-diagnosed malignant glioma patients receiving GLIADEL Implant during the trial.
Common Adverse Events Observed in
5% of Patients Receiving GLIADEL Implant at Initial SurgeryClass organ
Adverse events
Endocrine disorders
common
Diabetes mellitus
Metabolism and nutrition disorders
very common
Healing abnormal
common
Peripheral oedema
Nervous system disorders
very common
Hemiplegia, convulsion, confusion, brain oedema, aphasia, depression, somnolence, speech disorder
common
Amnesia, intracranial hypertension, personality disorder, anxiety, facial paralysis, neuropathy, ataxia, hypoesthesia, paresthesia, thinking abnormal, abnormal gait, dizziness, grand mal convulsion, hallucinations, insomnia, tremor
Eye disorders
common
Conjonctival oedema, abnormal vision, visual field defect
Cardiac disorders
very common
Deep thrombophlebitis
common
Pulmonary embolism, haemorrhage
Respiratory, thoracic and mediastinal disorders
common
Pneumonia
Gastrointestinal disorders
very common
Nausea, vomiting, constipation
common
Diarrhoea
Skin and subcutaneous tissue disorders
very common
Rash, alopecia
Renal and urinary disorders
common
Urinary tract infection, urinary incontinence
General disorders and administration site conditions
very common
Aggravation reaction, headache, asthenia, infection, fever, pain
common
Abdominal pain, back pain, face oedema, chest pain, abscess, accidental injury
Intracranial hypertension was present in more GLIADEL Implant-treated patients than in Placebo patients (9.2% vs. 1.7%). It was typically observed late, at the time of tumour recurrence, and was unlikely to be associated with GLIADEL Implant use.
CSF leak was more common in GLIADEL Implant-treated patients than in placebo patients. However intracranial infections and other healing abnormalities were not increased.
Surgery for Recurrent Disease
The following post-operative adverse events were observed in 4% or more of the 110 patients receiving GLIADEL Implant at recurrent surgery in a controlled clinical trial. Except for nervous system effects, where there is a possibility that the placebo implants could have been responsible, only events more common in the GLIADEL Implant 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 in
4% of Patients Receiving GLIADEL Implant at Recurrent SurgeryClass organ
Adverse events
Blood and lymphatic system disorders
common
Anaemia
Metabolism and nutrition disorders
very common
Healing abnormal
common
Hyponatraemia
Nervous system disorders
very common
Convulsion, hemiplegia, headache, somnolence, confusion
common
Aphasia, stupor, brain oedema, intracranial hypertension, meningitis or abscess
Cardiac disorders
common
Deep thrombophlebitis, Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
common
Pneumonia
Gastrointestinal disorders
common
Nausea, nausea and vomiting, oral moniliasis
Skin and subcutaneous tissue disorders
common
Rash
Renal and urinary disorders
very common
Urinary tract infection
General disorders and administration site conditions
very common
Fever
common
Infection, pain
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 Implant in all studies. The events listed were either not present pre-operatively or worsened post-operatively. Whether GLIADEL Implant caused these events cannot be determined.
Common Adverse Events in 1% to 4% of Patients Receiving GLIADEL Implant
Class organ
Adverse events
Blood and lymphatic system disorders
common
Thrombocytopenia, leukocytosis
Metabolism and nutrition disorders
common
Hyponatraemia, hyperglycaemia, hypokalaemia
Nervous system disorders
common
Hydrocephalus, depression, abnormal thinking, ataxia, dizziness, insomnia, hemiplegia, coma, amnesia, diplopia, paranoid reaction
uncommon
Cerebral haemorrhage, cerebral infarct
Eye Disorders
common
Visual defect, eye pain
Cardiac and vascular Disorders
common
Hypertension, hypotension
Respiratory, thoracic and mediastinal disorders
common
Infection, aspiration pneumonia
Gastrointestinal disorders
common
Diarrhoea, constipation, dysphagia, gastrointestinal haemorrhage, faecal incontinence
Skin and subcutaneous tissue disorders
common
Rash
Musculoskeletal and connective tissue disorders
common
Infection
Renal and urinary disorders
common
Urinary incontinence
General disorders and administration site conditions
common
Peripheral oedema, neck pain, accidental injury, back pain, allergic reaction, asthenia, chest pain, sepsis
The following four categories of adverse events are possibly related to treatment with GLIADEL Implant.
Seizures:
In the initial surgery trial, the incidence of seizures within the first 5 days after implantation was 2.5% in the GLIADEL Implant group.
In the surgery for recurrent disease trial, the incidence of post-operative seizures was 19% in patients receiving GLIADEL Implant. 12/22 (54%) of patients treated with GLIADEL Implant 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 Implant.
Brain Oedema:
Development of brain oedema with mass effect (due to tumour recurrence, intracranial infection, or necrosis) may necessitate re-operation and, in some cases, removal of GLIADEL Implant or its remnants.
Healing Abnormalities:
The following healing abnormalities have been reported in clinical trials of GLIADEL Implant: wound dehiscence, delayed wound healing, subdural, subgaleal or wound effusions, and cerebrospinal fluid leak.
In the initial surgery trial, cerebrospinal fluid leaks occurred in 5% of GLIADEL Implant recipients. During surgery, a water-tight dural closure should be obtained to minimise the risk of cerebrospinal fluid leak.
Intracranial Infection:
In the initial surgery trial, the incidence of brain abscess or meningitis was 5% in patients treated with GLIADEL Implant.
In the recurrent setting, the incidence of brain abscess or meningitis was 4% in patients treated with GLIADEL Implant.
In a published clinical study, cyst formation after GLIADEL Implant treatment has been reported. This reaction occurred in 10% of the patients observed in the study, however, the formation of cysts is possible after resection of a malignant glioma.