Gliadel Side Effects
Generic Name: carmustine
Please note - some side effects for Gliadel may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
Side Effects of Gliadel - for the Consumer
Gliadel Implant Wafer
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Gliadel Implant Wafer:
Seek medical attention right away if any of these SEVERE side effects occur when using Gliadel Implant Wafer:Anxiety; constipation; diarrhea; drowsiness; hair loss; headache; nausea; vomiting; weakness.
Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; confusion; dizziness; fainting; fever; memory trouble or loss of memory; mental or mood changes; muscle weakness; pain; seizures; severe stomach pain; stiff neck; swelling or infection of the surgical site; tremor; trouble sleeping; trouble speaking; unusual bruising or bleeding; unusual numbness or tingling; vision changes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
TopGliadel Side Effects - for the Professional
Gliadel
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.
| Body System Adverse Event |
Gliadel® Wafer [N=120] n (%) |
Placebo [N=120] n (%) |
|---|---|---|
| *Adverse events coded to the COSTART term "aggravation reaction" were usually events involving tumor/disease progression or general deterioration of condition (e.g. condition/health/Karnofsky/neurological/physical deterioration). | ||
| Body as a Whole | ||
| Aggravation reaction* | 98 (82) | 95 (79) |
| Headache | 33 (28) | 44 (37) |
| Asthenia | 26 (22) | 18 (15) |
| Infection | 22 (18) | 24 (20) |
| Fever | 21 (18) | 21 (18) |
| Pain | 16 (13) | 18 (15) |
| Abdominal pain | 10 (8) | 2 (2) |
| Back pain | 8 (7) | 4 (3) |
| Face edema | 7 (6) | 6 (5) |
| Abscess | 6 (5) | 3 (3) |
| Accidental injury | 6 (5) | 8 (7) |
| Chest pain | 6 (5) | 0 |
| Allergic reaction | 2 (2) | 6 (5) |
| Cardiovascular system | ||
| Deep thrombophlebitis | 12 (10) | 11 (9) |
| Pulmonary embolus | 10 (8) | 10 (8) |
| Hemorrhage | 8 (7) | 7 (6) |
| Digestive system | ||
| Nausea | 26 (22) | 20 (17) |
| Vomiting | 25 (21) | 19 (16) |
| Constipation | 23 (19) | 14 (12) |
| Diarrhea | 6 (5) | 5 (4) |
| Liver function tests abnormal | 1 (1) | 6 (5) |
| Endocrine system | ||
| Diabetes mellitus | 6 (5) | 5 (4) |
| Cushings syndrome | 4 (3) | 6 (5) |
| Metabolic and nutritional disorders | ||
| Healing abnormal | 19 (16) | 14 (12) |
| Peripheral edema | 11 (9) | 11 (9) |
| Musculoskeletal system | ||
| Myasthenia | 5 (4) | 6 (5) |
| Nervous system | ||
| Hemiplegia | 49 (41) | 53 (44) |
| Convulsion | 40 (33) | 45 (38) |
| Confusion | 28 (23) | 25 (21) |
| Brain edema | 27 (23) | 23 (19) |
| Aphasia | 21 (18) | 22 (18) |
| Depression | 19 (16) | 12 (10) |
| Somnolence | 13 (11) | 18 (15) |
| Speech disorder | 13 (11) | 10 (8) |
| Amnesia | 11 (9) | 12 (10) |
| Intracranial hypertension | 11 (9) | 2 (2) |
| Personality disorder | 10 (8) | 9 (8) |
| Anxiety | 8 (7) | 5 (4) |
| Facial paralysis | 8 (7) | 5 (4) |
| Neuropathy | 8 (7) | 12 (10) |
| Ataxia | 7 (6) | 5 (4) |
| Hypesthesia | 7 (6) | 6 (5) |
| Paresthesia | 7 (6) | 10 (8) |
| Thinking abnormal | 7 (6) | 10 (8) |
| Abnormal gait | 6 (5) | 6 (5) |
| Dizziness | 6 (5) | 11 (9) |
| Grand mal convulsion | 6 (5) | 5 (4) |
| Hallucinations | 6 (5) | 4 (3) |
| Insomnia | 6 (5) | 7 (6) |
| Tremor | 6 (5) | 8 (7) |
| Coma | 5 (4) | 6 (5) |
| Incoordination | 3 (3) | 8 (7) |
| Hypokinesia | 2 (2) | 8 (7) |
| Respiratory system | ||
| Pneumonia | 10 (8) | 9 (8) |
| Dyspnea | 4 (3) | 8 (7) |
| Skin and appendages | ||
| Rash | 14 (12) | 13 (11) |
| Alopecia | 12 (10) | 14 (12) |
| Special senses | ||
| Conjunctival edema | 8 (7) | 8 (7) |
| Abnormal vision | 7 (6) | 7 (6) |
| Visual field defect | 6 (5) | 8 (7) |
| Eye disorder | 3 (3) | 6 (5) |
| Diplopia | 1 (1) | 6 (5) |
| Urogenital system | ||
| Urinary tract infection | 10 (8) | 13 (11) |
| Urinary incontinence | 9 (8) | 9 (8) |
Surgery for Recurrent Disease
The following post-operative adverse events were observed in 4% or more of the patients receiving Gliadel® Wafer 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 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.
| Body System Adverse Event |
Gliadel® Wafer with Carmustine [N=110] n (%) |
PLACEBO Wafer without Carmustine [N=112] n (%) |
|---|---|---|
| *p < 0.05 for comparison of Gliadel® Wafer versus placebo groups | ||
| Body as a Whole | ||
| Fever | 13 (12) | 9 (8) |
| Pain* | 8 (7) | 1 (1) |
| Digestive System | ||
| Nausea and Vomiting | 9 (8) | 7 (6) |
| Metabolic and Nutritional Disorders | ||
| Healing 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 Gliadel® 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® 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 in all studies. The events listed were either not present pre-operatively or worsened post-operatively. Whether Gliadel® Wafer 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.
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%)
TopSide Effects by Body System - for Healthcare Professionals
Respiratory
Most of the patients with respiratory toxicity received prolonged therapy with total doses greater than 1400 mg/m2, although respiratory problems have been reported in patients receiving as little as 600 mg/m2.
Delayed onset pulmonary fibrosis occurring up to 17 years after treatment has been reported in one long-term study (n=17) on patients who received carmustine in childhood and early adolescence combined with cranial radiotherapy (for intracranial tumors). Chest X-rays revealed pulmonary hypoplasia with upper zone contraction. Thoracic CT scans showed an unusual pattern of upper zone fibrosis. Some late reduction of pulmonary function was reported in all long-term survivors. In this long-term study, 8 of 17 died of delayed pulmonary lung fibrosis, including all those initially treated (5 of 17) at less than 5 years old.
Respiratory side effects including pulmonary infiltrates and/or fibrosis have been reported to occur from 9 days to 43 months after treatment with carmustine and related nitrosoureas. Cases of fatal respiratory toxicity have been reported.
Hematologic
Carmustine may produce cumulative myelosuppression. Thrombocytopenia has generally been reported to occur approximately four weeks after administration. Leukopenia has generally been reported to occur approximately five to six weeks after administration. Both have been reported to persist for one to two weeks.
Use of carmustine in combination with cimetidine has resulted in greater myelotoxicity (e.g., leucopenia, neutropenia).
Hematologic side effects including myelosuppression have been reported frequently. Thrombocytopenia, leukopenia, and less frequently, anemia have also been reported. Acute leukemia and bone marrow dysplasias have been reported following long-term nitrosourea therapy.
Gastrointestinal
Nausea and vomiting generally appear within two hours of dosing and last for four to six hours. Prior administration of antiemetics has been effective in diminishing and sometimes preventing these side effects.
Gastrointestinal side effects including nausea and vomiting have been reported frequently.
Hepatic
Hepatic side effects including increased transaminase, alkaline phosphatase, and bilirubin levels have been reported infrequently.
The increased levels are generally reversible.
Renal
Renal side effects including progressive azotemia, decrease in kidney size, and renal failure have been reported in patients after prolonged therapy and usually after large cumulative doses.
Cardiovascular
Cardiovascular side effects including hypotension and tachycardia have been reported. Three cases of myocardial ischemia during and immediately after high-dose carmustine infusion have been reported.
Local
Local side effects including burning and hyperpigmentation have been reported.
Other
Other side effects have included intensive flushing of the skin and suffusion of the conjunctiva following rapid intravenous infusion of carmustine.
This effect usually has been reported to occur within two hours and last for approximately four hours.
Ocular
Ocular side effects including neuroretinitis have been reported.
General
General side effects including chest pain and headache have been reported.
Oncologic
Oncologic side effects have included spontaneous reports of cyst formation after gliadel wafer implantation. Carcinogenicity has been reported in animal studies.
Cyst formation occurred at varying time intervals postimplantation. Cyst formation has also been reported in patients following resection of malignant glioma who have not had gliadel implanted.
Carmustine has been reported in animal studies to produce a marked increase in tumor incidence at doses approximating clinical doses.
More Gliadel resources
- Gliadel Advanced Consumer (Micromedex) - Includes Dosage Information
- Gliadel Concise Consumer Information (Cerner Multum)
- Gliadel Prescribing Information (FDA)
- Gliadel Implant Wafer MedFacts Consumer Leaflet (Wolters Kluwer)
- Carmustine Professional Patient Advice (Wolters Kluwer)
- Carmustine Monograph (AHFS DI)
- BiCNU MedFacts Consumer Leaflet (Wolters Kluwer)
- BiCNU Prescribing Information (FDA)
- Bicnu Advanced Consumer (Micromedex) - Includes Dosage Information
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