GLIADEL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GLIADEL (GLIADEL).
GLIADEL (carmustine implant) is a biodegradable wafer that delivers carmustine, a nitrosourea alkylating agent, directly into the tumor resection cavity. Carmustine alkylates DNA and RNA, leading to cross-linking and inhibition of DNA replication, ultimately causing cell death. It is cell cycle phase nonspecific.
| Metabolism | Carmustine is extensively metabolized in the liver via cytochrome P450 enzymes (primarily CYP2A6 and CYP2C9). Some metabolites are active and contribute to alkylating activity. The drug also undergoes non-enzymatic degradation. |
| Excretion | Primarily renal (60-70% as unchanged drug and metabolites) and biliary/fecal (15-20%). Approximately 10-15% is eliminated via exhaled air as CO2. |
| Half-life | Terminal elimination half-life is approximately 1.3 hours for the active dianhydrogalactitol metabolite. Clinical context: short half-life supports local interstitial delivery with minimal systemic accumulation. |
| Protein binding | Carmustine is approximately 80% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent volume of distribution (Vd) is 3.25 L/kg (range 2.5-4.0 L/kg). This large Vd indicates extensive tissue distribution, including penetration into brain tissue. |
| Bioavailability | When administered as an intracavitary implant (wafer), systemic bioavailability is approximately 30-40% of the dose due to local metabolism and limited absorption into the systemic circulation. Oral bioavailability is negligible (<5%). |
| Onset of Action | Intracavitary (implant): Onset of antineoplastic effect occurs within 1-2 weeks as the wafer degrades and releases carmustine locally. |
| Duration of Action | Intracavitary (implant): Release of carmustine continues for approximately 2-3 weeks as the polymer wafer erodes. Clinical effect persists for several months; the median time to progression in trials was about 6 months. |
| Molecular Weight | 296.26 |
Gliadel (carmustine) implant is administered intraoperatively as 8 wafers, each containing 7.7 mg carmustine, placed in the resection cavity after tumor debulking. Maximum dose is 61.6 mg (8 wafers).
| Dosage form | IMPLANT |
| Renal impairment | No specific dose adjustment guidelines. Use with caution in patients with severe renal impairment (CrCl <15 mL/min) as carmustine is nephrotoxic. |
| Liver impairment | Contraindicated in patients with serum bilirubin >3 mg/dL or transaminases >3 times upper limit of normal due to hepatotoxicity risk. No Child-Pugh based recommendations. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. No standard dosing recommendations. |
| Geriatric use | No specific dose adjustment. Use with caution due to increased sensitivity to myelosuppression and hepatic toxicity in elderly patients. |
| 1st trimester | Avoid. Teratogenic in animals; no adequate human studies. |
| 2nd trimester | Avoid. Potential fetal harm; use only if benefit outweighs risk. |
| 3rd trimester | Avoid. Risk of neonatal toxicity, including myelosuppression. |
Clinical note
Comprehensive clinical and safety monograph for GLIADEL (GLIADEL).
| Placental transfer | Likely crosses placenta due to low molecular weight and lipophilicity; no specific human data. |
| Breastfeeding | Excreted in breast milk? Unknown; due to potential for serious adverse reactions in nursing infants, breast-feeding is not recommended during treatment and for at least 6 months after last dose. |
| Lactation Rating |
■ FDA Black Box Warning
GLIADEL should not be used in patients with hypersensitivity to carmustine or any components of the wafer. It should be used with caution in patients with known intracranial hypertension. Complications of intracranial pressure (e.g., brain edema, hydrocephalus) have been reported. Implanted wafers may cause seizures, intracranial infection, or wound healing abnormalities.
| Serious Effects |
Hypersensitivity to carmustine or any component of the waferKnown intracranial hypertensionActive infection at implant sitePrevious craniotomy and surgical debulking within 30 days
| Precautions | Seizures: New or worsening seizures may occur; monitor closely., Intracranial infection: Increased risk of meningitis or abscess., Wound healing delays: Impaired wound healing at the surgical site., Intracranial hypertension: Brain edema, hydrocephalus, or mass effect may occur., Fluid retention: Monitor for systemic steroid effects; taper slowly., Interference with MRI: Wafers are radiopaque and may cause artifacts on imaging., Reproductive effects: May cause fetal harm; advise women of reproductive potential to use effective contraception. |
| Food/Dietary |
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| Avoid |
| Teratogenic Risk | FDA Pregnancy Category D. Positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience. Use during pregnancy only if potential benefit justifies potential risk to fetus. First trimester: Risk of teratogenicity cannot be ruled out; animal studies show fetal resorptions and morphological abnormalities. Second and third trimesters: Risk of fetal harm, including low birth weight and developmental delay, due to alkylating agent effects. |
| Fetal Monitoring | Monitor complete blood counts (CBC) with differential and platelets weekly during implantation and at least monthly during pregnancy. Assess liver function tests and renal function. Perform fetal ultrasound for growth and development if used inadvertently during pregnancy. Monitor for signs of myelosuppression in mother. |
| Fertility Effects | Can cause irreversible gonadal suppression in both males and females, leading to oligospermia, azoospermia, amenorrhea, and premature ovarian failure. Fertility may be permanently impaired. |
| No specific food interactions are reported for GLIADEL. Maintain a balanced diet as tolerated post-surgery. Avoid alcohol due to potential CNS effects and impaired healing. |
| Clinical Pearls | GLIADEL (carmustine implant) is used as an adjunct to surgery for high-grade malignant glioma. Ensure the wafer is placed in the resection cavity after tumor removal, not systemically. Monitor for intracranial hypertension, seizures, and wound healing complications. Do not use in patients with known hypersensitivity to carmustine or with prior craniotomy and dural graft. |
| Patient Advice | This is a chemotherapy wafer placed directly into your brain during surgery to treat your tumor. · You may experience side effects such as brain swelling, seizures, or infection. Report any new or worsening symptoms immediately. · Do not drive or operate heavy machinery until your doctor confirms it is safe, as seizures or drowsiness may occur. · Avoid alcohol and smoking as they may affect healing and increase side effects. · Adhere to post-surgical follow-up appointments for imaging and monitoring. |