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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GLIADEL (GLIADEL).
| Breastfeeding | No data on excretion in human milk; potential for serious adverse reactions in nursing infants, including bone marrow suppression and carcinogenesis. M/P ratio unknown. Contraindicated during breastfeeding due to risk. |
| 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. |
■ 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 wafer","Prior craniotomy for recurrent GBM where GLIADEL was placed within the same surgical site (relative contraindication due to increased risk of infection)"]
| 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."] |
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| 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. |