Dosing and uses of BiCNU, Gliadel (carmustine)
Adult dosage forms and strengths
powder for injection
- 100mg
wafers
- 7.7mg
Brain Tumors, Multiple Myeloma, Hodgkin's Disease, NHL
BiCNU
- 150-200 mg/m² IV (single dose or divided 2 days) q6Weeks OR
- 75-100 mg/m²/day IV for 2 days q6Weeks
Adjunct to Surgery in Patients with Recurrent Glioblastoma Multiforme
GliadeL
- Up to 8 wafers placed in surgical resection cavity of brain
Adjunct to Surgery & Radiation in Patients with Maligmant Glioma
GliadeL
- Up to 8 wafers placed in surgical resection cavity of brain
Intracranial Malignancies (Orphan)
Orphan indication sponsor
- Direct Therapeutics, Inc; 460 Seaport Court, Suite 220; Redwood, CA 94063
Renal Impairment
CrCl 46-80 mL/min: Administer 80% of regular dose
CrCl 31-45 mL/min: Administer 75% of regular dose
CrCl ≤ 30 mL/min: Not recommended
Hepatic Impairment
Dose adjustment may be necessary; not studied
Other Indications & Uses
Off-label: Mycosis fungoides
Pediatric dosage forms and strengths
Safety & efficacy not established
Geriatric dosage forms and strengths
BiCNU
Brain Tumors, Multiple Myeloma, Hodgkin's Disease, NHL
150-200 mg/m² IV (single dose or divided 2 days) q6Weeks Or
75-100 mg/m²/day IV for 2 days q6Weeks
Monitor CBC, pulmonary function, LFTs, renal function
GliadeL
Adjunct to Surgery in Patients with Recurrent Glioblastoma Multiforme
Up to 8 wafers placed in surgical resection cavity of brain
Monitor CBC, pulmonary function, LFTs, renal function
Adjunct to Surgery & Radiation in Patients with Maligmant Glioma
Up to 8 wafers placed in surgical resection cavity of brain
Monitor CBC, pulmonary function, LFTs, renal function
BiCNU, Gliadel (carmustine) adverse (side) effects
>10%
Convulsions (19%)
Hemiplegia (19%)
Headache (15%)
Metabolic disorder (14%)
Somnolence (14%)
Fever (12%)
1-10%
Confusion (10%)
Aphasia (9%)
Nausea (8%)
Vomiting (8%)
Pain (7%)
Rash (5%)
Abscess (4%)
Cranial edema (4%)
ICP elevation (4%)
Meningitis (4%)
Hyperglycemia (3%)
HTN (3%)
Constipation (2%)
Diarrhea (2%)
Dizziness (2%)
Depression (2%)
Frequency not defined
Greater myelotoxicity reported when coadministered with cimetidine
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician
Bone marrow suppression (notably thrombocytopenia and leukopenia) is the most common and severe of the toxic effects that may result from carmustine administration. It may contribute to bleeding and infections. Monitor blood counts for at least 6 weeks after a dose. Do not give recommended dosage more frequently than every 6 weeks. Adjust dose based on nadir blood counts from prior dose
Pulmonary toxicity is dose related. Risk increases with cumulative doses > 1400 mg/m², history of lung disease and duration of therapy. Delayed cases of pulmonary fibrosis that can result in death have been reported 15 years after administration in children
Contraindications
Hypersensitivity
Cautions
Do not give more frequently than q6-8wk due to delayed myelosuppression
Risk of irreversible pulmonary fibrosis on long-term treatment
Injection site reactions may occur during administration; rapid infusion may cause burning along the vein and flushing of skin
Extravasation risk, monitor closely during infusion
Intra-arterial administration may cause ocular toxicity
Monitor renal function regularly during treatment
Avoid pregnancy
Pregnancy and lactation
Pregnancy category: d
Lactation: not known if excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of BiCNU, Gliadel (carmustine)
Mechanism of action
Alkylates and crosslinks DNA and RNA intefering with normal DNA function; may also inhibit enzyme processes by carbamylation of aminoacids in protein
Pharmacokinetics
Half-life elimination: 1.4 min (initial); 22 min (secondary)
Vd: 3.25 L/kg
Distribution: Readily crosses blood-brain barrier
Clearance: 56 mL/min/kg
Excretion: Urine (60-70%)
Administration
IV Incompatibilities
Solution: D5W (may be used in shorter time periods)
Additive: sodium bicarbonate
Y-site: allopurinoL
IV Compatibilities
Solution: Ns
Y-site: amifostine, aztreonam, cefepime, etoposide PO4, filgrastim, fludarabine, gemcitabine, granisetron, melphalan, ondansetron, piperacillin/tazobactam, sargramostim, teniposide, thiotepa, vinorelbine
IV Preparation
Initially dilute with 3 mL of supplied diluent (dehydrated alcohol); further dilute aseptically with 27 mL SWI to result in a concentration of 3.3 mg/mL in 10% alcohoL
Standard dilution: dose/150-500 mL D5W or Ns
IV Administration
Significant absorption to PVC containers; should be administered in either glass or Excel container
Infuse over 1-2 hr
High dose carmustine: maximum rate of infusion <3 mg/sq.meter/min to avoid excessive flushing, agitation, & hypotension; infusions should run over at least 2 hr
Extravasation Management
Elevate extremity
Inject long-acting dexamethasone or by hyaluronidase throughout tissue with a 25- to 37-gauge needle
Apply warm, moist compresses
Storage
Store intact vials under refrigeration