Dosing & Uses
Dosage Forms & Strengths
powder for injection
- 100mg
wafers
- 7.7mg
Brain Tumors, Multiple Myeloma, Hodgkin's Disease, NHL
Recurrent Glioblastoma
Indicated for recurrent glioblastoma as an adjunct to surgery
Gliadel
- Up to 8 wafers placed in surgical resection cavity of brain
Maligmant Glioma
Indicated for newly-diagnosed high-grade glioma as an adjunct to surgery and radiation
Gliadel
- Up to 8 wafers placed in surgical resection cavity of brain
Orphan Designations
Intracranial malignancies
- Sponsor
- Direct Therapeutics, Inc; 460 Seaport Court, Suite 220; Redwood, CA 94063
Conditioning treatment prior to hematopoietic progenitor cell transplantation
- Sponsor
- Adienne S.A.; Via Zurigo, 46 6900 Lugano Switzerland
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
Safety & efficacy not established
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
Recurrent Glioblastoma
Up to 8 wafers placed in surgical resection cavity of brain
Monitor CBC, pulmonary function, LFTs, renal function
Maligmant Glioma
Up to 8 wafers placed in surgical resection cavity of brain
Monitor CBC, pulmonary function, LFTs, renal function
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse 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
Cardiac disorders: Tachycardia and chest pain
Eye disorders: conjunctival edema, conjunctival hemorrhage, blurred vision and loss of depth perception
Gastrointestinal toxicity: Nausea, vomiting, anorexia, and diarrhea
Hepatotoxicity: Increased transaminase, increased alkaline phosphatase, increased bilirubin levels Infections and Infestations:
Infections: Opportunistic infections (including with fatal outcome)
Neoplasms benign, malignant and unspecified (including cysts and polyps): Acute leukemia, bone marrow dysplasias
Nephrotoxicity: Progressive azotemia, decrease in kidney size, renal failure
Nervous system disorders: Headaches, encephalopathy, and seizures
Pulmonary toxicity: Pneumonitis, interstitial lung disease
Reproductive system and breast disorders: Gynecomastia
Skin and subcutaneous tissue disorders: Burning sensation, hyperpigmentation, swelling, pain, erythema, skin necrosis, alopecia, allergic reaction
Vascular Disorders: Veno-occlusive disease
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
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; complete blood count should be monitored weekly for at least six weeks after each dose
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
Ocular toxicity associated with intracarotid route (investigational); safety and efficacy not established
Associated with moderate to high emetic potential; administer antiemetics to prevent nausea and vomiting
Monitor liver function tests periodically during therapy; reversible increases (rare) in bilirubin, alkaline phosphatase levels, and transaminases reported
Wafer implant associated with intracranial hypertension; brain edema reported in patients with newly diagnosed glioma; monitor closely for intracranial hypertension related to brain edema, inflammation, or necrosis of brain tissues surrounding resection; in refractory cases, removing the wafer may be necessary
Meningitis reported in patients with recurrent glioma receiving wafer implants; monitor postoperatively for signs/symptoms of meningitis and CNS infection
Renal failure, decreased kidney size, and progressive azotemia reported in patients receiving low or large cumulative doses or prolonged treatment; monitor renal function periodically
Long-term use associated with development of secondary malignancies (acute leukemia and bone marrow dysplasias)
Wafer implants associated with seizures; treatment-emergent seizures reported within 5 days of surgery; initiate optimal anti-seizure therapy prior to surgery
Impaired neurosurgical wound healing, including wound dehiscence, delayed healing, and subdural, subgleal or wound effusions associated with wafer implant treatment; cerebrospinal fluid leaks also reported; monitor for impaired neurosurgical wound healing following surgery
Avoid pregnancy
Contraception
- Advise female patients to avoid pregnancy during therapy because of risk of fetal harm
- Advise female patients of reproductive potential to use highly effective contraception during and for up to six months after completion of treatment
- Advise males with female sexual partners of reproductive potential to use effective contraception during therapy and for at least three months after final dose of carmustine
Fertility
- Based on nonclinical findings, male fertility may be compromised by therapy
Pregnancy & Lactation
Pregnancy
Therapy can cause fetal harm when administered to a pregnant woman; there are no available data on use in pregnant women
Animal data
- Drug is embryotoxic and teratogenic in rats at exposures less than exposure at recommended human dose based on body surface area (BSA) and embryotoxic in rabbits at exposures similar to exposures at the recommended human dose based on BSA; advise pregnant women of potential risk to a fetus
- Verify pregnancy status of females of reproductive potential prior to therapy
- Therapy can cause fetal harm when administered to a pregnant woman.
- Advise females of reproductive potential to use effective contraception for 6 months after therapy
- Based on its mechanism of action, advise males with female partners of reproductive potential to use effective contraception for 3 months following therapy
- Carmustine caused testicular degeneration in animals; advise male patients of potential risk of infertility
Lactation
No data are available regarding presence of drug or metabolites in human milk or effects on breastfed child or on milk production; because of potential for serious adverse reactions in breastfed children from therapy, advise women not to breastfeed following treatment and for at least 7 days after treatment
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
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
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Patient Handout
Formulary
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