No

Antineoplastic Agent, Alkylating Agent

Treatment of brain tumors (glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors), multiple myeloma, Hodgkin's disease (secondary therapy in combination with other approved drugs in patients who relapse while being treated with primary therapy or who fail to respond to primary therapy) and non-Hodgkin's lymphomas (secondary therapy in combination with other approved drugs in patients who relapse while being treated with primary therapy or who fail to respond to primary therapy), melanoma, lung cancer, colon cancer

D

Hypersensitivity to carmustine or any component, myelosuppression from previous chemotherapy or other causes

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Administer with caution to patients with depressed platelet, leukocyte or erythrocyte counts, renal or hepatic impairment. Bone marrow depression, notably thrombocytopenia and leukopenia, may lead to bleeding and overwhelming infections in an already compromised patient; will last for at least 6 weeks after a dose, do not give courses more frequently than every 6 weeks because the toxicity is cumulative.

>10%:

Cardiovascular: Hypotension is associated with HIGH-DOSE administration secondary to the high alcohol content of the diluent

Central nervous system: Dizziness and ataxia

Dermatologic: Hyperpigmentation of skin

Gastrointestinal: Nausea and vomiting occur within 2-4 hours after drug injection; dose-related

Emetic potential:

<200 mg: Moderately high (60% to 90%)

greater than or equal to 200 mg: High (>90%)

Time course of nausea/vomiting: Onset: 2-6 hours; Duration: 4-6 hours

Hematologic: Myelosuppressive: Delayed, occurs 4-6 weeks after administration and is dose-related; usually persists for 1-2 weeks; thrombocytopenia is usually more severe than leukopenia. Myelofibrosis and preleukemic syndromes have been reported.

WBC: Moderate

Platelets: Severe

Onset (days): 14

Nadir (days): 21-35

Recovery (days): 42-50

Local: Burning at injection site

Irritant chemotherapy: Pain at injection site

Ocular: Ocular toxicity, and retinal hemorrhages

1% to 10%:

Dermatologic: Facial flushing is probably due to the ethanol used in reconstitution, alopecia

Gastrointestinal: Stomatitis, diarrhea, anorexia

Hematologic: Anemia

<1%: Hyperpigmentation, dermatitis, reversible toxicity, increased LFTs in 20%, fibrosis occurs mostly in patients treated with prolonged total doses >1400 mg/m² or with bone marrow transplantation doses; risk factors include a history of lung disease, concomitant bleomycin, or radiation therapy; PFTs should be conducted prior to therapy and monitored; patients with predicted FVC or DL_co <70% are at a higher risk; azotemia, decrease in kidney size

Symptoms of overdose include nausea, vomiting, thrombocytopenia, leukopenia

There are no known antidotes and treatment is primarily symptomatic and supportive

Increased toxicity:

Etoposide: Reported to cause severe hepatic dysfunction with hyperbilirubinemia, ascites, and thrombocytopenia

Store intact vials under refrigeration; vials are stable for 36 days at room temperature

Initially dilute with 3 mL of absolute alcohol diluent. Further dilute with 27 mL SWI to result in a concentration of 3.3 mg/mL with 10% ethanol. Initial solutions are stable for 8 hours at room temperature (25°C) and 24 hours at refrigeration (2°C to 8°C) and protected from light.

Further dilution in D₅W or NS is stable for 8 hours at room temperature (25°C) and 48 hours at refrigeration (4°C) in glass or Excel® protected from light

Incompatible with sodium bicarbonate; compatible with cisplatin

Standard I.V. dilution: Dose/150-500 mL D₅W or NS

Must use glass or Excel® containers for administration

Protect from light

Stable for 8 hours at room temperature (25°C) and 48 hours under refrigeration (4°C)

Interferes with the normal function of DNA by alkylation and cross-linking the strands of DNA, and by possible protein modification

Absorption: Highly lipid soluble

Distribution: Readily crosses the blood-brain barrier producing CSF levels equal to 15% to 70% of blood plasma levels; distributes into breast milk

Metabolism: Rapid

Half-life (biphasic): Initial: 1.4 minutes; Secondary: 20 minutes (active metabolites may persist for days and have a plasma half-life of 67 hours)

Elimination: ~60% to 70% excreted in the urine within 96 hours and 6% to 10% excreted as CO₂ by the lungs

I.V. (refer to individual protocols):

Adults: 150-200 mg/m² every 6 weeks as a single dose or divided into daily injections on 2 successive days; next dose is to be determined based on hematologic response to the previous dose. Listed are the suggested carmustine doses, based upon the nadir after the prior dose.

• Leukocytes >4000 mm³ and platelets >100,000 mm³: Give 100% of prior dose
• Leukocytes 3000-3999 mm³ and platelets 75,000-99,999 mm³: Give 100% of prior dose
• Leukocytes 2000-2999 mm³ and platelets 25,000-74,999 mm³: Give 70% of prior dose
• Leukocytes <2000 mm³ and platelets <25,000 mm³: Give 50% of prior dose

Primary brain cancer: 150-200 mg/m² every 6-8 weeks

Autologous BMT: ALL OF THE FOLLOWING DOSES ARE FATAL WITHOUT BMT

Combination therapy: Up to 300-900 mg/m²

Single agent therapy: Up to 1200 mg/m² (fatal necrosis is associated with doses >2 g/m²)

Hemodialysis: Supplemental dosing is not required

Dosing adjustment in hepatic impairment: Dosage adjustment may be necessary; however, no specific guidelines are available

CBC with differential and platelet count, pulmonary function, liver function, and renal function tests; monitor blood pressure during administration

Dizziness is common

May cause myelosuppression; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This drug can only be administered by infusion. Limit oral intake for 4-6 hours before therapy. Do not use of alcohol, aspirin-containing products, and OTC medications without consulting prescriber. It is important to maintain adequate nutrition and hydration during therapy (2-3 L/day of fluids unless instructed to restrict fluid intake); frequent small meals may help. Take 2-3 L/day of fluids. You may experience nausea or vomiting (frequent small meals, frequent mouth care, sucking lozenges, or chewing gum may help). If this is ineffective, consult prescriber for antiemetic medication. You may experience loss of hair (reversible). You will be more susceptible to infection (avoid crowds and exposure to infection as much as possible). You will be more sensitive to sunlight; use sunblock, wear protective clothing and dark glasses, or avoid direct exposure to sunlight. Frequent mouth care with soft toothbrush or cotton swabs and frequent mouth rinses may help relieve mouth sores. Report fever, chills, unusual bruising or bleeding, signs of infection, excessive fatigue, yellowing of eyes or skin, or change in color of urine or stool. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant during or for 1 month following therapy. Male: Do not cause a female to become pregnant. Male/female: Consult prescriber for instruction on appropriate barrier contraceptive measures. This drug may cause severe fetal defects. Do not breast-feed.

Must administer in glass containers; accidental skin contact may cause transient burning and brown discoloration of the skin

Powder for injection: 100 mg/vial packaged with 3 mL of absolute alcohol for use as a sterile diluent

Aronin PA, Mahaley MS Jr, Rudnick SA, et al, "Prediction of BCNU Pulmonary Toxicity in Patients With Malignant Gliomas," N Engl J Med, 1980, 303(4):183-8.

Buzaid AC and Murren J, "Chemotherapy for Advanced Malignant Melanoma," Int J Clin Lab Res, 1992, 21(3):205-9.

Colvin M, Hartner J and Summerfield M, "Stability of Carmustine in the Presence of Sodium Bicarbonate," Am J Hosp Pharm, 1980, 37(5):677-8.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Lesser GJ and Grossman SA, "The Chemotherapy of Adult Primary Brain Tumors," Cancer Treat Rev, 1993, 19(3):261-81.

Mahendra P, Johnson D, Scott MA, et al, "Peripheral Blood Progenitor Cell Transplantation: A Single Centre Experience Comparing Two Mobilisation Regimens in 67 Patients," Bone Marrow Transplant, 1996, 17(4):503-7.

O'Driscoll BR, Hasleton PS, Taylor PM, et al, "Active Lung Fibrosis Up to 17 Years After Chemotherapy With Carmustine (BCNU) in Childhood," N Engl J Med, 1990, 323(6):378-82.

Wiencke JK and Wiemels J, "Genotoxicity of 1,3,-bis(2-chloroethyl)-1-nitrosourea (BCNU)," Mutat Res, 1995, 339(2):91-119.