car·mus·tine (kär m s-t n )n. An alkylating agent used to treat various cancers, including brain tumors, non-Hodgkin's lymphoma, melanoma, and multiple myeloma. Also called BCNU. |
carmustine
carmustine [kahr-mus´tēn]
carmustine Warning - Hazardous drug!
BCNU, BiCNU, Gliadel Wafer
Pharmacologic class: Alkylating agent
Therapeutic class: Antineoplastic
Pregnancy risk category D
FDA Boxed Warning
• Give under supervision of physician experienced in cancer chemotherapy.
• Most common and severe toxic effect is bone marrow suppression - notably thrombocytopenia and leukopenia, which may contribute to bleeding and overwhelming infections in already compromised patient. Monitor blood counts weekly for at least 6 weeks after dose. Don't give courses more often than every 6 weeks.
Action
Unclear. Thought to interfere with bacterial cell-wall synthesis by cross-linking strands of DNA and disrupting RNA transcription, causing cell to rupture and die. Exhibits minimal immunosuppressant activity.
Availability
Intracavitary wafer implant: 7.7 mg (available in packages of eight wafers)
Powder for injection: 100-mg vials
⊘Indications and dosages
➣ Brain tumor; multiple myeloma; Hodgkin's disease; other lymphomas
Adults and children: 150 to 200 mg/m2 I.V. as a single dose q 6 to 8 weeks, or 75 to 100 mg/m2/day for 2 days q 6 weeks, or 40 mg/m2/day for 5 days q 6 weeks. Repeat dose q 6 weeks if platelet count exceeds 100,000/mm3 and white blood cell (WBC) count exceeds 4,000/mm3.
➣ Adjunct to brain surgery
Adults: Up to 61.6 mg (eight wafers) implanted in surgical cavity created during brain tumor resection
Dosage adjustment
• Based on WBC and platelet counts
Off-label uses
• Mycosis fungoides
Contraindications
• Hypersensitivity to drug
• Radiation therapy
• Chemotherapy
• Pregnancy or breastfeeding
Precautions
Use cautiously in:
• infection; depressed bone marrow reserve; respiratory, hepatic, or renal impairment
• females of childbearing age.
Administration
• Know that drug may be used alone or in conjunction with other treatments, such as surgery or radiation.
• Follow facility policy when preparing, administering, and handling drug.
• Reconstitute drug by dissolving vial of 100 mg with 3 ml of sterile dehydrated alcohol (provided with drug), followed by 27 ml of sterile water for injection; yields solution with concentration of 3.3 mg carmustine/ml. Solution may be further diluted with 5% dextrose injection and delivered by I.V. infusion over 1 to 2 hours.
• Know that infusion lasting less than 1 hour causes intense pain and burning at I.V. site.
• Infuse solution in glass containers only; drug is unstable in plastic I.V. bags.
• Know that skin contact with reconstituted drug may cause transient hyper-pigmentation. If contact occurs, wash skin thoroughly with soap and water.
• Be aware that oxidized regenerated cellulose may be placed over wafers to secure them against surgical cavity surface.
• Know that resection cavity should be irrigated after wafer placement and that dura should be closed in watertight fashion.
| Route | Onset | Peak | Duration |
| I.V. | Immediate | 15 min | 6 wk |
| Intracavitary | Unknown | Unknown | Unknown |
Adverse reactions
CNS: ataxia, drowsiness
GI: nausea, vomiting, diarrhea, esophagitis, stomatitis, anorexia
GU: azotemia, renal failure, nephrotoxicity
Hematologic: anemia, leukopenia, thrombocytopenia, cumulative bone marrow depression, bone marrow dysplasia
Hepatic: hepatotoxicity
Respiratory: pulmonary fibrosis, pulmonary infiltrates
Skin: alopecia, hyperpigmentation, facial flushing, abnormal bruising
Other: I.V. site pain, secondary malignancies
Interactions
Drug-drug. Anticoagulants, aspirin, nonsteroidal anti-inflammatory drugs: increased risk of bleeding
Antineoplastics: additive bone marrow depression
Cimetidine: potentiation of bone marrow depression
Digoxin, phenytoin: decreased blood levels of these drugs
Live-virus vaccines: decreased antibody response to vaccines, increased risk of adverse reactions
Drug-diagnostic tests. Alkaline phosphatase, aspartate aminotransferase, bilirubin, nitrogenous compounds (urea): increased levels
Hemoglobin, WBCs: decreased values
Drug-behaviors. Smoking: increased risk of respiratory toxicity
Patient monitoring
• Assess baseline kidney and liver function tests.
• Monitor CBC for up to 6 weeks after giving dose to detect delayed bone marrow toxicity.
• Know that pulmonary function tests should be performed before therapy begins and regularly throughout therapy to assess for toxicity.
Patient teaching
• Instruct patient to report signs and symptoms of allergic response and other adverse reactions.
• Inform patient that severe flushing may follow I.V. dose but should subside in 2 to 4 hours.
• Tell patient to avoid activities that can cause injury. Advise him to use soft toothbrush and electric razor to avoid gum and skin injury.
• Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.
• Instruct patient to monitor urinary output and report significant changes.
• Inform patient that drug may cause hair loss.
• Advise patient that he'll undergo regular blood testing during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.
carmustine
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