carmustine (Rx)

>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

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

Pregnancy

Limited available data on use in pregnant women are insufficient to inform of drug-associated risk for major birth defects and miscarriage; consider the benefits and risks of carmustine for the mother and possible risks to the fetus when prescribing carmustine to a pregnant woman

Lactation

There is no information regarding presence of carmustine in human milk, effects on breastfed infant, or effects on milk production; because many drugs are excreted in human milk and because of potential for serious adverse events (eg, carcinogenicity and myelosuppression) in nursing infants, nursing should be discontinued while patient is receiving therapy

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%)

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