Carmustine

Less serious, more common side effects include:

• nausea
• vomiting
• headache
• loss of balance or coordination
• pale skin
• flushing
• fainting
• dizziness
• fast or irregular heartbeat
• chest pain
• darkened skin

Tell your doctor right away if you experience any of these symptoms:

• swelling, pain, redness, burning, or leakage of fluid at the injection site
• rash
• itching
• swelling of the face, lips, or throat
• difficulty breathing
• fever
• sore throat
• chills
• aches and pains
• unusual bleeding or bruising
• black and tarry stools
• red blood in stools
• bloody vomit
• vomited material that looks like coffee grounds
• extreme tiredness
• paleness
• lack of energy
• loss of appetite
• pain in the upper right part of the stomach
• yellowing of the skin or eyes
• decreased urination
• swelling of the hands, feet, ankles, or lower legs
• changes in vision

Tell your doctor about any side effect that is bothersome or doesn't go away.

See "Drug Precautions" for serious side effects.

This is not a complete list of carmustine drug interactions. Ask your doctor or pharmacist for more information.

Injectable:

• Carmustine comes in powder form. Liquid is added to carmustine and then it is injected slowly, over at least 2 hours, intravenously (into a vein) by a healthcare professional in a medical facility (hospital or clinic). It is usually given once every 6 weeks. The dose is sometimes divided into two doses and is given 2 days in a row, every 6 weeks.
• Your doctor will order weekly blood tests to measure certain cells in your blood. If your blood cell counts are too low, your doctor may order a delay in treatment.

Topical:

• This medication also comes in a wafer form that is implanted within the cranium (skull) via surgical procedure.

WARNINGS

Carmustine for injection should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents.

Bone marrow suppression, notably thrombocytopenia and leukopenia, which may contribute to bleeding and overwhelming infections in an already compromised patient, is the most common and severe of the toxic effects of this medication.

Since the major toxicity is delayed bone marrow suppression, blood counts should be monitored weekly for at least 6 weeks after a dose. At the recommended dosage, courses of carmustine should not be given more frequently than every 6 weeks.

The bone marrow toxicity is cumulative and therefore dosage adjustment must be considered on the basis of nadir blood counts from prior dose.

Pulmonary toxicity appears to be dose related. Patients receiving greater than 1400 mg/m2 cumulative dose are at significantly higher risk than those receiving less.

Delayed pulmonary toxicity can occur years after treatment, and can result in death, particularly in patients treated in childhood.

Carmustine is injected into a vein through an IV. A healthcare provider will give you this injection.

Carmustine is usually given once every 6 weeks. You may be given either a single injection or multiple injections over a 2-day period. Follow your doctor's dosing instructions very carefully.

Tell your caregivers if you feel any burning or pain around the IV needle when carmustine is injected.

Carmustine can cause nausea and vomiting that may last up to 6 hours after your injection. You may be given anti-nausea medications to help prevent these side effects.

Carmustine can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your kidneys, liver, and lung function may also need to be tested. Your cancer treatments may be delayed based on the results of these tests.

Carmustine can have long lasting effects on your body. Your blood will need to be tested weekly for at least 6 weeks after you receive a dose of carmustine.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Brain Tumors: Conventional Chemotherapy

Adjunct to radiation therapy following surgery for palliative treatment of malignant glioma (i.e., astrocytoma, ependymoma, medulloblastoma, brainstem glioma) and metastatic brain tumors.105 120 125

Among several preferred chemotherapeutic regimens for anaplastic astrocytoma and glioblastoma multiforme.120 125 Has not been shown to increase survival time, but a trend toward a higher long-term survival rate (e.g., at 18 months) has been observed.126 127

Adjuvant or salvage therapy for oligodendroglioma.120 127 128

Surgery with or without radiation therapy currently considered standard treatment for ependymoma and medulloblastoma.c Radiation therapy considered standard treatment for brainstem glioma.c

Brain Tumors: Intracranial Wafer Implant

Adjunct to surgery and radiation for treatment of newly diagnosed high-grade malignant glioma.124 135 Among several preferred chemotherapeutic regimens for anaplastic astrocytoma and glioblastoma multiforme.120

Adjunct to surgery for treatment of recurrent glioblastoma multiforme.120 124 135 137

Multiple Myeloma

Carmustine-containing regimens considered alternative therapy for palliative treatment of multiple myeloma.105 120 138

Hodgkin’s Disease

Used in combination with other agents as secondary therapy for treatment of refractory or relapsed Hodgkin’s disease.105

Combination regimens containing other agents currently are preferred as initial or alternative therapy for this cancer.120 141

Non-Hodgkin’s Lymphoma

Used in combination with other agents as secondary therapy for treatment of refractory or relapsed non-Hodgkin’s lymphomas.105

Combination regimens containing other agents currently are preferred as initial or alternative therapy for these cancers.120 144

Melanoma

Has been used alone114 116 or in combination therapy114 116 119 for palliative treatment of metastatic melanoma†; however, low response rate and substantial toxicity limit this use of carmustine.117 122

Cutaneous T-cell Lymphoma

Used topically† for palliative treatment of cutaneous T-cell lymphoma (mycosis fungoides)†.120 123 149 150

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastics.105 124

Administration

Administer by IV infusion105 or intracranially as wafer implants.124

Has been administered by intra-arterial† (into the carotid artery) route; however, such administration has been associated with ocular toxicity105 (blindness), fatal encephalopathy, and inferior survival.132

Has been administered topically† as a 0.05–0.4% hydroalcoholic solution or as an ointment, but dosage forms for such use are not commercially available in US; consult specialized references.100 120 149 150

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Vials are for single use only.105

Use glass containers for administration.105

Handle cautiously (e.g., use gloves); avoid exposure during handling of powder and preparation of IV solution.105

If skin or mucosal contact occurs, immediately wash affected area(s) thoroughly with soap and water.105

Add 3 mL of diluent provided by manufacturer (sterile dehydrated [absolute] alcohol) to vial containing 100 mg of carmustine; then add 27 mL of sterile water for injection.105 Resulting solution contains 3.3 mg/mL carmustine in 10% ethanol.105

Dilute with 5% dextrose injection.105

Administer by IV infusion over 1–2 hours.105 More rapid administration associated with adverse effects.105 (See Local Effects under Cautions.)

Intracranial Wafer Implant

Handle with care (cytotoxic material);124 use double surgical gloves and discard outer gloves into biohazard waste container after use.124

Wafers broken in half may be used; discard in biohazard container if broken in >2 pieces.124

Deliver aluminum foil laminate pouches containing wafer to operating room; do not open until ready to implant.124 Outside surface of outer foil pouch is not sterile.124

Use surgical instrument dedicated to handling carmustine wafers to implant the wafers.124

Implant intracranially in the resection cavity following surgical resection of brain tumor.124

Place oxidized regenerated cellulose (Surgicel) over wafers to secure them against surface of resection cavity.124 Following placement of wafers, irrigate resection cavity and close dura in a watertight fashion to minimize risk of CSF leak.124

Dosage

Adults

As monotherapy in previously untreated patients, 150–200 mg/m2 administered as a single dose or in divided doses (e.g., 75–100 mg/m2 on 2 successive days) at intervals of at least 6 weeks.105

Reduce dosage if used in combination with other myelosuppressive drugs or in patients with compromised bone marrow function.105

Adjust subsequent dosages based on nadir blood counts from preceding dose (see Dosage Modification for Toxicity under Dosage and Administration).105

Up to 8 wafers (total carmustine dose: 61.6 mg) intracranially to cover as much of the resection cavity as possible (slight overlapping permissible).124 If size and shape of cavity will not allow placement of 8 wafers, use maximum possible number.124

Do not place >8 wafers intracranially per surgical procedure.124

In clinical trials, chemotherapy was withheld for at least 4 weeks (6 weeks for nitrosoureas) prior to and 2 weeks after surgery;124 external beam radiation therapy was administered no sooner than 3 weeks after surgery.151

As monotherapy in previously untreated patients, 150–200 mg/m2 administered as a single dose or in divided doses (e.g., 75–100 mg/m2 on 2 successive days) at intervals of at least 6 weeks.105

Reduce dosage if used in combination with other myelosuppressive drugs or in patients with compromised bone marrow function.105

Adjust subsequent dosages based on nadir blood counts from preceding dose (see Dosage Modification for Toxicity under Dosage and Administration).105

As monotherapy in previously untreated patients, 150–200 mg/m2 administered as a single dose or in divided doses (e.g., 75–100 mg/m2 on 2 successive days) at intervals of at least 6 weeks.105

Reduce dosage if used in combination with other myelosuppressive drugs or in patients with compromised bone marrow function.105

Adjust subsequent dosages based on nadir blood counts from preceding dose (see Dosage Modification for Toxicity under Dosage and Administration).105

As monotherapy in previously untreated patients, 150–200 mg/m2 administered as a single dose or in divided doses (e.g., 75–100 mg/m2 on 2 successive days) at intervals of at least 6 weeks.105

Reduce dosage if used in combination with other myelosuppressive drugs or in patients with compromised bone marrow function.105

Adjust subsequent dosages based on nadir blood counts from preceding dose (see Dosage Modification for Toxicity under Dosage and Administration).105

Usual topical dosage is 10 mg once daily for 7–14 weeks (maximum: 17 weeks).149 150 If response is inadequate, after a rest interval of 6 weeks, administer second course of topical therapy with 20 mg once daily for 4–8 weeks, as tolerated.149 150

Topical dosage form not commercially available in US; consult specialized references for specific information on topical use.149 150

Dosage Modification for Toxicity

Do not administer repeat courses until leukocyte count >4000/mm3, platelet count >100,000/mm3, and an adequate number of neutrophils is present on peripheral blood smear.105

Bone marrow toxicity is cumulative; adjust subsequent dosages based on nadir blood counts from previous dose.105

Alternatively, to avoid potential overdosage associated with manufacturer’s suggested modifications, some clinicians recommend reducing subsequent dosage by 25% when platelet nadirs are 50,000–74,999/mm3; by 50% for nadirs of 25,000–49,999/mm3; and by 75% for nadirs <25,000/mm3.d

Prescribing Limits

Adults

Maximum 8 wafers per surgical procedure.124

Special Populations

Geriatric Patients

Select IV dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.105 148 (See Geriatric Use under Cautions.)

• Alkylates DNA and RNA.105 124 May inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.105 Overall result is thought to be the inhibition of both DNA and RNA synthesis.d

• Cytotoxic effect of wafer depends on release of sufficient amounts of carmustine in the tumor cavity to achieve tumoricidal concentrations.124

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

BiCNU: 100 mg (1 ea) [contains alcohol, usp]

Wafer, Implant:

Gliadel Wafer: 7.7 mg (8 ea) [contains polifeprosan 20]

Brain tumors:

Injection: Palliative treatment of brain tumors including glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors

Wafer (implant): Treatment of newly-diagnosed high-grade malignant glioma (as an adjunct to surgery and radiation); treatment of recurrent glioblastoma multiforme (as adjunct to surgery)

Hodgkin lymphoma, relapsed/refractory: Injection: Palliative treatment (secondary) of Hodgkin lymphoma (in combination with other antineoplastics) that has relapsed with or was refractory to primary therapy

Multiple myeloma: Injection: Palliative treatment of multiple myeloma (in combination with prednisone)

Non-Hodgkin lymphomas, relapsed/refractory: Injection: Palliative treatment (secondary) of non-Hodgkin lymphoma (in combination with other antineoplastics) that has relapsed with or was refractory to primary therapy

Injection: CBC with differential and platelet count (weekly for at least 6 weeks after a dose), pulmonary function tests (FVC, DLCO; at baseline and frequently during treatment), liver function (periodically), renal function tests (periodically); monitor blood pressure and vital signs during administration, monitor infusion site for possible infiltration; monitor for signs/symptoms of pulmonary toxicity

Wafer: Monitor postoperatively for seizures, impaired neurosurgical wound healing, and signs/symptoms of meningitis, CNS infection, and obstructive hydrocephalus; monitor closely for intracranial hypertension related to brain edema, inflammation, or necrosis of brain tissue surrounding resection.

For use as a single agent in previously untreated patients: 150 to 200 mg/m2 IV every 6 weeks. This dose can be given as a single or divided daily injections (75 to 100 mg/m2 on two successive days). When used with other myelosuppressive drugs or in patients in whom bone marrow reserve is depleted, doses should be adjusted accordingly. A repeat course should not be administered until platelets are >100,000/mm3 and leukocytes are >4,000/mm3. An adequate number of neutrophils should be present on a peripheral blood smear. Blood counts should be monitored weekly. Repeat courses should not be administered before 6 weeks because of delayed and cumulative toxicity.

Data not available