Carmustine Prescribing Information
Bone marrow toxicity is a dose-limiting, common and severe toxic effect of carmustine occurring 4 to 6 weeks after drug administration (thrombocytopenia occurs at about 4 weeks post-administration persisting for 1 to 2 weeks; leukopenia occurs at 5 to 6 weeks after a dose of carmustine persisting for 1 to 2 weeks; thrombocytopenia is generally more severe than leukopenia; anemia is less frequent and less severe compared to thrombocytopenia and/or leukopenia) Complete blood count should therefore be monitored weekly for at least six weeks after a dose. Repeat doses of carmustine should not be given more frequently than every six weeks. The bone marrow toxicity of carmustine is cumulative and therefore the dosage adjustment must be considered on the basis of nadir blood counts from prior dose
The following serious adverse reactions are described elsewhere in the labeling:
- Myelosuppression[see Warnings and Precautions (5.1)]
- Pulmonary toxicity[see Warnings and Precautions (5.2)]
- Administration Reactions[see Warnings and Precautions (5.3)]
- Carcinogenicity[see Warnings and Precautions (5.4)]
- Ocular Toxicity[see Warnings and Precautions (5.5)]
The following adverse reactions associated with the use of carmustine were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Tachycardia and chest pain.
Conjunctival edema, conjunctival hemorrhage, blurred vision and loss of depth perception
Nausea, vomiting, anorexia, and diarrhea
Increased transaminase, increased alkaline phosphatase, increased bilirubin levels
Opportunistic infection (including with fatal outcome).
Acute leukemia, bone marrow dysplasias.
Progressive azotemia, decrease in kidney size, renal failure
Headaches, encephalopathy, and seizures
Pneumonitis, interstitial lung disease
Gynecomastia
Burning sensation, hyperpigmentation, swelling, pain, erythema, skin necrosis, alopecia, allergic reaction
Veno-occlusive disease.
Most common adverse reactions (>1%) are nausea, vomiting, renal toxicity, pneumonitis, pulmonary toxicity, myelosuppression
The recommended dose of carmustine for injection as a single agent in previously untreated patients is 150 mg/m2to 200 mg/m2intravenously every 6 weeks. Administer as a single dose or divided into daily injections such as 75 mg/m2to 100 mg/m2on two successive days. Lower the dose when carmustine for injection is used with other myelosuppressive drugs or in patients in whom bone marrow reserve is depleted. Administer carmustine for injection for the duration according to the established regimen. Premedicate each dose with anti-emetics.
Adjust doses subsequent to the initial dose according to the hematologic response of the patient to the preceding dose. The following schedule is suggested as a guide to dosage adjustment:
| Nadir After Prior Dose | Percentage of Prior Dose to be Given | |
| Leukocytes/mm3 | Platelets/mm3 | |
| >4,000 | >100,000 | 100% |
| 3,000-3,999 | 75,000 to 99,999 | 100% |
| 2,000-2,999 | 25,000 to 74,999 | 70% |
| <2,000 | <25,000 | 50% |
The hematologic toxicity can be delayed and cumulative. Monitor blood counts weekly. Do not administer a repeat course of carmustine for injection until circulating blood elements have returned to acceptable levels (platelets above 100 Gi/L, leukocytes above 4 Gi/L and absolute neutrophil count above 1 Gi/L). The usual interval between courses is 6 weeks.
Evaluate renal function prior to administration and periodically during treatment. For patients with compromised renal function, monitor for toxicity more frequently. Discontinue carmustine for injection if the creatinine clearance is less than 10 mL/min. Do not administer carmustine for injection to patients with compromised renal function. Monitor transaminases and bilirubin periodically during treatment.
2 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
The following serious adverse reactions are described elsewhere in the labeling:
- Myelosuppression[see Warnings and Precautions (5.1)]
- Pulmonary toxicity[see Warnings and Precautions (5.2)]
- Administration Reactions[see Warnings and Precautions (5.3)]
- Carcinogenicity[see Warnings and Precautions (5.4)]
- Ocular Toxicity[see Warnings and Precautions (5.5)]
The following adverse reactions associated with the use of carmustine were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Tachycardia and chest pain.
Conjunctival edema, conjunctival hemorrhage, blurred vision and loss of depth perception
Nausea, vomiting, anorexia, and diarrhea
Increased transaminase, increased alkaline phosphatase, increased bilirubin levels
Opportunistic infection (including with fatal outcome).
Acute leukemia, bone marrow dysplasias.
Progressive azotemia, decrease in kidney size, renal failure
Headaches, encephalopathy, and seizures
Pneumonitis, interstitial lung disease
Gynecomastia
Burning sensation, hyperpigmentation, swelling, pain, erythema, skin necrosis, alopecia, allergic reaction
Veno-occlusive disease.
Most common adverse reactions (>1%) are nausea, vomiting, renal toxicity, pneumonitis, pulmonary toxicity, myelosuppression
Safety and effectiveness in children have not been established. Delayed onset pulmonary fibrosis occurring up to 17 years after treatment has been reported in a long-term study of patients who received carmustine in childhood and early adolescence (1 to 16 years). Eight out of the 17 patients (47%) who survived childhood brain tumors, including all the 5 patients initially treated at less than 5 years of age, died of pulmonary fibrosis.
Carmustine for injection is a nitrosourea indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in the following:
- Brain tumors glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors ()
1 INDICATIONS AND USAGECarmustine for injection is a nitrosourea indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in the following:
- Brain tumors glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors
- Multiple myeloma-in combination with prednisone
- Relapsed or refractory Hodgkin's lymphoma in combination with other approved drugs
- Relapsed or refractory Non-Hodgkin's lymphomas in combination with other approved drugs
Carmustine for injection is indicated as palliative therapy as a single agent or in established combination therapy in the following:
- Brain tumors glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors.
- Multiple myeloma in combination with prednisone.
- Relapsed or refractory Hodgkin's lymphoma in combination with other approved drugs.
- Relapsed or refractory Non-Hodgkin's lymphomas in combination with other approved drugs.
- Multiple myeloma-in combination with prednisone ()
1 INDICATIONS AND USAGECarmustine for injection is a nitrosourea indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in the following:
- Brain tumors glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors
- Multiple myeloma-in combination with prednisone
- Relapsed or refractory Hodgkin's lymphoma in combination with other approved drugs
- Relapsed or refractory Non-Hodgkin's lymphomas in combination with other approved drugs
Carmustine for injection is indicated as palliative therapy as a single agent or in established combination therapy in the following:
- Brain tumors glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors.
- Multiple myeloma in combination with prednisone.
- Relapsed or refractory Hodgkin's lymphoma in combination with other approved drugs.
- Relapsed or refractory Non-Hodgkin's lymphomas in combination with other approved drugs.
- Relapsed or refractory Hodgkin's lymphoma in combination with other approved drugs ()
1 INDICATIONS AND USAGECarmustine for injection is a nitrosourea indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in the following:
- Brain tumors glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors
- Multiple myeloma-in combination with prednisone
- Relapsed or refractory Hodgkin's lymphoma in combination with other approved drugs
- Relapsed or refractory Non-Hodgkin's lymphomas in combination with other approved drugs
Carmustine for injection is indicated as palliative therapy as a single agent or in established combination therapy in the following:
- Brain tumors glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors.
- Multiple myeloma in combination with prednisone.
- Relapsed or refractory Hodgkin's lymphoma in combination with other approved drugs.
- Relapsed or refractory Non-Hodgkin's lymphomas in combination with other approved drugs.
- Relapsed or refractory Non-Hodgkin's lymphomas in combination with other approved drugs ()
1 INDICATIONS AND USAGECarmustine for injection is a nitrosourea indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in the following:
- Brain tumors glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors
- Multiple myeloma-in combination with prednisone
- Relapsed or refractory Hodgkin's lymphoma in combination with other approved drugs
- Relapsed or refractory Non-Hodgkin's lymphomas in combination with other approved drugs
Carmustine for injection is indicated as palliative therapy as a single agent or in established combination therapy in the following:
- Brain tumors glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors.
- Multiple myeloma in combination with prednisone.
- Relapsed or refractory Hodgkin's lymphoma in combination with other approved drugs.
- Relapsed or refractory Non-Hodgkin's lymphomas in combination with other approved drugs.
- Recommended Dosage: As a single agent, 150 mg/m
2 to 200 mg/m
2 carmustine for injection intravenously every 6 weeks as a single dose or divided into daily injections such as 75 mg/m
2 to 100 mg/m
2 on two successive days. Adjust dose for combination therapy or in patients with reduced bone marrow reserve ()2.1 DosageThe recommended dose of carmustine for injection as a single agent in previously untreated patients is 150 mg/m2to 200 mg/m2intravenously every 6 weeks. Administer as a single dose or divided into daily injections such as 75 mg/m2to 100 mg/m2on two successive days. Lower the dose when carmustine for injection is used with other myelosuppressive drugs or in patients in whom bone marrow reserve is depleted. Administer carmustine for injection for the duration according to the established regimen. Premedicate each dose with anti-emetics.
Adjust doses subsequent to the initial dose according to the hematologic response of the patient to the preceding dose. The following schedule is suggested as a guide to dosage adjustment:
Nadir After Prior Dose Percentage of Prior Dose to
be GivenLeukocytes/mm3 Platelets/mm3 >4,000 >100,000 100% 3,000-3,999 75,000 to 99,999 100% 2,000-2,999 25,000 to 74,999 70% <2,000 <25,000 50% The hematologic toxicity can be delayed and cumulative. Monitor blood counts weekly. Do not administer a repeat course of carmustine for injection until circulating blood elements have returned to acceptable levels (platelets above 100 Gi/L, leukocytes above 4 Gi/L and absolute neutrophil count above 1 Gi/L). The usual interval between courses is 6 weeks.
Evaluate renal function prior to administration and periodically during treatment. For patients with compromised renal function, monitor for toxicity more frequently. Discontinue carmustine for injection if the creatinine clearance is less than 10 mL/min. Do not administer carmustine for injection to patients with compromised renal function. Monitor transaminases and bilirubin periodically during treatment.
[see Adverse Reactions (6)]. - Administer reconstituted solution only as a slow intravenous infusion over at least 2 hours. ( )2.2 Preparation and Administration of Intravenous Solution
- Dissolve carmustine for injection with 3 mL of the supplied sterile diluent (Dehydrated Alcohol Injection, USP).
- Aseptically add 27 mL Sterile Water for Injection, USP.
- Each mL of resulting solution contains 3.3 mg of carmustine in 10% ethanol. Such solutions should be protected from light.
- The reconstituted solution is a clear, colorless to yellowish solution.
- Once reconstituted, the solution must be further diluted with Sodium Chloride Injection, USP or 5% Dextrose Injection, USP.
- Examine reconstituted vials for crystal formation prior to use. If crystals are observed, they may be re-dissolved by warming the vial to room temperature with agitation.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
- After reconstitution as recommended, carmustine for injection is stable for 24 hours under refrigeration 2° to 8°C (36° to 46°F) in glass container. Examine reconstituted vials for crystal formation prior to use. If crystals are observed, they may be redissolved by warming the vial to room temperature with agitation.
- Vials reconstituted as directed and further diluted with 500 mL Sodium Chloride Injection, USP or 5% Dextrose Injection, USP, in glass or polypropylene containers to a concentration of 0.2 mg/mL, should be stored at room temperature, protected from light and utilized within 8 hours. These solutions are also stable 24 hours under refrigeration 2° to 8°C (36° to 46°F) and an additional 6 hours at room temperature protected from light.
- Administer reconstituted solution by slow intravenous infusion over at least two hours. Administration of carmustine for injection over a period of less than two hours can lead to pain and burning at the site of injection. Monitor the injected area during the administration. The rate of administration of the intravenous infusion should not be more than 1.66 mg/m2/min.
- See Section 16.2 for important instructions on the storage and handling of the injection. Carmustine for injection is a cytotoxic drug. Follow applicable special handling and disposal procedures.1
- The lyophilized dosage formulation contains no preservatives and is not intended for use as a multiple dose vial.
Accidental contact of reconstituted carmustine for injection with the skin has caused transient hyperpigmentation of the affected areas. Wear impervious gloves to minimize the risk of dermal exposure impervious gloves when handling vials containing carmustine for injection. Immediately wash the skin or mucosa thoroughly with soap and water if carmustine for injection lyophilized material or solution contacts the skin or mucosa1.
For injection: 100 mg of carmustine lyophilized powder in a single-dose vial for reconstitution and a vial containing 3mL sterile diluent (Dehydrated Alcohol Injection, USP)
- Lactation: Advise lactating females not to breastfeed ()8.2 LactationRisk Summary
There is no information regarding the presence of carmustine in human milk, the effects on the breastfed infant, or the effects on milk production. Because many drugs are excreted in human milk and because of the potential for serious adverse events (e.g., carcinogenicity and myelosuppression) in nursing infants, nursing should be discontinued while taking carmustine.
- Hypersensitivity ()
4 CONTRAINDICATIONS- Hypersensitivity
Carmustine for injection is contraindicated in patients with previous hypersensitivity to carmustine or its components.