Carmustine - Carmustine

Bone marrow toxicity is a dose-limiting, common and severe toxic effect of Carmustine for Injection occurring 4-6 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 for Injection 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 for Injection should not be given more frequently than every six weeks. The bone marrow toxicity of Carmustine for Injection 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 for Injection 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.

The recommended dose of Carmustine for Injection, USP as a single agent in previously untreated patients is 150 to 200 mg/m²intravenously every 6 weeks. Administer as a single dose or divided into daily injections such as 75 to 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:

The hematologic toxicity can be delayed and cumulative. Monitor blood counts weekly. Do not administer a repeat course of Carmustine for Injection, USP 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, USP if the creatinine clearance is less than 10 mL/min. Do not administer Carmustine for Injection, USP to patients with compromised renal function. Monitor transaminases and bilirubin periodically during treatment.

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 for Injection 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.

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 for Injection in childhood and early adolescence (1-16 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,