FDA label c1780c96-9c2b-4b57-a863-6bbe54216cac

WARNINGS BiCNU (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 BiCNU (see WARNINGS and ADVERSE REACTIONS ). Since the major toxicity is delayed bone marrow suppression, blood counts should be monitored weekly for at least 6 weeks after a dose (see ADVERSE REACTIONS ). At the recommended dosage, courses of BiCNU should not be given more frequently than every 6 weeks. The bone marrow toxicity of BiCNU is cumulative and therefore dosage adjustment must be considered on the basis of nadir blood counts from prior dose (see “Dosage Adjustment Table” under DOSAGE AND ADMINISTRATION ). Pulmonary toxicity from BiCNU appears to be dose related. Patients receiving greater than 1400 mg/m 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 (see ADVERSE REACTIONS and PRECAUTIONS: Pediatric Use ).

WARNINGS Since the major toxicity is delayed bone marrow suppression, blood counts should be monitored weekly for at least 6 weeks after a dose (see ADVERSE REACTIONS ). At the recommended dosage, courses of BiCNU should not be given more frequently than every 6 weeks. The bone marrow toxicity of BiCNU is cumulative; therefore, dosage adjustment must be considered on the basis of nadir blood counts from prior dose (see “Dosage Adjustment Table” under DOSAGE AND ADMINISTRATION ). Pulmonary toxicity from BiCNU appears to be dose related. Patients receiving greater than 1400 mg/m 2 cumulative dose are at significantly higher risk than those receiving less. Additionally delayed onset pulmonary fibrosis occurring up to 17 years after treatment has been reported in patients who received BiCNU in childhood and early adolescence (see ADVERSE REACTIONS ). Long-term use of nitrosoureas has been reported to be associated with the development of secondary malignancies. Liver and renal function tests should be monitored periodically (see ADVERSE REACTIONS ). BiCNU (carmustine for injection) may cause fetal harm when administered to a pregnant woman. BiCNU has been shown to be embryotoxic in rats and rabbits and teratogenic in rats when given in doses equivalent to the human dose. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking (receiving) this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant. BiCNU has been administered through an intraarterial intracarotid route; this procedure is investigational and has been associated with ocular toxicity. Injection site reactions may occur during the administration of BiCNU (see ADVERSE REACTIONS: Other Toxicities ). Given the possibility of extravasation, close monitoring of the infusion site for possible infiltration during drug administration is recommended. A specific treatment for extravasation reactions is unknown at this time.

ADVERSE REACTIONS Pulmonary Toxicity Pulmonary toxicity characterized by pulmonary infiltrates and/or fibrosis has been reported to occur from 9 days to 43 months after treatment with BiCNU and related nitrosoureas. Most of these patients were receiving prolonged therapy with total doses of BiCNU greater than 1400 mg/m 2 . However, there have been reports of pulmonary fibrosis in patients receiving lower total doses. Other risk factors include past history of lung disease and duration of treatment. Cases of fatal pulmonary toxicity with BiCNU have been reported. Additionally, delayed onset pulmonary fibrosis occurring up to 17 years after treatment has been reported in a long-term study with 17 patients who received BiCNU in childhood and early adolescence (1–16 years) in cumulative doses ranging from 770 to 1800 mg/m 2 combined with cranial radiotherapy for intracranial tumors. Chest x-rays demonstrated pulmonary hypoplasia with upper zone contraction. Gallium scans were normal in all cases. Thoracic CT scans have demonstrated an unusual pattern of upper zone fibrosis. There was some late reduction of pulmonary function in all long-term survivors. This form of lung fibrosis may be slowly progressive and has resulted in death in some cases. In this long-term study, 8 of 17 died of delayed pulmonary lung fibrosis, including all those initially treated (5 of 17) at less than 5 years of age. Hematologic Toxicity A frequent and serious toxicity of BiCNU is delayed myelosuppression. It usually occurs 4 to 6 weeks after drug administration and is dose related. Thrombocytopenia occurs at about 4 weeks postadministration and persists for 1 to 2 weeks. Leukopenia occurs at 5 to 6 weeks after a dose of BiCNU and persists for 1 to 2 weeks. Thrombocytopenia is generally more severe than leukopenia. However, both may be dose-limiting toxicities. BiCNU may produce cumulative myelosuppression, manifested by more depressed indices or longer duration of suppression after repeated doses. The occurrence of acute leukemia and bone marrow dysplasias has been reported in patients following long-term nitrosourea therapy. Anemia also occurs, but is less frequent and less severe than thrombocytopenia or leukopenia. Greater myelotoxicity (e.g., leukopenia and neutropenia) has been reported when carmustine was combined with cimetidine (see PRECAUTIONS: Drug Interactions ). Gastrointestinal Toxicity Nausea and vomiting after intravenous administration of BiCNU are noted frequently. This toxicity appears within 2 hours of dosing, usually lasting 4 to 6 hours, and is dose related. Prior administration of antiemetics is effective in diminishing and sometimes preventing this side effect. Hepatotoxicity A reversible type of hepatic toxicity, manifested by increased transaminase, alkaline phosphatase and bilirubin levels, has been reported in a small percentage of patients receiving BiCNU. Nephrotoxicity Renal abnormalities consisting of progressive azotemia, decrease in kidney size, and renal failure have been reported in patients who received large cumulative doses after prolonged therapy with BiCNU and related nitrosoureas. Kidney damage has also been reported occasionally in patients receiving lower total doses. Other Toxicities Accidental contact of reconstituted BiCNU with skin has caused burning and hyperpigmentation of the affected areas. Rapid intravenous infusion of BiCNU may produce intensive flushing of the skin and suffusion of the conjunctiva within 2 hours, lasting about 4 hours. It is also associated with burning at the site of injection although true thrombosis is rare. Local soft tissue toxicity has been reported following extravasation of BiCNU. Infiltration of BiCNU may result in swelling, pain, erythema, burning sensation, and skin necrosis. Neuroretinitis, chest pain, headache, allergic reaction, hypotension, and tachycardia have been reported as part of ongoing surveillance.