bicnu

Important safety information

Administration Reactions: Extravasation may occur; monitor infusion site closely during administration (5.3) Carcinogenicity: Potentially carcinogenic to humans. Monitor patient periodically for such signs and apprise the patient of the symptoms for which they need to seek medical help. (5.4) Ocular Toxicity: Has occurred when administered via unapproved intraarterial intracarotid route. (5.5) Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to avoid pregnancy. (5.6) 5.1 Myelosuppression 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 [see Adverse Reactions (6) ] . Greater myelotoxicity (e.g., leukopenia and neutropenia) has been reported when carmustine was combined with cimetidine [see Drug Interactions (7) ] . 5.2 Pulmonary toxicity Cases of fatal pulmonary toxicity with Carmustine for Injection have been reported. Pulmonary toxicity characterized by pulmonary infiltrates and/or fibrosis has been reported to occur from 9 days to 43 months after treatment with Carmustine for Injection and related nitrosoureas. Pulmonary toxicity from Carmustine for Injection is dose-related. Patients receiving greater than 1400 mg/m 2 cumulative dose are at significantly higher risk than those receiving less. However, there have been reports of pulmonary fibrosis in patients receiving lower total doses. Interstitial fibrosis (with lower doses) occurred rarely. Additionally, delayed onset pulmonary fibrosis occurring up to 17 years after treatment has been reported in patients who received Carmustine for Injection (in cumulative doses ranging from 770 to 1800 mg/m 2 combined with cranial radiotherapy for intracranial tumors) in childhood and early adolescence. Other risk factors include past history of lung disease and duration of treatment. Baseline pulmonary function studies should be conducted along with frequent pulmonary function tests during treatment. Patients with a baseline below 70% of the predicted forced vital capacity (FVC) or carbon monoxide diffusing capacity (DLCO) are particularly at risk. 5.3 Administration Reactions Injection site reactions may occur during the administration of Carmustine for Injection. Rapid intravenous infusion of Carmustine for Injection 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. 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. 5.4 Carcinogenicity Long-term use of nitrosoureas, such as Carmustine for Injection, has been reported to be associated with the development of secondary malignancies. Carmustine was carcinogenic when administered to laboratory animals [see Nonclinical Toxicity (13.1) ] . Nitrosourea therapy, such as Carmustine for Injection, has carcinogenic potential in humans. Patients treated with Carmustine for Injection should be monitored long-term for development of second malignancies. 5.5 Ocular Toxicity Carmustine for Injection has been administered through an intraarterial intracarotid route; this procedure is investigational and has been associated with ocular toxicity. Safety and effectiveness of the intra-arterial route have not been established. 5.6 Embryo-Fetal Toxicity Carmustine was embryotoxic in rats and rabbits and teratogenic in rats when given in doses lower than the maximum cumulative human dose based on body surface area. There are no adequate and well- controlled studies in pregnant women. Advise pregnant women of the potential risk to the fetus [ see Use in Specific Populations ( 8.1 , 8.3 ) ]. Advise females of reproductive potential to use highly effective contraception during and after treatment with Carmustine for Injection for at least 6 months after therapy. Advise males of reproductive potential to use effective contraception during and after treatment with Carmustine for Injection for at least 3 months after therapy [see Use in Specific Populations ( 8.1 , 8.3 )].