FDA label 41126f73-4e7d-4f0f-bdc1-ff89bbba6fb5

WARNINGS CeeNU (lomustine) 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 CeeNU (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 CeeNU should not be given more frequently than every 6 weeks. The bone marrow toxicity of CeeNU 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 ).

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 CeeNU should not be given more frequently than every 6 weeks. The bone marrow toxicity of CeeNU 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 CeeNU appears to be dose related (see ADVERSE REACTIONS ). Long-term use of nitrosoureas has been reported to be possibly associated with the development of secondary malignancies. Liver and renal function tests should be monitored periodically (see ADVERSE REACTIONS ). Pregnancy Category D CeeNU can cause fetal harm when administered to a pregnant woman. CeeNU is embryotoxic and teratogenic in rats and embryotoxic in rabbits at dose levels 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.

ADVERSE REACTIONS Hematologic Toxicity The most frequent and most serious toxicity of CeeNU 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 CeeNU and persists for 1 to 2 weeks. Approximately 65% of patients receiving 130 mg/m 2 develop white blood counts below 5000 wbc/mm 3 . Thirty-six percent developed white blood counts below 3000 wbc/mm 3 . Thrombocytopenia is generally more severe than leukopenia. However, both may be dose-limiting toxicities. CeeNU 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 have been reported in patients following long-term nitrosourea therapy. Anemia also occurs, but is less frequent and less severe than thrombocytopenia or leukopenia. Pulmonary Toxicity Pulmonary toxicity characterized by pulmonary infiltrates and/or fibrosis has been reported rarely with CeeNU. Onset of toxicity has occurred after an interval of 6 months or longer from the start of therapy with cumulative doses of CeeNU usually greater than 1100 mg/m 2 . There is 1 report of pulmonary toxicity at a cumulative dose of only 600 mg. Delayed onset pulmonary fibrosis occurring up to 17 years after treatment has been reported in patients who received related nitrosoureas in childhood and early adolescence (1–16 years) combined with cranial radiotherapy for intracranial tumors. There appeared to be some late reduction of pulmonary function of 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 of carmustine, all those initially treated at less than 5 years of age died of delayed pulmonary fibrosis. Gastrointestinal Toxicity Nausea and vomiting may occur 3 to 6 hours after an oral dose and usually last less than 24 hours. Prior administration of antiemetics is effective in diminishing and sometimes preventing this side effect. Nausea and vomiting can also be reduced if CeeNU is administered to fasting patients. 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 CeeNU. 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 CeeNU. Kidney damage has also been reported occasionally in patients receiving lower total doses. Other Toxicities Stomatitis, alopecia, optic atrophy, and visual disturbances, such as blindness, have been reported infrequently. Neurological reactions, such as disorientation, lethargy, ataxia, and dysarthria have been noted in some patients receiving CeeNU. However, the relationship to medication in these patients is unclear.