WARNINGS
Sincethe major toxicity is delayed bone marrow suppression, blood counts shouldbe monitored weekly for at least 6 weeks after a dose (see ADVERSEREACTIONS). At the recommended dosage, courses of CeeNU shouldnot be given more frequently than every 6 weeks.
Thebone marrow toxicity of CeeNU is cumulative and therefore dosage adjustmentmust be considered on the basis of nadir blood counts from prior dose (see dosage adjustment table under DOSAGEAND ADMINISTRATION).
Pulmonary toxicityfrom CeeNU appears to be dose related (see ADVERSEREACTIONS).
Long-term use of nitrosoureashas been reported to be possibly associated with the development of secondarymalignancies.
Liver and renal function tests shouldbe monitored periodically (see ADVERSE REACTIONS).
Pregnancy Category D
CeeNU can cause fetal harm when administeredto a pregnant woman. CeeNU is embryotoxic and teratogenic in rats and embryotoxicin rabbits at dose levels equivalent to the human dose. There are no adequateand well controlled studies in pregnant women. If this drug is used duringpregnancy, or if the patient becomes pregnant while taking (receiving) thisdrug, the patient should be apprised of the potential hazard to the fetus.Women of childbearing potential should be advised to avoid becoming pregnant.
PRECAUTIONS
General
Inall instances where the use of CeeNU is considered for chemotherapy, the physicianmust evaluate the need and usefulness of the drug against the risks of toxiceffects or adverse reactions. Most such adverse reactions are reversible ifdetected early. When such effects or reactions do occur, the drug should bereduced in dosage or discontinued and appropriate corrective measures shouldbe taken according to the clinical judgment of the physician. Reinstitutionof CeeNU therapy should be carried out with caution and with adequate considerationof the further need for the drug and alertness as to possible recurrence oftoxicity.
Information for the Patient
Patientsreceiving CeeNU should be given the following information and instructionsby the physician:
- Patients should be told that CeeNU is an anticancer drug and belongsto the group of medicines known as alkylating agents.
- In order to provide the proper dose of CeeNU, patients should beaware that there may be 2 or more different types and colors of capsules inthe container dispensed by the pharmacist.
- Patients should be told that CeeNU is given as a single oral doseand will not be repeated for at least 6 weeks.
- Patients should be told that nausea and vomiting usually last lessthan 24 hours, although loss of appetite may last for several days.
- If any of the following reactions occur, notify the physician: fever,chills, sore throat, unusual bleeding or bruising, shortness of breath, drycough, swelling of feet or lower legs, mental confusion, or yellowing of eyesand skin.
- Patients should be told to wear gloves when handling CeeNU Capsules.
Laboratory Tests
Due to delayed bone marrow suppression,blood counts should be monitored weekly for at least 6 weeks after a dose.
Baselinepulmonary function studies should be conducted along with frequent pulmonaryfunction tests during treatment. Patients with a baseline below 70% of thepredicted Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity(DLCO) are particularly at risk.
SinceCeeNU may cause liver dysfunction, it is recommended that liver function testsbe monitored periodically.
Renal function tests shouldalso be monitored periodically.
Carcinogenesis, Mutagenesis, Impairment of Fertility
CeeNUis carcinogenic in rats and mice, producing a marked increase in tumor incidencein doses approximating those employed clinically. Nitrosourea therapy doeshave carcinogenic potential in humans (see ADVERSEREACTIONS). CeeNU also affects fertility in male rats at dosessomewhat higher than the human dose.
Pregnancy
Pregnancy Category D
See WARNINGS.
Nursing Mothers
It is not known whether this drug isexcreted in human milk. Because many drugs are excreted in human milk andbecause of the potential for serious adverse reactions in nursing infantsfrom CeeNU, a decision should be made whether to discontinue nursing or todiscontinue the drug, taking into account the importance of the drug to themother.
Pediatric Use
See ADVERSEREACTIONS: Pulmonary Toxicity, and DOSAGEAND ADMINISTRATION.
Geriatric Use
No data from clinical studies of CeeNUare available for patients 65 years of age and over to determine whether theyrespond differently than younger patients. Other reported clinical experiencehas not identified differences in responses between elderly and younger patients.In general, dose selection for an elderly patient should be cautious, reflectingthe greater frequency of decreased hepatic, renal, or cardiac function andof concomitant disease or other drug therapy.
Lomustineand its metabolites are known to be substantially excreted by the kidney,and the risk of toxic reactions to this drug may be greater in patients withimpaired renal function. Because elderly patients are more likely to havedecreased renal function, care should be taken in dose selection, and renalfunction should be monitored.
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