Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 07 February 2017

Indication(s)

INDICATIONS AND USAGE CeeNU has been shown to be useful as a single agent in addition to other treatment modalities, or in established combination therapy with other approved chemotherapeutic agents in the following: Brain tumors—both primary and metastatic, in patients who have already received appropriate surgical and/or radiotherapeutic procedures. Hodgkin’s disease—secondary therapy in combination with other approved drugs in patients who relapse while being treated with primary therapy, or who fail to respond to primary therapy.

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Advisory information

contraindications
CONTRAINDICATIONS CeeNU should not be given to individuals who have demonstrated a previous hypersensitivity to it.
Special warnings and precautions
PRECAUTIONS General In all instances where the use of CeeNU is considered for chemotherapy, the physician must evaluate the need and usefulness of the drug against the risks of toxic effects or adverse reactions. Most such adverse reactions are reversible if detected early. When such effects or reactions do occur, the drug should be reduced in dosage or discontinued and appropriate corrective measures should be taken according to the clinical judgment of the physician. Reinstitution of CeeNU therapy should be carried out with caution and with adequate consideration of the further need for the drug and alertness as to possible recurrence of toxicity. Information for Patients Provide patients with the following information and instructions: In order to provide the proper dose of CeeNU, the dose may be made up of 2 or more different strengths and colors of capsules. Each strength must be dispensed separately by the pharmacist. CeeNU is given as a single oral dose and will not be repeated for at least 6 weeks. Daily use of the recommended dose may lead to toxicities and fatal outcomes. Patients may experience nausea and vomiting that usually last less than 24 hours. Patients may also experience loss of appetite that may last for several days. Instruct patients to contact their physician if they develop any of the following reactions: fever, chills, sore throat, unusual bleeding or bruising, shortness of breath, dry cough, swelling of feet or lower legs, mental confusion, or yellowing of eyes and skin. Instruct patients to wear impervious (rubber or latex) 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. 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. Since CeeNU may cause liver dysfunction, it is recommended that liver function tests be monitored periodically. Renal function tests should also be monitored periodically. Carcinogenesis, Mutagenesis, Impairment of Fertility CeeNU is carcinogenic in rats and mice, producing a marked increase in tumor incidence in doses approximating those employed clinically. Nitrosourea therapy does have carcinogenic potential in humans (see ADVERSE REACTIONS ). CeeNU also affects fertility in male rats at doses somewhat higher than the human dose. Pregnancy Pregnancy Category D See WARNINGS . Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from CeeNU, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use See ADVERSE REACTIONS: Pulmonary Toxicity and DOSAGE AND ADMINISTRATION . Geriatric Use No data from clinical studies of CeeNU are available for patients 65 years of age and over to determine whether they respond differently than younger patients. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Lomustine and 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 with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and renal function should be monitored.
Adverse reactions
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/m2 develop white blood counts below 5000 wbc/mm3. Thirty-six percent developed white blood counts below 3000 wbc/mm3. 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/m2. 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.

Usage information

Dosing and administration
DOSAGE AND ADMINISTRATION The recommended dose of CeeNU in adult and pediatric patients as a single agent in previously untreated patients is 130 mg/m2 as a single oral dose every 6 weeks (see PRECAUTIONS: Information for Patients and HOW SUPPLIED: Directions to the Pharmacist ). In individuals with compromised bone marrow function, the dose should be reduced to 100 mg/m2 every 6 weeks. When CeeNU is used in combination with other myelosuppressive drugs, the doses should be adjusted accordingly. All doses of CeeNU must be rounded to the nearest 10 mg by the prescriber (see HOW SUPPLIED ). Doses subsequent to the initial dose should be adjusted according to the hematologic response of the patient to the preceding dose. The following schedule is suggested as a guide to dosage adjustment: Nadir After Prior Dose Percentage of Prior Dose to be Given Leukocytes (/mm3) Platelets (/mm3) ≥4000 ≥100,000 100% 3000–3999 75,000–99,999 100% 2000–2999 25,000–74,999 70% <2000 <25,000 50% A repeat course of CeeNU should not be given until circulating blood elements have returned to acceptable levels (platelets above 100,000/mm3; leukocytes above 4000/mm3), and this is usually in 6 weeks. Adequate number of neutrophils should be present on a peripheral blood smear. Blood counts should be monitored weekly and repeat courses should not be given before 6 weeks because the hematologic toxicity is delayed and cumulative.
Pregnancy and lactation
Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from CeeNU, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

More information

Category Value
Authorisation number NDA017588
Agency product number 7BRF0Z81KG
Orphan designation No
Product NDC 0015-3032,0015-3030,0015-3031
Date Last Revised 01-01-2001
Type HUMAN PRESCRIPTION DRUG
RXCUI 197896
Storage and handling Stability CeeNU Capsules are stable for the lot life indicated on package labeling when stored in well-closed containers at 25°C (77°F); excursions permitted to 15°C–30°C (59°F–86°F) [see USP Controlled Room Temperature]. Avoid excessive heat (over 40°C, 104°F).
Marketing authorisation holder E.R. Squibb & Sons, L.L.C.
Warnings 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 thrombocytop