Ceenu (Lomustine) (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 (Lomustine) (see and ).

Since the major toxicity is delayed bone marrow suppression, blood counts should be monitored weekly for at least 6 weeks after a dose (see ). At the recommended dosage, courses of Ceenu (Lomustine) should not be given more frequently than every 6 weeks.

The bone marrow toxicity of Ceenu (Lomustine) is cumulative and therefore dosage adjustment must be considered on the basis of nadir blood counts from prior dose (see under ).

Ceenu (Lomustine) (lomustine) (CCNU) is one of the nitrosoureas used in the treatment of certain neoplastic diseases. It is 1-(2-chloro-ethyl)-3-cyclohexyl-1-nitrosourea. It is a yellow powder with the empirical formula of CHClNO and a molecular weight of 233.71. Ceenu (Lomustine) is soluble in 10% ethanol (0.05 mg per mL) and in absolute alcohol (70 mg per mL). Ceenu (Lomustine) is relatively insoluble in water (

It is relatively un-ionized at a physiological pH.

Inactive ingredients in Ceenu (Lomustine) Capsules are magnesium stearate and mannitol.

The structural formula is:

Ceenu (Lomustine) is available in 10 mg, 40 mg, and 100 mg capsules for oral administration.

Although it is generally agreed that Ceenu (Lomustine) alkylates DNA and RNA, it is not cross resistant with other alkylators. As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.

Ceenu (Lomustine) may be given orally. Following oral administration of radioactive Ceenu (Lomustine) at doses ranging from 30 mg/m to 100 mg/m, about half of the radioactivity given was excreted in the urine in the form of degradation products within 24 hours.

The serum half-life of the metabolites ranges from 16 hours to 2 days. Tissue levels are comparable to plasma levels at 15 minutes after intravenous administration.

Because of the high lipid solubility and the relative lack of ionization at physiological pH, Ceenu (Lomustine) crosses the blood-brain barrier quite effectively. Levels of radioactivity in the CSF are 50% or greater than those measured concurrently in plasma.

Ceenu (Lomustine) 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:

Ceenu (Lomustine) should not be given to individuals who have demonstrated a previous hypersensitivity to it.

Since the major toxicity is delayed bone marrow suppression, blood counts should be monitored weekly for at least 6 weeks after a dose (see ). At the recommended dosage, courses of Ceenu (Lomustine) should not be given more frequently than every 6 weeks.

The bone marrow toxicity of Ceenu (Lomustine) is cumulative and therefore dosage adjustment must be considered on the basis of nadir blood counts from prior dose (see under ).

Pulmonary toxicity from Ceenu (Lomustine) appears to be dose related (see ).

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 ).

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 (DL) are particularly at risk.

Since Ceenu (Lomustine) may cause liver dysfunction, it is recommended that liver function tests be monitored periodically.

Renal function tests should also be monitored periodically.

No data from clinical studies of Ceenu (Lomustine) 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.

The most frequent and most serious toxicity of Ceenu (Lomustine) 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 (Lomustine) and persists for 1 to 2 weeks. Approximately 65% of patients receiving 130 mg/m develop white blood counts below 5000 wbc/mm. Thirty-six percent developed white blood counts below 3000 wbc/mm. Thrombocytopenia is generally more severe than leukopenia. However, both may be dose-limiting toxicities.

Ceenu (Lomustine) 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 characterized by pulmonary infiltrates and/or fibrosis has been reported rarely with Ceenu (Lomustine) . Onset of toxicity has occurred after an interval of 6 months or longer from the start of therapy with cumulative doses of Ceenu (Lomustine) usually greater than 1100 mg/m. 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.

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 (Lomustine) . However, the relationship to medication in these patients is unclear.

Accidental overdose with lomustine has been reported, including fatal cases. Accidental overdose has been associated with bone marrow suppression, abdominal pain, diarrhea, vomiting, anorexia, lethargy, dizziness, abnormal hepatic function, cough, and shortness of breath.

No proven antidotes have been established for Ceenu (Lomustine) overdosage. In case of overdose, appropriate supportive measures should be taken.

The recommended dose of Ceenu (Lomustine) in adult and pediatric patients as a single agent in previously untreated patients is 130 mg/m as a single oral dose every 6 weeks (see and ). In individuals with compromised bone marrow function, the dose should be reduced to 100 mg/m every 6 weeks. When Ceenu (Lomustine) is used in combination with other myelosuppressive drugs, the doses should be adjusted accordingly.

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:

Ceenu (Lomustine) Capsules are available in individual bottles of 20 capsules each.

The total dose prescribed by the physician can be obtained (to within 10 mg) by determining the appropriate combination of capsule strengths. Only the appropriate number of Ceenu (Lomustine) capsules required for a single administration should be dispensed.

The appropriate number of capsules of each size should be placed in a single vial. Each color-coded capsule is imprinted with the dose in milligrams. In order to provide the proper dose of Ceenu (Lomustine) , patients should be aware that there may be 2 or more different types and colors of capsules in the container. Patients should be told that Ceenu (Lomustine) is taken as a single oral dose and will not be repeated for at least 6 weeks.

Caution should be exercised when handling Ceenu (Lomustine) Capsules. Procedures for proper handling and disposal of anticancer drugs should be utilized. Several guidelines on this subject have been published. To minimize the risk of dermal exposure, always wear impervious gloves when handling bottles containing Ceenu (Lomustine) Capsules. Ceenu (Lomustine) Capsules should not be broken. Personnel should avoid exposure to broken capsules. If contact occurs, wash immediately and thoroughly. More information is available in the references listed below.