Trade Names:CeeNU- Capsules 10 mg- Capsules 40 mg- Capsules 100 mg
Its mechanism of action involves the inhibition of both DNA and RNA synthesis through DNA alkylation. Lomustine has been shown to affect a number of cellular processes including RNA, protein synthesis, and the processing of ribosomal and nucleoplasmic messenger RNA; DNA base component structure; the rate of DNA synthesis and DNA polymerase activity. It is cell cycle nonspecific.
Bioavailability is 100%.
Vd is 3.25 L/kg. High lipid solubility; crosses blood-brain barrier readily. Levels of radioactivity in the CSF are at least 50% of those in plasma.
Readily degraded, apparently in the liver, to several cytotoxic metabolites.
Plasma t ½ of the metabolites is about 16 h to 2 days. The average terminal t ½ is 22 min. Cl is 56 mL/min/kg. 60% to 70% of the total dose is excreted in the urine in 96 h and 6% is expired as CO 2 .
Brain tumors, Hodgkin disease.
PO 100 to 130 mg/m 2 administered as a single dose every 6 wk. Do not administer repeat doses of lomustine until leukocyte and platelet counts have recovered to acceptable levels (usually 4,000/mm 3 and 100,000/mm 3 , respectively). Reduce lomustine dose if administered with other myelosuppressive drugs. Give 100 mg/m 2 to patients with compromised bone marrow function. Some clinicians advocate dosage reductions of 25% when platelet nadirs are 50,000 to 74,999/mm 3 , 50% when platelet nadirs are 25,000 to 49,999/mm 3 , and 75% when platelet nadirs are less than 25,000/mm 3 .Children
PO 75 to 150 mg/m 2 administered as a single dose every 6 wk. Do not administer repeat doses of lomustine until leukocyte and platelet counts have recovered to acceptable levels (usually 4,000/mm 3 and 100,000/mm 3 , respectively). Follow dosage adjustment guidelines recommended for adults.Suggested Lomustine Dose Following Initial DoseAdults
PO Give 100% of the prior dose if the leukocytes are greater than 3,000 cells/mm 3 and the platelets are greater than 75,000 cells/mm 3 . Give 70% of the prior dose if the leukocytes are 2,000 to 2,999 cells/mm 3 and the platelets are 25,000 to 74,999 cells/mm 3 . Give 50% of the prior dose if the leukocytes are less than 2,000 cells/mm 3 and the platelets less than 25,000 cells/mm.
Store in well-closed containers at room temperature. Avoid excessive heat (greater than 104°F).
Lomustine is soluble in alcohol. Some sources recommend avoidance of alcohol on days that lomustine is administered to avoid possible effects on the absorption of lomustine, although there is no documentation of an interaction.
None well documented.
Disorientation; lethargy; ataxia; slurred speech.
Very high potential for nausea and vomiting with doses at least 60 mg/m 2 , moderate to high potential for nausea and vomiting with doses less than 60 mg/m 2 ; anorexia; transient elevation of LFTs.
Bone marrow suppression, nadir at 4 to 6 wk.
Renal failure associated with large cumulative dose.
Acute leukemia and myelodysplastic disorders have occurred after long-term nitrosourea therapy.
The most frequent and serious toxicity is delayed myelosuppression. It usually occurs 4 to 6 wk after drug administration and is dose-related. Thrombocytopenia occurs approximately 4 wk after a dose. Leukopenia occurs approximately 5 to 6 wk after a dose and persists for 1 to 2 wk. About 65% of patients develop WBC less than 5,000/mm 3 , and 36% of patients develop WBC less than 3,000/mm 3 . Thrombocytopenia is generally more severe than leukopenia. Anemia also occurs but is less frequent.
Monitor blood counts weekly for 6 wk after a dose. Monitor liver and renal function periodically.Baseline pulmonary function tests
Conduct baseline pulmonary function studies during treatment. Patients with a baseline less than 70% of the predicted forced vital capacity (FVC) or carbon monoxide diffusing capacity (DL CO ) are particularly at risk.
Category D .
There have been reports of persistent testicular damage causing infertility.
A reversible type of hepatic toxicity manifested by increased transaminase, alkaline phosphatase, and bilirubin levels has occurred in a small percentage of patients.
Decreased kidney size, progressive azotemia, and renal failure have occurred in patients who received large cumulative doses after prolonged therapy.
Pulmonary toxicity characterized by pulmonary infiltrates or fibrosis occurs rarely and appears to be dose-related. Onset of toxicity has occurred after an interval of at least 6 mo from start of therapy with cumulative doses usually greater than 1100 mg/m 2 .
Long-term use of nitrosoureas may be associated with development of secondary malignancies.
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