EFFECTIVENESS & SAFETY
Warnings and Precautions
The following warnings and precautions are associated with the use of Gleostine®.
Gleostine® causes myelosuppression that can result in fatal infections and bleeding. Myelosuppression from Gleostine® is delayed, dose-related, and cumulative. It usually occurs 4 to 6 weeks after drug administration and persists for 1 to 2 weeks. Thrombocytopenia is generally more severe than leukopenia. Cumulative myelosuppression from Gleostine® is manifested by greater severity and longer duration of cytopenias.
Monitor blood counts for at least 6 weeks after each dose. Do not give Gleostine® more frequently than every 6 weeks. Adjust dose based on nadir blood counts from prior dose [see Dosage and Administration (2.3)].
Risk of Overdosage
Fatal toxicity occurs with overdosage of Gleostine®. Dispensing or administering more than one dose can lead to fatal toxicity.
Prescribe only one dose at a time. Dispense only enough capsules for one dose. Both physician and pharmacist should emphasize to the patient that only one dose of Gleostine® is taken every 6 weeks. Learn more about Dosage and Administration.
Pulmonary toxicity characterized by pulmonary infiltrates and/or fibrosis occurs with Gleostine®. Patients with a baseline below 70% of the predicted Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity (DLCO) are at increased risk. The onset of pulmonary toxicity occurs after an interval of 6 months or longer from the start of therapy, with cumulative doses of Gleostine® usually greater than 1100 mg/m2. Obtain baseline pulmonary function tests prior to initiating treatment and repeat frequently during treatment. Permanently discontinue Gleostine® in patients diagnosed with pulmonary fibrosis.
Secondary malignancies, including acute leukemia and myelodysplasia, occur with long term use.
Hepatic toxicity, manifested by increased levels of transaminases, alkaline phosphatase, and bilirubin occurs with Gleostine®. Monitor liver function.
Progressive renal failure with a decrease in kidney size occurs with Gleostine®. Monitor renal function.
Based on animal data and its mechanism of action, Gleostine® can cause fetal harm when administered to a pregnant woman. Embryo-fetal toxicity and teratogenicity occurred in rats and rabbits receiving lomustine daily during organogenesis at doses approximately two to four times the total human dose of 130 mg/m2 over 6 weeks (0.18 to 0.27 times the single human dose of 130 mg/m2) based on body surface area (BSA). See Important Safety Information below for more on the risks of Gleostine® to pregnant women.