GLEOSTINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GLEOSTINE (GLEOSTINE).
GLEOSTINE (lomustine) is a nitrosourea alkylating agent that crosslinks DNA and RNA, inhibiting DNA synthesis and repair. It is cell cycle phase-nonspecific.
| Metabolism | Primarily metabolized by hepatic microsomal enzymes; undergoes hydroxylation and further degradation to active and inactive metabolites. Renal excretion of metabolites. |
| Excretion | Renal: 60% (as metabolites), Fecal: <5% (unchanged and metabolites), Biliary: minimal |
| Half-life | 16-48 hours (terminal), with an active metabolite half-life of up to 5 days, requiring dose adjustment for renal impairment |
| Protein binding | 50% (albumin and lipoproteins; variable due to lipid solubility) |
| Volume of Distribution | 4.4 L/kg (high, indicating extensive tissue penetration, including CNS) |
| Bioavailability | Oral: 100% (complete absorption, but highly variable due to lipid solubility and metabolism) |
| Onset of Action | Oral: 4-6 hours (myelosuppression onset), CNS effects may begin within hours |
| Duration of Action | Myelosuppression may persist for 4-6 weeks; nadir at 4-6 weeks for thrombocytopenia and 5-6 weeks for leukopenia |
130 mg/m2 orally every 6 weeks as a single dose; alternatively, 75 mg/m2 orally every 3 weeks.
| Dosage form | CAPSULE |
| Renal impairment | No specific guidelines; use with caution in renal impairment. GFR 10-50 mL/min: consider dose reduction by 25-50%. GFR <10 mL/min: consider alternative therapy. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 25-50%. Child-Pugh C: avoid use. |
| Pediatric use | 100-130 mg/m2 orally every 6 weeks; not established for patients <3 years. |
| Geriatric use | Start at lower end of dosing range (75-100 mg/m2) due to increased sensitivity and renal function decline; monitor closely for myelosuppression. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GLEOSTINE (GLEOSTINE).
| Breastfeeding | Contraindicated. Excreted in human milk; M/P ratio unknown. Potential for severe neonatal myelosuppression and carcinogenesis. Discontinue breastfeeding or drug. |
| Teratogenic Risk | Category D. First trimester: High risk of congenital malformations (e.g., neural tube defects, skeletal anomalies). Second and third trimesters: Risk of fetal growth restriction, myelosuppression, and carcinogenesis. Avoid in pregnancy unless life-threatening maternal condition. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: BONE MARROW SUPPRESSION, CARCINOGENICITY, AND PULMONARY TOXICITY. Lomustine causes severe and prolonged myelosuppression, which may be delayed and cumulative. Pulmonary toxicity, including pulmonary fibrosis, can occur at cumulative doses. It is carcinogenic, with increased risk of secondary malignancies.
| Serious Effects |
Hypersensitivity to lomustine or any component of the formulation; severe myelosuppression; concurrent use with yellow fever vaccine.
| Precautions | Myelosuppression (monitor CBCs weekly for at least 6 weeks); pulmonary toxicity (dyspnea, cough, pulmonary infiltrates); hepatotoxicity; nephrotoxicity; carcinogenicity; secondary leukemia; impaired fertility; embryofetal toxicity; use in geriatric patients may increase toxicity. |
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| Monitor maternal CBC with differential, liver and renal function, and fetal growth via ultrasound. Consider amniocentesis for AFP levels and karyotype. |
| Fertility Effects | Causes gonadal suppression and irreversible infertility in both sexes. Amenorrhea, oligospermia, and azoospermia may occur. |