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 |
| Molecular Weight | 259.3 |
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 | Contraindicated due to teratogenicity; may cause fetal harm. |
| 2nd trimester | Contraindicated; can cause fetal malformations and growth retardation. |
| 3rd trimester | Contraindicated; risk of neonatal toxicity and adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for GLEOSTINE (GLEOSTINE).
| Placental transfer | Known to cross the placenta; animal studies show transfer and fetal toxicity. |
| Breastfeeding | Contraindicated; excreted in breast milk, potential for serious adverse reactions in nursing infants. |
| Lactation Rating | L5 |
■ 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 |
PregnancyHypersensitivity to lomustine or any componentSevere bone marrow suppression
| 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. |
| Food/Dietary | Take on an empty stomach. No specific food interactions, but avoid grapefruit or grapefruit juice as it may alter metabolism (though evidence is limited). Avoid alcohol due to hepatotoxicity. |
Loading safety data…
| 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 | 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. |
| Clinical Pearls | GLEOSTINE (lomustine) is a nitrosourea alkylating agent used in brain tumors and Hodgkin lymphoma. Due to high lipid solubility, it crosses the blood-brain barrier effectively. Cumulative myelosuppression, especially thrombocytopenia, is dose-limiting and can be delayed (nadir at 4-6 weeks). Monitor CBC weekly for at least 6 weeks after each dose. Administer on an empty stomach to reduce nausea; premedicate with antiemetics. Hepatic and renal impairment require dose reduction. Risk of pulmonary fibrosis increases with cumulative doses >1100 mg/m². |
| Patient Advice | Take this medication on an empty stomach (1 hour before or 2 hours after meals) to decrease nausea. · Do not crush or chew capsules; swallow whole. · You may experience delayed bone marrow suppression; report any signs of infection, bleeding, or unusual bruising. · Avoid live vaccines during treatment and for 6 months after. · Use effective contraception during treatment and for at least 6 months after the last dose. · Avoid alcohol as it may increase liver toxicity. · Notify your doctor immediately if you experience shortness of breath or persistent cough. |