LOMUSTINE
Clinical safety rating: avoid
Contraindicated (not allowed)
Alkylating agent that crosslinks DNA, inhibits DNA synthesis, and produces interstrand crosslinks via chloroethyl carbonium ion formation. Also has carbamoylating activity.
| Metabolism | Extensively metabolized in the liver via CYP450 enzymes (CYP2A6, CYP2B6, CYP2C8, CYP2D6, CYP3A4). Undergoes rapid hydroxylation to active metabolites. |
| Excretion | Renal excretion approximately 50% (as metabolites), biliary/fecal excretion approximately 20%; remainder unaccounted, likely metabolized. |
| Half-life | Biphasic: initial half-life ~6 hours; terminal half-life ~16-48 hours (mean 24 hours). Metabolites have prolonged half-life up to 72 hours. Clinical context: accumulation with repeated dosing, requiring 6-week intervals. |
| Protein binding | Approximately 50% bound to plasma proteins (albumin). |
| Volume of Distribution | Not well characterized; estimates suggest high Vd (≥5 L/kg) due to lipophilicity and extensive tissue distribution, including CNS. |
| Bioavailability | Oral: nearly 100% (rapid and complete absorption). |
| Onset of Action | Oral: Clinical effects (myelosuppression) observed within 2-4 weeks. |
| Duration of Action | Myelosuppression (thrombocytopenia, leukopenia) nadir at 4-6 weeks, recovery may take several weeks; cumulative toxicity. |
| Molecular Weight | 233.69 |
130 mg/m² orally as a single dose every 6 weeks; subsequent doses adjusted based on hematologic response.
| Dosage form | CAPSULE |
| Renal impairment | If GFR 10-50 mL/min: reduce dose by 25%; if GFR <10 mL/min: reduce dose by 50%. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25%; Child-Pugh C: reduce dose by 50%. |
| Pediatric use | 130 mg/m² orally every 6 weeks; dose adjustments based on nadir counts. |
| Geriatric use | Initiate at 100 mg/m² orally every 6 weeks; monitor renal function and hematologic toxicity closely. |
| 1st trimester | Avoid. Teratogenic; risk of fetal malformations. |
| 2nd trimester | Avoid. Risk of fetal growth restriction and organ damage. |
| 3rd trimester | Avoid. Risk of neonatal myelosuppression and toxicity. |
Clinical note
Other bone marrow suppressants may have additive effects Can cause delayed myelosuppression and pulmonary fibrosis.
| Placental transfer | Crosses placenta; documented in animal studies and human cases. |
| Breastfeeding | Contraindicated; excreted in breast milk and can cause severe neonatal myelosuppression. |
| Lactation Rating | L5 |
■ FDA Black Box Warning
Bone marrow suppression (myelosuppression), especially delayed and cumulative leukopenia and thrombocytopenia. Pulmonary toxicity (fibrosis) at cumulative doses >1,100 mg/m². Secondary malignancies (acute leukemias, myelodysplastic syndromes).
| Common Effects | Hodgkin's lymphoma |
| Serious Effects |
PregnancyBreastfeedingSevere myelosuppressionHypersensitivity to lomustine
| Precautions | Bone marrow suppression (monitor CBC weekly for at least 6 weeks). Pulmonary toxicity (pulmonary fibrosis, pneumonitis). Increased risk with higher cumulative doses. Nephrotoxicity (especially when combined with cisplatin). Hepatotoxicity. Carcinogenicity (secondary malignancies). Use with caution in renal/hepatic impairment. Monitor renal and hepatic function. |
| Food/Dietary |
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| Teratogenic Risk | Lomustine is contraindicated in pregnancy. It is a nitrosourea alkylating agent with potent teratogenic and embryotoxic effects. First trimester exposure is associated with major congenital malformations, including central nervous system, craniofacial, and skeletal defects. Second and third trimester exposure may cause fetal growth restriction, myelosuppression, and increased risk of neonatal death. Potential for long-term neurodevelopmental impairment exists. Use effective contraception during treatment. |
| Fetal Monitoring | Complete blood count (CBC) with differential and platelets weekly during therapy. Hepatic and renal function tests monthly. Pulmonary function tests and chest X-ray as indicated for pulmonary toxicity. In pregnant patients (if inadvertently exposed), serial fetal ultrasound for growth and anatomy, and consideration of amniocentesis for chromosomal abnormalities after first trimester exposure. |
| Fertility Effects | Lomustine causes dose-dependent gonadal toxicity. In males, it leads to oligospermia, azoospermia, and permanent infertility due to spermatogonial depletion. In females, it may cause ovarian failure, premature menopause, and reduced fertility, particularly in patients aged over 30. Effects are often irreversible. |
| Grapefruit and grapefruit juice should be avoided as they may increase lomustine levels. Take on an empty stomach; avoid food for at least 2 hours before and 1 hour after dosing. No other known dietary restrictions. |
| Clinical Pearls | Lomustine is a nitrosourea alkylating agent that crosses the blood-brain barrier, making it useful for brain tumors. Cumulative myelosuppression, especially thrombocytopenia, is dose-limiting and often delayed (4-6 weeks). Monitor CBC weekly. Administer on an empty stomach to reduce nausea. Due to high lipid solubility, it distributes widely, including into breast milk. Avoid live vaccines during and after treatment. |
| Patient Advice | Take lomustine on an empty stomach with a full glass of water. · Do not eat for at least 2 hours before and 1 hour after taking the dose. · Avoid grapefruit and grapefruit juice during treatment. · Watch for signs of infection (fever, sore throat) or bleeding (easy bruising, black stools). · Notify your doctor immediately if you experience shortness of breath or severe nausea/vomiting. · Use effective contraception during treatment and for at least 6 months after. · Do not receive live vaccines while on lomustine. |