CARMUSTINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CARMUSTINE (CARMUSTINE).
Carmustine is a nitrosourea alkylating agent that forms interstrand crosslinks in DNA, thereby inhibiting DNA replication and transcription. It is cell cycle phase-nonspecific and also has some alkylating activity against RNA and proteins.
| Metabolism | Carmustine is rapidly metabolized in the liver via microsomal enzymes, including CYP2B6 and possibly other CYP450 isoforms. Its metabolites are excreted renally. |
| Excretion | Renal (60-70% as metabolites); <1% unchanged; biliary/fecal minimal (~6%) |
| Half-life | Terminal half-life 15-30 minutes (biphasic: initial 1-4 min, terminal due to slow release from tissues); prolonged with hepatic impairment |
| Protein binding | ~80% (reversible binding to albumin, undergoes rapid degradation and spontaneous carbamoylation) |
| Volume of Distribution | 3-4 L/kg (extensive tissue distribution, crosses blood-brain barrier with CSF levels 15-30% of plasma) |
| Bioavailability | Oral: <10% (not used); Intracavitary (wafer): >90% local concentration |
| Onset of Action | IV: Antineoplastic effect within 3-4 weeks; wafer (implant): Local effect within days |
| Duration of Action | Therapeutic effect persists for weeks; myelosuppression peaks 4-6 weeks after dosing and may last 2-3 weeks |
150-200 mg/m2 intravenously every 6 weeks as a single dose or divided into daily doses of 75-100 mg/m2 on 2 consecutive days every 6 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | For CrCl 10-50 mL/min: administer 75% of dose. For CrCl <10 mL/min: administer 50% of dose. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 25%; Class C: reduce dose by 50%. |
| Pediatric use | 200-250 mg/m2 intravenously every 4-6 weeks as a single dose or 100 mg/m2/day intravenously for 2 consecutive days every 6 weeks. |
| Geriatric use | Start at lower end of dosing range (e.g., 150 mg/m2) due to increased susceptibility to myelosuppression and renal impairment; monitor blood counts and renal function closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CARMUSTINE (CARMUSTINE).
| Breastfeeding | Contraindicated during breastfeeding; M/P ratio not established; excreted in breast milk; potential for severe neonatal toxicity (myelosuppression, carcinogenesis). |
| Teratogenic Risk | Teratogenic in animals; human data limited but contraindicated in pregnancy, especially first trimester due to alkylating agent mutagenic effects; second/third trimester risk of fetal growth restriction, preterm birth, and neonatal myelosuppression. |
| Fetal Monitoring |
■ FDA Black Box Warning
Carmustine causes dose-related, delayed, and cumulative bone marrow suppression (leukopenia, thrombocytopenia) that may be severe and fatal. It also causes pulmonary fibrosis, which may be fatal, especially with cumulative doses > 1400 mg/m². Do not exceed recommended cumulative dose.
| Serious Effects |
Hypersensitivity to carmustine or any component of the formulation. Patients with preexisting bone marrow suppression (e.g., leukopenia, thrombocytopenia). Do not use in patients with active infections.
| Precautions | Monitor CBCs weekly for at least 6 weeks after each dose. Cumulative pulmonary toxicity (fibrosis, pneumonitis) may occur, especially in patients receiving high cumulative doses or concurrent pulmonary irradiation. Renal and hepatic toxicity may occur. Delayed myelosuppression may require dose reduction or delay. Increased risk of infection, bleeding, and secondary malignancies (e.g., acute leukemia). |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may affect drug metabolism. No other specific food interactions reported; maintain adequate hydration. |
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| Monitor complete blood count (CBC) with differential, liver function tests (LFTs), renal function, pulmonary function tests (PFTs) for interstitial pneumonitis; fetal ultrasound for growth restriction and anomalies; consider amniocentesis for chromosomal damage if exposed. |
| Fertility Effects | Causes ovarian failure (premature menopause) and azoospermia (potentially permanent); increased risk of infertility due to gonadotoxic effects. |
| Clinical Pearls | Carmustine is a nitrosourea alkylating agent that crosses the blood-brain barrier, making it useful for brain tumors. It causes delayed and cumulative myelosuppression, especially thrombocytopenia, with nadir at 4-6 weeks. Administer intravenously over 1-2 hours to reduce pain and phlebitis; avoid extravasation as it is a vesicant. Pulmonary fibrosis is a dose-limiting toxicity; monitor pulmonary function tests. Use with caution in patients with renal impairment as it is nephrotoxic. |
| Patient Advice | This drug may cause serious lung problems; report any cough, shortness of breath, or chest pain immediately. · Your blood counts will be monitored regularly as this drug can cause low blood cell counts, increasing infection and bleeding risk. · Avoid alcohol and aspirin or NSAIDs unless approved by your doctor to reduce bleeding risk. · This drug may cause nausea and vomiting; take antiemetics as prescribed. · Notify your doctor if you experience easy bruising, bleeding, fever, or signs of infection. · Use effective contraception during treatment and for up to 6 months after the last dose, as carmustine can harm a fetus. |