BICNU
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BICNU (BICNU).
Carmustine (BCNU) is a nitrosourea alkylating agent that crosslinks DNA and RNA, inhibits DNA synthesis, and carbamoylates proteins.
| Metabolism | Hepatic metabolism via cytochrome P450 enzymes (primarily CYP2A6 and CYP2B6); undergoes rapid biotransformation to active metabolites; renal excretion of metabolites. |
| Excretion | Renal excretion accounts for approximately 60-70% of the administered dose, with about 10% excreted unchanged. Biliary/fecal excretion accounts for less than 10%. |
| Half-life | The terminal elimination half-life of BCNU is 15-30 minutes for the parent drug, but active metabolites persist with a half-life of 5-6 hours. Due to rapid degradation, the overall cytotoxic effect is prolonged. |
| Protein binding | Approximately 80% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd is approximately 3.3 L/kg (range 0.9-4.7 L/kg), indicating extensive tissue distribution and penetration into cerebrospinal fluid. |
| Bioavailability | Not applicable; BCNU is administered exclusively intravenously. Oral absorption is incomplete and erratic, so no oral bioavailability is reported. |
| Onset of Action | Intravenous administration: Clinical effect (myelosuppression) observed within 3-5 weeks; antitumor response may take several weeks to months. |
| Duration of Action | Myelosuppression (especially thrombocytopenia) may last 4-6 weeks; nadir occurs at 4-5 weeks. Delayed and cumulative bone marrow suppression is a key clinical note. |
150-200 mg/m2 IV every 6 weeks, administered as a single dose or divided into 2 doses on consecutive days.
| Dosage form | INJECTABLE |
| Renal impairment | If GFR 30-50 mL/min: reduce dose by 25%; if GFR <30 mL/min: reduce dose by 50% or consider alternative. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25%; Child-Pugh C: contraindicated or reduce dose by 50% with close monitoring. |
| Pediatric use | 200-250 mg/m2 IV every 6 weeks; reduce dose by 25-50% if prior myelosuppressive therapy or compromised marrow function. |
| Geriatric use | No specific dose adjustment; monitor renal and hepatic function; increased risk of myelosuppression; consider starting at lower end of dosing range. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BICNU (BICNU).
| Breastfeeding | No data are available on the presence of carmustine in human breast milk, its effects on the breastfed infant, or its effects on milk production. Because of the potential for serious adverse reactions in the breastfed infant, including myelosuppression and carcinogenesis, breastfeeding is not recommended during treatment with BICNU and for at least 7 days after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | BICNU (carmustine) is an alkylating agent with demonstrated teratogenicity in animal models. In pregnant women, use is contraindicated in the first trimester due to risk of major congenital malformations. Second and third trimester exposure may cause fetal growth restriction, neurodevelopmental impairment, and neonatal myelosuppression. There is a high risk of spontaneous abortion. |
■ FDA Black Box Warning
Causes dose-related bone marrow suppression, particularly thrombocytopenia and leukopenia, which may be delayed. Cumulative myelosuppression is common. Pulmonary toxicity (fibrosis) is dose-related and can be fatal. Risk of secondary malignancies including acute leukemia and myelodysplasia.
| Serious Effects |
Hypersensitivity to carmustine or any component; pre-existing severe bone marrow suppression; acute infection; concurrent yellow fever vaccine; pregnancy (when possible).
| Precautions | Severe myelosuppression requiring frequent blood count monitoring; pulmonary toxicity (fibrosis) with cumulative doses >1400 mg/m²; hepatotoxicity; renal impairment; increased risk of secondary malignancies; carcinogenicity; may cause fetal harm; use in pregnancy only if benefit outweighs risk; caution in patients with infection, bleeding, or prior chemotherapy/radiation. |
| Food/Dietary | No known significant food interactions. However, patients should avoid grapefruit and grapefruit juice due to potential CYP3A4 interaction (caution, though minimal data). Maintain adequate hydration to reduce renal toxicity risk. |
Loading safety data…
| Fetal Monitoring | Maternal monitoring includes complete blood counts (CBC) with differential prior to each dose and regularly during therapy to monitor for myelosuppression; hepatic function tests (AST, ALT, bilirubin) and renal function tests (serum creatinine, BUN) periodically due to hepatotoxicity and nephrotoxicity; pulmonary function tests due to risk of pulmonary fibrosis; and fetal monitoring via ultrasound for growth, anatomy, and amniotic fluid volume if exposure occurs during pregnancy. Consider periodic fetal echocardiography if exposure in first trimester. |
| Fertility Effects | BICNU is gonadotoxic. In males, it can cause oligospermia, azoospermia, and testicular atrophy, which may be irreversible. In females, it can cause ovarian failure, premature menopause, and infertility due to depletion of ovarian follicles. Fertility preservation counseling should be offered prior to treatment. |
| Clinical Pearls | BICNU (carmustine) is a nitrosourea alkylating agent that crosses the blood-brain barrier, making it useful for brain tumors. It causes dose-limiting pulmonary fibrosis; cumulative lifetime dose should not exceed 1,400 mg/m². Monitor renal and hepatic function due to potential toxicity. Delayed myelosuppression occurs 4-6 weeks after administration. Pre-medicate with antiemetics due to high emetogenic potential. Avoid live vaccines during treatment. |
| Patient Advice | This drug may cause severe nausea and vomiting; take prescribed antiemetics as directed. · Report any shortness of breath, cough, or fever immediately as these may indicate lung problems. · Wash hands frequently and avoid crowds to reduce infection risk due to low blood cell counts. · Use effective contraception during treatment and for at least 6 months after completion. · Do not receive live vaccines (e.g., MMR, flu nasal spray) while on this medication. · Avoid alcohol consumption as it may increase liver toxicity risk. |