carmustine (BCNU, BiCNU, Carmubris)

Introduction

Tradename: BiCNU.

Indications

• brain tumors (astrocytoma)
• multiple myeloma
• Hodgkin's disease
• non-Hodgkin's lymphoma
• melanoma
• lung cancer
• stem-cell transplantation

Contraindications

• pregnancy*

* contraception indicated during therapy

pregnancy category = ?

Dosage

• 150-200 mg/m2 every 6 weeks
• max cumulative dose: 1400 mg/m2
• do NOT mix with solutions containing bicarbonate
• administer in glass container

Powder for injection: 100 mg

Caution: do not mix with solution containing bicarbonate.

Pharmacokinetics

• rapidly distributes to all tissues
• CSF concentration is about 70 times blood concentration
• metabolized by liver, removed by kidney
• 1/2 life is 20 minutes
• not removed by dialysis

elimination via kidney

1/2life = 20 minutes

elimination by hemodialysis = -

Adverse effects

• common (> 10%)
  • pain at site of injection
  • nausea/vomiting
    • occurs within 2-4 hours
    • high emetic potential
  • increased LFTs (reversible hepatic toxicity)
• less common (1-10%)
  • anemia, stomatitis, facial flushing, alopecia, diarrhea, anorexia
• uncommon (< 1%)
  • myelosuppression: delayed 4-6 weeks
  • interstitial pneumonitis & pulmonary fibrosis* (prolonged or high doses)
  • hyperpigmentation, dermatitis
  • renal failure,
  • ocular toxicity & retinal hemorrhages
  • ataxia, dizziness
• other: seizures

* monitor: pulmonary function testing, baseline & periodically, DLCO < 70% predicted indicates high risk

• drug adverse effects of alkylating agents

Drug interactions

• cimetidine may decrease metabolism of BCNU, thus increasing toxicity
• amphotericin may enhance cellular uptake of BCNU
• digoxin
• phenytoin

Test interactions

increases serum K+

Mechanism of action

alkylating agent

More general terms

• alkylating agent nitrosourea

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2578