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ACUTE EXPOSURE INFORMATION

  1. USES: Chlorambucil is used to treat patients with chronic lymphatic (lymphocytic) leukemia, malignant lymphomas, including lymphosarcoma, giant follicular lymphoma, and Hodgkin's disease.
  1. PHARMACOLOGY: Chlorambucil is an aromatic nitrogen mustard derivative and alkylating agent that interferes with DNA replication and induces cellular apoptosis by accumulation of cytosolic p53 and activation of the apoptosis promoter, BAX.
  1. TOXICOLOGY: After an overdose, the effects of decreased DNA synthesis and cell death are noticed primarily in organ systems with rapidly dividing cells (bone marrow, gastrointestinal tract).
  1. EPIDEMIOLOGY: Overdose is rare, but can be life-threatening.
  1. WITH THERAPEUTIC USE
    1. Myelosuppression is the dose-limiting toxicity of chlorambucil and has an onset of 1 to 14 days. Leukopenia, thrombocytopenia, neutropenia, anemia, and pancytopenia have been reported. Blood counts continue to fall after discontinuing therapy; a nadir is usually reached in 10 days to 2 weeks. Bone marrow effects are most often reversible; however, irreversible bone marrow failure has been reported. INFREQUENT: Nausea, vomiting, diarrhea, and oral ulceration. RARE: Tremors, muscular twitching, myoclonus, confusion, agitation, ataxia, flaccid paresis, hallucinations, seizures, skin hypersensitivity reactions (eg, rashes, urticaria, angioedema, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis), pulmonary fibrosis, hepatotoxicity, jaundice, drug fever, peripheral neuropathy, and interstitial pneumonia.
  1. WITH POISONING/EXPOSURE
    1. Excessive dosage or prolonged administration can induce severe myelosuppression. Patients who receive a total of 6.5 mg/kg or more in one course of therapy with continuous dosing are most likely to develop severe neutropenia. Nausea, vomiting, acute renal failure, agitation, irritability, ataxia, muscle twitching, seizures, lethargy, myoclonus, and coma have also been reported.
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