History

• Discovered in 1961
  • Pulmonary toxicity was reported soon after discovery

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Indications

Myeloproliferative Disorders (see xxxx)

• xxx

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Pharmacology

• Alkylating Agent

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Administration

• IV: xxx

Dose Adjustment

• Hepatic
• Renal

Drug Interactions

• Metronidazole (see Metronidazole)

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Adverse Effects

Hematologic Adverse Effects

• Myleosuppression

Pulmonary Adverse Effects

Pneumonitis (see Pneumonia and Interstitial Lung Disease)

• Incidence: approximately 6% (range: 2.5-43%)
• Risk Factors
  • Pulmonary toxicity may be related to concomitant chemotherapy or radiation therapy
  • Pulmonary toxicity is not related to cumulative dose or age
• Diagnosis
  • CXR/Chest CT: combined alveolar infiltrates (due to desquamation of epithelial cells into alveoli) and interstitial infiltrates
    • Desquamation of alveolar cells may so extensive in some cases as to mimic pulmonary alveolar proteinosis
• Clinical
  • Average Latency Between Busulfan Treatment and Onset of Pulmonary Symptoms: 3.5 years (range: 6 weeks-10 years)
    • Typically insidious onset
  • Cough
  • Dyspnea
  • Fever
• Treatment
  • Discontinue Busulfan
  • Corticosteroids (see Corticosteroids): not clear that corticosteroids have any benefit though
  • Whole Lung Lavage: may be used for cases with extensive desquamation
    • Less effective than in idiopathic alveolar proteinosis
• Prognosis: 80% mortality

Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)

• Epidemiology: xxx

Other Adverse Effects

• xxx

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References

• Busulfan and Metronidazole: An Often Forgotten but Significant Drug Interaction. Ann Pharmacother July/August 2011 vol. 45 no. 7/8: e39