Interactions between busulfan and Metronidazole (metronidazole)
metronidazole and busulfan (Major Drug-Drug)
GENERALLY AVOID: Coadministration with metronidazole may significantly increase the plasma concentrations of busulfan. The mechanism of interaction has not been described. In a group of patients receiving myeloablative therapy with busulfan (1 mg/kg orally for 4 days) prior to undergoing hematopoietic stem cell transplantation, five patients who were coadministered metronidazole (400 mg orally three times daily for 4 days) had an 87% increase in mean busulfan trough concentrations compared to ten patients who were administered busulfan alone. In nine patients who received metronidazole only for the last 2 days of busulfan administration, busulfan concentrations increased 79% compared to the first 2 days. In patients who received busulfan and metronidazole concomitantly for 4 days, all experienced elevated liver transaminases (AST, ALT) and bilirubin. Three patients also experienced veno-occlusive disease (one died with multi-organ failure), while one developed hemorrhagic cystitis. In the group who received metronidazole only on the last two days of busulfan therapy, six had elevated liver function tests, but no veno-occlusive disease was observed.
MANAGEMENT: Due to the potential for severe toxicity and mortality associated with elevated busulfan plasma levels, concomitant use with metronidazole should be avoided.
