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Drugs that Decrease Busulfan (IV Busulfex) Clearance: Itraconazole decreases busulfan clearance by up to 25%. Metronidazole decreases the clearance of busulfan to a greater extent than does itraconazole; metronidazole coadministration has been associated with increased busulfan toxicity. Fluconazole (200 mg) has been used with Busulfan (IV Busulfex).
Because Busulfan (IV Busulfex) is eliminated from the body via conjugation with glutathione, use of acetaminophen prior to (less than 72 hours) or concurrent with Busulfan (IV Busulfex) may result in reduced busulfan clearance based upon the known property of acetaminophen to decrease glutathione levels in the blood and tissues.
Drugs that Increase Busulfan (IV Busulfex) Clearance: Phenytoin increases the clearance of busulfan by 15% or more, possibly due to the induction of glutathione-S-transferase. Since the pharmacokinetics of Busulfan (IV Busulfex) were studied in patients treated with phenytoin, the clearance of Busulfan (IV Busulfex) at the recommended dose may be lower and exposure (AUC) higher in patients not treated with phenytoin.
