7.1 Drugs that Decrease Busulfan Injection 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 Injection.
Decreased clearance of busulfan was observed with concomitant use with deferasirox. The mechanism of this interaction is not fully elucidated. Discontinue iron chelating agents well in advance of administration of Busulfan Injection to avoid increased exposure to busulfan.
Because busulfan is eliminated from the body via conjugation with glutathione, use of acetaminophen prior to (less than 72 hours) or concurrent with Busulfan Injection may result in reduced busulfan clearance based upon the known property of acetaminophen to decrease glutathione levels in the blood and tissues.
7.2 Drugs that Increase Busulfan Injection 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 Injection were studied in patients treated with phenytoin, the clearance of Busulfan Injection at the recommended dose may be lower and exposure (AUC) higher in patients not treated with phenytoin.