Ketoconazole Busulfan

ITRACONAZOLE, KETOCONAZOLE BUSULFAN t busulfan levels, with risk of toxicity of busulfan, e.g. veno-ocdusive disease and pulmonaiy fibrosis Itraconazole is a potent inhibitor of CYP3A4. Busulfan clearance may be 1 by 25% and the AUC of busulfan may t by 1500 pmol/min Dose adjustments are necessary if concomitant administration is considered absolutely necessary best, however, to avoid concomitant use. Monitor clinically for veno-ocdusive disease and pulmonaiy toxicity in transplant patients. Monitor busulfan blood levels as an AUC below 1500 pmol/min tends to prevent toxicity... 

Itraconazole, but not fluconazole, modestly reduces the clearance of busulfan. There is some limited evidence to surest that the use of busulfan with ketoconazole may increase the risk of hepatic veno-occlusive disease. 

T. Dodo, K. Uchida, T. Hirose, T. Fukuta, C. Kojima, I. Shiraishi, E. Kato, T. Hoiiba, H. Mineshima, Y. Okuda, M. Maeda, N. Katsutani, K. Hirano and T. Aoki, Increases in discontinuous rib cartilage and fused carpal bones in rat foetuses exposed to the teratogens, busulfan, acetazolamide, vitamin A, and ketoconazole. Hum. Exp. Toxicol, 2010, 29, 439-450. 

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