Busulfan with itraconazole

The pharmacokinetics of busulfan in 26 bone marrow transplant patients, who had received busulfan without concurrent antifungal therapy, were compared with those in 13 similar patients given busulfan with itraconazole and in 13 given busulfan with fluconazole. The busulfan clearance was decreased by 20% by itraconazole (probably because itraconazole inhibits the metabolism of busulfan by the liver) but busulfan clearance... 

BUSULFAN ANTIFUNGALS -ITRACONAZOLE t busulfan levels, with risk of toxicity of busulfan, e.g. veno-ocdusive disease and pulmonary fibrosis Itraconazole is a potent inhibitor of CYP3A4. Busulfan clearance may be f by 25%, and the AUC of busulfan may t by 1500 p,mol/L Monitor clinically for veno-ocdusive disease and pulmonaiy toxicity in transplant patients. Monitor busulfan blood levels as AUC below 1500 p,mol/L per minute tends to prevent toxicity... 

Reduced elimination and increased toxicity of busulfan co-administered with itraconazole has been postulated (67). 

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. 

In 13 patients given bone marrow transplantation, the clearance of busulfan was reduced by an average of 20% in patients taking itraconazole compared with control patients and patients taking fluconazole (40). 

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