Abstract:
:We performed a randomized trial to compare the safety and efficacy of itraconazole with fluconazole in preventing fungal infections in patients undergoing allogeneic stem cell transplantation (SCT). Itraconazole (intravenous 200 mg daily, or oral solution 2.5 mg/kg 3 times daily) and fluconazole (intravenous or oral, 400 mg daily) were administered with the start of conditioning therapy, until at least 120 days after SCT. After enrollment of the first 197 patients, a data and safety monitoring board reviewed potential drug-related toxicities. Patients who received itraconazole developed higher serum bilirubin and creatinine values in the first 20 days after SCT, with highest values in patients who received itraconazole concurrent with cyclophosphamide (CY) conditioning. Analysis of CY metabolism in a subset of patients demonstrated higher exposure to toxic metabolites among recipients of itraconazole compared with fluconazole. These data suggest that azole antifungals, through differential inhibition of hepatic cytochrome P-450 isoenzymes, affect CY metabolism and conditioning-related toxicities.
journal_name
Bloodjournal_title
Bloodauthors
Marr KA,Leisenring W,Crippa F,Slattery JT,Corey L,Boeckh M,McDonald GBdoi
10.1182/blood-2003-07-2512subject
Has Abstractpub_date
2004-02-15 00:00:00pages
1557-9issue
4eissn
0006-4971issn
1528-0020pii
2003-07-2512journal_volume
103pub_type
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