Frequency of potential azole drug-drug interactions and consequences of potential fluconazole drug interactions.
OBJECTIVE
To assess the frequency of potential azole-drug interactions and consequences of interactions between fluconazole and other drugs in routine inpatient care.


METHODS
We performed a retrospective cohort study of hospitalized patients treated for systemic fungal infections with an oral or intravenous azole medication between July 1997 and June 2001 in a tertiary care hospital. We recorded the concomitant use of medications known to interact with azole antifungals and measured the frequency of potential azole drug interactions, which we considered to be present when both drugs were given together. We then performed a chart review on a random sample of admissions in which patients were exposed to a potential moderate or major drug interaction with fluconazole. The list of azole-interacting medications and the severity of interaction were derived from the DRUGDEX System and Drug Interaction Facts.


RESULTS
Among the 4,185 admissions in which azole agents (fluconazole, itraconazole or ketoconazole) were given, 2,941 (70.3%) admissions experienced potential azole-drug interactions, which included 2,716 (92.3%) admissions experiencing potential fluconazole interactions. The most frequent interactions with potential moderate to major severity were co-administration of fluconazole with prednisone (25.3%), midazolam (17.5%), warfarin (14.7%), methylprednisolone (14.1%), cyclosporine (10.7%) and nifedipine (10.1%). Charts were reviewed for 199 admissions in which patients were exposed to potential fluconazole drug interactions. While four adverse drug events (ADEs) caused by fluconazole were found, none was felt to be caused by a drug-drug interaction (DDI), although in one instance fluconazole may have contributed.


CONCLUSIONS
Potential fluconazole drug interactions were very frequent among hospitalized patients on systemic azole antifungal therapy, but they had few apparent clinical consequences.
Yu
D Tony
DT
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Division of General Medicine, Boston, MA, USA.
Peterson
Josh F
JF
Seger
Diane L
DL
Gerth
William C
WC
Bates
David W
DW
D016907:Adverse Drug Reaction Reporting Systems; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001393:Azoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D004347:Drug Interactions; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy; D012189:Retrospective Studies
D000935:Antifungal Agents; D001393:Azoles; D015725:Fluconazole