Long QTc interval and torsade de pointes caused by fluconazole.
OBJECTIVE
To describe a patient who developed torsade de pointes while being treated with fluconazole.


METHODS
A 33-year-old woman with a 5 year history of systemic lupus erythematosus was admitted to the intensive care unit because of respiratory insufficiency due to Candida albicans pneumonia. Therapy with intravenous fluconazole 200 mg/day, with dose later adjusted according to her renal function, was started. Prolongation of the QTc interval and torsade de pointes occurred. Initially, domperidone, which had been initiated the day before fluconazole, was suspected as the possible cause and was discontinued; ultimately, both drugs were discontinued. However, torsade de pointes recurred several weeks later when the patient was treated with fluconazole for a second time and disappeared again on withdrawal of the drug. According to the Naranjo probability scale, this adverse reaction was highly probable.


CONCLUSIONS
The risk of torsade de pointes does not correlate in a linear fashion with prolongation of the QTc interval, but an interval beyond 500 msec is considered a significant risk factor. Given that both fluconazole and domperidone are metabolized by the cytochrome P450 system, they may intensify each other's proarrhythmic effects, particularly in patients with concurrent renal dysfunction. These risks are of particular concern in patients whose baseline QTc interval is prolonged for any reason.


CONCLUSIONS
From the case history, as well as use of the Naranjo scale, we concluded that fluconazole was the highly probable cause of the development of torsade de pointes in our patient.
Pham
C Phu
CP
Department of Intensive Care, Twenteborg Hospital Almelo, Netherlands.
de Feiter
Peter W
PW
van der Kuy
P Hugo M
PH
van Mook
Walther Nka
WN
D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D002177:Candidiasis / Q000150:complications / Q000188:drug therapy / Q000382:microbiology; D004294:Domperidone / Q000627:therapeutic use; D005260:Female; D015725:Fluconazole / Q000009:adverse effects*; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy / Q000382:microbiology; D016171:Torsades de Pointes / Q000139:chemically induced*
D000935:Antifungal Agents; D004294:Domperidone; D015725:Fluconazole