From the Guidelines
Fluconazole can prolong the QTc interval, particularly in patients with risk factors or when used concomitantly with other QT-prolonging medications. The risk of QTc prolongation is a concern with azole antifungals, including fluconazole, as they can inhibit the CYP3A4 enzyme, leading to increased plasma concentrations of other QT-prolonging medications 1. According to the most recent guidelines, fluconazole, itraconazole, posaconazole, and voriconazole may cause QTc prolongation, and the potential for QTc prolongation is exacerbated by the combination of azoles and other drugs, such as fluoroquinolones, macrolides, and ondansetron 1.
Key points to consider:
- Fluconazole is an azole antifungal that inhibits the CYP3A4 enzyme, which can lead to increased plasma concentrations of other QT-prolonging medications when used concomitantly 1.
- The risk of QTc prolongation is dose-dependent, with higher doses posing a greater risk than standard doses 1.
- Patients with pre-existing cardiac conditions, electrolyte abnormalities, congenital long QT syndrome, or those taking other QT-prolonging medications are at increased risk 1.
- Healthcare providers should consider ECG monitoring in high-risk patients, particularly when using higher doses or when combining fluconazole with other QT-prolonging drugs 1.
It is essential to weigh the benefits and risks of using fluconazole, especially in patients with risk factors for QTc prolongation, and to consider alternative antifungal therapies if necessary 1. The mechanism involves fluconazole's inhibition of the hERG potassium channels in cardiac cells, which delays ventricular repolarization and extends the QT interval, potentially leading to torsades de pointes, a life-threatening ventricular arrhythmia 1.
From the FDA Drug Label
Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram. Fluconazole causes QT prolongation via the inhibition of Rectifier Potassium Channel current (Ikr). During post-marketing surveillance, there have been rare cases of QT prolongation and torsade de pointes in patients taking fluconazole.
Yes, fluconazole can prolong the QTc interval. This is due to its inhibition of the Rectifier Potassium Channel current (Ikr) and has been observed in rare cases during post-marketing surveillance, including reports of torsade de pointes 2.
From the Research
Fluconazole and QTc Interval Prolongation
- Fluconazole, an antifungal medication, has been associated with QTc interval prolongation, which can increase the risk of torsades de pointes and other cardiac arrhythmias 3, 4, 5, 6.
- Studies have shown that fluconazole can inhibit the hERG K(+) channel, leading to QTc interval prolongation 5.
- The risk of QTc interval prolongation and torsades de pointes is higher in patients with underlying cardiac conditions, electrolyte imbalances, or those taking other medications that can prolong the QTc interval 3, 6.
- Fluconazole has been reported to cause QTc interval prolongation even at low doses, and serial electrocardiographic monitoring may be necessary in patients at risk of ventricular arrhythmias 4.
Clinical Implications
- Patients initiated on fluconazole should be closely monitored for QTc-interval prolongation, especially if they have underlying cardiac conditions or are taking other medications that can prolong the QTc interval 3.
- The use of fluconazole should be avoided in patients with a baseline QTc interval prolongation, and alternative antifungal medications should be considered 3.
- Healthcare providers should be aware of the potential for fluconazole to cause QTc interval prolongation and take steps to minimize this risk, including monitoring electrolyte levels and adjusting medication doses as needed 6.
Comparison with Other Antifungal Medications
- Isavuconazole, another antifungal medication, has been shown to shorten the QTc interval, whereas fluconazole can prolong it 7.
- The differences in QTc interval effects between these two medications may be important considerations in the selection of antifungal therapy, particularly in patients at risk of cardiac arrhythmias 7.