Can Posaconazole (Noxafil) cause QT interval prolongation?

From the Guidelines

Posaconazole can cause QT prolongation, as evidenced by recent clinical guidelines 1. This antifungal medication has been associated with prolongation of the QT interval on electrocardiogram, which represents the time for electrical depolarization and repolarization of the ventricles. The risk appears to be dose-dependent and is more significant with higher serum concentrations. Some key points to consider include:

• Patients with pre-existing cardiac conditions, electrolyte abnormalities (particularly hypokalemia or hypomagnesemia), or those taking other QT-prolonging medications are at increased risk.
• Healthcare providers should consider baseline and periodic ECG monitoring in high-risk patients taking posaconazole.
• Electrolyte levels should also be monitored and corrected if abnormal.
• The mechanism behind this effect involves posaconazole's ability to block certain potassium channels in cardiac cells, which affects cardiac repolarization.
• If a patient develops significant QT prolongation while on posaconazole, dose adjustment or medication change may be necessary, especially if the QTc interval exceeds 500 milliseconds or increases by more than 60 milliseconds from baseline. It's also worth noting that the potential for QTc prolongation is a concern exacerbated by the combination of azoles and other drugs (eg, fluoroquinolones, macrolides, ondansetron) and with some chemotherapies (eg, nilotinib for chronic myeloid leukemia) 1. In contrast to some other medications, isavuconazonium sulfate has been associated with dose-dependent QTc shortening in healthy individuals 1. However, the focus remains on posaconazole's potential to cause QT prolongation, as highlighted in the most recent guidelines 1.

From the FDA Drug Label

Arrhythmias and QTc Prolongation: Posaconazole has been shown to prolong the QTc interval and cause cases of TdP. Administer with caution to patients with potentially proarrhythmic conditions. Do not administer with drugs known to prolong QTc interval and metabolized through CYP3A4. Some azoles, including posaconazole, have been associated with prolongation of the QT interval on the electrocardiogram. In addition, cases of torsades de pointes have been reported in patients taking posaconazole.

Posaconazole can cause QT prolongation. It is recommended to administer with caution to patients with potentially proarrhythmic conditions and not to administer with drugs known to prolong the QTc interval and metabolized through CYP3A4 2, 2, 2.

• Key points:
  • Posaconazole has been shown to prolong the QTc interval
  • Cases of torsades de pointes have been reported in patients taking posaconazole
  • Administer with caution to patients with potentially proarrhythmic conditions
  • Do not administer with drugs known to prolong QTc interval and metabolized through CYP3A4

From the Research

Posaconazole and QT Prolongation

• Posaconazole has been associated with QT interval prolongation in some cases, as reported in a study published in The American journal of case reports 3.
• The study described a case of a septic patient with severe immunodeficiency who developed QT interval prolongation and suffered from episodes of cardiac arrest due to polymorphic ventricular tachycardia after posaconazole administration.
• Another study published in The Journal of antimicrobial chemotherapy found a statistically significant increase in QTc interval from baseline, but no association was found between posaconazole serum concentrations and QTc interval prolongation 4.

Risk Factors for QT Prolongation

• The risk of QT prolongation is increased in the presence of coexisting risk factors, such as underlying immunodeficiency, sepsis, and the use of other medications that can prolong the QT interval 3, 5.
• Electrolyte disturbances, cardiovascular status, and pathological conditions can also contribute to QT prolongation 6, 5.

Monitoring and Management

• Close cardiac monitoring is recommended in cases where posaconazole administration is combined with coexisting risk factors, as they may lead to severe ECG abnormalities and cardiac arrhythmias 3.
• The use of posaconazole should be carefully considered in patients with risk factors for QT prolongation, and alternative treatments should be explored if possible.