Fluconazole-Induced Torsade de Pointes

Tholakanahalli, Venkatakrishna N.; Potti, Anil; Hanley, James F.; Merliss, Andrew

doi:10.1345/aph.10210

Cited by 50 publications

(30 citation statements)

References 12 publications

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“…Lidocaine is known to exacerbate or has proarrhythmogenic effects before given magnesium sulfate, it might have been concerned with deterioration of Tdp. FCZ administration also appears to be associated with QT prolongation syndrome, although how FCZ causes QT elongation is as yet unknown [1][2][3][4].…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, it is not known whether FCZ has such pharmacological properties; however, in all of the four recently reported cases of Tdp associated with FCZ administration [1][2][3][4] (Table I), prodromal QT prolongation following FCZ administration had occurred before Tdp. It is of note that for as yet unknown reasons, more female than male individuals sustain Tdp, and indeed, all these reported cases were female and so is the present case.…”

Section: Discussionmentioning

confidence: 99%

“…A few cases of QT prolongation followed by torsades de pointes (Tdp) have been reported upon fluconazole (FCZ) administration [1][2][3][4]. We hereby present a patient with acute myeloblastic leukemia (AML) who developed QT prolongation, which triggered Tdp following FCZ administration.…”

Section: Introductionmentioning

confidence: 97%

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Torsades de pointes upon fluconazole administration in a patient with acute myeloblastic leukemia

et al. 2006

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Prolonged QT syndrome often causes torsades de pointes (Tdp), a potentially lethal arrhythmia. A 55-year-old woman with M4Eo who was receiving consolidation chemotherapy had an episode of prolonged QT and Tdp following fluconazole (FCZ) administration. Intravenous supplementation of magnesium sulfate and multiple attempts at electrocardioversion led to recovery from the arrhythmia. FCZ appears to contribute to the development of QT prolongation, in particular with low concentrations of serum potassium or magnesium. Although mechanisms of Tdp development in patients with QT prolongation remain to be determined, it is possible that FCZ administration leads to manifestation of Tdp. Special cautions should be exercised upon the emergence of QT prolongation following FCZ administration. Am. J. Hematol. 81:366-369, 2006. V V C 2006 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Torsades de pointes upon fluconazole administration in a patient with acute myeloblastic leukemia

et al. 2006

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“…Fluconazole-induced prolongation of the QTc interval has been reported in the literature and depressed potassium ion channels have been confirmed as the responsible mechanism [3,5,6,7,8]. Interestingly, the arrhythmogenic effect of amiodarone also involves the blockade of potassium channels and an associated prolongation of ventricular repolarization and the QTc interval [9].…”

Section: Discussionmentioning

confidence: 99%

Sudden Cardiac Arrest Triggered by Coadministration of Fluconazole and Amiodarone

Wang

Chen²,

Lei³

et al. 2017

Cardiology

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Fluconazole for fungal infections and amiodarone for arrhythmia are commonly prescribed medications, and coadministration of such medications is sometimes inevitable in clinical practice. However, both medications have been associated with prolonged QTc intervals and subsequent arrhythmias, which are sometimes fatal. We present the case of a 75-year-old man with sudden cardiac arrest triggered by coadministration of fluconazole and amiodarone, which raises the need for caution regarding coadministration of these medications. To our knowledge, this case has not been previously described.

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“…Prophylaxis with these agents has been shown to decrease both bacterial and fungal infections (1-5), and recommendations for use are incorporated as part of the Infectious Diseases Society of America's clinical practice guidelines on the use of antimicrobial agents in neutropenic patients with cancer (6) and the National Comprehensive Cancer Network's guidelines on prevention and treatment of cancer-related infections (7). However, both classes of agents have the potential to prolong the QTc interval and increase the risk for torsades de pointes (TdP) (8-10), with episodes of TdP reported with both azoles and fluoroquinolones (11)(12)(13)(14)(15)(16)(17)(18)(19).…”

mentioning

confidence: 99%

Effect of Combined Fluoroquinolone and Azole Use on QT Prolongation in Hematology Patients

Zeuli

Wilson

Estes

2013

Antimicrob Agents Chemother

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bQTc prolongation is a risk factor for development of torsades de pointes (TdP). Combination therapy with fluoroquinolones and azoles is used in patients with hematologic malignancies for prophylaxis and treatment of infection. Both drug classes are implicated as risk factors for QTc prolongation. The cumulative effect on and incidence of QTc prolongation for this combination have not been previously described. A retrospective chart review was performed with hospitalized inpatients from 1 September 2008 to 31 January 2010 comparing QTc interval data from electrocardiogram (ECG) assessment at baseline and after the initiation of combination therapy. Ninety-four patients were eligible for inclusion. The majority, 88 patients (93.6%), received quinolone therapy with levofloxacin. Fifty-three patients (56.4%) received voriconazole; 40 (42.6%) received fluconazole. The overall mean QTc change from baseline was 6.1 (95% confidence interval [CI], 0.2 to 11.9) ms. Twenty-one (22.3%) of the studied patients had clinically significant changes in the QTc while receiving combination fluoroquinolone-azole therapy. Statistically significant risk factors for clinically significant changes in QTc were hypokalemia (P ‫؍‬ 0.03) and a left-ventricular ejection fraction of <55% (P ‫؍‬ 0.02). Low magnesium (P ‫؍‬ 0.11), exposure to 2 or more drugs with the potential to prolong the QTc interval (P ‫؍‬ 0.17), and female sex (P ‫؍‬ 0.21) trended toward significance. Combination therapy with fluoroquinolone and azole antifungals is associated with increased QTc from baseline in hospitalized patients with hematologic malignancies. One in five patients had a clinically significant change in the QTc, warranting close monitoring and risk factor modification to prevent the possibility of further QTc prolongation and risk of TdP. C ombination fluoroquinolone-azole prophylaxis and therapy is common in the hematology patient population. Prophylaxis with these agents has been shown to decrease both bacterial and fungal infections (1-5), and recommendations for use are incorporated as part of the Infectious Diseases Society of America's clinical practice guidelines on the use of antimicrobial agents in neutropenic patients with cancer (6) and the National Comprehensive Cancer Network's guidelines on prevention and treatment of cancer-related infections (7). However, both classes of agents have the potential to prolong the QTc interval and increase the risk for torsades de pointes (TdP) (8-10), with episodes of TdP reported with both azoles and fluoroquinolones (11)(12)(13)(14)(15)(16)(17)(18)(19).The risk of QTc prolongation and TdP in hematology patients on a combination of fluoroquinolone and azole therapy has not been well defined. While it is known that both classes of agents have been associated with QTc prolongation and torsades de pointes, it is not well understood to what degree the combination can increase the QTc interval within this population or whether the combination poses an increased risk of TdP.The measured QT interval from an el...

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Fluconazole-Induced Torsade de Pointes

Abstract: Clinicians should be aware that fluconazole, even at low doses, may cause prolongation of the QT interval, leading to TDP. Serial electrocardiographic monitoring may be considered when fluconazole is administered in patients who are at risk for ventricular arrhythmias.

Cited by 50 publications

References 12 publications

Torsades de pointes upon fluconazole administration in a patient with acute myeloblastic leukemia

Torsades de pointes upon fluconazole administration in a patient with acute myeloblastic leukemia

Sudden Cardiac Arrest Triggered by Coadministration of Fluconazole and Amiodarone

Effect of Combined Fluoroquinolone and Azole Use on QT Prolongation in Hematology Patients

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