Prolonged QT interval and torsades de pointes caused by the combination of fluconazole and amitriptyline

Dorsey, Steven; Biblo, Lee A.

doi:10.1016/s0735-6757(00)90027-5

Cited by 62 publications

(34 citation statements)

References 5 publications

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“…The same combination caused TdP in a patient suffering from cryptococcal pneumonia [38]. The coadministration of astemizole and ketoconazole caused TdP in a 63-yearold woman [39].…”

Section: Antifungalsmentioning

confidence: 99%

Proarrhythmic Potential of Antimicrobial Agents

et al. 2008

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Several antiarrhythmic and non-cardiovascular drug therapies including antimicrobial agents have been implicated as the causes for QT interval prolongation, torsades de pointes (TdP) ventricular tachycardia and sudden cardiac death. Most of the drugs that have been associated with the lengthening of the QT interval or development of TdP can also block the rapidly activating component of the delayed rectifier potassium current (IKr) in the ventricular cardiomyocytes. This article presents a review of the current literature on the QT interval prolonging effect of antimicrobials based on the results of the in vitro, in vivo studies and case reports. Our observations were derived from currently available Medline database. As we found, the most frequently QT interval prolonging antimicrobials are erythromycin, clarithromycin, fluoroquinolones, halofantrine, and pentamidine. Almost every antimicrobial-associated QT interval prolongation occurs in patients with multiple risk factors of the following: drug interactions, female gender, advanced age, structural heart disease, genetic predisposition, and electrolyte abnormalities. In conclusion, physicians should avoid prescribing antimicrobials having QT prolonging potential for patients with multiple risk factors. Recognition and appropriate treatment of TdP are also indispensable.

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“…The same combination caused TdP in a patient suffering from cryptococcal pneumonia [38]. The coadministration of astemizole and ketoconazole caused TdP in a 63-yearold woman [39].…”

Section: Antifungalsmentioning

confidence: 99%

Proarrhythmic Potential of Antimicrobial Agents

et al. 2008

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“…Azole antifungals (e.g. fluconazole, ketoconazole) are associated with the acquired long QT syndrome and ventricular arrhythmias (Moss, 1999;Tonini et al, 1999;Wassmann et al, 1999;Dorsey & Biblo, 2000;Tamargo, 2000). Since azole antifungals inhibit multiple cytochrome P450 enzymes in the liver and gastrointestinal tract, the mechanism of arrhythmogenesis is considered to be a rise in the plasma concentration of QT-interval prolonging drugs (e.g., class III antiarrhythmic drugs, some H 1 -receptor antagonists and antibiotics) that use the same metabolic pathway (Albengres et al, 1998;Venkatakrishnan et al, 2000;Roden, 2001).…”

Section: Introductionmentioning

confidence: 99%

Blockade of HERG cardiac K⁺ current by antifungal drug miconazole

Kikuchi

Nagatomo

Abe

et al. 2005

British J Pharmacology

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1 Miconazole, an imidazole antifungal agent, is associated with acquired long QT syndrome and ventricular arrhythmias. Miconazole increases the plasma concentration of QT-prolonging drugs by inhibiting the hepatic cytochrome P450 metabolic pathway, but whether it has direct effects on cardiac ion channels has not been elucidated. 2 To determine the mechanism underlying these clinical findings, we investigated the effect of miconazole on human ether-a-go-go-related gene (HERG) K þ channels. 3 HERG channels were heterologously expressed in human embryonic kidney 293 (HEK293) cells and whole-cell currents were recorded using a patch-clamp technique (231C). 4 Miconazole inhibited HERG peak tail current in a concentration-dependent manner (0.4-40 mM) with an IC 50 of 2.1 mM (n ¼ 3-5 cells at each concentration, Hill coefficient 1.2). HERG block was not frequency-dependent. It required channel activation, occurred rapidly, and had very slow dissociation properties. 5 The activation curve was shifted in a negative direction (V 1/2 : À9.572.3 mV in controls and À15.372.4 mV after 4 mM miconazole, Po0.05, n ¼ 6). Miconazole did not change other channel kinetics (activation, deactivation, onset of inactivation, recovery from inactivation, steady-state inactivation). 6 The S6 domain mutation, F656C, abolished the inhibitory action of miconazole on HERG current indicating that miconazole preferentially binds to an aromatic amino-acid residue within the pore-S6 region. 7 Our findings indicate that miconazole causes HERG channel block by binding to a common drug receptor, and this involves preferential binding to activated channels. Thus, miconazole prolongs the QT interval by direct inhibition of HERG channels.

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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%

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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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Prolonged QT interval and torsades de pointes caused by the combination of fluconazole and amitriptyline

Cited by 62 publications

References 5 publications

Proarrhythmic Potential of Antimicrobial Agents

Proarrhythmic Potential of Antimicrobial Agents

Blockade of HERG cardiac K⁺ current by antifungal drug miconazole

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

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Prolonged QT interval and torsades de pointes caused by the combination of fluconazole and amitriptyline

Cited by 62 publications

References 5 publications

Proarrhythmic Potential of Antimicrobial Agents

Proarrhythmic Potential of Antimicrobial Agents

Blockade of HERG cardiac K+ current by antifungal drug miconazole

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

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Blockade of HERG cardiac K⁺ current by antifungal drug miconazole