2014
DOI: 10.1007/s12012-014-9274-y
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Torsades de Pointes Induced by the Concomitant Use of Ivabradine and Azithromycin: An Unexpected Dangerous Interaction

Abstract: A 68-year-old man had a cardiac syncope. He was known to have a long QT-interval and was treated with ivabradine for paroxysmal sinusal tachycardia. In the last 5 days, azithromycin had been prescribed for sinusitis. An electrocardiogram showed torsades de pointes (TdP). Azithromycin is known to prolong the QT-interval. Ivabradine does not affect the QT-interval but has a conditional risk of TdP when taken with other drugs that block its metabolic breakdown. This case presents the specific problem of a patient… Show more

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Cited by 40 publications
(25 citation statements)
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“…We also observed changes to refractory period and steepening of the left ventricular basal action potential restitution curve with the drug [2], effects that are associated with increased risk of ventricular fibrillation. Ivabradine has been thought to have a good cardiac safety profile [3], but within the last year the drug has been added to the "CredibleMeds" database of drugs associated with QT prolongation and Torsades de Pointes (TdP) as carrying a conditional risk of TdP [4], and case reports of TdP in patients receiving ivabradine together with other medications have begun to appear [5,6]. The characterization of hERG interactions of the drug is therefore timely.…”
mentioning
confidence: 99%
“…We also observed changes to refractory period and steepening of the left ventricular basal action potential restitution curve with the drug [2], effects that are associated with increased risk of ventricular fibrillation. Ivabradine has been thought to have a good cardiac safety profile [3], but within the last year the drug has been added to the "CredibleMeds" database of drugs associated with QT prolongation and Torsades de Pointes (TdP) as carrying a conditional risk of TdP [4], and case reports of TdP in patients receiving ivabradine together with other medications have begun to appear [5,6]. The characterization of hERG interactions of the drug is therefore timely.…”
mentioning
confidence: 99%
“…The cumulative effects of QTc prolongation and bradycardia could result in torsades de pointes (TdP) arrhythmia [4]. TdP has been reported at least 24 times to the European Medicines Agency and in two cases in the literature [4,8,9]. The first case report was complicated by coingestion of diltiazem and ranolazine [8].…”
Section: Discussionmentioning
confidence: 99%
“…Both of these are metabolized by CYP3A4, and diltiazem also inhibits CYP3A4 [8]. The second case was complicated by the patient's baseline prolonged QTc as shown on EKG prior to ivabradine administration, and by coingestion of azithromycin [9]. Neither case involved supratherapeutic dosing of ivabradine.…”
Section: Discussionmentioning
confidence: 99%
“…29 Despite this evidence, the results of the corresponding clinical trials have been unequivocally negative, irrespective of whether the calcium antagonists were administered before, during or after ischemia. 30, 31 Another possibility of reducing calcium overload is to inhibit the sodium-hydrogen exchange. Again, the literature reports promising experimental results when the inhibitors were used during ischemia, 32 but failure when provided during PCI.…”
Section: Calcium Paradoxmentioning
confidence: 99%