Torsades de pointes induced by erythromycin and terfenadine

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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“…Terfenadine (with erythromycin [122,123], with troleandomycin [124]), astemizole (with erythromycin [125]), loratidine Antipsychotics…”

Section: Antiarrhythmicsmentioning

confidence: 99%

Proarrhythmic Potential of Antimicrobial Agents

et al. 2008

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“…As a result, erythromycin has a potential for increasing serum concentrations of drugs metabolized via this system. The interaction of erythromycin and terfenadine is well documented to cause QTc interval prolongation by both increased serum terfenadine concentrations by CYP450 enzyme inhibition of erythromycin and by erythromycin itself [Paris et al 1994;Biglin et al 1994]. The half-life of erythromycin is 23 hours.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Erythromycin, QTc interval prolongation, and torsade de pointes: Case reports, major risk factors and illness severity

Hancox¹,

Hasnain

Vieweg

et al. 2014

Therapeutic Advances in Infection

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Abstract:Objectives: Erythromycin is a macrolide antibiotic that is widely used for various infections of the upper respiratory tract, skin, and soft tissue. Similar to other macrolides (clarithromycin, azithromycin), erythromycin has been linked to QTc interval prolongation and torsade de pointes (TdP) arrhythmia. We sought to identify factors that link to erythromycin-induced/ associated QTc interval prolongation and TdP. Methods and Results: In a critical evaluation of case reports, we found 29 cases: 22 women and 7 men (age range 1895 years). With both oral and intravenous erythromycin administration, there was no significant relationship between dose and QTc interval duration in these cases. Notably, all patients had severe illness. Other risk factors included female sex, older age, presence of heart disease, concomitant administration of either other QTc prolonging drugs or agents that were substrates for or inhibitors of CYP3A4. Most patients had at least two risk factors. Conclusions: On the basis of case report evaluation, we believe that major risk factors for erythromycin-associated TdP are female sex, heart disease and old age, particularly against a background of severe illness. Coadministration of erythromycin with other drugs that inhibit or are metabolized by CYP3A4 or with QTc prolonging drugs should be avoided in this setting.

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“…The basis of concern surrounding drug-induced QT interval prolongation arises from recent experience suggesting a link between this characteristic and cardiac arrhythmias (21,38,45,48,52) including torsade de pointe that may progress to a fatal ventricular fibrillation. A cursory examination of the compounds associated with these properties reveal a highly diverse chemical structure set and seemingly nonrelated pharmacological targets.…”

Section: Introductionmentioning

confidence: 99%

The Dog's Role in the Preclinical Assessment of QT Interval Prolongation

Gralinski¹

2003

Toxicol Pathol

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During the development of a new therapeutic, few pharmacodyamic outcomes currently receive as much scrutiny as the effect of a potential medication on the electrocardiographic QT interval. The recent withdrawal from marketing of several drugs due to potential drug-related cardiac arrhythmias have greatly increased concern about drug-related changes on the QT interval. In order to reduce the incidence of these idiosyncratic episodes, regulatory agencies have suggested that sponsors use more rigorous methodology during the safety evaluation of new pharmaceuticals. Along with enhanced electrocardiographic assessments during clinical trials, advanced preclinical examinations of effect on QT interval and ventricular repolarization have become de rigueur. In this arena, the beagle dog is the preclinical species often associated with the most reliable predictivity for human safety assessment. To this end, canine models of cardiovascular safety assessment are discussed along with the relevance of these assays to human electrocardiography.

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Torsades de pointes induced by erythromycin and terfenadine

Cited by 51 publications

References 25 publications

Proarrhythmic Potential of Antimicrobial Agents

Proarrhythmic Potential of Antimicrobial Agents

Erythromycin, QTc interval prolongation, and torsade de pointes: Case reports, major risk factors and illness severity

The Dog's Role in the Preclinical Assessment of QT Interval Prolongation

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