Torsades de Pointes Induced by Erythromycin

Gitler, Bernard; Berger, L.; Buffa, Salvatore D.

doi:10.1378/chest.105.2.368

Cited by 60 publications

(21 citation statements)

References 32 publications

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“…Of the 29 cases examined here (Table 1), QTc interval data are available for 26: of these, only one case had a QTc interval of <500 ms and 16 cases had QTc intervals of 600 ms or greater. This is in broad agreement with an earlier review of eight cases of TdP with erythromycin found patients had QTc intervals between $560 ms and 700 ms [Gitler et al 1994]. The lack of a clear correlation between erythromycin dose and QTc interval in our analysis is suggestive that, in the setting of patients experiencing erythromycin-induced arrhythmia, drug dose alone is not strongly predictive of outcome.…”

Section: Discussionsupporting

confidence: 91%

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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Section: Discussionsupporting

confidence: 91%

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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“…This is not surprising, as structurally similar macrolides have also been shown to cause QT interval prolongation [5]. The mechanism by which clarithromycin induces QT prolongation is thought to be through the inhibition of the rapidly activating delayed rectifier potassium current (I Kr ) in cardiac myocytes [6].…”

Section: Abstract: Acquired Long Qt Syndrome • Clarithromycin • Torsamentioning

confidence: 99%

Torsades de pointesfollowing clarithromycin treatment

Gysel

Vieweg

Hasnain

et al. 2013

Expert Review of Cardiovascular Therapy

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A 75-year-old woman presenting with pre-syncope, shortness of breath and nausea was admitted to the emergency department following treatment with clarithromycin. Shortly after admission she developed a prolonged QT interval leading to torsades de pointes (TdP) and cardiac arrest. She was successfully cardioverted and clarithromycin was discontinued resulting in restoration of her usual QT interval. This case is an example of acquired long QT syndrome; a disorder that can be precipitated by macrolide antibiotics such as clarithromycin. Additional risk factors present in this case include: female gender, old age, heart disease, hypokalemia and hypomagnesemia. In this manuscript we comprehensively review past cases of clarithromycin-induced long QT syndrome (LQTS) and discuss them within the context of this case.

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“…In fact, EM itself is known to induce QT prolongation or TdP. [6][7][8] Lin et al 9 reported a case of TdP associated with QT prolongation induced by the concomitant use of quinidine and EM without an increase of plasma quinidine concentrations; they concluded that the adverse reaction caused by quinidine and EM coadministration might be based on their pharmacodynamic interaction. However, the significance of the pharmacodynamic interaction between DP and EM remains to be evaluated quantitatively.…”

Section: Introductionmentioning

confidence: 99%

Pharmacodynamic analysis of the electrocardiographic interaction between disopyramide and erythromycin in rats

Hanada

Ohtani

Kotaki

et al. 1999

Journal of Pharmaceutical Sciences

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Disopyramide (DP) is known to induce QT prolongation and Torsades de Pointes (TdP) when administered concomitantly with erythromycin (EM). To define and evaluate quantitatively the arrhythmogenic risk of the concomitant administration of DP and EM, we investigated the influence of EM on the pharmacokinetics and pharmacodynamics of DP in rats. The time profiles of change in QT interval and plasma concentration of each drug were evaluated during and after constant intravenous infusion of DP (6.0 or 15.0 mg/kg/h), EM (4.0 or 8.0 mg/kg/h), and coadministration of DP and EM (DP 6.0 mg/kg/h plus EM 4.0 mg/kg/h). Each agent induced QT prolongation at plasma concentrations within the therapeutic range in humans. DP-induced QT prolongation was proportional to its plasma concentration. In the case of EM, the Emax model with an "effect compartment" could explain the relationship between plasma EM concentrations and changes in QT interval. Although coadministration of EM with DP gave enhanced QT prolongation compared to dosing with DP alone, EM did not affect the pharmacokinetics of DP. In conclusion, it was shown that a pharmacodynamic interaction contributes to the electrocardiographic adverse reaction (i.e., QT prolongation) induced by coadministration of DP and EM in rats.

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Torsades de Pointes Induced by Erythromycin

Cited by 60 publications

References 32 publications

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

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

Torsades de pointesfollowing clarithromycin treatment

Pharmacodynamic analysis of the electrocardiographic interaction between disopyramide and erythromycin in rats

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