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

Therapeutic Advances in Infectious Disease

Volumn 2, Issue 2, 2014, Pages 47-59

  Hancox, Jules C ^a   Hasnain, Mehrul ^a   Vieweg, W Victor R ^a   Gysel, Michael ^b   Baranchuk, Adrian ^b   Methot, Michelle ^b  

^a MEMORIAL UNIVERSITY OF NEWFOUNDLAND   (Canada)

^b QUEEN S UNIVERSITY   (Canada)

Author keywords

drug induced QTc interval prolongation; erythromycin; risk factors; torsade de pointes

Indexed keywords

EID: 84993811153     PISSN: 20499361     EISSN: 2049937X     Source Type: Journal    
DOI: 10.1177/2049936114527744     Document Type: Article

References (70)

1. Abi-Gerges N. Philp K. Pollard C. Wakefield I. Hammond T. Valentin J. (2004) Sex differences in ventricular repolarization: from cardiac electrophysiology to Torsades de Pointes. Fund Clin Pharmacol 18: 139–141.
2. Abo-Salem E. Fowler J. Attari M. Cox C. Perez-Verdia A. Panikkath R. et al (2014) Antibiotic-induced cardiac arrhythmias. Cardiovasc Therapeut 32: 19–25.
3. Ando F. Kuruma A. Kawano S. (2011) Synergic effects of beta-estradiol and erythromycin on hERG currents. J Membr Biol 241: 31–38.
4. Bednar M. Harrigan E. Anziano R. Camm A. Ruskin J. (2001) The QT interval. Prog Cardiovasc Dis 43: 1–45.
5. Bednar M. Harrigan E. Ruskin J. (2002) Torsades de pointes associated with nonantiarrhythmic drugs and observations on gender and QTc. Am J Cardiol 89: 1316–1319.
6. Biglin K. Faraon M. Constance T. Lieh-Lai M. (1994) Drug-induced torsades de pointes: a possible interaction of terfenadine and erythromycin. Ann Pharmacother 28: 282.
7. Brandriss M. Richardson W. Barold S. (1994) Erythromycin-induced QT prolongation and polymorphic ventricular tachycardia (torsades de pointes): case report and review. Clin Infect Dis 18: 995–998.
8. Chennareddy S. Siddique M. Karim M. Kudesia V. (1996) Erythromycin-induced polymorphous ventricular tachycardia with normal QT interval. Am Heart J 132: 691–694.
9. Duncan R. Ridley J. Dempsey C. Leishman D. Leaney J. Hancox J. et al (2006) Erythromycin block of the HERG K+ channel: accessibility to F 656 and Y652. Biochem Biophys Res Comm 341: 500–506.
10. Freedman R. Anderson K. Green L. Mason J. (1987) Effect of erythromycin on ventricular arrhythmias and ventricular repolarization in idiopathic long QT syndrome. Am J Cardiol 59: 168–169.
11. Gintant G. (2008) Preclinical Torsades-de-Pointes screens: advantages and limitations of surrogate and direct approaches in evaluating proarrhythmic risk. Pharmacol Ther 119: 199–209.
12. Gitler B. Berger L. Buffa S. (1994) Torsades de pointes induced by erythromycin. Chest 105: 368–372.
13. Giudicessi J. Ackerman M. (2013) Azithromycin and risk of sudden cardiac death: guilty as charged or falsely accused? Cleveland Clin J Med 80: 539–544.
14. Goldschmidt N. zaz-Livshits T. Gotsman Nir-Paz R. Ben-Yehuda A. Muszkat M. (2001) Compound cardiac toxicity of oral erythromycin and verapamil. Ann Pharmacother 35: 1396–1399.
15. Guelon D. Bedock B. Chartier C. Haberer J. (1986) QT prolongation and recurrent “torsades de pointes” during erythromycin lactobionate infusion. Am J Cardiol 58: 666.
16. Guo J. Zhan S. Lees-Miller J. Teng G. Duff H. (2005) Exaggerated block of hERG (KCNH2) and prolongation of action potential duration by erythromycin at temperatures between 37℃ and 42℃. Heart Rhythm 2: 860–866.
17. Gysel M. Vieweg W. Hasnain M. Hancox J. Kunanithy V. Baranchuk A. (2013) Torsades de pointes following clarithromycin treatment. Expert Rev Cardiovasc Ther 11: 1485–1493.
18. Haefeli W. Schoenenberger R. Weiss P. Ritz R. (1992) Possible risk for cardiac arrhythmia related to intravenous erythromycin. Intensive Care Med 18: 469–473.
19. Hancox J. Hasnain M. Vieweg W. Breden-Crouse E. Baranchuk A. (2013) Azithromycin, cardiovascular risks, QTc interval prolongation, torsade de pointes, and regulatory issues: a narrative review based on the study of case reports. Ther Adv Infect Dis 1: 155–165.
20. Hancox J. McPate M. El Harchi A. Zhang Y. (2008) The hERG potassium channel and hERG screening for drug-induced torsades de pointes. Pharmacol Therapeut 119: 118–132.
21. Hinterseer M. Irlbeck M. Ney L. Beckmann B. Pfeufer A. Steinbeck G. et al (2006) Acute respiratory distress syndrome with transiently impaired left ventricular function and Torsades de Pointes arrhythmia unmasking congenital long QT syndrome in a 25-yr-old woman. Br J Anaesth 97: 150–153.
22. Howard P. (2013) Azithromycin-induced proarrhythmia and cardiovascular death. Ann Pharmacother 47: 1547–1551.
23. Hsieh M. Chen S. Chiang C. Tai C. Lee S. Wen Z. et al (1996) Drug-induced torsades de pointes in one patient with congenital long QT syndrome. Int J Cardiol 54: 85–88.
24. Indik J. Pearson E. Fried K. Woosley R. (2006) Bazett and Fridericia QT correction formulas interfere with measurement of drug-induced changes in QT interval. Heart Rhythm 3: 1003–1007.
25. James A. Choisy S. Hancox J. (2007) Recent advances in understanding sex differences in cardiac repolarization. Prog Biophys Mol Biol 94: 265–319.
26. Justo D. Zeltser D. (2006) Torsades de pointes induced by antibiotics. Eur J Int Med 17: 254–259.
27. Kannankeril P. Roden D. (2007) Drug-induced long QT and torsade de pointes: recent advances. Curr Opin Cardiol 22: 39–43.
28. Katapadi K. Kostandy G. Katapadi M. Hussain K. Schifter D. (1997) A review of erythromycin-induced malignant tachyarrhythmia - torsade de pointes. A case report. Angiology 48: 821–826.
29. Keating M. Sanguinetti M. (2001) Molecular and cellular mechanisms of cardiac arrhythmias. Cell 104: 569–580.
30. Kirsch G. Trepakova E. Brimecombe J. Sidach S. Erickson H. Kochan M. et al (2004) Variability in the measurement of hERG potassium channel inhibition: effects of temperature and stimulus pattern. J Pharmacol Toxicol Methods 50: 93–101.
31. Kogut C. Breden-Crouse E. Vieweg W. Hasnain M. Baranchuk A. Digby G. et al (2013) Selective serotonin reuptake inhibitors and torsades de pointes. New concepts and new directions derived from systematic review of case reports. Ther Adv Drug Safety 4: 189–198.
32. Koh T. (2001) Risk of torsades de pointes from oral erythromycin with concomitant carbimazole (methimazole) administration. Pacing Clin Electrophysiol 24: 1575–1576.
33. Kuryshev Y. Ficker E. Wang L. Hawryluk P. Dennis A. Wible B. et al (2005) Pentamidine-induced long QT syndrome and block of hERG trafficking. J Pharmacol Exp Ther 312: 316–323.
34. Kyrmizakis D. Chimona T. Kanoupakis E. Papadakis C. Velegrakis G. Helidonis E. (2002) QT prolongation and torsades de pointes associated with concurrent use of cisapride and erythromycin. Am J Otolaryngol 23: 303–307.
35. Lin J. Quasny H. (1997) QT prolongation and development of torsades de pointes with the concomitant administration of oral erythromycin base and quinidine. Pharmacotherapy 17: 626–630.
36. Lindsay J. Jr. Smith M. Light J. (1990) Torsades de pointes associated with antimicrobial therapy for pneumonia. Chest 98: 222–223.
37. Lu H. Vlaminckx E. van de Water A. Rohrbacher J. Hermans A. Gallacher D. (2007) In-vitro experimental models for the risk assessment of antibiotic-induced QT prolongation. Eur J Pharmacol 577: 222–232.
38. McComb J. Campbell N. Cleland J. (1984) Recurrent ventricular tachycardia associated with QT prolongation after mitral valve replacement and its association with intravenous administration of erythromycin. Am J Cardiol 54: 922–923.
39. Naranjo C. Busto U. Sellers E. Sandor P. Ruiz I. Robertes E. et al (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30: 239–245.
40. Nattel S. Ranger S. Talajic M. Lemery R. Roy D. (1990) Erythromycin-induced long QT syndrome: concordance with quinidine and underlying cellular electrophysiologic mechanism. Am J Med 89: 235–238.
41. Oberg K. Bauman J. (1995) QT interval prolongation and torsades de pointes due to erythromycin lactobionate. Pharmacotherapy 15: 687–692.
42. Orban Z. MacDonald L. Peters M. Guslits B. (1995) Erythromycin-induced cardiac toxicity. Am J Cardiol 75: 859–861.
43. Owens R. Jr. (2004) QT prolongation with antimicrobial agents – understanding the significance. Drugs 64: 1091–1124.
44. Paris D. Parente T. Bruschetta H. Guzman E. Niarchos A. (1994) Torsades de pointes induced by erythromycin and terfenadine. Am J Emerg Med 12: 636–638.
45. Pickham D. Helfenbein E. Shinn J. Chan G. Funk M. Weinacker A. et al (2012) High prevalence of corrected QT interval prolongation in acutely ill patients is associated with mortality: results of the QT in Practice (QTIP) study. Crit Care Med 40: 394–399.
46. Ragosta M. Weihl A. Rosenfeld L. (1989) Potentially fatal interaction between erythromycin and disopyramide. Am J Med 86: 465–466.
47. Raschi E. Poluzzi E. Koci A. Moretti U. Sturkenboom M. de Ponti F. (2013) Macrolides and Torsadogenic risk: emerging issues from the FDA pharmacovigilance database. J Pharmacovigilance 1: 104.
48. Ray W. Murray K. Hall K. Arbogast P. Stein C. (2012) Azithromycin and the risk of cardiovascular death. N Eng J Med 366: 1881–1890.
49. Ray W. Murray K. Meredith S. Narasimhulu S. Hall K. Stein C. (2004) Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med 351: 1089–1096.
50. Rezkalla M. Pochop C. (1994) Erythromycin induced Torsades de Pointes: case report and review of the literature. S D J Med 47: 161–164.
51. Schoenenberger R. Haefeli W. Weiss P. Ritz R. (1990) Association of intravenous erythromycin and potentially fatal ventricular tachycardia with Q-T prolongation (torsades de pointes). BMJ 300: 1375–1376.
52. Selvaraj et al. (2013).
53. Shaffer D. Singer S. Korvick J. Honig P. (2002) Concomitant risk factors in reports of torsades de pointes associated with macrolide use: review of the United States Food and Drug Administration Adverse Event Reporting System. Clin Infect Dis 35: 197–200.
54. Stanat S. Carlton C. Crumb W. Jr. Agrawal K. Clarkson C. (2003) Characterization of the inhibitory effects of erythromycin and clarithromycin on the HERG potassium channel. Mol Cell Biochem 254: 1–7.
55. Suefke S. Djonlagic H. Kibbel T. (2012) Severe bacterial infection: increased mortality in elderly women with low body weight taking drugs prolonging the QTc interval. Med Klin Intensivmed Notfmed 107: 275–284.
56. Svanström H. Pasternak B. Hviid A. (2013) Use of azithromycin and death from cardiovascular causes. N Eng J Med 368: 1704–1712.
57. Tschida S. Guay D. Straka R. Hoey L. Johanning R. Vance-Bryan K. (1996) QTc-interval prolongation associated with slow intravenous erythromycin lactobionate infusions in critically ill patients: a prospective evaluation and review of the literature. Pharmacotherapy 16: 663–674.
58. Vandenberg J. Walker B. Campbell T. (2001) HERG K+ channels: friend and foe. TIPS 22: 240–246.
59. Vieweg W. Hancox J. Hasnain M. Koneru J. Gysel M. Baranchuk A. (2013 a) Clarithromycin, QTc interval prolongation and torsades de pointes: the need to study case reports. Ther Adv Infect Dis 1: 121–138.
60. Vieweg W. Hasnain M. Howland R. Clausen T. Koneru J. Kogut C. et al (2013 b) Methadone, QTc interval prolongation and torsade de pointes: Case reports offer the best understanding of this problem. Ther Adv Psychopharmacol 3: 219–232.
61. Vieweg W. Hasnain M. Howland R. Hettema J. Kogut C. Wood M. et al (2012) Citalopram, QTc interval prolongation, and Torsade de Pointes. How should we apply the recent FDA ruling? Am J Med 125: 859–868.
62. Vogt A. Zollo R. (1997) Long Q-T syndrome associated with oral erythromycin used in preoperative bowel preparation. Anesth Analg 85: 1011–1013.
63. Volberg W. Koci B. Su W. Lin J. Zhou J. (2002) Blockade of human cardiac potassium channel human ether-a-go-go-related gene (HERG) by macrolide antibiotics. J Pharmacol Exp Ther 302: 320–327.
64. Wisialowski T. Crimin K. Engtrakul J. O'Donnell J. Fermini B. Fossa A. (2006) Differentiation of arrhythmia risk of the antibacterials moxifloxacin, erythromycin, and telithromycin based on analysis of monophasic action potential duration alternans and cardiac instability. J Pharmacol Exp Ther 318: 352–359.
65. Wong C. Windle J. (1995) Erythromycin induced torsades de pointes. Nebr Med J 80: 285–286.
66. Yap Y. Camm A. (2003) Drug induced QT prolongation and torsades de pointes. HEART 89: 1363–1372.
67. Zeltser D. Justo D. Halkin A. Prokhorov V. Heller K. Viskin S. (2003) Torsade de pointes due to noncardiac drugs: most patients have easily identifiable risk factors. Medicine (Baltimore) 82: 282–290.
68. Zhanel G. Dueck M. Hoban D. Vercaigne L. Embil J. Gin A. et al (2001) Review of macrolides and ketolides: focus on respiratory tract infections. Drugs 61: 443–498.
69. Zhou Z. Vorperian V. Gong Q. Zhang S. January C. (1999) Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole. J Cardiovasc Electrophysiol 10: 836–843.
70. Zuckerman J. (2004) Macrolides and ketolides: azithromycin, clarithromycin, telithromycin. Infect Dis Clin North Am 18: 621–649, xi.