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Can Pharm J (Ott). 2016 May;149(3):139-52. doi: 10.1177/1715163516641136. Epub 2016 Apr 08.

Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management.

Canadian pharmacists journal : CPJ = Revue des pharmaciens du Canada : RPC

James E Tisdale

Affiliations

  1. College of Pharmacy, Purdue University, and the School of Medicine, Indiana University, Indianapolis, Indiana, USA.

PMID: 27212965 PMCID: PMC4860751 DOI: 10.1177/1715163516641136

Abstract

Torsades de pointes (TdP) is a life-threatening arrhythmia associated with prolongation of the corrected QT (QTc) interval on the electrocardiogram. More than 100 drugs available in Canada, including widely used antibiotics, antidepressants, cardiovascular drugs and many others, may cause QTc interval prolongation and TdP. Risk factors for TdP include QTc interval >500 ms, increase in QTc interval ≥60 ms from the pretreatment value, advanced age, female sex, acute myocardial infarction, heart failure with reduced ejection fraction, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, treatment with diuretics and elevated plasma concentrations of QTc interval-prolonging drugs due to drug interactions, inadequate dose adjustment of renally eliminated drugs in patients with kidney disease and rapid intravenous administration. Pharmacokinetic drug interactions associated with the highest risk of TdP include antifungal agents, macrolide antibiotics (except azithromycin) and drugs to treat human immunodeficiency virus interacting with amiodarone, disopyramide, dofetilide or pimozide. Other important pharmacokinetic interactions include antidepressants (bupropion, duloxetine, fluoxetine, paroxetine) interacting with flecainide, quinidine or thioridazine. Pharmacists play an important role in minimizing the risk of drug-induced QTc interval prolongation and TdP through knowledge of drugs that are associated with a known or possible risk of TdP, individualized assessment of risk of drug-induced QTc interval prolongation, awareness of drug interactions most likely to result in TdP and attention to dose reduction of renally eliminated QTc interval-prolonging drugs in patients with kidney disease. Treatment of hemodynamically stable TdP consists of discontinuation of the offending drug(s), correction of electrolyte abnormalities and administration of intravenous magnesium sulfate 1 to 2 g.

References

  1. Circulation. 1988 Feb;77(2):392-7 - PubMed
  2. Ann Noninvasive Electrocardiol. 2004 Oct;9(4):366-74 - PubMed
  3. CMAJ. 2005 Mar 15;172(6):765-7 - PubMed
  4. Arch Mal Coeur Vaiss. 1966 Feb;59(2):263-72 - PubMed
  5. Circulation. 2002 Apr 23;105(16):1943-8 - PubMed
  6. Am Heart J. 1991 Feb;121(2 Pt 1):601-2 - PubMed
  7. Circulation. 2015 Nov 3;132(18 Suppl 2):S444-64 - PubMed
  8. J Electrocardiol. 2010 Nov-Dec;43(6):572-6 - PubMed
  9. Circulation. 2010 Mar 2;121(8):1047-60 - PubMed
  10. Crit Care Med. 2012 Feb;40(2):394-9 - PubMed
  11. Medicine (Baltimore). 2003 Jul;82(4):282-90 - PubMed
  12. Circulation. 2010 Nov 2;122(18 Suppl 3):S729-67 - PubMed
  13. Am J Med. 2003 Feb 1;114(2):135-41 - PubMed
  14. J Am Coll Cardiol. 2006 Aug 1;48(3):471-7 - PubMed
  15. Circulation. 2000 Nov 7;102(19):2385-90 - PubMed
  16. Curr Probl Cardiol. 2008 Nov;33(11):629-94 - PubMed
  17. J Am Coll Cardiol. 2004 Apr 7;43(7):1211-6 - PubMed
  18. Ann Epidemiol. 2003 Aug;13(7):530-6 - PubMed
  19. Am J Epidemiol. 2011 Aug 15;174(4):403-11 - PubMed
  20. Circulation. 2015 Jan 27;131(4):e29-322 - PubMed
  21. Circulation. 1991 Sep;84(3):1136-44 - PubMed
  22. Curr Med Res Opin. 2013 Dec;29(12):1719-26 - PubMed
  23. Clin Infect Dis. 2002 Jul 15;35(2):197-200 - PubMed
  24. N Engl J Med. 1999 Sep 16;341(12 ):857-65 - PubMed
  25. Am J Cardiol. 2009 Mar 15;103(6):887-90 - PubMed
  26. Drug Saf. 2012 Jun 1;35(6):459-70 - PubMed
  27. J Am Coll Cardiol. 1996 Jul;28(1):130-6 - PubMed
  28. Ann Intern Med. 2009 Mar 17;150(6):387-95 - PubMed
  29. Am J Cardiol. 1998 Jan 15;81(2):238-40 - PubMed
  30. Circulation. 1996 Oct 1;94(7):1613-21 - PubMed
  31. Circ Cardiovasc Qual Outcomes. 2014 May;7(3):381-90 - PubMed
  32. Circ Cardiovasc Qual Outcomes. 2013 Jul;6(4):479-87 - PubMed
  33. Perit Dial Int. 1997 Mar-Apr;17(2):207-8 - PubMed

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