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Risk management of QTc-prolongation in patients receiving haloperidol: an epidemiological study in a University hospital in Belgium

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Abstract

Background Many drugs, including haloperidol, are linked with a risk of QTc-prolongation, which can lead to Torsade de Pointes and sudden cardiac death. Objective To investigate the prevalence of concomitant risk factors for QTc-prolongation in patients treated with haloperidol, and the use of safety measures to minimize this risk. Setting: University Hospitals of Leuven, Belgium. Methods A retrospective epidemiological study was performed. On 15 consecutive Mondays, all patients with a prescription for haloperidol were included. A risk score for QTc-prolongation, inspired by the pro-QTc score of Haugaa et al., was calculated based on gender, comorbidities, lab results and concomitant QTc-prolonging drugs (each factor counting for one point). Available electrocardiograms before and during the treatment of haloperidol were registered. Main outcome measure: Management of the risk of QTc-prolongation. Results Two hundred twenty-two patients were included (59.0 % men, median age 77 years) of whom 26.6 % had a risk score of ≥4 (known to significantly increase the mortality). Overall, 24.3 % received haloperidol in combination with other drugs with a known risk of Torsade de Pointes. Half of the patients had an electrocardiogram in the week before the start of haloperidol; only in one-third a follow-up electrocardiogram during haloperidol treatment was performed. Of the patients with a moderately (n = 41) or severely (n = 14) prolonged QTc-interval before haloperidol, 48.8 % and 42.9 % respectively had a follow-up electrocardiogram. In patients with a risk score ≥4, significantly more electrocardiograms were taken before starting haloperidol (p = 0.020). Conclusions Although many patients had risk factors for QTc-prolongation (including the use of other QTc-prolonging drugs) or had a prolonged QTc on a baseline electrocardiogram, follow-up safety measures were limited. Persistent efforts should be taken to develop decision support systems to manage this risk.

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References

  1. Sultana J, Cutroneo P, Trifiro G. Clinical and economic burden of adverse drug reactions. J Pharmacol Pharmacother. 2013;4:S73–7.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Davies EC, Green CF, Taylor S, Williamson PR, Mottram DR, Pirmohamed M. Adverse drug reactions in hospital in-patients: a prospective analysis of 3695 patient-episodes. PLoS One. 2009;4:e4439.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Howard RL, Avery AJ, Slavenburg S, Royal S, Pipe G, Lucassen P, et al. Which drugs cause preventable admissions to hospital? A systematic review. Br J Clin Pharmacol. 2007;63:136–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Routledge PA, O’Mahony MS, Woodhouse KW. Adverse drug reactions in elderly patients. Br J Clin Pharmacol. 2004;57:121–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350:1013–22.

    Article  CAS  PubMed  Google Scholar 

  6. Beach SR, Celano CM, Noseworthy PA, Januzzi JL, Huffman JC. QTc prolongation, torsades de pointes, and psychotropic medications. Psychosomatics. 2013;54:1–13.

    Article  PubMed  Google Scholar 

  7. Drew BJ, Ackerman MJ, Funk M, Gibler WB, Kligfield P, Menon V, et al. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. J Am Coll Cardiol. 2010;55:934–47.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Pickham D, Helfenbein E, Shinn JA, Chan G, Funk M, Weinacker A, et al. 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. 2012;40:394–9.

    Article  PubMed  Google Scholar 

  9. Arizona Center for Education and Research on Therapeutics (AZCERT). QT-drug lists by risk groups (online), 2014. http://www.crediblemeds.org. Accessed 31 Aug 2014.

  10. Ames D, Camm J, Cook P, Falkai P, Gury C, Hurley R, et al. Minimizing the risks associated with QTc prolongation in people with schizophrenia. A consensus statement by the cardiac safety in schizophrenia group. Encephale. 2002;28:552–62.

    CAS  PubMed  Google Scholar 

  11. Royal College of Psychiatrists, Consensus statement on high-dose antipsychotic medication, London, 2005.

  12. Breier A, Meehan K, Birkett M, David S, Ferchland I, Sutton V, et al. A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia. Arch Gen Psychiatry. 2002;59:441–8.

    Article  CAS  PubMed  Google Scholar 

  13. Harrigan EP, Miceli JJ, Anziano R, Watsky E, Reeves KR, Cutler NR, et al. A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition. J Clin Psychopharmacol. 2004;24:62–9.

    Article  CAS  PubMed  Google Scholar 

  14. Meyer-Massetti C, Cheng CM, Sharpe BA, Meier CR, Guglielmo BJ. The FDA extended warning for intravenous haloperidol and torsades de pointes: how should institutions respond? J Hosp Med. 2010;5:E8–16.

    Article  PubMed  Google Scholar 

  15. Miceli JJ, Tensfeldt TG, Shiovitz T, Anziano R, O’Gorman C, Harrigan RH. Effects of oral Ziprasidone and oral Haloperidol on QTc interval in patients with Schizophrenia or Schizoaffective disorder. Pharmacotherapy. 2010;30:127–35.

    Article  CAS  PubMed  Google Scholar 

  16. Miceli JJ, Tensfeldt TG, Shiovitz T, Anziano RJ, O’Gorman C, Harrigan RH. Effects of high-dose ziprasidone and haloperidol on the QTc interval after intramuscular administration: a randomized, single-blind, parallel-group study in patients with schizophrenia or schizoaffective disorder. Clin Ther. 2010;32:472–91.

    Article  CAS  PubMed  Google Scholar 

  17. Ozeki Y, Fujii K, Kurimoto N, Yamada N, Okawa M, Aoki T, et al. QTc prolongation and antipsychotic medications in a sample of 1017 patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:401–5.

    Article  CAS  PubMed  Google Scholar 

  18. Reilly JG, Ayis SA, Ferrier IN, Jones SJ, Thomas SH. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet. 2000;355:1048–52.

    Article  CAS  PubMed  Google Scholar 

  19. Vieweg WV, Wood MA, Fernandez A, Beatty-Brooks M, Hasnain M, Pandurangi AK. Proarrhythmic risk with antipsychotic and antidepressant drugs: implications in the elderly. Drugs Aging. 2009;26:997–1012.

    Article  CAS  PubMed  Google Scholar 

  20. FDA alert: Information for Healthcare Professionals: Haloperidol (marketed as Haldol, Haldol Decanoate and Haldol Lactate), 9/2007. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm085203.htm. Accessed 16 Jan 2015.

  21. WHO Collaborating Centre for Drug Statistics Methodology: ATC/DDD Index (online), 2014. http://www.whocc.no/atc_ddd_index. Accessed 31 Aug 2014.

  22. Haugaa KH, Bos JM, Tarrell RF, Morlan BW, Caraballo PJ, Ackerman MJ. Institution-wide QT alert system identifies patients with a high risk of mortality. Mayo Clin Proc. 2013;88:315–25.

    Article  PubMed  Google Scholar 

  23. Davey P. How to correct the QT interval for the effects of heart rate in clinical studies. J Pharmacol Toxicol Methods. 2002;48:3–9.

    Article  CAS  PubMed  Google Scholar 

  24. U.S.Department of Health and Human Services. Guidance for Industry: E14 Clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs. 2005.

  25. Blom MT, Bardai A, van Munster BC, Nieuwland MI, de Jong H, van Hoeijen DA, et al. Differential changes in QTc duration during in-hospital haloperidol use. PLoS One. 2011;6:e23728.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cheung D, Wolfe B, Wald H, Cumbler E. Unsafe use of intravenous haloperidol: evaluation of recommendation-concordant care in hospitalized elderly adults. J Am Geriatr Soc. 2013;61:160–1.

    Article  PubMed  Google Scholar 

  27. Muzyk AJ, Rayfield A, Revollo JY, Heinz H, Gagliardi JP. Examination of baseline risk factors for QTc interval prolongation in patients prescribed intravenous haloperidol. Drug Saf. 2012;35:547–53.

    Article  CAS  PubMed  Google Scholar 

  28. McAnulty J, Halperin B, Kron J, Larsen G, Raitt M, Swenson R, et al. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med. 1997;337:1576–83.

    Article  Google Scholar 

  29. Soteriades ES, Evans JC, Larson MG, Chen MH, Chen L, Benjamin EJ, et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347:878–85.

    Article  PubMed  Google Scholar 

  30. Wilber DJ, Zareba W, Hall WJ, Brown MW, Lin AC, Andrews ML, et al. Time dependence of mortality risk and defibrillator benefit after myocardial infarction. Circulation. 2004;109:1082–4.

    Article  PubMed  Google Scholar 

  31. Fanoe S, Kristensen D, Fink-Jensen A, Jensen HK, Toft E, Nielsen J, et al. Risk of arrhythmia induced by psychotropic medications: a proposal for clinical management. Eur Heart J. 2014;35:1306–15.

    Article  PubMed  Google Scholar 

  32. Jardin CG, Putney D, Michaud S. Assessment of drug-induced torsade de pointes risk for hospitalized high-risk patients receiving QT-prolonging agents. Ann Pharmacother. 2014;48:196–202.

    Article  PubMed  Google Scholar 

  33. Vandael E, Marynissen T, Reyntens J, Spriet I, Vandenberghe J, Willems R, et al. Frequency of use of QT-interval prolonging drugs in psychiatry in Belgium. Int J Clin Pharm. 2014;36:757–65.

    Article  PubMed  Google Scholar 

  34. Warnier MJ, Rutten FH, Souverein PC, de Boer A, Hoes AW, De Bruin ML. Are ECG monitoring recommendations before prescription of QT prolonging drugs applied in daily practice? The example of haloperidol. Pharmacoepidemiol Drug Saf. 2015;24:701–8.

    Article  CAS  PubMed  Google Scholar 

  35. Fongemie JM, Al-Qadheeb NS, Estes NA, Roberts RJ, Temtanakitpaisan Y, Ruthazer R, et al. Agreement between ICU clinicians and electrophysiology cardiologists on the decision to initiate a QTc-interval prolonging medication in critically ill patients with potential risk factors for torsade de pointes: a comparative, case-based evaluation. Pharmacotherapy. 2013;33:589–97.

    Article  PubMed  Google Scholar 

  36. Patel N, Veve M, Kwon S, McNutt LA, Fish D, Miller CD. Frequency of electrocardiogram testing among HIV-infected patients at risk for medication-induced QTc prolongation. HIV Med. 2013;14:463–71.

    Article  CAS  PubMed  Google Scholar 

  37. Muzyk AJ, Rivelli SK, Jiang W, Heinz H, Rayfield A, Gagliardi JP. A computerized physician order entry set designed to improve safety of intravenous haloperidol utilization: a retrospective study in agitated hospitalized patients. Drug Saf. 2012;35:725–31.

    Article  CAS  PubMed  Google Scholar 

  38. Ng TM, Bell AM, Hong C, Hara JM, Touchette DR, Danskey KN, et al. Pharmacist monitoring of QTc interval-prolonging medications in critically ill medical patients: a pilot study. Ann Pharmacother. 2008;42:475–82.

    Article  PubMed  Google Scholar 

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Acknowledgments

We want to thank the University Hospitals Leuven and the treating physicians to approve this epidemiological study. We especially want to thank the IT service of the hospital for delivering the retrospective query that was very helpful to select patients treated with haloperidol.

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Correspondence to Eline Vandael.

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PhD-student EV is supported by funding of the Belgian government agency for Innovation by Science and Technology (IWT). RW is supported as a clinical researcher by the Fund for Scientific Research Flanders.

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None declared.

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Vandael, E., Vandenberk, B., Vandenberghe, J. et al. Risk management of QTc-prolongation in patients receiving haloperidol: an epidemiological study in a University hospital in Belgium. Int J Clin Pharm 38, 310–320 (2016). https://doi.org/10.1007/s11096-015-0242-9

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