Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The risk of cardiac toxicity increases when berberine is combined with other drugs that prolong QT or that inhibit its metabolism, producing a pharmacokinetic and pharmacodynamic "double hit".
“The risk increases when berberine is combined with other drugs that prolong QT or that inhibit its metabolism, producing a pharmacokinetic and pharmacodynamic “double hit” [39,91]”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [91]
The drug-interactions passage (indexed as Abstract; page unavailable) says that combining QT-prolonging drugs can additively lengthen the QT interval and that drugs inhibiting clearance can increase QT-prolongation and torsades de pointes risk. It does not identify berberine or establish that inhibiting berberine’s metabolism produces this risk; the claimed berberine-specific “double hit” therefore goes beyond the source. (LLM, conf=0.86)
Experimental — accuracy not yet measuredBerberine belongs to the broader group of drugs and supplements with a risk of induced arrhythmia, monitorable through pharmacovigilance, in which the pharmacist's assessment has a preventive role.
“This places berberine within the broader group of drugs and supplements with a risk of induced arrhythmia, monitorable through pharmacovigilance, in which the pharmacist’s assessment has a preventive role [91,93,94].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [91]
The paper’s opening passage and “When is pharmacist intervention necessary?” section (page not specified in our copy) describe drug-induced QT prolongation, arrhythmia risk, and pharmacists’ preventive role in assessing and reducing that risk. Our copy does not identify berberine as an arrhythmia-risk substance or establish the claim about supplements and pharmacovigilance. (LLM, conf=0.86)
Experimental — accuracy not yet measuredBecause controlled clinical interaction studies remain rare, detecting safety signals for berberine-drug pairs depends, in practice, on spontaneous reporting and disproportionality analyses in pharmacovigilance databases.
“Because controlled clinical interaction studies remain rare, detecting safety signals for berberine–drug pairs depends, in practice, on spontaneous reporting and disproportionality analyses in pharmacovigilance databases, which underscores the importance of structured recording of supplement use [91,119].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [91]
The paper discusses QT-prolonging drug interactions and recommends risk assessment and ECG monitoring (Abstract, page unavailable). Searches for berberine, supplement-use recording, spontaneous reporting, and disproportionality analysis found no passage addressing the claimed approach to detecting berberine–drug safety signals. (LLM, conf=0.76)
Experimental — accuracy not yet measuredUnder-reporting to pharmacovigilance systems pushes the other way, and the paper cannot say which of the two (publication bias vs under-reporting) dominates.
“Under-reporting to pharmacovigilance systems pushes the other way, and we cannot say which of the two dominates [91,119].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [91]
The paper’s discussion of QT-prolonging drugs and risk factors (indexed as Abstract; page not supplied) does not address under-reporting to pharmacovigilance systems or publication bias. Searches for those terms and for spontaneous adverse-event reporting found no passage comparing their effects. The citing authors’ statement that they cannot say which dominates is their own conclusion. (LLM, conf=0.74)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Heart Disease and Stroke Statistics—2015 Update: A Report From the American Heart Association
Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., de Ferranti, S., Després, J.-P., Fullerton, H. J., Howard, V. J., et al. (2015) · Circulation · doi:10.1161/cir.0000000000000152 · Cited by 5,797 · see citing works
Part 8: Adult Advanced Cardiovascular Life Support
Neumar, R. W., Otto, C. W., Link, M. S., Kronick, S. L., Shuster, M., Callaway, C. W., Kudenchuk, P. J., Ornato, J. P., McNally, B., Silvers, S. M., et al. (2010) · Circulation · doi:10.1161/circulationaha.110.970988 · Cited by 1,629 · see citing works
Part 7: Adult Advanced Cardiovascular Life Support
Link, M. S., Berkow, L., Kudenchuk, P. J., Halperin, H. R., Hess, E. P., Moitra, V. K., Neumar, R. W., O’Neil, B. J., Paxton, J. H., Silvers, S. M., et al. (2015) · Circulation · doi:10.1161/cir.0000000000000261 · Cited by 1,150 · see citing works
Dofetilide in Patients with Congestive Heart Failure and Left Ventricular Dysfunction
Torp-Pedersen, C. T., Møller, M., Bloch-Thomsen, P.-E., Køber, L., Sandøe, E., Egstrup, K., Agner, E., Carlsen, J. E., Videbæk, J., Marchant, B., et al. (1999) · New England Journal of Medicine · doi:10.1056/nejm199909163411201 · Cited by 1,012 · see citing works
The long QT syndrome. Prospective longitudinal study of 328 families.
Moss, A. J., Schwartz, P. J., Crampton, R. S., Tzivoni, D., Locati, E. H., MacCluer, J. W., Hall, W. J., Weitkamp, L., Vincent, G. M., & Garson, A. (1991) · Circulation · doi:10.1161/01.cir.84.3.1136 · Cited by 966 · see citing works
Drew, B. J., Ackerman, M. J., Funk, M., Gibler, W. B., Kligfield, P., Menon, V., Philippides, G. J., Roden, D. M., & Zareba, W. (2010) · Circulation · doi:10.1161/circulationaha.109.192704 · Cited by 821 · see citing works
Littmann, L., Bustin, D. J., & Haley, M. W. (2013) · Medical Principles and Practice · doi:10.1159/000354195 · Cited by 739 · see citing works
Treatment of torsade de pointes with magnesium sulfate.
Tzivoni, D., Banai, S., Schuger, C. D., Benhorin, J., Keren, A., Gottlieb, S., & Stern, S. (1988) · Circulation · doi:10.1161/01.cir.77.2.392 · Cited by 611 · see citing works
Allelic Variants in Long-QT Disease Genes in Patients With Drug-Associated Torsades de Pointes
Yang, P., Kanki, H., Drolet, B., Yang, T., Wei, J., Viswanathan, P. C., Hohnloser, S. H., Shimizu, W., Schwartz, P. J., Stanton, M. S., et al. (2002) · Circulation · doi:10.1161/01.cir.0000014448.19052.4c · Cited by 551 · see citing works
Stambler, B. S., Wood, M. A., Ellenbogen, K. A., Perry, K. T., Wakefield, L. K., & VanderLugt, J. T. (1996) · Circulation · doi:10.1161/01.cir.94.7.1613 · Cited by 485 · see citing works
Singh, S., Zoble, R. G., Yellen, L., Brodsky, M. A., Feld, G. K., Berk, M., & Billing, C. B. (2000) · Circulation · doi:10.1161/01.cir.102.19.2385 · Cited by 433 · see citing works
[Ventricular tachycardia with 2 variable opposing foci].
Dessertenne, F. (1966) · PubMed · Cited by 414 · see citing works
Tisdale, J. E., Jaynes, H. A., Kingery, J. R., Mourad, N. A., Trujillo, T. N., Overholser, B. R., & Kovacs, R. J. (2013) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.113.000152 · Cited by 391 · see citing works
Self-citationEllenbogen, K. A., Stambler, B. S., Wood, M. A., Sager, P. T., Wesley, R. C., Meissner, M. D., Zoble, R. G., Wakefield, L. K., Perry, K. T., VanderLugt, J. T., et al. (1996) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(96)00121-0 · Cited by 370 · see citing works
QTc Interval Screening in Methadone Treatment
Krantz, M. J., Martin, J., Stimmel, B., Mehta, D., & Haigney, M. C. (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-150-6-200903170-00103 · Cited by 334 · see citing works
Torsade de Pointes Due to Noncardiac Drugs
Zeltser, D., Justo, D., Halkin, A., Prokhorov, V., Heller, K., & Viskin, S. (2003) · Medicine · doi:10.1097/01.md.0000085057.63483.9b · Cited by 273 · see citing works
Torsades de Pointes Associated With Intravenous Haloperidol in Critically Ill Patients
Sharma, N. D., Rosman, H., Padhi, I. D., et al. (1998) · The American Journal of Cardiology · doi:10.1016/s0002-9149(97)00888-6 · Cited by 233 · see citing works
QT interval prolongation and the risk of torsades de pointes: essentials for clinicians
Trinkley, K. E., Page, R. L., II, Lien, H., Yamanouye, K., & Tisdale, J. E. (2013) · Current Medical Research and Opinion · doi:10.1185/03007995.2013.840568 · Cited by 231 · see citing works
Self-citationGoldenberg, I., Zaręba, W., & Moss, A. J. (2008) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2008.07.002 · Cited by 208 · see citing works
Spectrum of drugs prolonging QT interval and the incidence of torsades de pointes
Darpö, B. (2001) · European Heart Journal Supplements · doi:10.1016/s1520-765x(01)90009-4 · Cited by 203 · see citing works
Prescription of QT-prolonging drugs in a cohort of about 5 million outpatients
Curtis, L. H., Østbye, T., Sendersky, V., Hutchison, S., LaPointe, N. M. A., Al‐Khatib, S. M., Yasuda, S. U., Dans, P. E., Wright, A., Califf, R. M., et al. (2003) · The American Journal of Medicine · doi:10.1016/s0002-9343(02)01455-9 · Cited by 175 · see citing works
Shaffer, D., Singer, S., Korvick, J. A., & Honig, P. K. (2002) · Clinical Infectious Diseases · doi:10.1086/340861 · Cited by 151 · see citing works
Drug-induced diseases : prevention, detection, and management
Tisdale, J. E., & Miller, D. A. (2010) · Cited by 151 · see citing works
Self-citationPrescription of QT-prolonging drugs in a cohort of about 5 million outpatients
Curtis, L. H., Østbye, T., & Sendersky, V. (2003) · ACC Current Journal Review · doi:10.1016/s1062-1458(03)00200-9 · Cited by 149 · see citing works
Pickham, D. M., Helfenbein, E. D., Shinn, J. A., Chan, G. K., Funk, M., Weinacker, A. B., Liu, J., & Drew, B. J. (2011) · Critical Care Medicine · doi:10.1097/ccm.0b013e318232db4a · Cited by 145 · see citing works
Zhang, Y., Ouyang, P., Post, W. S., Dalal, D., Vaidya, D. M., Blasco‐Colmenares, E., Soliman, E. Z., Tomaselli, G. F., & Güallar, E. (2011) · American Journal of Epidemiology · doi:10.1093/aje/kwr172 · Cited by 127 · see citing works
Estrogen and Progestin Use and the QT Interval in Postmenopausal Women
Kadish, A. H., Greenland, P., Limacher, M. C., Frishman, W. H., Daugherty, S. A., & Schwartz, J. B. (2004) · Annals of Noninvasive Electrocardiology · doi:10.1111/j.1542-474x.2004.94580.x · Cited by 105 · see citing works
Moss, A. J., Zarebra, W., & Robinson, J. L. (1995) · Cardiology in Review · doi:10.1097/00045415-199503000-00003 · Cited by 98 · see citing works
Effects of Testosterone on Ventricular Repolarization in Hypogonadic Men
Charbit, B., Christin‐Maître, S., Démolis, J., Soustre, E., Young, J., & Funck‐Brentano, C. (2009) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2008.11.041 · Cited by 96 · see citing works
Tisdale, J. E., Jaynes, H. A., Kingery, J. R., Overholser, B. R., Mourad, N. A., Trujillo, T. N., & Kovacs, R. J. (2014) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.113.000651 · Cited by 93 · see citing works
Self-citationTisdale, J. E., Wroblewski, H. A., Overholser, B. R., Kingery, J. R., Trujillo, T. N., & Kovacs, R. J. (2012) · Drug Safety · doi:10.2165/11598160-000000000-00000 · Cited by 85 · see citing works
Self-citationDrug withdrawals from the Canadian market for safety reasons, 1963-2004
Lexchin, J. (2005) · Canadian Medical Association Journal · doi:10.1503/cmaj.045021 · Cited by 78 · see citing works
Pratt, C. M., Singh, S. N., Al‐Khalidi, H. R., Brum, J. M., Holroyde, M. J., Marcello, S. R., Schwartz, P. J., & Camm, A. J. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2003.10.057 · Cited by 72 · see citing works
Carnethon, M. R., Anthony, M. S., Cascio, W. E., Folsom, A. R., Rautaharju, P. M., Liao, D., Evans, G. W., & HEISS, G. M. (2003) · Annals of Epidemiology · doi:10.1016/s1047-2797(03)00050-4 · Cited by 64 · see citing works
Pratt, C. M., Al‐Khalidi, H. R., Brum, J. M., Holroyde, M. J., Schwartz, P. J., Marcello, S. R., Borggrefe, M., Dorian, P., & Camm, A. J. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.04.075 · Cited by 52 · see citing works
Pickham, D. M., Helfenbein, E. D., Shinn, J. A., Chan, G. K., Funk, M., & Drew, B. J. (2010) · Journal of Electrocardiology · doi:10.1016/j.jelectrocard.2010.05.016 · Cited by 38 · see citing works
Singh, S. N., Lazin, A., Cohen, A., et al. (1991) · American Heart Journal · doi:10.1016/0002-8703(91)90735-z · Cited by 26 · see citing works
Tang, S. C. W., Lo, C. Y., Lo, W. K., et al. (1997) · Peritoneal Dialysis International · doi:10.1177/089686089701700223 · Cited by 9 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- [5]5. Bazett HC. An analysis of time relationships of the electrocardiogram. Heart 1920;7:353-70. [Google Scholar]
- [7]7. Dessertenne F. La tachycardie ventriculaire à deux foyers opposes variables. Arch Mal Coeur Vaiss 1966;59:263-72. [PubMed] [Google Scholar]
- [13]13. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). Guidance for Industry. E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs. Rockville (MD): US Department of Health and Human Services; 2005. [Google Scholar]
- [17]17. RxList. Top 200 drugs list. Available: www.rxlist.com/script/main/hp.asp (accessed Sept. 22, 2015). [Google Scholar]
- [37]37. Manz M, Pfeiffer D, Jung W, et al. Intravenous treatment with magnesium in recurrent persistent ventricular tachycardia. New Trends Arrhythmias 1991;7:437-42. [Google Scholar]
Cited by
Sorted by citations
Ali, Z., Ismail, M., Khan, F., & Sajid, H. (2021) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2021.1846717 · Cited by 21 · see citing works
Dumitru, C. N., Marcu, T., Dumitru, A. O., Tudor, S. S., Ferțu, I. D., Elisei, A.-M., & Goroftei, L. (2026) · Pharmaceuticals · doi:10.3390/ph19081313 · Cited by 2 · see citing works
“This places berberine within the broader group of drugs and supplements with a risk of induced arrhythmia, moni-torable through pharmacovigilance, in which the pharmacist’s assessment has a preventive role [91,93,94].”
Influential
- Authors
- Tisdale, J. E.
- Affiliations
- Indiana University Indianapolis (US)
- Corresponding author
- Tisdale, James E.
- ORCID
- Tisdale, James E.
- Venue
- Canadian Pharmacists Journal / Revue des Pharmaciens du Canada
- Published
- 2016-04-08
- Volume
- 149
- Issue
- 3
- Pages
- 139-152
- ISSN
- 0828-6914 (ISSN-L)
- 1715-1635
- 1913-701X
- PMC
- PMC4860751
- OpenAlex
- W2322526196
- Cited by
- 209
- References
- 38
- Citations by year
- 2026: 16 · 2025: 15 · 2024: 25 · 2023: 17 · 2022: 30 · 2021: 18 · 2020: 31 · 2019: 20 · 2018: 16 · 2017: 18 · 2016: 3
- FWCI
- 3.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Canadian Pharmacists Journal / Revue des Pharmaciens du Canada (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- torsades de pointes, QTc prolongation, drug-induced arrhythmia, pharmacokinetic interactions, macrolide antibiotics, antifungal agents, antidepressants, HIV drugs, renal dose adjustment, magnesium sulfate, electrolyte imbalance, risk factors, pharmacist role
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
