An Online Module to Evaluate the Validity of an Algorithm to assess the Risk for DrugInduced Qtc Prolongation in the Psychiatric Population

Introduction: QTc interval prolongation leads to serious complications making it a concern for all clinicians. Assessing the risk of QTc interval prolongation, especially in the psychiatric population, can be challenging for pharmacists due to the complexity of regimens in this population and the difficulty in retrieving the needed information for the risk assessment. Guidelines and protocols for QTc prolongation risk assessment may vary among clinicians and few algorithms exist that address the prevention, management or monitoring of drug-induced QTc prolongation in the psychiatric population. Hence, there is a need for a validated comprehensive algorithm that helps clinicians in with the assessment of the risk of QTc prolongation. Aim: The study aims to pilot an educational module that guides experts through an algorithm for the assessment, management and monitoring of drug-induced QTc prolongation in the psychiatric population. Methods: This study involved developing an online education module using Articulate Presenter® to introduce a comprehensive literature-based algorithm to subject-matter experts. The orientation was followed by an anonymous, self-administered survey with quantitative and qualitative components to assess the content validity of the QTc Prolongation Algorithm. Results: Feedback from the first pilot test with faculty members indicated that the module’s interface was crowded. The module was updated accordingly. The results from the second pilot test with cardiologists were that the module provided a thorough explanation of the algorithm steps and rationale. Furthermore, some cardiologists commented that the algorithm was time consuming, however, most supported the implementation of the algorithm saying that it is easy to use, systematic, stepbased and would be helpful if implemented. Conclusion/Future directions: The results show that the module was helpful in introducing cardiologists to the algorithm and that the implementation of the algorithm after minor alterations can prove to be useful as a tool for risk assessment of QTc prolongation

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Drug-induced QTc interval prolongation: A proposal towards an efficient and safe anticancer drug development

European Journal of Cancer ◽

10.1016/j.ejca.2007.10.001 ◽

2008 ◽

Vol 44 (4) ◽

pp. 494-500 ◽

Cited By ~ 30

Author(s):

Giuseppe Curigliano ◽

Gianluca Spitaleri ◽

Howard J. Fingert ◽

Filippo de Braud ◽

Cristiana Sessa ◽

...

Keyword(s):

Drug Development ◽

Anticancer Drug ◽

Qtc Interval ◽

Interval Prolongation ◽

Drug Induced ◽

Qtc Interval Prolongation ◽

Anticancer Drug Development

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Translating the gap in the evaluation of drug-induced QTc-interval prolongation from in vivo to the clinic

Journal of Pharmacological and Toxicological Methods ◽

10.1016/j.vascn.2014.03.055 ◽

2014 ◽

Vol 70 (3) ◽

pp. 324

Author(s):

Vincent F.S. Dubois ◽

Piet van der Graaf ◽

Derek Leishman ◽

David Gallacher ◽

Nick McMahon ◽

...

Keyword(s):

Qtc Interval ◽

Interval Prolongation ◽

Drug Induced ◽

Qtc Interval Prolongation

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Risk of QTc interval prolongation among cancer patients treated with tyrosine kinase inhibitors.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3033 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3033-3033

Author(s):

Anan Abdelmoti Abu Rmilah ◽

Grace Lin ◽

Joerg Herrmann

Keyword(s):

Tyrosine Kinase ◽

Cancer Patients ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

Complication Rates ◽

Qtc Interval ◽

Interval Prolongation ◽

Qtc Prolongation ◽

Qtc Interval Prolongation ◽

Life Threatening

3033 Background: QTc interval prolongation can lead to life-threatening complications such as torsade de pointes (TdP), ventricular tachycardia (VT), and sudden cardiac death (SCD). It can occur with various tyrosine kinase inhibitors (TKIs) but comparative analyses on the incidence and complication rates are scarce. We thus conducted a comprehensive analysis of TKI use and QTc prolongation in clinical practice. Methods: We retrospectively reviewed the electronic medical records of all cancer patients who were treated with TKI between 01/2005 and 12/2018 at our institution. QTc prolongation was defined as a QTc ≥ 450 ms or 460 ms among male or female patients, respectively. For each type of TKIs, we determined the administration rate and incidence of QTc interval prolongation. We also studied the frequency of QTc prolongation ≥ 500 ms, rate of increase of the QTc interval by ≥ 60 ms, and the development of complications (VT, TdP and SCD). Results: In the present study, we analyzed the data of 685 cancer patients (431 male and 254 female), including 299 patients with RCC, 188 with chronic leukemia, 55 with acute leukemia, 65 with thyroid cancer, 48 with lung cancer and 39 with GIST. These patients received 902 TKI administrations and QTc prolongation was reported in 1/3 of these (289 administrations). The highest frequency was seen with imatinib, nilotinib and dasatinib (30, 40 and 50%). Among cases of QTc prolongation, a QTc interval ≥ 500 ms was documented in 53 (18.3%) and QTc progression ≥ 60 ms in 72 (25%). Complications were found in 14 cases (5%) including VT in 9, TdP in 2 and SCD in 3 administrations. Conclusions: The current findings suggest that TKI therapy leads to QTc prolongation in 1/3 of patients on average and most commonly with the Bcr-Abl TKIs, imatinib, nilotinib and dasatinib. While SCD is rare (1%) it can still evolve and in 5% of all QTc prolongations with TKIs are potentially life-threatening. These data support recommendations for serial ECGs in cancer patients undergoing TKI therapy. [Table: see text]

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Minimizing the Risks Associated with Significant QTc Prolongation in People with Schizophrenia: A Consensus Statement by The Cardiac Safety in Schizophrenia Group

Australasian Psychiatry ◽

10.1046/j.1440-1665.2002.00419.x ◽

2002 ◽

Vol 10 (2) ◽

pp. 115-124 ◽

Cited By ~ 11

Author(s):

David Ames ◽

John Camm ◽

Peter Cook ◽

Peter Falkai ◽

Charles Gury ◽

...

Keyword(s):

Antipsychotic Drugs ◽

Consensus Statement ◽

Morbidity And Mortality ◽

Team Approach ◽

Qtc Interval ◽

Cardiac Safety ◽

Interval Prolongation ◽

Qtc Prolongation ◽

Schizophrenia Group ◽

Qtc Interval Prolongation

Cardiac Safety in Schizophrenia Group Objectes: This study was designed to help identify and clarify issues associated with cardiac safety in schizophrenia, particularly QTc interval prolongation; to raise awareness among psychiatrists of the cardiac issues involved in prescribing for schizophrenia and help psychiatrists minimise the potential cardiac risks associated with treating schizophrenia. Methods: The currently available literature on cardiac dysfunction associated with antipsychotic treatments was reviewed by an independent panel of international psychiatric and cardiology experts. Following individual review, a joint meeting was held and a consensus statement produced. Results: Prolongation of QTc interval is relatively common among antipsychotic drugs although there is marked variation in the extent to which the different agents exert their effect. If a patient is considered to be at high risk of significantly prolonged QTc interval (e.g. increasing age, female gender, comorbid cardiovascular disease) prescription of an antipsychotic drug with low QTc prolonging potential is recommended. Evaluation of a patient's risk factors for significant QTc prolongation is an important part of patient assessment at presentation. To significantly reduce the risk of morbidity and mortality from prolonged QTc interval a team approach involving the hospital emergency psychiatric care team, the office-based psychiatrist, the primary care physician, the cardiologist and the pharmacist is advocated. Conclusions: Significant QTc interval prolongation caused by some antipsychotics is a risk factor that may lead to sudden death in patients with schizophrenia receiving these medications. Not all antipsychotic drugs prolong QTc interval. Careful clinical and pharmacological management of the patient with schizophrenia can significantly reduce the risks of morbidity and mortality from QTc interval prolongation.

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Effects of Methadone on Corrected Q-T Interval Prolongation in Critically Ill Children

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-23.2.119 ◽

2018 ◽

Vol 23 (2) ◽

pp. 119-124 ◽

Cited By ~ 1

Author(s):

Travis S. Heath ◽

Rachel G. Greenberg ◽

Susan R. Hupp ◽

David A. Turner ◽

Christoph P. Hornik ◽

...

Keyword(s):

Critically Ill ◽

Tertiary Care ◽

Substantial Effect ◽

Critically Ill Children ◽

Admission Diagnosis ◽

Qtc Interval ◽

Interval Prolongation ◽

Qtc Prolongation ◽

Qtc Interval Prolongation ◽

Before And After

OBJECTIVES This study aimed to determine the association between methadone use and corrected Q-T interval (QTc) prolongation in critically ill children METHODS A retrospective cohort study of critically ill children receiving methadone at a tertiary care pediatric hospital was conducted. Patients younger than 19 years who had been admitted to the intensive care unit between January 1, 2009, and June 21, 2013, who had received methadone while inpatients, and who had had electrocardiograms (ECGs) performed within 30 days before and after methadone initiation were included. The primary outcome was the net change in QTc interval between baseline and postmethadone ECGs. Secondary outcomes included percent change in QTc interval and the proportion of patients whose QTc intervals changed from normal to prolonged following methadone initiation. We also evaluated potential predictors of QTc interval prolongation, including age, sex, admission diagnosis category, exposure to other QTc-prolonging medications, presence of congenital heart disease or known arrhythmias, and methadone daily dose and route of administration. RESULTS Sixty-four patients met the inclusion criteria. The median (25th, 75th percentiles) change in QTc interval following methadone initiation was −8 msec (−34, 13.5 msec; p = 0.19). Five patients (8%) had a baseline normal QTc interval that became prolonged after methadone initiation. We identified no statistically significant predictors of QTc prolongation after methadone initiation. CONCLUSIONS In this dedicated pediatric safety study, methadone initiation did not result in prolongation of the QTc interval. Although these findings suggest methadone initiation may not have a substantial effect of QTc prolongation in critically ill children, a controlled, prospective evaluation in this population remains warranted.

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Hydroxychloroquine and QTc: beyond COVID-19

Geriatric Care ◽

10.4081/gc.2020.9064 ◽

2020 ◽

Vol 6 (4) ◽

Cited By ~ 1

Author(s):

Alberto Castagna ◽

Francesco Vetta ◽

Giuseppe Attisani ◽

Raffaele Costa ◽

Carmen Ruberto ◽

...

Keyword(s):

Focal Point ◽

Elderly Subjects ◽

Cardiac Repolarization ◽

Qtc Interval ◽

Interval Prolongation ◽

Qtc Prolongation ◽

Antiviral Effects ◽

Qtc Interval Prolongation ◽

Electrocardiogram Monitoring ◽

Potential Use

Hydroxychloroquine is an antimalarial drug also known for its anti-inflammatory and antiviral effects, which have raised the interest of many researchers for its potential use in COVID-19 patients. It is known that this drug, being able to influence the cardiac repolarization phase with QTc interval prolongation, can be potentially harmful, chiefly in elderly subjects with frailty syndrome, several comorbidities and polypharmacotherapy. Therefore, although electrocardiogram monitoring of QTc prolongation is the focal point for reducing the arrhythmic risk of these patients, in order to identify the most exposed patients, the traditional Comprehensive Geriatric Assessment should be combined with a multiparametric risk score for QTc prolongation.

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Role of Co-occurring Alcohol and Substances Abuse on QTc Interval Prolongation Among Psychiatric Patients: A Cross-sectional National Survey

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.2151 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S201-S202

Author(s):

M. Corbo ◽

T. Acciavatti ◽

F. Fiori ◽

R. Santacroce ◽

A. Aguglia ◽

...

Keyword(s):

National Survey ◽

Psychotropic Drugs ◽

Polymorphic Ventricular Tachycardia ◽

Qtc Interval ◽

Interval Prolongation ◽

Qtc Prolongation ◽

Cross Sectional ◽

Star Network ◽

Qtc Interval Prolongation

IntroductionQTc interval prolongation is considered a risk factor for fatal polymorphic ventricular tachycardia, which can result in sudden cardiac death. Most psychotropic drugs have a dose-dependent potential to prolong the QTc interval. However, other factors require appropriate consideration, including: age; gender; other medications; electrolyte abnormalities; severe comorbid conditions, such as co-occurring alcohol or substances abuse/dependence.ObjectivesThe objective was to study the potential mediating roles of alcohol/substances abuse on QTc prolongation.AimsThe Italian research group STAR Network, in collaboration with the Young Italian Psychiatrists Association, aimed to evaluate the frequency of QTc interval prolongation in a sample of patients under treatment with psychotropic drugs through a cross-sectional national survey.MethodsA sample of 2411 unselected patients were enrolled after performing an ECG during the recruitment period. Sociodemographic and clinical characteristics were collected from medical records. Collected data underwent statistical analysis.ResultsA total of 11.2% of patients reported alcohol abuse, and only 8.9% psychotropic substances. According to the threshold, less than 20% of patients had a borderline value of QTc, and 1% a pathological value. Patients with co-occurring alcohol misuse and drug abuse were more likely to have longer QTc interval.ConclusionsThe present study describes the frequency of QTc prolongation in real-world clinical practice. Before prescribing a psychotropic drug, the physician should carefully assess its risks and benefits to avoid this type of adverse reaction, particularly when additional risk factors are present. The potential role of alcohol and substances on QTc length could be particularly useful in emergency settings.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Assessing the Probability of Drug-Induced QTc-Interval Prolongation During Clinical Drug Development

Clinical Pharmacology & Therapeutics ◽

10.1038/clpt.2011.202 ◽

2011 ◽

Vol 90 (6) ◽

pp. 867-875 ◽

Cited By ~ 21

Author(s):

A S Y Chain ◽

K M Krudys ◽

M Danhof ◽

O Della Pasqua

Keyword(s):

Drug Development ◽

Qtc Interval ◽

Interval Prolongation ◽

Drug Induced ◽

Clinical Drug Development ◽

Qtc Interval Prolongation ◽

Clinical Drug

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Drug-Induced QTc-Interval Prolongation in the Intensive Care Unit: Incidence and Predictors

Journal of Pharmacy Practice ◽

10.1177/0897190009356549 ◽

2010 ◽

Vol 23 (1) ◽

pp. 19-24 ◽

Cited By ~ 16

Author(s):

Tien M. H. Ng ◽

Keith M. Olsen ◽

Megan A. McCartan ◽

Susan E. Puumala ◽

Katie M. Speidel ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Beta Blockers ◽

Qtc Interval ◽

Qtc Prolongation ◽

Drug Induced ◽

Icu Patients ◽

End Point ◽

Increased Risk ◽

Qtc Interval Prolongation

There is a paucity of information regarding QTc prolongation in critically ill patients. A prospective observational study was conducted to assess the incidence and predictors of QTc prolongation associated with medications in intensive care unit (ICU) patients. Consecutive adult patients prescribed prespecified QTc-prolonging medications were assessed for development of the combined incidence of QTc >500 ms at anytime and QTc increase >60 ms above baseline. Over 3 months, 200 consecutive patients (63 ± 18 years; 52% female; 73% Caucasian; baseline QTc 447.3 ± 51.5 ms) were evaluated. The primary end point occurred in 48% of the patients (QTc >500 ms 40%, QTc increase >60 ms 29%). The majority of patients experienced a QTc >470 or 450 ms (60.5%). Mean increase in QTc at 48 hours was 20 ± 35 ms. Upon multivariate analysis, length of stay [odds ratio 1.30, 95% confidence interval (1.15, 1.47)] and baseline QTc [1.01 (1.01, 1.02)] were associated with an increased risk for the primary end point, while beta-blockers [0.41 (0.20, 0.81)] were associated with a risk reduction. In conclusion, increased risk of proarrhythmia, as assessed by QTc prolongation, occurs in the majority of ICU patients when prescribed medications with electrophysiologic properties. Increased vigilance is warranted. The possible protective effect of beta-blockers requires confirmation.

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