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

IntroductionIn 2011, the FDA issued an alert recommending not to prescribe citalopram high doses, due to QT prolongation risk. We explored the clinical background of QT interval prolongation related to serotonin selective reuptake inhibitors (SSRI) use and the clinical implications of safety issues.MethodologyA review was conducted to clarify the mechanisms associated with the occurrence of TdP when using SSRI and investigating therapeutic measures to avoid/minimize these effects. The literature search was conducted in PubMed data reviewing articles between 2001 and 2016.Results(1) Related to risk factors/intraclass differences: risk factors are increase in QTc interval ≥60 ms from the pretreatment value, advanced age, female sex, acute myocardial infarction and electrolytic abnormalities among others. Citalopram appears more likely than others to induce this phenomenon but its importance is under current debate. (2) Related to dose: drug-induced QTc interval prolongation and TdP was associated to citalopram in doses > 40 mg/day. However, psychotropic drug-induced sudden cardiac death may be an outlier in the absence of identified risk factors for QTc interval prolongation and TdP. (3) Related to poly-pharmacy/management: there is an additive effect when using SSRI and antipsychotics (EKG control is recommended in those cases). Cross-sectional studies showed that SSRI use was not associated with QT interval prolongation. This could be explained by the EKG intra-intersubject variability.ConclusionsThere is little evidence that drug-associated QTc interval prolongation by itself is sufficient to predict TdP. Future research needs to improve its precision to better understand the factors that facilitate/attenuate that progression. Clarifying this may lead to a safer SSRI use.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Download Full-text

Drug‐induced QTc interval prolongation in PCR‐positive non‐ICU COVID‐19 patients with diverse findings on chest computed tomography

International Journal of Clinical Practice ◽

10.1111/ijcp.14583 ◽

2021 ◽

Author(s):

Ferhat Ozyurtlu ◽

Nurullah Cetin ◽

Veysel Yavuz

Keyword(s):

Computed Tomography ◽

Qtc Interval ◽

Interval Prolongation ◽

Drug Induced ◽

Chest Computed Tomography ◽

Qtc Interval Prolongation

Download Full-text

Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice

Current Drug Safety ◽

10.2174/1574886311207040262 ◽

2016 ◽

Vol 11 (1) ◽

pp. 86-98 ◽

Cited By ~ 9

Author(s):

Guillermo A. Keller ◽

Paulino A. Alvarez ◽

Marcelo L. Ponte ◽

Waldo H. Belloso ◽

Claudia Bagnes ◽

...

Keyword(s):

Multicenter Study ◽

Qtc Interval ◽

Clinical Factors ◽

Interval Prolongation ◽

Drug Induced ◽

Qtc Interval Prolongation

Download Full-text

Dextropropoxyphene effects on QTc-interval prolongation: Frequency and characteristics in relation to plasma levels

Journal of Opioid Management ◽

10.5055/jom.2018.0466 ◽

2018 ◽

Vol 14 (5) ◽

pp. 335-344 ◽

Cited By ~ 1

Author(s):

Guillermo Alberto Keller, MD, PhD ◽

Cecilia Villa Etchegoyen, MD ◽

Nicolás Fernandez, PharmD, PhD ◽

Nancy Mónica Olivera, PharmD, PhD ◽

Patricia Noemí Quiroga, PharmD, PhD ◽

...

Keyword(s):

Public Hospital ◽

Outcome Measure ◽

General Ward ◽

Qtc Interval ◽

Plasma Drug ◽

Interval Prolongation ◽

Drug Induced ◽

Qt Interval Prolongation ◽

Qtc Interval Prolongation ◽

Therapeutic Doses

Objective: To evaluate frequency and risk factors for dextropropoxyphene-induced QT-interval prolongation in the clinical setting.Design: Prospective, noninterventional, observational, longitudinal cohort approach. Electrocardiograms were blindly evaluated by independent professionals.Setting: General ward of a public hospital of metropolitan Buenos Aires.Patients, Participants: Ninety-two patients with indication of receiving dextropropoxyphene for analgesic purposes were included consecutively. All patients finished the study.Interventions: All patients were monitored with electrocardiographic controls (previous to drug administration and during steady state) to diagnose and quantify changes in the duration of the QTc interval.Main Outcome Measure: Frequency of drug-induced QTc interval prolongation, QTc interval correlation with plasma drug, and metabolite levels.Results: Ninety-two patients were studied (50 percent males). All patients received a (mean ± SD [range]) dextropropoxyphene dose of 125 ± 25[100-150] mg/d. Dextropropoxyphene and norpropoxyphene concentrations were 112 ± 38[45-199] and 65 ± 33[13-129] ng/mL, respectively. The intra-treatment QTc interval was 450 ms in only one patient (only with the Hodge correction). There were no cases of QTc 500 ms, and there were no significant differences in the results considering different correction formulas (Bazzet, Fridericia, Framingham, Hodges). Dextropropoxyphene concentrations correlated with QTc (R 0.45) interval and ΔQTc (R 0.52-0.87), whereas norpropoxyphene correlation was even greater for QTc (R 0.40-0.64) and ΔQTc (R 0.47-0.92). Depending on the QTc correction formula, eight patients presented ΔQTc 30 ms and one patient with ΔQTc 60 ms. No patient presented arrhythmia during the study.Conclusions: The authors did not observe a relationship between dextropropoxyphene and QTc interval prolongation at the therapeutic doses used in Argentina.

Download Full-text

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

University of the Future: Re-Imagining Research and Higher Education ◽

10.29117/quarfe.2020.0231 ◽

2020 ◽

Author(s):

Iman Ashraf Qubaiah ◽

Waad Abubaker Elamin ◽

Doaa Elsayed Mahmoud ◽

Shorouk Akram Homs ◽

Enge Sherif Tawfik ◽

...

Keyword(s):

Risk Assessment ◽

Online Education ◽

Qtc Interval ◽

Pilot Test ◽

Interval Prolongation ◽

Qtc Prolongation ◽

Drug Induced ◽

Qtc Interval Prolongation ◽

Assessment Guidelines ◽

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

Download Full-text