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

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.

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SSRIs and QT interval prolongation management. A review

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1393 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S750-S750

Author(s):

A. Ballesteros ◽

H. Saiz ◽

Á.S. Rosero ◽

A. Portilla ◽

L. Montes ◽

...

Keyword(s):

Risk Factors ◽

Qt Interval ◽

Future Research ◽

Current Debate ◽

Qtc Interval ◽

Interval Prolongation ◽

Drug Induced ◽

Cross Sectional ◽

Qt Interval Prolongation ◽

Qtc Interval Prolongation

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.

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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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Absence of relevant QT interval prolongation in not critically ill COVID-19 patients

Scientific Reports ◽

10.1038/s41598-020-78360-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Juan Jiménez-Jáimez ◽

Rosa Macías-Ruiz ◽

Francisco Bermúdez-Jiménez ◽

Ricardo Rubini-Costa ◽

Jessica Ramírez-Taboada ◽

...

Keyword(s):

Critically Ill ◽

Qt Interval ◽

Treatment Initiation ◽

Qtc Interval ◽

Risk Markers ◽

Interval Prolongation ◽

Qt Interval Prolongation ◽

Qtc Interval Prolongation ◽

Ambulatory Patients ◽

Reported Data

AbstractSARS-CoV-2 is a rapidly evolving pandemic causing great morbimortality. Medical therapy with hydroxicloroquine, azitromycin and protease inhibitors is being empirically used, with reported data of QTc interval prolongation. Our aim is to assess QT interval behaviour in a not critically ill and not monitored cohort of patients. We evaluated admitted and ambulatory patients with COVID-19 patients with 12 lead electrocardiogram at 48 h after treatment initiation. Other clinical and analytical variables were collected. Statistical analysis was performed to assess the magnitude of the QT interval prolongation under treatment and to identify clinical, analytical and electrocardiographic risk markers of QT prolongation independent predictors. We included 219 patients (mean age of 63.6 ± 17.4 years, 48.9% were women and 16.4% were outpatients. The median baseline QTc was 416 ms (IQR 404–433), and after treatment QTc was prolonged to 423 ms (405–438) (P < 0.001), with an average increase of 1.8%. Most of the patients presented a normal QTc under treatment, with only 31 cases (14.1%) showing a QTc interval > 460 ms, and just one case with QTc > 500 ms. Advanced age, longer QTc basal at the basal ECG and lower potassium levels were independent predictors of QTc interval prolongation. Ambulatory and not critically ill patients with COVID-19 treated with hydroxychloroquine, azithromycin and/or antiretrovirals develop a significant, but not relevant, QT interval prolongation.

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Meperidine-induced QTc-interval prolongation: prevalence, risk factors, and correlation to plasma drug and metabolite concentrations

International Journal of Clinical Pharmacology and Therapeutics ◽

10.5414/cp202612 ◽

2017 ◽

Vol 55 (03) ◽

pp. 275-285 ◽

Cited By ~ 8

Author(s):

Guillermo Alberto Keller ◽

María Cedilia Villa Etchegoyen ◽

Nicolás Fernández ◽

Nancy Mónica Olivera ◽

Patricia Noemi Quiroga ◽

...

Keyword(s):

Risk Factors ◽

Qtc Interval ◽

Plasma Drug ◽

Interval Prolongation ◽

Qtc Interval Prolongation ◽

Metabolite Concentrations

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Corrected QT interval prolongation during anesthetic induction for laryngeal mask airway insertion with or without cisatracurium

Journal of International Medical Research ◽

10.1177/0300060518764185 ◽

2018 ◽

Vol 46 (5) ◽

pp. 1990-2000 ◽

Cited By ~ 3

Author(s):

Chengluan Xuan ◽

Nan Wu ◽

Yanhui Li ◽

Xiaoting Sun ◽

Qunshu Zhang ◽

...

Keyword(s):

Laryngeal Mask Airway ◽

Operating Room ◽

Qt Interval ◽

Laryngeal Mask ◽

Laryngeal Mask Airway Insertion ◽

Qtc Interval ◽

Interval Prolongation ◽

Anesthetic Induction ◽

Qt Interval Prolongation ◽

Qtc Interval Prolongation

Objective This study was performed to observe the occurrence of corrected QT (QTc) interval prolongation during anesthetic induction for laryngeal mask airway insertion and the effects of cisatracurium administration on the QTc interval. Methods Eighty-eight patients were assigned to two groups: the cisatracurium administration group (n = 45) and non-cisatracurium administration group (n = 43). The QTc interval was continuously recorded by a 12-lead Holter electrocardiogram beginning in the hospital ward and continuing until after anesthetic induction. Results In the cisatracurium administration group, the QTc interval significantly increased from 417.9 ± 27.9 to 451.6 ± 32.5 ms after arrival in the operating room and significantly decreased to 432.4 ± 32.5 ms after a 15-minute rest; it significantly increased to 459.7 ± 23.8 ms again after propofol and fentanyl injection. However, the QTc interval decreased after cisatracurium injection. In the non-cisatracurium administration group, the QTc interval initially showed changes similar to those in the cisatracurium group until fentanyl and propofol were injected. Conclusions The QTc interval was significantly prolonged on arrival in the operating room and after propofol and fentanyl injection. The QTc interval did not significantly change by laryngeal mask airway insertion regardless of the administration of cisatracurium.

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Monitoring of QTc interval in patients with COVID-19. First experience with a portable EKG-recording device

EP Europace ◽

10.1093/europace/euab116.516 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

M Abellas Sequeiros ◽

C Lozano Granero ◽

C Garcia Sebastian ◽

E Franco Diez ◽

A Hernandez Madrid ◽

...

Keyword(s):

Qt Interval ◽

Intraclass Correlation ◽

Early Discharge ◽

Recording Device ◽

Qtc Interval ◽

Interval Prolongation ◽

Daily Monitoring ◽

Qt Interval Prolongation ◽

Qtc Interval Prolongation ◽

Group 2

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Off-label use of drugs with potential for QT interval prolongation was common in COVID-19 patients. We tested a portable EKG recording device to measure and monitor corrected QT (QTc) intervals in a cohort of COVID-19 patients treated with azithromycin, hydroxychloroquine, lopinavir/ritonavir, or combinations of these drugs. Methods and results Sixty-nine patients hospitalized with pneumonia and confirmed SARS-CoV 2 infection were included in an observational single-centre study. Six-lead EKG recordings were obtained using a KardiaMobile6L® at physicians’ discretion. In a subgroup of 16 patients with early discharge, a device was provided for at-home daily monitoring. Significant QTc interval prolongation was observed in patients taking a combination of 2 or 3 drugs (426 ± 33 vs 408 ± 33 ms, p = 0,002; and 435 ± 30 vs 394 ± 31 ms, p = 0,001, respectively). The use of the device prompted a change in the treatment of 9 patients (13%) because of prolongation of QTc interval and anticoagulation was started in one patient because of atrial fibrillation diagnosis. In the subgroup of patients with daily recording, QTc interval prolongation peaked at day 2 ± 1,8, with a shorter final QT interval than that recorded before drug initiation (350,0 ± 31,4 vs 381,0 ± 21,2; p = 0,019), pointing to a possible role of the disease itself in QT interval modification. To assess the consistency of measurements of QTc interval, a random sample of 120 EKG recordings were analyzed by two different physicians. Inter-operator intraclass correlation coefficient was 0,702, 95% CI (0,578-0,789). Conclusions Portable EKG-recording device was useful for QTc interval monitoring in COVID-19 patients receiving drugs with QTc prolonging potential, allowing physicians to adapt management. Significant QT prolongation was observed in these patients. Characteristics of the three groups.Group 1(one drug)N= 9 (13,0%)Group 2(two drugs)N= 37 (53,6%)Group 3(three drugs)N= 23 (33,3%)p-valueClinical characteristicsAge (years)55,0 ± 18,366,0 ± 16,258,0 ± 15,8p = 0,248Male sex (%)6 (66,7%)25 (67,6%)18 (78,3%)p = 0,643Dislipidaemia (%)5 (55,6%)9 (24,3%)7 (30,4%)p = 0,749Diabetes (%)7 (77,8%)4 (10,8%)5 (21,7%)p = 0,525Hypertension (%)3 (33,3%)16 (43,2%)8 (34,8%)p = 0,387Previous cardiopathy (%)6 (66,7%)11 (29,7%)3 (13,0%)p = 0,305COPD (%)7 (77,8%)6 (16,2%)1 (8,7%)p = 0,679COPDchronic obstructive pulmonary disease.Abstract Figure. Baseline and maximum QTc intervals

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