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1.
Int J Med Sci ; 16(7): 1018-1022, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341415

RESUMO

Introduction: Macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and ceftriaxone are known to be associated with Torsades de pointes/QT prolongation (TdP/QTP). Other antibiotics may also lead to TdP/QTP, but no study has systemically compared TdP/QTP associations for many available antibiotics. Objectives: The objective of this study was to evaluate the association between TdP/QTP and many available antibiotics using the FDA Adverse Event Report System (FAERS). Methods: FAERS reports from January 1, 2015 to December 31, 2017 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify TdP/QTP cases. We calculated the Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the association between antibiotics and TdP/QTP. An association was considered to be statistically significant when the lower limit of the 95%CI was greater than 1.0. Results: A total of 2,042,801 reports (including 3,960 TdP/QTP reports) were considered, after inclusion criteria were applied. Macrolides had the greatest proportion of TdP/QTP reports. Of the 4,092 reports associated with macrolides, 108 reports (2.6%) were associated with TdP/QTP. Significant TdP/QTP RORs (95%CI) for the antibiotics were (in descending order): macrolides 14.32 (11.80-17.38), linezolid 12.41 (8.52-18.08), amikacin 11.80 (5.57-24.97), imipenem-cilastatin 6.61 (3.13-13.94), fluoroquinolones 5.68 (4.78-6.76), penicillin combinations 3.42 (2.35-4.96), and ceftriaxone 2.55 (1.41-4.62). Conclusion: This study confirms prior evidence for TdP/QTP associations with macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and ceftriaxone. This study also identifies a new association between amikacin and TdP/QTP.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Antibacterianos/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Torsades de Pointes/induzido quimicamente , Adulto , Feminino , Humanos , Síndrome do QT Longo/epidemiologia , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Torsades de Pointes/epidemiologia , Estados Unidos , United States Food and Drug Administration/estatística & dados numéricos
2.
J Oncol Pharm Pract ; 25(1): 198-204, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29298624

RESUMO

Since the introduction of regulatory drug approval guidance on the evaluation of QT interval prolongation, an increasing number of drug monographs has included cautions on the risk of QT prolongation. For example, QT prolongation is mentioned in the Canadian product monographs of 29 drugs commonly seen in oncology practice. This presents two major challenges. First, most guidelines and risk predictive tools for QT prolongation have been developed for hospitalized patients in acute care settings. In contrast, most QT-prolonging oncology drugs are used in medically stable patients in the ambulatory setting. Second, many oncology drugs are unique for their indications and non-QT prolonging alternative agents are often not available. In this review, we will outline an empiric initial approach to ambulatory cancer patients who are treated with oncology drugs which may prolong QT interval. This includes the predictive value of QT prolongation on torsades de pointes, the risk factors of the patients and the drugs, and the limitations of existing guidance in this area.


Assuntos
Assistência Ambulatorial/métodos , Antineoplásicos/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Neoplasias/tratamento farmacológico , Eletrocardiografia/métodos , Humanos , Síndrome do QT Longo/epidemiologia , Síndrome do QT Longo/fisiopatologia , Neoplasias/epidemiologia , Neoplasias/fisiopatologia , Fatores de Risco , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/epidemiologia , Torsades de Pointes/fisiopatologia
3.
J Clin Psychopharmacol ; 39(1): 72-77, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30531476

RESUMO

OBJECTIVE: The aim of our study was to assess the impact of psychiatric medications and concomitant risk factors on the prevalence of QTc prolongation and torsades de pointes (TdP) in hospitalized subjects. We examined the association between individual risk scores and QTc prolongation and proposed an evidence-based protocol for electrocardiogram monitoring on psychotropic medications. METHOD: Electrocardiograms (ECGs) of subjects hospitalized over a 1-year period were analyzed for QTc prolongation, associated risk factors, and use of medications. Analysis was performed using logistic regression to identify independent predictors of QTc prolongation, and the Pearson χ test was used for risk score assessment. RESULTS: A total of 1249 ECGs of 517 subjects were included in this study. Eighty-seven subjects had QTcB intervals greater than 470 milliseconds for females and greater than 450 milliseconds for males. Twelve (2.3%) subjects had QTcB of 500 milliseconds or greater, or greater than 60 milliseconds of change from baseline. Of these subjects, only 1 case of QTc interval change was related to routine use of psychiatric medications. There were no incidents of TdP. Age, diabetes, hypokalemia, overdose, diphenhydramine, and haloperidol were significant independent predictors of QTc prolongation. Risk scores were significantly correlated with QTc prolongation (P = 0.001). CONCLUSION: Our retrospective review study found that the occurrence of TdP and QTc prolongation was low in this subject population. QT abnormalities were associated with known risk factors, and risk scores correlated well with QTc prolongation. Providers can use the protocol proposed in this study, which incorporates risk scores and the CredibleMeds classification system to determine the need for ECG monitoring and to guide treatment.


Assuntos
Síndrome do QT Longo/epidemiologia , Psicotrópicos/efeitos adversos , Medição de Risco/métodos , Torsades de Pointes/epidemiologia , Adulto , Idoso , Estudos Transversais , Eletrocardiografia , Feminino , Georgia/epidemiologia , Humanos , Pacientes Internados/estatística & dados numéricos , Síndrome do QT Longo/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Torsades de Pointes/induzido quimicamente , Adulto Jovem
4.
Psychiatry Res ; 270: 341-347, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30292087

RESUMO

Severe mental disorders have been reported to be associated with an increased cardiovascular risk. To measure the potential risk excess as compared, not with the baseline cardiovascular risk for the general population, but with the cardiovascular risk associated with drug iatrogenia. 197 reported cases of cardiovascular adverse reaction to antipsychotic drugs as compared to the reported cases of this type of adverse reactions to drugs other than antipsychotics entered in the Spanish Pharmacovigilance System database (FEDRA) (1995-2018) in an observational case/non-case study. Risk estimates of association were reporting odds ratio (ROR), and, chi-square test (χ2). Overall disproportionality for the whole drug class was found [ROR 2.3 (95% CI 2.0-2.7)], χ2 = 127.07]. When the two types of antipsychotics (typical and atypical) were analysed separately, we also found statistically significant disproportionality, and this disproportionality is similar between both groups, with disproportionality measures around 2.30, with the confidence intervals not including the 1. The disproportionality observed suggests a risk excess that might be greater than expected, which holds particularly true for torsade de pointes, sudden death and cardiac arrhythmias in patients treated with any of the two types of antipsychotics. There was no significant risk for ischaemic heart disease.


Assuntos
Antipsicóticos/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Transtornos Mentais/tratamento farmacológico , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/epidemiologia , Aleitamento Materno , Estudos de Casos e Controles , Criança , Pré-Escolar , Bases de Dados Factuais , Morte Súbita/epidemiologia , Exposição Dietética , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Razão de Chances , Farmacovigilância , Fatores de Risco , Espanha/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Torsades de Pointes/epidemiologia , Adulto Jovem
5.
Eur J Clin Pharmacol ; 74(12): 1645-1651, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30112668

RESUMO

INTRODUCTION: Several drug classes (antiarrhythmics, antimicrobials, antidepressants, phenothiazines, opiates, prokinetics of digestive tract, etc.) have been related to ventricular hyperkinetic arrhythmias such as torsade de pointes (TdP). TdPs are usually heralded by an abnormal prolongation of heart rate-corrected QT interval on the electrocardiogram, so-called drug-induced long heart rate-corrected QT (diLQTc). We do not know to what extent the drug-induced QTc prolongation is able to predict malignant arrhythmias. Thus, we have retrospectively examined the clinical history of patients with diLQTc. METHODS: The case record, concerning the period January 2008-December 2017, was collected from two hospitals. diLQTc was defined as drug-induced heart rate-corrected QT of ≥ 450 ms or ≥ 470 ms, respectively in male or female patients. The primary purpose was to verify whether in diLQTc patients the length of this electrocardiographic segment was associated with the risk of symptoms or events (TdP, ventricular fibrillation). RESULTS: Seventy-three validated cases of diLQTc were gathered. Among them, the QTc duration was not able to predict the occurrence of symptoms or events (odds ratio, 0.998; 95% CI, 0.984 to 1.013; p = 0.8821). Likewise, a diQTc lasting longer than 500 ms compared to diQTc comprised between 450 and 500 ms was not associated with an increased risk of arrhythmic events. CONCLUSIONS: In our diLQTc patients, QTc duration did not predict occurrence of symptoms, or arrhythmic events. Thus, other determinants should be postulated to clarify why sometimes diQTc prolongation propitiates ventricular malignant arrhythmias whereas in other cases this arrhythmogenic effect is lacking.


Assuntos
Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Eletrocardiografia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/epidemiologia , Fibrilação Ventricular/induzido quimicamente , Fibrilação Ventricular/epidemiologia
6.
Pharmacoepidemiol Drug Saf ; 27(12): 1316-1324, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30106193

RESUMO

PURPOSE: Our aim was to describe trends in the prescription of domperidone for insufficient lactation in England, the characteristics of women prescribed it postpartum, and the impact of a 2014 European Medicines Agency (EMA) recommendation to restrict its use due to a potential increased risk of sudden cardiac death associated with its use. METHODS: We conducted a population-based cohort study with interrupted time series analysis using data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics. We identified women with live births from 2002 to 2015, excluding those with nonlactation indications for domperidone (n = 247 349). We evaluated trends in the prescription rate of domperidone in the 6 months postpartum and differences in this rate before and after the EMA recommendation. RESULTS: Domperidone was prescribed among 1438 deliveries at a rate of 1.24 per 100 person-years. This rate increased from 0.56 to 2.1 per 100 person-years between 2002-2004 and 2011-2013 (rate ratio: 3.8; 95% confidence interval [CI], 3.2-4.6). Prescribing decreased in level by 0.35 (95% CI, -0.86 to 0.16) per 100 person-years immediately following the recommendation with little change in trend (0.003; 95% CI, -0.059 to 0.065 per 100 person-years). Following the recommendation, prescription of doses >30 mg and coprescription of drugs with a risk of torsade de pointes decreased. No arrhythmic events were observed among domperidone users. CONCLUSIONS: Although we observed an important increase in prescribing during the study period, domperidone remains infrequently prescribed postpartum in England. While overall prescribing changed little, some prescribing practices became more restricted following the EMA's recommendation.


Assuntos
Domperidona/administração & dosagem , Antagonistas de Dopamina/administração & dosagem , Revisão de Uso de Medicamentos , Lactação/efeitos dos fármacos , Adulto , Estudos de Coortes , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Domperidona/efeitos adversos , Antagonistas de Dopamina/efeitos adversos , Relação Dose-Resposta a Droga , Prescrições de Medicamentos/normas , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Inglaterra/epidemiologia , União Europeia/organização & administração , Feminino , Órgãos Governamentais/normas , Humanos , Análise de Séries Temporais Interrompida , Guias de Prática Clínica como Assunto , Fatores de Risco , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/epidemiologia , Torsades de Pointes/prevenção & controle , Adulto Jovem
7.
Postgrad Med ; 130(8): 660-665, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30145917

RESUMO

OBJECTIVES: Patients admitted in coronary care units are susceptible to QT interval prolongation due to numerous risk factors. The purpose of this study was to identify the prevalence of risk factors for QT interval prolongation; QT prolonging medications; drug-drug interactions; their predictors; and torsades de pointes risks of drugs. METHODS: After obtaining approval, this cross-sectional study was carried out during one-year period in coronary care units of two major tertiary care hospitals of Khyber Pakhtunkhwa, Pakistan. The Arizona Center for Education and Research on Therapeutics QT drugs lists and Micromedex DrugReax® were used to identify the QT prolonging medications and QT prolonging drug-drug interactions. RESULTS: Total 649 patients were included in this study. The most frequent QT prolonging risk factors included use of ≥ 1 QT prolonging drugs (74.9%) and myocardial infarction (61.3%). Total 181 patients were presented with 361 QT prolonging drug-drug interactions. There was significant association of the occurrence of QT prolonging drug-drug interactions with female gender (p = 0.01), 9-10 prescribed medications (p = 0.001), and > 10 prescribed medications (p < 0.001). CONCLUSIONS: The majority of patients presented with multiple risk factors for QT prolongation in coronary care units which may precipitate lethal outcomes.


Assuntos
Unidades de Cuidados Coronarianos/estatística & dados numéricos , Interações de Medicamentos , Torsades de Pointes/induzido quimicamente , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Comorbidade , Estudos Transversais , Diabetes Mellitus/epidemiologia , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão , Polimedicação , Prevalência , Fatores de Risco , Fatores Sexuais , Centros de Atenção Terciária/estatística & dados numéricos , Torsades de Pointes/epidemiologia
8.
Heart Rhythm ; 15(4): 478-484, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29605013

RESUMO

BACKGROUND: Compared with men, women have longer corrected QT (QTc) intervals, lower clearance of dofetilide, and higher rates of drug-induced torsades de pointes, but the dofetilide dosing algorithm is the same for men and women. OBJECTIVE: The purpose of this study was to evaluate the tolerability of the 500 µg twice daily dose of dofetilide for men and women. METHODS: Men and women admitted to Duke University Medical Center (January 1, 2006, to October 19, 2012) for the initiation of dofetilide 500 µg twice daily were matched 1:1 on age and estimated creatinine clearance. Electrocardiograms throughout dosing were analyzed, and rates of dofetilide discontinuations and dose reductions were compared in unadjusted and adjusted analyses. RESULTS: For 220 matched men and women, the median age was 62.5 years (interquartile range 55-69 years) and the median eCrCl was 98.1 mL/min (interquartile range 77.6-126.2 mL/min). Women were less likely than men to have hypertension and interventricular conduction delay but were otherwise similar. During dofetilide initiation, women were more likely than men to have their dofetilide dose discontinued or reduced (55% vs 32%; P < .001). In most women (82%) and men (69%), the reason for dose adjustment was significant QTc prolongation. In the adjusted analysis, female sex was associated with higher rates of dofetilide dose discontinuations or reductions (odds ratio 3.01; 95% confidence interval 1.58-5.71; P < .01). CONCLUSION: More than half of women who initiated on 500 µg twice daily of dofetilide required medication discontinuations or dose reductions, mostly because of QTc prolongation. Additional studies are needed to evaluate the optimal dosing algorithm of dofetilide in women.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Tolerância a Medicamentos , Eletrocardiografia/efeitos dos fármacos , Fenetilaminas/efeitos adversos , Sulfonamidas/efeitos adversos , Torsades de Pointes/induzido quimicamente , Idoso , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/fisiopatologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Fenetilaminas/administração & dosagem , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Sulfonamidas/administração & dosagem , Torsades de Pointes/epidemiologia , Torsades de Pointes/fisiopatologia
9.
Am J Cardiol ; 121(2): 182-187, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29174490

RESUMO

Patients with long QT syndrome (LQTS) are at a high risk of cardiac events. Many patients with LQTS are treated with antidepressant drugs (ADs). We investigated the LQTS genotype-specific risk of recurrent cardiac arrhythmic events (CAEs) associated with AD therapy. The study included 59 LQT1 and 72 LQT2 patients from the Rochester-based LQTS Registry with corrected QT (QTc) prolongation and a history of AD therapy. Using multivariate Anderson-Gill models, we estimated the LQTS genotype-specific risk of recurrent CAEs (ventricular tachyarrhythmias, aborted cardiac arrest, or sudden cardiac death) associated with time-dependent ADs. Specifically, we examined the risk associated with all ADs, selective serotonin reuptake inhibitor (SSRI), and ADs classified on the CredibleMeds list (www.CredibleMeds.org) as "Conditional" or "Known risk of Torsades de pointes (TdP)." After adjusting for baseline QTc duration, sex, and time-dependent beta-blocker usage, there was an increased risk of recurrent CAEs associated with ADs in LQT1 patients (hazard ratio = 3.67, 95% confidence interval 1.98-6.82, p < 0.001) but not in LQT2 patients (hazard ratio = 0.89, 95% confidence interval 0.49-1.64, p = 0.716; LQT1 vs LQT2 interaction, p < 0.001). Similarly, LQT1 patients who were on SSRIs or ADs with "Known risk of TdP" had a higher risk of recurrent CAEs than those patients off all ADs, whereas there was no association in LQT2 patients. ADs with "Conditional risk of TdP" were not associated with the risk of recurrent CAEs in any of the groups. In conclusion, the risk of recurrent CAEs associated with time-dependent ADs is higher in LQT1 patients but not in LQT2 patients. Results suggest a LQTS genotype-specific effect of ADs on the risk of arrhythmic events.


Assuntos
Antidepressivos/uso terapêutico , Arritmias Cardíacas/epidemiologia , Morte Súbita Cardíaca/epidemiologia , Síndrome do QT Longo/epidemiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Eletrocardiografia , Feminino , Genótipo , Parada Cardíaca/epidemiologia , Humanos , Síndrome do QT Longo/genética , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Taquicardia Ventricular/epidemiologia , Torsades de Pointes/epidemiologia , Fibrilação Ventricular/epidemiologia
10.
Indian Heart J ; 69(6): 707-713, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29174246

RESUMO

AIM: To define the incidence, presentation, and outcomes of drug-induced Torsades de Pointes (TdP) with intravenous (IV) amiodarone. METHODS: From January 2014 to August 2016 a total of 268 patients received IV amiodarone, 142 for ventricular tachycardia, 104 for atrial flutter/fibrillation, and 22 for incessant atrial tachycardia. A uniform dosing of amiodarone to yield 1gm/day was used in all patients. RESULTS: Four of the 268 patients (M:F 1:3) with mean age of 51.25+9.17years developed pause dependent TdP degenerating to VF, after a mean dose of 690+176.63mg, infused over 12+5.88h. The QTc that was 505+9.02ms at the time of TdP normalized to 433.75+6.13ms 48-72h after stopping amiodarone. There was no immediate or late mortality, and patients are well at 5-10 months of follow-up. None of the patients tested positive for LQTS genes. CONCLUSION: The incidence of drug-induced TdP with IV amiodarone is about 1.5%. Risk factors include female sex, left ventricular dysfunction, electrolyte abnormalities, baseline prolonged QTc, concomitant beta-blocker, and digoxin therapy. Amiodarone induced TdP has favorable prognosis if recognized and treated promptly, and these patients should not receive amiodarone by any route in future.


Assuntos
Amiodarona/efeitos adversos , Torsades de Pointes/epidemiologia , Amiodarona/administração & dosagem , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Eletrocardiografia , Feminino , Humanos , Incidência , Índia/epidemiologia , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/fisiopatologia
11.
Int J Clin Pharm ; 39(6): 1256-1264, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28895028

RESUMO

Background QT prolongation and associated arrhythmias, torsades de pointes (TdP), are considerable negative outcomes of many antipsychotic and antidepressant agents frequently used by psychiatric patients. Objective To identify the prevalence, levels, and predictors of QT prolonging drug-drug interactions (QT-DDIs), and AZCERT (Arizona Center for Education and Research on Therapeutics) classification of drugs involved in QT-DDIs. Setting Psychiatry wards of three major tertiary care hospitals of Khyber-Pakhtunkhwa, Pakistan. Method This was a multicenter cross-sectional study. Micromedex DrugReax was used for identification of QT-DDIs. TdP risks were identified by the AZCERT classification. Multivariate logistic regression analysis was performed to identify predictors of QT-DDIs. Main outcome measure Prevalence of QT-DDIs (overall, age-wise and gender-wise) and their levels of severity and documentation; AZCERT classes of drugs involved in QT-DDIs; and odds ratios for predictors of QT-DDIs. Results Of 600 patients, 58.5% were female. Median age was 25 years (IQR = 20-35). Overall 51.7% patients had QT-DDIs. Of total 698 identified QT-DDIs, most were of major-severity (98.4%) and fair-documentation (93.7%). According to the AZCERT classification, 36.4% of the interacting drugs were included in list-1 (known risk of TdP), 26.9% in list-2 (possible risk of TdP) and 27.5% in list-3 (conditional risk of TdP). Drugs commonly involved in QT-DDI were olanzapine (n = 146), haloperidol (138), escitalopram (122), risperidone (91), zuclopenthixol (87), quetiapine (n80) and fluoxetine (74). In multivariate logistic regression analysis, QT-DDIs were significantly associated with 6-7 prescribed medications (p = 0.04) and >7 medications (p = 0.03). Similarly, there was significant association of occurrence of QT-DDIs with 2-3 QT drugs (p < 0.001) and >3 QT drugs (p < 0.001). Conclusion A considerable number of patients are exposed to QT-DDIs in psychiatry. There is a need to implement protocol for monitoring the outcomes of QT-DDIs.


Assuntos
Antidepressivos/efeitos adversos , Antipsicóticos/efeitos adversos , Interações de Medicamentos , Síndrome do QT Longo/epidemiologia , Unidade Hospitalar de Psiquiatria/estatística & dados numéricos , Torsades de Pointes/epidemiologia , Adulto , Antidepressivos/classificação , Antipsicóticos/classificação , Estudos Transversais , Humanos , Masculino , Paquistão/epidemiologia , Prevalência , Centros de Atenção Terciária , Adulto Jovem
12.
Int J Cardiol ; 243: 511-515, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28576628

RESUMO

BACKGROUND: Multiple risk factors play a role in the development of QTc-prolongation and Torsade de Pointes (TdP). Cases of TdP are underreported and data on the incidence of TdP is scarce. The aim of this study was to investigate the incidence of TdP in a Belgian university hospital and describe the characteristics of TdP-cases using a risk score. METHODS: All cases from 2011 till 2013 coded with the ICD-9 code 427.1 in the University Hospitals of Leuven were selected. The medical files were reviewed and demographical, medical, medication and electrocardiographic data were collected. We focused on TdP-cases that were probably caused by the acquired long QT-syndrome. The RISQ-PATH score was used to quantify the risk in these cases (≥10 points as high risk for QTc-prolongation/TdP). RESULTS: Over three years, 41 TdP-cases were identified of which 19 cases were secondary to the acquired long QT-syndrome (52.6% females, mean age of 74±12years). This corresponds with an incidence of 0.16‰/year in a hospital population. Most of the patients (N=17) were treated with at least one QTc-prolonging drug (most frequently amiodarone, sotalol and furosemide) of whom 12 patients with ≥1 QTc-prolonging drug of list 1 of CredibleMeds. Fifteen patients had an electrocardiogram in a 24-hours interval before the TdP with a prolonged QTc-interval (≥450/470ms). All the patients had a RISQ-PATH score≥10. CONCLUSIONS: Although the incidence of 0.16‰/year might seem low, this means that approximately 173 possibly lethal TdP-cases can be expected in Belgian hospitals each year. All TdP-cases were associated with a high RISQ-PATH score.


Assuntos
Vigilância da População , Centros de Atenção Terciária , Torsades de Pointes/diagnóstico , Torsades de Pointes/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Eletrocardiografia/tendências , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária/tendências , Torsades de Pointes/fisiopatologia
14.
Acta Clin Belg ; 72(6): 385-390, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28335691

RESUMO

OBJECTIVES: Post-marketing surveillance is very important, especially for rare adverse drug reactions like QTc-prolongation and Torsade de Pointes (TdP). The objective of this study was to investigate the characteristics of Belgian cases of drug-related TdP reported in the EudraVigilance database. METHODS: The EudraVigilance database was searched for Belgian post-marketing cases of TdP reported between December 2001-April 2015. These cases were identified with MedDRA preferred terms. Duplicate reports were excluded. Each included case report was reviewed to collect data about age, gender, seriousness, suspected drug, concomitant drugs, causality, and other known risk factors for QTc-prolongation. RESULTS: Between 2001 and 2015, only 31 cases coded as TdP were identified; 16 cases were also coded as 'prolonged QT' and 2 patients died. In total, 21 suspected drugs were implicated and most of them (N = 11) were part of list 1 of CredibleMeds. The most common suspected drugs were citalopram (N = 4) and amiodarone (N = 3). In 18 cases, a pharmacodynamic drug-drug interaction with risk of QTc-prolongation was present. Most patients (N = 25) had ≥2 other risk factors for QTc-prolongation. CONCLUSION: Over 15 years, only a low number of Belgian cases of TdP were identified in the EudraVigilance database. In most case reports, multiple risk factors for QTc-prolongation could be detected. This illustrates that there is a clear underreporting of QTc-prolongation and TdP in Belgium. Initiatives are needed to improve the awareness and knowledge of health care professionals regarding the risk of QTc-prolongation and TdP, both to prevent cases of TdP and to stimulate the reporting of these cases.


Assuntos
Torsades de Pointes/induzido quimicamente , Idoso , Bélgica/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Torsades de Pointes/epidemiologia
15.
Pacing Clin Electrophysiol ; 40(6): 667-671, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28220940

RESUMO

BACKGROUND: Dofetilide is a pure IKr blocker and is one of the few drugs specifically studied and approved in the United States for the management of persistent atrial fibrillation (AF). Dofetilide has been noted to have a high rate of pharmacologic conversion during initial dosing in prior smaller studies. The intent of the study was to examine the safety of an inpatient loading strategy, and the incidence and patterns of pharmacologic conversion by dofetilide during the treatment of persistent AF in a large consecutive cohort. METHODS AND RESULTS: This is a retrospective analysis of 308 consecutive patients with persistent AF electively admitted for inpatient dofetilide loading. The initiation dose of dofetilide was determined by the creatinine clearance. Overall, 88% (n = 271) successfully completed initiation of dofetilide and were discharged in sinus rhythm. The most common reason for failure to complete initiation of dofetilide loading was QTc prolongation in 24 patients (7.8%), and torsade de pointes occurred in three patients (1%). Pharmacologic conversion was observed in 56% (n = 151) after a median of two doses. The rate of pharmacologic conversion based on the final dose was 75%, 9%, and 0% for 500 mcg, 250 mcg, and 125 mcg, respectively (P < 0.05). CONCLUSIONS: Dofetilide is a well-tolerated antiarrhythmic drug with a low incidence of proarrhythmia and an especially high rate of pharmacologic conversion in patients with persistent AF.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Eletrocardiografia/efeitos dos fármacos , Síndrome do QT Longo/epidemiologia , Fenetilaminas/administração & dosagem , Sulfonamidas/administração & dosagem , Torsades de Pointes/epidemiologia , Antiarrítmicos/administração & dosagem , Fibrilação Atrial/diagnóstico , Causalidade , Doença Crônica , Estudos de Coortes , Comorbidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Feminino , Humanos , Síndrome do QT Longo/diagnóstico , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Torsades de Pointes/diagnóstico , Resultado do Tratamento
16.
J Am Pharm Assoc (2003) ; 57(2S): S63-S67, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28073687

RESUMO

OBJECTIVE: The purpose of this investigation was to identify and characterize post-marketing reports of cardiotoxicity, including torsades de pointes (TdP), associated with loperamide use. METHODS: We searched the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database for post-marketing reports of serious cardiac adverse events associated with loperamide use from December 28, 1976 (U.S. drug approval date), through December 14, 2015. We also conducted a Pubmed and Google Scholar search to identify additional published reports of cardiotoxicity associated with loperamide in the medical literature through February 11, 2016. RESULTS: Forty-eight cases of serious cardiac adverse events associated with loperamide use composed the case series. The most frequently reported cardiac adverse events were syncope (n = 24), cardiac arrest (n = 13), QT-interval prolongation (n = 13), ventricular tachycardia (n = 10), and TdP (n = 7). There were 10 cases that resulted in death. Of the 48 cases, the most commonly reported reasons for use can be characterized as drug abuse (n = 22) and diarrhea treatment (n = 17). More than one-half of the 48 cases were reported after 2010. Of the 22 drug abuse cases, the median daily dose was 250 mg (range 70 mg to 1600 mg) and events occurred as early as 6 hours after a dose and as long as 18 months after initiation of loperamide. Thirteen of the 22 cases reported using loperamide for euphoric or analgesic effects, and 9 reported use to prevent opioid withdrawal symptoms. CONCLUSION: The FAERS case reports provide evidence to suggest that high doses of loperamide are associated with TdP and other serious cardiac adverse events. The majority of cases in this series occurred in the setting of drug abuse for the purpose of preventing opioid withdrawal or to produce euphoric effects. It is important for both clinicians and patients to be aware of this potential risk, because prompt therapy and discontinuation of the offending agent are often essential to management and prevention of loperamide-induced cardiac arrhythmias.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Cardiotoxicidade/etiologia , Loperamida/efeitos adversos , Torsades de Pointes/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cardiotoxicidade/fisiopatologia , Criança , Pré-Escolar , Bases de Dados Factuais , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Loperamida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Torsades de Pointes/epidemiologia , Estados Unidos , United States Food and Drug Administration , Adulto Jovem
17.
Heart Rhythm ; 14(1): 90-95, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27650425

RESUMO

BACKGROUND: Female gender increases the risk of torsades de pointes (TdP) in the long QT syndrome, and this increased risk is assumed to be due to their longer QT interval. OBJECTIVE: The purpose of this study was to study the interplay between gender, duration of the QT interval, and risk of TdP during AV block. METHODS: We studied 250 patients (48% women) with AV block. QT interval was measured at the time of most severe bradycardia. We then constructed different receiver operating characteristic curves for the QTc of males and females for predicting TdP. RESULTS: As expected, patients with TdP had longer QTc intervals than did patients with uncomplicated AV block (564 ± 81 ms vs 422 ± 62 ms, P < .001). This correlation between longer QTc and higher risk of TdP was true for both genders. However, the QT of females with TdP was shorter than the respective value for males with TdP. Despite similar severity of bradycardia, the QT was shorter for females (QT 672 ± 88 ms vs 727 ± 57 ms for females with TdP vs males with TdP, P = .022). The QTc/TdP risk curve for females was shifted to the left in comparison to the pertinent graph for males. Female gender was an independent predictor of TdP. CONCLUSION: Women are at increased risk for developing TdP during AV block, but this increased risk is independent of their longer QT interval. Females develop TdP with QT intervals that are not necessarily arrhythmogenic for males.


Assuntos
Bloqueio Atrioventricular/epidemiologia , Causas de Morte , Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Síndrome do QT Longo/epidemiologia , Torsades de Pointes/epidemiologia , Análise de Variância , Bloqueio Atrioventricular/diagnóstico , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Identidade de Gênero , Humanos , Síndrome do QT Longo/diagnóstico , Masculino , Razão de Chances , Prevalência , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Taxa de Sobrevida , Torsades de Pointes/diagnóstico
18.
Drug Saf ; 40(2): 133-144, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27896662

RESUMO

INTRODUCTION: Drugs that potentially prolong the QT interval carry the risk of life-threatening Torsades de pointes (TdP) ventricular arrhythmia. OBJECTIVE: The objective of this study was to investigate the potential additive risk for ventricular arrhythmia with concomitant prescriptions of QT-prolonging drugs. METHODS: Claims data for persons aged ≥65 years between 2010 and 2012 in Germany were analyzed and all cases hospitalized for ventricular arrhythmia were selected. In a case-crossover analysis, exposure with QT-prolonging drugs according to the Arizona Center for Education and Research on Therapeutics (AZCERT) classification of 'known,' 'conditional,' and 'possible' TdP risk was determined in respective event and control windows preceding hospitalization. Conditional logistic regression was applied to derive odds ratios (ORs). RESULTS: Among 6,849,622 health-insured persons, we identified 2572 patients newly hospitalized for ventricular arrhythmia. Drugs with 'known' risk were more frequently prescribed in the event window than in the control window (309 vs. 239; P < 0.001). The number of drugs with an attributed 'known' risk of TdP was significantly associated with hospitalization for ventricular arrhythmia (OR: 2.22; 95% confidence interval [1.51-3.25]; P < 0.001), while increased risk estimates were also obtained upon categorization into one and two or more drugs compared with no drugs for the combined group of drug with 'known' (1.52 [1.16-2.00]) and 'conditional' risk (2.20 [1.42-3.41]). Pairwise comparisons and trend tests based on these classification categories could not demonstrate a significantly increased risk of two or more drugs compared with one drug. CONCLUSION: Beyond suitable single-drug classifications for QT-associated risk estimation, the situation when there is co-prescription of several drugs appears to be complex and may not be extrapolated to all possible multi-drug combinations.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Síndrome do QT Longo/induzido quimicamente , Torsades de Pointes/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/epidemiologia , Estudos Cross-Over , Bases de Dados Factuais , Interações de Medicamentos , Feminino , Alemanha , Hospitalização/estatística & dados numéricos , Humanos , Modelos Logísticos , Síndrome do QT Longo/epidemiologia , Masculino , Torsades de Pointes/epidemiologia
19.
Heart Rhythm ; 14(1): 98-107, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27756708

RESUMO

BACKGROUND: Ventricular fibrillation may be caused by premature ventricular contractions (PVCs) whose coupling intervals are <300 ms, a characteristic of the short-coupled variant of torsades de pointes (scTdP). OBJECTIVE: The purpose of this study was to analyze the underlying cardiac ryanodine receptor (RyR2) variants in patients with scTdP. METHODS: Seven patients with scTdP (mean age 34 ± 12 years; 4 men and 3 women) were enrolled in this study. The RyR2 gene was screened by targeted gene sequencing methods; variant minor allele frequency was confirmed in 3 databases; and the pathogenicity was investigated in silico analysis using multiple tools. The activity of wild-type and mutant RyR2 channels was evaluated by monitoring Ca2+ signals of HEK293 cells with a [3H]ryanodine binding assay. RESULTS: The mean coupling interval of PVCs was 282 ± 13 ms. The 12-lead electrocardiogram had no specific findings except PVCs with an extremely short-coupling interval. Genetic analysis revealed 3 novel RyR2 variants and 1 polymorphism, all located in the cytoplasmic region. p.Ser4938Phe was not detected in 3 databases, and in silico analysis indicated its pathogenicity. In functional analysis, p.Ser4938Phe demonstrated loss of function and impaired RyR2 channel Ca2+ release, while 2 other variants, p.Val1024Ile and p.Ala2673Val, had mild gain-of-function effects but were similar to the polymorphism p.Asn1551Ser. CONCLUSION: We identified an RyR2 variant associated with reduced Ca2+ release and short-coupled torsades de pointes ventricular arrhythmia. The mechanisms of arrhythmogenesis remain unclear.


Assuntos
Canais de Cálcio/metabolismo , Regulação da Expressão Gênica , Variação Genética , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Taquicardia Ventricular/genética , Torsades de Pointes/genética , Adulto , Análise Mutacional de DNA , Eletrocardiografia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Amostragem , Taxa de Sobrevida , Taquicardia Ventricular/epidemiologia , Taquicardia Ventricular/fisiopatologia , Torsades de Pointes/epidemiologia , Torsades de Pointes/fisiopatologia , Adulto Jovem
20.
Rev Epidemiol Sante Publique ; 65(1): 1-8, 2017 Feb.
Artigo em Francês | MEDLINE | ID: mdl-27988172

RESUMO

OBJECTIVES: Observational retrospective studies have linked domperidone and prolonged QT interval, ventricular arrhythmias and risk of sudden death. Since then, antiemetic prescription was applied to other molecules (including metopimazine). The aim of this study was to evaluate the profile of adverse cardiac effects associated with QT prolongation for each antiemetic available in France. METHODS: We conducted disproportionality analyses (case/non-case method), based on the observations recorded consecutively in the French national pharmacovigilance database between 2004 and 2013. Cases were defined by following MedDRA terms: prolongation of the QT interval, syncope, sudden death, cardiac arrest, ventricular arrhythmias including torsades de pointes; non-cases were other adverse events reported during the same period. We analyzed the presence of each antiemetic among cases and non-cases and measured the disproportionality by reporting odds ratios (ROR). We validate the assay with a positive control (methadone) and a negative control (acetaminophen). RESULTS: We compared 2093 cases (94 with antiemetics) to 253,665 non-cases (7015 with antiemetics). Among antiemetics, adverse cardiac effects studied were more frequently found with notifications including domperidone (ROR=2.0, 95% CI=[1.3; 3.0]), ondansetron (ROR=1.8, 95% CI=[1.3; 2.6]) and granisetron (ROR=3.4, 95% CI=[1.5; 7.6]). Metopimazine was not statistically associated with that risk (ROR=2.0; 95% CI=[0.8; 4.8]). CONCLUSION: We confirmed a risk of cardiac adverse event related to prolongation of the QT interval with domperidone and setrons. These results suggest caution when prescribing antiemetics and encourage systematic reporting of adverse cardiac effects observed with these molecules.


Assuntos
Antieméticos/efeitos adversos , Domperidona/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/epidemiologia , Síndrome de Brugada/induzido quimicamente , Síndrome de Brugada/epidemiologia , Doença do Sistema de Condução Cardíaco , Bases de Dados Factuais , Morte Súbita Cardíaca/epidemiologia , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Estudos Retrospectivos , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/epidemiologia , Adulto Jovem
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