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array:24 [ "pii" => "S2387020615001527" "issn" => "23870206" "doi" => "10.1016/j.medcle.2014.01.009" "estado" => "S300" "fechaPublicacion" => "2015-03-15" "aid" => "2890" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2013" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2015;144:269-74" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 78 "formatos" => array:2 [ "HTML" => 62 "PDF" => 16 ] ] "Traduccion" => array:1 [ "es" => array:18 [ "pii" => "S0025775314001201" "issn" => "00257753" "doi" => "10.1016/j.medcli.2014.01.027" "estado" => "S300" "fechaPublicacion" => "2015-03-15" "aid" => "2890" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "subdocumento" => "rev" "cita" => "Med Clin. 2015;144:269-74" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 346 "formatos" => array:2 [ "HTML" => 296 "PDF" => 50 ] ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Revisión</span>" "titulo" => "Prolongación del intervalo QT inducido por fármacos: ¿conocemos sus riesgos?" 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"documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2015;144:275-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 59 "formatos" => array:2 [ "HTML" => 47 "PDF" => 12 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>" "titulo" => "Adaptive authorization: A new way for the early access of new drugs?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "275" "paginaFinal" => "278" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Autorización progresiva: ¿un nuevo camino hacia el acceso temprano de nuevos medicamentos?" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rafael Dal-Ré, Xavier Carné" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Rafael" "apellidos" => "Dal-Ré" ] 1 => array:2 [ "nombre" => "Xavier" "apellidos" => "Carné" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775314005727" "doi" => "10.1016/j.medcli.2014.06.011" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775314005727?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S238702061500159X?idApp=UINPBA00004N" "url" => "/23870206/0000014400000006/v1_201512090148/S238702061500159X/v1_201512090148/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S2387020615001229" "issn" => "23870206" "doi" => "10.1016/j.medcle.2014.01.007" "estado" => "S300" "fechaPublicacion" => "2015-03-15" "aid" => "2904" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2015;144:265-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 79 "formatos" => array:2 [ "HTML" => 65 "PDF" => 14 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Regulatory T cells, maternal–foetal immune tolerance and recurrent miscarriage: New therapeutic challenging opportunities" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "265" "paginaFinal" => "268" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Linfocitos T reguladores, tolerancia maternofetal y aborto recurrente: nuevas oportunidades terapéuticas" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1426 "Ancho" => 1901 "Tamanyo" => 363515 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">C</span>ells and cytokines related to the foetal–maternal “tolerant” microenvironment. Bottom: After encountering paternal-derived antigens in the periphery or in the genital tract, antigen-specific Tregs are generated. This specific Treg population could expand later, as paternal–foetal alloantigens are continuously released to the periphery. Tregs would then migrate into foetal–maternal interface where they would help to create a site of immune privilege characterized by high levels of protective molecules, e.g. HO-1, LIF, IDO, TGFβ, IL-10 and PIBF. Furthermore, Tregs maintain adequate NK3/NK1 cell subpopulation preventing trophoblast injury and permit a sufficient angiogenesis. In the end, Tregs may down-regulate maternal allo-response to foetal–paternal antigens, preventing apoptosis of trophoblast cells.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Jaume Alijotas-Reig, Taisiia Melnychuk, Josep Maria Gris" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Jaume" "apellidos" => "Alijotas-Reig" ] 1 => array:2 [ "nombre" => "Taisiia" "apellidos" => "Melnychuk" ] 2 => array:2 [ "nombre" => "Josep Maria" "apellidos" => "Gris" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020615001229?idApp=UINPBA00004N" "url" => "/23870206/0000014400000006/v1_201512090148/S2387020615001229/v1_201512090148/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Drug-induced QT interval prolongation: Do we know the risks?" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "269" "paginaFinal" => "274" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Elena Villamañán, Eduardo Armada, Margarita Ruano" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Elena" "apellidos" => "Villamañán" "email" => array:1 [ 0 => "evillabueno@telefonica.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Eduardo" "apellidos" => "Armada" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Margarita" "apellidos" => "Ruano" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Farmacia, Hospital Universitario La Paz, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Cardiología, Hospital Universitario La Paz, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Prolongación del intervalo QT inducido por fármacos: ¿conocemos sus riesgos?" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Currently, sudden cardiac death (SCD) is an important public health issue in developed countries. Approximately 12% of natural deaths occur suddenly; of these, 88% are due to cardiac problems, which is the cause of death of more than 50% of the patients with coronary heart disease.<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">1,2</span></a> Most SCD cases are caused by acute ventricular arrhythmias (80–85%) and are due to coronary disease.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">3</span></a> However, they are sometimes caused by arrhythmias as a consequence of the prolongation of the QT interval.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A significant risk factor for these disorders is the use of QT-prolonging drugs.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">6</span></a> In fact, in recent years, one of the most frequent reasons for withdrawing drugs from the market or restricting their use has been the prolongation of the QT interval. This is because, despite their low prevalence, it is well known that severe episodes due to this cause may lead to deadly consequences.<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">6,7</span></a> Nowadays, the prolongation of the QT interval with or without related proarrhythmic effect is, together with the hepatotoxicity, the most common cause for the withdrawal of commercialised drugs.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">It is important for clinicians to know the risks involved in the use of these drugs in certain patients.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">8</span></a> Generally, this risk is considered when prescribing antiarrhythmic drugs, although not only these agents have this effect. There are several non-cardiovascular drugs that may potentially prolong the QT interval and worsen or provoke <span class="elsevierStyleItalic">torsade de pointes</span> (TdP). This possibility is even higher in patients with other associated factors, such as comorbidity, advanced age, liver or kidney failure, baseline cardiac disease or electrolytic alterations and, in addition, patients who frequently receive intravenous drugs. At the same time, some QT-prolonging drugs can modify heart rate (HR), which, together with certain clinical situations that can also affect HR, further complicate QT variations and their consequences.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Currently, several regulatory agencies require identifying possible risk for QT interval prolongation before and after the authorisation of drugs. In 2005, the European Medicines Agency (EMA) published a document with recommendations for the assessment of QT interval prolongation and the proarrhythmic potential for non-antiarrhythmic drugs. Since then, these guidelines are an essential requirement in the authorisation process of new drugs in Europe.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">10</span></a> That year, the U.S. Food and Drug Administration (FDA) published guidelines addressed to the industry, with rules for the clinical evaluation of QT/QTc (corrected QT) interval prolongation before the commercialisation of a drug in USA.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">11</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In light of the above, it is important for clinicians to be aware of the risks involved with the use of these drugs in certain patients. In this review, we will analyse QT-prolonging drugs, risk factors that may increase the possibilities of TdP and drug combinations that could exacerbate this situation.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Drugs that prolong the QT interval and may cause <span class="elsevierStyleItalic">torsades de pointes</span></span><p id="par0030" class="elsevierStylePara elsevierViewall">The relationship between certain drug treatments and the prolongation of the QT interval has long been known. The appearance of syncopes related to the beginning of the treatment with quinidine was observed for the first time in the 1920s. In the 1960s, a “pause-dependent” polymorphic ventricular tachycardia was identified as an underlying mechanism.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">12</span></a> In 1966, the term <span class="elsevierStyleItalic">torsade de pointes</span> was conceived to describe a specific ventricular tachycardia detected in elderly women with heart block.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Nevertheless, despite the clinical importance of the lengthening of the QT interval and the correlation with certain drugs in its incidence, contrary to expectations, published studies are scarce. Also, this lack of data means that there is not enough information regarding the number of hospitalised patients with prolonged QT, the frequency by which patients who are prescribed QT-prolonging drugs develop long QT syndrome or TdP, or a clear consensus about the degree of prolongation required to suspend treatment QT-prolonging drugs.</p><p id="par0040" class="elsevierStylePara elsevierViewall">As for drugs commercialised after 2005, information about their impact on QT interval derives from clinical trials because, as previously stated, this is required by regulatory agencies before their commercialisation. Meanwhile, due to the lack of regulations, information regarding old drugs derives from a series of non-controlled cases.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Regarding already commercialised drugs, the following is a description of the main drug groups that potentially affect the QT interval.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antiarrhythmic drugs</span><p id="par0050" class="elsevierStylePara elsevierViewall">This is the only drug group for which there is information available about its association with QT interval and TdP.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">14</span></a> As per this data, the incidence of TdP for antiarrhythmic sodium and potassium channel blockers, such as quinidine, disopyramide and procainamide, as well as those that only block potassium channels, such as sotalol, is between 1 and 10%.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">14</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">It is important to highlight that, while class Ia antiarrhythmic drugs are clearly related with the appearance of TdP, their association with class III is not that clear. Thus, according to what was deduced from the results of 17 studies that included 2878 patients between 1982 and 1993, the incidence of TdP with amiodarone is only 0.7%.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">15</span></a> This incidence is higher in women and patients with renal failure or congestive heart failure, among others.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antihistamines</span><p id="par0060" class="elsevierStylePara elsevierViewall">Within this drug group, the lengthening of the QT interval has been observed for some of the second generation antihistamines (mainly terfenadine). Some resulted in TdP,<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">16</span></a> although these cases occurred because of doses that exceeded recommended amounts or regular doses that were administered together with cytochrome P450 inhibitors, or in patients with liver failure. Non-sedating or third generation antihistamines, such as loratadine, cetirizine or ebastine (most recently commercialised) have not been related to QT prolongation or TdP.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Antimicrobial drugs</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Antibiotics</span><p id="par0065" class="elsevierStylePara elsevierViewall">The association of arrhythmias related to QT interval prolongation with antibiotics is not very frequent. Moreover, the known cases were due to macrolide and fluoroquinolone use.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">18,19</span></a> Among the macrolides, erythromycin and clarithromycin have been related to ventricular arrhythmias<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">14,20–23</span></a> and SCD.<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">24,25</span></a> The treatment with azithromycin has also been related to TdP cases.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">26</span></a> Moreover, an important retrospective study published in 2012 with an extensive patient sample demonstrated that, after 5 days of treatment with this drug, there was an increase in deaths due to cardiovascular causes compared with people treated with amoxicillin, ciprofloxacin or no treatment. In addition, the risk was even higher in some cases, such as in patients with baseline cardiovascular disease or those who presented prolonged QT intervals.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">27</span></a> In light of these results, both the FDA as well as the EMA sent security alerts about this risk associated with the use of azithromycin.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The second group of antibiotics that affect the QT interval is made up of fluoroquinolones. This is a class effect, even though there are differences between them. In the previously mentioned study, levofloxacin demonstrated a risk of cardiovascular death similar to azithromycin. Thus, it would not be an alternative to the use of macrolides in this type of patients. Among them, ciprofloxacin seems to be the safest.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">18</span></a> Furthermore, the available information reveals that 24% of TdP cases associated with fluoroquinolones took place when other drugs that prolong the QT interval were administrated, 62% in patients with baseline cardiac disease, 7% in patients with renal failure and 17% in patients with hypokalaemia or hypomagnesaemia, and 67% in women.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">18,23</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Antifungal medicines</span><p id="par0075" class="elsevierStylePara elsevierViewall">Ketoconazole, itraconazole, fluconazole and voriconazole have been associated with cases of long QT and appearance of TdP. Ketoconazole and itraconazole prolong the QT interval by blocking potassium channels. However, most reported cases were due to a co-administration with other QT-prolonging drugs that metabolise the same way. This is because they are inhibitors of cytochrome P450 isoform 3 A4.<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">17,18</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Antimalarial drugs</span><p id="par0080" class="elsevierStylePara elsevierViewall">This group of drugs deserves special attention. Quinine and quinidine have been shown to prolong QT at regular doses. In addition, their cardiotoxicity is higher in patients with renal disease and after 3 days of treatment.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">17</span></a> It is recommended to monitor the patient when a quinidine infusion is administered.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Mefloquine seems to be the safest treatment in terms of cardiotoxicity; nevertheless, it must not be associated with halofantrine due to the increased risk of SCD.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">18</span></a></p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Antiviral drugs: protease inhibitors</span><p id="par0090" class="elsevierStylePara elsevierViewall">Protease inhibitor antiviral drugs are potentially capable of predisposing patients for TdP due to QT prolongation since they are related to HERG channel block.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">28</span></a> It has been proved that this risk is higher in patients with a QT interval >500<span class="elsevierStyleHsp" style=""></span>ms and in those patients in which it increases between 30 and 60 times when they are treated with these drugs versus levels before treatment.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">29</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Antidepressants and antipsychotics</span><p id="par0095" class="elsevierStylePara elsevierViewall">Even though their incidence is uncertain, the use of tricyclic antidepressants like amitriptyline, doxepin, desipramine, imipramine and clomipramine has been associated with QT prolongation, TdP and SCD.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">17</span></a> The new selective re-uptake of serotonin antidepressants, such as citalopram, are only associated with cases of TdP in patients with an overdose.<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">30</span></a> Other non-tricyclic antidepressants, such as trazodone, have also been involved in TdP development in high doses.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">31</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">As regards antipsychotic drugs related to QT interval prolongation, sudden deaths have been recorded due to its use at normal doses as well as overdoses.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">17</span></a> A recent assessment that compared classic antipsychotics to new ones showed that, in both groups, there was a similar associated risk for SCD, which, furthermore, was dose-dependent.<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">32</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">The Arizona Centre for Education and Research on Therapeutics, a worldwide reference centre in this matter, offers on its website<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">33</span></a> updated lists of commercialised drugs in the USA and the rest of the world that potentially prolong the interval and increase the risk of TdP. In those lists, the drugs are classified according to the degree of attribution of the causal relationship between the medicine and the event:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1.</span><p id="par0110" class="elsevierStylePara elsevierViewall">Defined: there is evidence that the use of these drugs may lead QT interval prolongation and TdP risk.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2.</span><p id="par0115" class="elsevierStylePara elsevierViewall">Possible: there is evidence that these drugs may prolong the QT interval, but there is not enough evidence of TdP risk.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3.</span><p id="par0120" class="elsevierStylePara elsevierViewall">Conditioned: the evidence suggests that these drugs could prolong the QT interval only under certain conditions (excessive doses, drug interactions, etc.).</p></li></ul></p><p id="par0125" class="elsevierStylePara elsevierViewall">Following this approach and based on these lists, we have made a table with drugs available in our country that are related with QT interval increase (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Risk factors that may affect the QT interval</span><p id="par0130" class="elsevierStylePara elsevierViewall">Among the patients treated with QT-prolonging drugs, not all of them develop lengthening of the QT interval. When this does occur, some patients develop TdP, while others do not. This fact indicates that there are persons who are more prone than others to develop QT interval prolongation even when undergoing the same treatment.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">34</span></a> The data confirm that there must be a series of circumstances, including genetic conditionings and other risk factors, that trigger this ventricular arrhythmia. It is important that clinicians are aware of these factors to prevent the appearance of this life-threatening episode (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">8,14</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">In hospitalised patients, the appearance of TdP increases significantly with the use of several drugs and concomitant diseases. Therefore, close follow-up is necessary.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">14</span></a> Several studies have reported evidence that the incidence of TdP is almost double in women and higher in patients over the age of 65.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">14</span></a> The presence of hypokalaemia is also a predisposing factor, probably because of a change in the function of IKr potassium channels, which results in dispersion of repolarisation, as well as hypomagnesaemia. In addition, it is well-known that treatment with QT-prolonging drugs, together with these risk factors, is more likely to cause a QT prolongation in genetically susceptible patients than in unsusceptible patients. Also, TdP risk is variable even among people with the same degree of QT interval prolongation.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Pharmacological interactions that favour the prolongation of the QT interval</span><p id="par0140" class="elsevierStylePara elsevierViewall">In clinical practice, pharmacological interactions usually occur because of the prescribing physician's unawareness about them or because, in spite of the potential risk, the benefit is greater, or there is no therapeutic alternative. In a recent study, Armahizer et al.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">35</span></a> proved that up to 37% of QT prolongation cases in a unit of critical patients were caused by pharmacological interactions.</p><p id="par0145" class="elsevierStylePara elsevierViewall">The risk of QT prolongation is increased by synergy when several QT-prolonging drugs are used at the same time or due to pharmacological interactions. These situations may significantly increase morbidity and mortality.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">35</span></a> Such risk, as we have already mentioned, is even higher in hospitalised patients because of their clinical situation, which is generally more complex and requires further new treatments.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">35</span></a> These interactions may be pharmacokinetic. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> illustrates the main interactions of this type involving QT-prolonging drugs.<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">34,35</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">Another type of interaction that may cause QT prolongation is the pharmacodynamic type, generally due to the concomitant use of a certain drug that exacerbates some risk factor for this interval prolongation. An example would be the concomitant use of a QT-lengthening drug with another drug that modifies the potassium current or disturbs its plasma concentrations (such as antiarrhythmic drug<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>diuretic). This can also occur due to the use of quinidine<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>sotalol by obstruction of potassium currents. It is better to avoid the association of QT-prolonging drugs with those that favour risk factors, these mainly being drugs that cause bradycardia (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>) or hypokalaemia (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>).</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Recommendations</span><p id="par0155" class="elsevierStylePara elsevierViewall">According to the latest recommendations collected from the clinical practice guidelines published in 2006 by the American College of Cardiology, the American Heart Association and the European Society of Cardiology,<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">36</span></a> QT-prolonging drug treatment should be suspended when there is clear evidence (class <span class="elsevierStyleSmallCaps">i</span>, level A) of association with long QT syndrome. However, this guideline does not define the QTc value for which the treatment should be interrupted.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Ongoing monitoring is recommended in patients treated with QT drugs and a history of TdP when, after its administration, a QTc<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>500<span class="elsevierStyleHsp" style=""></span>ms or an increase of at least 60<span class="elsevierStyleHsp" style=""></span>ms compared to baseline rate is observed. <a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a> shows the main recommendations to improve the use of these medications and prevent TdP.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">8,37</span></a></p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">In this respect, the usage of new technologies can play a relevant role in the prevention of TdP caused by QT-prolonging drugs. For instance, through electronic drug prescription, it is possible to alert the prescribing physician about possible interactions and risk factors of TdP caused by QT-prolonging drugs.<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">38</span></a> Recently, some centres in the USA have been implementing an electronic alert system associated with the electrocardiogram (ECG), which identifies patients with death risk related to QT interval. When a patient has an ECG performed, the system alerts the clinician when the sick person is at risk and provides recommendations about a course of action.<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">39</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusion</span><p id="par0170" class="elsevierStylePara elsevierViewall">Clinicians are facing a growing number of patients treated with QT-prolonging drugs or situations that increase the risk for QT interval prolongation and TdP, whose management is unknown. Many of these drugs are not cardiovascular and there is no awareness of this risk.</p><p id="par0175" class="elsevierStylePara elsevierViewall">Despite the severity of an incident caused by the prolongation of the QT interval, there are very few studies conducted on this matter and they are mainly about case series reported to the regulatory agencies. It would be desirable for more studies to be conducted in the future to provide information about this matter and help physicians make decisions based on corroborated data, thus minimising the risks of this severe and life-threatening adverse effect.</p><p id="par0180" class="elsevierStylePara elsevierViewall">In this article, our aim was to update and introduce different situations that may exacerbate the risk of QT lengthening related to treatment with QT-prolonging drugs.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflict of interest</span><p id="par0185" class="elsevierStylePara elsevierViewall">The authors declare that there are no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres587321" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec603122" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres587322" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec603121" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Drugs that prolong the QT interval and may cause torsades de pointes" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Antiarrhythmic drugs" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Antihistamines" ] 2 => array:3 [ "identificador" => "sec0025" "titulo" => "Antimicrobial drugs" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Antibiotics" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Antifungal medicines" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Antimalarial drugs" ] ] ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Antiviral drugs: protease inhibitors" ] 4 => array:2 [ "identificador" => "sec0050" "titulo" => "Antidepressants and antipsychotics" ] ] ] 6 => array:2 [ "identificador" => "sec0055" "titulo" => "Risk factors that may affect the QT interval" ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Pharmacological interactions that favour the prolongation of the QT interval" ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Recommendations" ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Conclusion" ] 10 => array:2 [ "identificador" => "sec0075" "titulo" => "Conflict of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-10-29" "fechaAceptado" => "2014-01-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec603122" "palabras" => array:5 [ 0 => "QT interval prolongation" 1 => "<span class="elsevierStyleItalic">Torsade de pointes</span>" 2 => "Drugs" 3 => "Risk factors" 4 => "Drug interactions" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec603121" "palabras" => array:5 [ 0 => "Prolongación del intervalo QT" 1 => "<span class="elsevierStyleItalic">Torsade de pointes</span>" 2 => "Fármacos" 3 => "Factores de riesgo" 4 => "Interacciones farmacológicas" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Sudden cardiac death is an important cause of mortality in developed countries, most of them being consequence of acute ventricular arrhythmias. These arrhythmias, in some cases, owe to QT interval prolongation.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A major risk factor for this condition is the use of drugs that prolong the QT interval. In fact, in recent years, one of the most common reasons for drug withdrawal or usage restrictions has been drug induced QT interval prolongation that involves both cardiovascular and non-cardiovascular drugs.</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Taking into account the severity that the occurrence of such an event may have, it is important for clinicians to know the risks of these drugs in certain patients. In this review we analyse the drugs that prolong the QT interval, the risk factors that can enhance QT prolongation and the drug interactions that can increase these risks.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La muerte súbita cardiaca es una causa importante de mortalidad en los países desarrollados. La mayoría de ellas derivan de arritmias ventriculares agudas que, en algunas ocasiones, se producen como consecuencia de la prolongación del intervalo QT.</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Un importante factor de riesgo para esta alteración es el uso de fármacos que prolongan este intervalo. De hecho, en los últimos años, uno de los motivos más frecuentes de retirada del mercado de medicamentos o de restricciones de uso ha sido la prolongación del intervalo QT, e implica tanto fármacos cardiovasculares como no cardiovasculares.</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Dada la gravedad que puede conllevar la aparición de un suceso por esta causa, es importante que los clínicos conozcan los riegos del uso de estos fármacos en determinados pacientes. En esta revisión analizamos los fármacos que prolongan el intervalo QT, los factores de riesgo que pueden influir y las combinaciones de fármacos que pueden agravar esta situación.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as: Villamañán E, Armada E, Ruano M. Prolongación del intervalo QT inducido por fármacos: ¿conocemos sus riesgos? Med Clin (Barc). 2015;144:269–274.</p>" ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Category \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Antipsychotics \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Antidepressants \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Anti-infective drugs \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Antiarrhythmic drugs \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Others \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Defined \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amisulpride \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Citalopram \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Azithromycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amiodarone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Alfuzonsin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clozapine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Escitalopram \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clarithromycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Disopyramide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Arsenic, trioxide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Droperidol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Erythromycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dronedarone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Chloroquine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Haloperidol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moxifloxacin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Flecainide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Domperidone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pimozide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Procainamide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Methadone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Quinidine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ondansetron \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pentamidine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vemurafenib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Possible \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Chlorpromazine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mirtazapine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Atazanavir \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Famotidine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lithium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Venlafaxine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Foscarnet \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Felbamate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Olanzapine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Levofloxacin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fingolimod \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Paliperidone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Norfloxacin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Granisetron \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Quetiapine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ofloxacin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Indapamide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Risperidone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Roxithromycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lapatinib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sertindole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Saquinavir \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nicardipine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Telithromycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nilotinib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Voriconazole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Oxytocin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Promethazine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ranolazine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tacrolimus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tamoxifen \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tizanidine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tolterodine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vardenafil \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Conditioned \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amitriptyline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amantadine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sotalol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diphenhydramine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clomipramine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ciprofloxacin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Galantamine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Doxepin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cotrimoxazole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Solifenacin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fluoxetine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fluconazole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Imipramine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Itraconazole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nortriptyline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ketoconazole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Paroxetine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ritonavir \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sertraline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Trazodone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Trimipramine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Others<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ziprasidone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Maprotiline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Atomoxetine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ebastine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mequitazine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Methylphenidate \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab959085.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Drugs available in Spain that prolong the QT interval and do not appear in the AZERT list.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Drugs that may prolong the QT interval.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">DPQT: drugs that prolong the QT interval.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Female gender \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Electrolyte disorders (hypokalaemia, hypomagnesaemia and hypocalcaemia) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bradycardia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Recent conversion from atrial fibrillation to sinus rhythm \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Cardiac failure and heart attack \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Treatment with digitalis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Liver failure \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">High concentrations of DPQT or treatment with more than one DPQT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Quick infusion of DPQT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Base prolonged QT interval \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Subclinical long QT syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Advanced age \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">QTc >500<span class="elsevierStyleHsp" style=""></span>ms or an increase of at least 60<span class="elsevierStyleHsp" style=""></span>ms compared to baseline value \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab959084.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Risk factors of <span class="elsevierStyleItalic">torsade de pointes</span> induced by drugs.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">DPQT: drugs that prolong the QT interval.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drugs group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">DPQT \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Interacting drugs \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Antiarrhythmic drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Disopyramide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Erythromycin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Procainamide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amiodarone, cimetidine, trimethoprim \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Quinidine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amiodarone, cimetidine, erythromycin, verapamil \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Antipsychotics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Haloperidol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fluoxetine, venlafaxine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ziprasidone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fluconazole, itraconazole, ketoconazole \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Antidepressants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amitriptyline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cimetidine, fluconazole, fluoxetine, ritonavir \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Desipramine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Venlafaxine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Anti-infective drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Erythromycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ritonavir \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab959086.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Pharmacokinetic interactions of drugs that prolong the QT interval.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Therapeutic group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drugs \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Anti-angina drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ivabradine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ranolazine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Antiarrhythmic drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Class I</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Disopyramide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Flecainide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hydroquinidine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lidocaine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mexiletine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propafenone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Quinidine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Class III</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amiodarone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sotalol \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Anticholinergic drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Donepezil \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Galantamine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rivastigmine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Antiepileptic drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fosphenytoin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Antihypertensive drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clonidine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moxonidine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Antimalarial drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mefloquine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Beta-adrenergic blockers</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Calcium antagonists \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verapamil \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diltiazem \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Cholinergic drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Acetylcholine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pilocarpine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Ergotic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dihydroergotamine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Cholinesterase inhibitors \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Neostigmine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pyridostigmine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Opiates \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Methadone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fentanyl \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Antiplatelet agents \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ticagrelor \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab959083.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Drugs that cause bradycardia.</p>" ] ] 4 => array:7 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type of drug \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Active substance \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Beta-adrenergic agonists bronchodilators \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Albuterol, terbutaline, isoproterenol, formoterol, salbutamol, salmeterol \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Tocolytic agents \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ritodrine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Decongestants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pseudoephedrine, phenylpropanolamine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Xanthine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Theophylline \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Catecholamine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Adrenaline, noradrenaline, dopamine, dobutamine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Calcium antagonists \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nifedipine, nitrendipine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Insulin</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Anaesthetics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Thiopental, lidocaine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Cell proliferation inductors \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hydroxocobalamin, granulocyte–monocyte colony-stimulating factor \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Diuretics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Acetazolamide, chlorthalidone, hydrochlorothiazide, indapamide, furosemide, torsemide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mineralocorticosteroid drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fludrocortisone, hydrocortisone (high doses), carbenoxolone, mifepristone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">High doses of antibiotics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Penicillin, oxacillin, piperacillin, meropenem, tetracycline, neomycin, polymyxin B, colistin, bacitracin, aminoglycosides, capreomycin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Antifungal medicines \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amphotericin B, itraconazole, fluconazole \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Chemotherapy and other neurotoxic drugs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cisplatin, tenofovir, foscarnet \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Immunosuppressants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Methotrexate, sirolimus, tensirolimus, leflunomide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Infliximab, ondansetron, bicarbonate, laxatives, phosphate enemas \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab959082.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Hypokalaemia-causing drugs.</p>" ] ] 5 => array:7 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">DPQT: drugs that prolong the QT interval.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Know the drugs that may prolong the interval. Most of them are detailed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. For further updated information, visit <span class="elsevierStyleInterRef" id="intr0005" href="http://www.qtdrugs.org/">www.qtdrugs.org</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Know the risk factors for <span class="elsevierStyleItalic">torsade de pointes</span> caused by drugs (advanced age, female gender, heart disease, electrolytic disorders, renal or liver failure, bradycardia, familiar history or genetic predisposition) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Concomitant treatment with other DPQT or possibilities of pharmacokinetic or pharmacodynamic interactions \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Before undergoing a treatment with DPQT, individually assess the risk/benefit and possible available therapeutic alternatives, and avoid high risk DPQT as much as possible. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Determine the QT interval value before initiating a DPQT treatment. Then, monitor said value during the process by always using the same method and same measuring equipment. Furthermore, apply a formula that corrects the value according to the heart frequency. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Inform the patient about the risks and interactions of the use of some drugs. Also, provide the patient adequate written documentation. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab959081.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Recommendations for the prevention of <span class="elsevierStyleItalic">torsade de pointes</span> caused by drugs.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:39 [ 0 => array:3 [ "identificador" => "bib0200" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiología de la muerte súbita cardiaca" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Asmundis" 1 => "P. 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