Letter to the Editor
Ischemic stroke due to possible interaction of rivaroxaban with primidone in a patient with atrial fibrillation
Ictus isquémico por posible interacción de rivaroxabán con primidona en paciente con fibrilación auricular
María Sáez-Torres de Vicente
, Pablo Martínez Puig, Luisa Valverde Toresano
Corresponding author
Servicio de Farmacia, Hospital Universitario Reina Sofía, Córdoba, Spain
Read
2
Timeswas read the article
2
Total PDF
0
Total HTML
Share statistics
array:24 [ "pii" => "S2387020621000462" "issn" => "23870206" "doi" => "10.1016/j.medcle.2019.12.019" "estado" => "S300" "fechaPublicacion" => "2021-03-12" "aid" => "5108" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2020" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Clin. 2021;156:255-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S002577532030124X" "issn" => "00257753" "doi" => "10.1016/j.medcli.2019.12.024" "estado" => "S300" "fechaPublicacion" => "2021-03-12" "aid" => "5108" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Clin. 2021;156:255-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Editor</span>" "titulo" => "Ictus isquémico por posible interacción de rivaroxabán con primidona en paciente con fibrilación auricular" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "255" "paginaFinal" => "256" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Ischemic stroke due to possible interaction of rivaroxaban with primidone in a patient with atrial fibrillation" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "María Sáez-Torres de Vicente, Pablo Martínez Puig, Luisa Valverde Toresano" "autores" => array:3 [ 0 => array:2 [ "nombre" => "María" "apellidos" => "Sáez-Torres de Vicente" ] 1 => array:2 [ "nombre" => "Pablo" "apellidos" => "Martínez Puig" ] 2 => array:2 [ "nombre" => "Luisa" "apellidos" => "Valverde Toresano" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020621000462" "doi" => "10.1016/j.medcle.2019.12.019" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621000462?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S002577532030124X?idApp=UINPBA00004N" "url" => "/00257753/0000015600000005/v1_202102240836/S002577532030124X/v1_202102240836/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020621000450" "issn" => "23870206" "doi" => "10.1016/j.medcle.2019.12.018" "estado" => "S300" "fechaPublicacion" => "2021-03-12" "aid" => "5093" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Clin. 2021;156:256" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "The endovascular treatment reduces the inflammatory activity in the infected aortic wall" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:1 [ "paginaInicial" => "256" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La exclusión endovascular reduce la actividad inflamatoria de la pared aórtica infectada" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "José Antonio González-Fajardo, Marina Ansuátegui-Vicente, Sergio Revuelta-Suero" "autores" => array:3 [ 0 => array:2 [ "nombre" => "José Antonio" "apellidos" => "González-Fajardo" ] 1 => array:2 [ "nombre" => "Marina" "apellidos" => "Ansuátegui-Vicente" ] 2 => array:2 [ "nombre" => "Sergio" "apellidos" => "Revuelta-Suero" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775320301093" "doi" => "10.1016/j.medcli.2019.12.017" "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/S0025775320301093?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621000450?idApp=UINPBA00004N" "url" => "/23870206/0000015600000005/v1_202103120836/S2387020621000450/v1_202103120836/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2387020620304034" "issn" => "23870206" "doi" => "10.1016/j.medcle.2020.04.021" "estado" => "S300" "fechaPublicacion" => "2021-03-12" "aid" => "5125" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Clin. 2021;156:254-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Reply" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "254" "paginaFinal" => "255" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Respuesta" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Patricia Richi, Martina Steiner, Santiago Muñoz-Fernández" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Patricia" "apellidos" => "Richi" ] 1 => array:2 [ "nombre" => "Martina" "apellidos" => "Steiner" ] 2 => array:2 [ "nombre" => "Santiago" "apellidos" => "Muñoz-Fernández" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775320301603" "doi" => "10.1016/j.medcli.2020.03.001" "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/S0025775320301603?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020620304034?idApp=UINPBA00004N" "url" => "/23870206/0000015600000005/v1_202103120836/S2387020620304034/v1_202103120836/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Ischemic stroke due to possible interaction of rivaroxaban with primidone in a patient with atrial fibrillation" "tieneTextoCompleto" => true "saludo" => "To the Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "255" "paginaFinal" => "256" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "María Sáez-Torres de Vicente, Pablo Martínez Puig, Luisa Valverde Toresano" "autores" => array:3 [ 0 => array:4 [ "nombre" => "María" "apellidos" => "Sáez-Torres de Vicente" "email" => array:1 [ 0 => "maria23_224@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Pablo" "apellidos" => "Martínez Puig" ] 2 => array:2 [ "nombre" => "Luisa" "apellidos" => "Valverde Toresano" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Farmacia, Hospital Universitario Reina Sofía, Córdoba, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Ictus isquémico por posible interacción de rivaroxabán con primidona en paciente con fibrilación auricular" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Atrial fibrillation (AF) is a supraventricular tachyarrhythmia in which the atrium is activated in an uncoordinated manner without effective contraction. On the electrocardiogram, the P wave is absent, and the atrial activity and R-R intervals are irregular. Its presence increases the risk of stroke and peripheral thromboembolism due to the ease of thrombus formation in the left atrium (LA).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Anticoagulant treatment in patients with AF should be individualized in a shared decision, weighing the risks of stroke and bleeding, according to the values and preferences of the patient. The choice of treatment should be based on the risk of thromboembolism regardless of whether the AF is paroxysmal, persistent, or permanent. In patients with nonvalvular AF with previous stroke, transient ischemic attack (TIA), or CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc of 2 or higher, oral anticoagulation with dicoumarins, dabigatran, rivaroxaban, apixaban or edoxaban is recommended.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of an 80-year-old woman with a history of arterial hypertension, hypothyroidism, Parkinson's and AF with a rapid ventricular response, anticoagulated for 3 months, who was admitted due to speech alteration of sudden onset along with weakness on the right side of the body. The CT scan shows a loss of differentiation between grey matter and white matter in the left occipital lobe and multiple hypodense lesions in the basal ganglia compatible with stroke, which was confirmed by magnetic resonance imaging, after which the patient was diagnosed with ischaemic stroke of probable cardioembolic origin.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The patient was undergoing treatment with rivaroxaban 20 mg/24 h; bisoprolol 5 mg/24 h; rotigotine 8 mg/patches/24 h; pramipexole 2.10 mg/24 h; primidone 250 mg/8 h; levodopa 200/carbidopa 50/entacapone 200 mg/8 h; furosemide 40 mg/24 h; ramipril 5/HCTZ 25 mg/24 h; omeprazole 20 mg/24 h, and levothyroxine 100 µg/24 h, with good adherence.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Rivaroxaban is a highly selective, direct, factor Xa inhibitor, inhibition of factor Xa interrupts the intrinsic and extrinsic pathways of the blood coagulation cascade, inhibiting both thrombin formation and thrombus formation. Intestinal absorption and renal elimination of rivaroxaban is dependent on the intestinal and renal permeability of the P-glycoprotein (P-gp) transporter protein system and is also a substrate for cytochrome P 450 3A4 (CYP3A4) enzymes.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Therefore, a drug-drug interaction may occur when administered concomitantly with drugs that affect the activity of P-gp or CYP3A4 systems.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Administration with CYP3A4-inducing agents (e.g., phenytoin, carbamazepine, phenobarbital) may lead to a decrease in serum levels, thus decreasing the anticoagulant activity of rivaroxaban. Several antiepileptic drugs are known to affect the activity of P-gp and CYP3A4, however, the clinical relevance of this drug-drug interaction with direct-acting anticoagulants is largely unknown. According to the European Medicines Agency (EMA), concomitant administration with potent CYP3A4 inducers should be avoided unless the patient is closely monitored for signs or symptoms of thrombosis.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">When the patient's treatment was reviewed, it was found that she had been taking rivaroxaban and primidone (a prodrug of phenobarbital, a potent CYP3A4 inducer), with this interaction possibly triggering the lack of anticoagulant efficacy of rivaroxaban and the consequent stroke, so the neurology department was informed, and primidone was deprescribed.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The effect of interaction with CYP3A4 inducers has been studied for rifampicin, where rivaroxaban AUC and maximum serum concentration (Cmax) were found to be approximately 50% and 22% lower, respectively, when a single dose of rivaroxaban (20 mg) was administered to people taking rifampicin (up to 600 mg/day).<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Cases have been reported showing proportional decreases in the effects of rivaroxaban, such as a 67-year-old woman who died with extensive pulmonary embolism after use in combination with rifampicin<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and a 55-year-old man who experienced recurrent deep vein thrombosis when rivaroxaban was combined with carbamazepine.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">We conclude from our case that the concomitant use of rivaroxaban with primidone should be avoided as described in the SmPC. There is a need to increase our knowledge and awareness of the risk of interactions with direct-acting anticoagulants.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Sáez-Torres de Vicente M, Martínez Puig P, Valverde Toresano L. Ictus isquémico por posible interacción de rivaroxabán con primidona en paciente con fibrilación auricular. Med Clin (Barc). 2021;156:255–256.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:1 [ 0 => "William J. Powers" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/STR.0000000000000158" "Revista" => array:6 [ "tituloSerie" => "Stroke" "fecha" => "2018" "volumen" => "49" "paginaInicial" => "e46" "paginaFinal" => "e99" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29367334" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Robert G. Hart" 1 => "Lesly A. Pearce" 2 => "Maria I. Aguilar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/0003-4819-146-12-200706190-00007" "Revista" => array:6 [ "tituloSerie" => "Annals of internal medicine" "fecha" => "2007" "volumen" => "146" "paginaInicial" => "857" "paginaFinal" => "867" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17577005" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recurrent venous thrombosis under rivaroxaban and carbamazepine for symptomatic epilepsy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Claudia Stöllberger" 1 => "Josef Finsterer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pjnns.2017.01.010" "Revista" => array:6 [ "tituloSerie" => "Neurologia i neurochirurgia polska" "fecha" => "2017" "volumen" => "51" "paginaInicial" => "194" "paginaFinal" => "196" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28215696" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Xarelto (rivaroxaban) [prescribinginformation]. Titusville, NJ: Janssen Pharma-ceuticals Inc.; March 2017." ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical challenges related to novel oral anticoagulants: drug-drug interactions and monitoring" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:1 [ 0 => "Renske Altena" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3324/haematol.2013.097287" "Revista" => array:5 [ "tituloSerie" => "Haematologica" "fecha" => "2014" "volumen" => "99" "paginaInicial" => "e26" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24497568" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015600000005/v1_202103120836/S2387020621000462/v1_202103120836/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015600000005/v1_202103120836/S2387020621000462/v1_202103120836/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621000462?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2021 March | 0 | 2 | 2 |
