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Gómez del Cañizo, M. Rodríguez-Izquierdo Jiménez, E. Peña Vallejo, J.M. Duarte Ojeda, F. de la Rosa Kehrman, A. Rodríguez Antolín, F. Guerrero Ramos" "autores" => array:7 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Gómez del Cañizo" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Rodríguez-Izquierdo Jiménez" ] 2 => array:2 [ "nombre" => "E." "apellidos" => "Peña Vallejo" ] 3 => array:2 [ "nombre" => "J.M." "apellidos" => "Duarte Ojeda" ] 4 => array:2 [ "nombre" => "F." "apellidos" => "de la Rosa Kehrman" ] 5 => array:2 [ "nombre" => "A." "apellidos" => "Rodríguez Antolín" ] 6 => array:2 [ "nombre" => "F." 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Esteban, S. Méndez, J. Salinas" "autores" => array:3 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Esteban" "email" => array:1 [ 0 => "estebote@telefonica.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "S." "apellidos" => "Méndez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "Salinas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Urología, Hospital Nacional de Parapléjicos, Toledo, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Urología, Hospital Universitario Sanitas La Moraleja, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Urología, Hospital Universitario Clínico San Carlos, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Posicionamiento de la AEU en la administración transdérmica de fármacos: una evolución determinante en la terapia urológica funcional" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Overactive bladder syndrome (OBS) is a frequent chronic medical condition with a major impact on patients' health and quality of life, which can affect the performance of daily activities and social relationships. The prevalence in Spain<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> is 21.5% (25.6% in women and 17.4% in men). Its treatment represents a challenge for the professionals involved, since it is rarely curative and adherence to such treatments is low.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Antimuscarinics have been available for the treatment of non-neurogenic overactive bladder refractory to non-pharmacologic management for years. However, their side effects (dry mouth, constipation, blurred vision, dizziness, and cognitive impairment) limit the therapy’s tolerability and are responsible for the low adherence.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Conventional oral route remains being the most frequently used for the administration of anticholinergics. However, the transdermal route is also currently available.</p><p id="par0020" class="elsevierStylePara elsevierViewall">A comparative study of antimuscarinics (Cochrane) concludes that if extended-release formulations of oxybutynin or tolterodine are available, they would be preferable to those of immediate-release, due to the lower risk of dry mouth.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The route of administration has also been observed as key factor to increasing adherence. Recently, Herbison et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> published a meta-analysis in which all evaluated anticholinergics (trospium, oral oxybutynin, transdermal oxybutynin, fesoterodine, propiverine, darifenacin, solifenacin, tolterodine, imidafenacin) showed to be better than placebo, all with a similar effect. None of them were clearly superior. However, transdermal oxybutynin caused less dry mouth than the other treatments, so it is worth considering it as first-line treatment.</p><p id="par0030" class="elsevierStylePara elsevierViewall">There is concern about possible cognitive impairment in older patients. It has been seen that cognitive impairment increased from 24.1% before treatment to 41.1% in patients subjected to treatment with oral oxybutinin.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Müller-Arteaga et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> evaluated transdermal oxybutynin treatment in 70 elderly patients with OBS. There was a significant improvement in all storage symptoms (except for stress urinary incontinence) and improvement in the bladder control self-assessment questionnaire, with 84.3% adherence to treatment. No cognitive impairment was observed after one month of treatment with transdermal oxybutynin.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Oxybutynin is a strong muscarinic receptor antagonist that has an anticholinergic effect, achieved by binding to M3 receptors and blocking cholinergic activation.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The primary metabolite of oxybutynin after first-pass liver metabolism, N-desethyloxybutynin (N-DEO), is considered largely responsible for its associated anticholinergic side effects because of its high affinity for the salivary gland M3 muscarinic receptors. For this reason, other routes of administration have been sought that obviate the hepatic pass. The transdermal route owns this characteristic. Moreover, unlike other anticholinergics, the lipophilicity and low molecular weight of oxybutynin allows its transdermal absorption, increasing bioavailability. With this route of administration, its effectiveness has been preserved, reducing systemic side effects; some anticholinergic side effects may appear, such as local site reactions.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> In fact, according to Zobrist et al.,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> N-DEO plasma levels are low with this form of administration, since first-pass gastrointestinal and hepatic metabolism is avoided, which would reduce anticholinergic side effects. Another advantage of the transdermal route is that oxybutynin passes directly into the systemic circulation, providing much more stable serum levels.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Oxybutynin transdermal patch allows a prolonged release with a usual dose of two patches per week, applied to the abdomen, buttock or hip, and provides a continuous delivery, reducing maximum and minimum fluctuations in plasma levels.</p><p id="par0050" class="elsevierStylePara elsevierViewall">When administering oxybutynin by transdermal route, it is important that patients receive instructions on the proper handling of the patch, since adequate use (alternating skin sites and not repeating them for at least a week) reduces the possibility of developing a reaction at the application site.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The OSCAR study showed significant improvements from treatment initiation in terms of urinary frequency, nocturia, number of urgent episodes and number of urge incontinence, according to the voiding diary. A total of 38.1% of the patients had adverse events, mainly at the application site (27.6%), and most were of mild or moderate intensity. There was a low incidence of systemic adverse events, of which none was considered severe. Only six patients (5.7%) reported the presence of dry mouth after one year of treatment. Twelve months after initiating treatment, 58 patients (55.2%) continued receiving OXY-TDS, with 92.9% of the patients perceiving it as comfortable or very comfortable.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In the MATRIX study, significant and clinically relevant improvements were found with the administration of the transdermal oxybutynin patch. The treatment was well tolerated, with low rates of anticholinergic adverse effects (dry mouth 2.6%, constipation 1.5% and dizziness 0.7%). Application-site reactions (pruritus, erythema, dermatitis and irritation) were found in 14.0% of patients.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The review by Salinas-Casado et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> shows that patients treated with transdermal oxybutynin improve their symptoms, with a similar efficacy to that observed in patients treated with oral oxybutynin or tolterodine. Symptomatic improvement occurs from the second or third week of treatment and in a sustained way until the end of treatment. In addition, transdermal oxybutynin, compared to oral oxybutynin or tolterodine, presents a better safety profile in terms of systemic adverse reactions.</p><p id="par0070" class="elsevierStylePara elsevierViewall">After an exhaustive review of the national and international literature available, we can affirm that transdermal drugs in general, and the administration of oxybutynin by transdermal route in particular, have a similar clinical efficacy to orally administered drugs and cause less frequent adverse effects, particularly dry mouth, thus producing a lower rate of treatment abandonment.</p><p id="par0075" class="elsevierStylePara elsevierViewall">All this translates into clinical benefit and improved quality of life for patients. Transdermal drugs can and should be considered as first-line treatment for overactive bladder.</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: Esteban M, Méndez S, Salinas J. Posicionamiento de la AEU en la administración transdérmica de fármacos: una evolución determinante en la terapia urológica funcional. 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AEU positioning statement on transdermal drug administration: determinant evolution of functional urologic therapy
Posicionamiento de la AEU en la administración transdérmica de fármacos: una evolución determinante en la terapia urológica funcional
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