Prescription of transdermal patches in Colombia: A real-world evidence study.

BACKGROUND: Transdermal drug delivery has contributed positively to medical practice. However, prescriptions that do not meet minimum quality criteria and medication errors are common. OBJECTIVE: The objective was to determine how transdermal patches are being prescribed to a group of patients in Colombia, the compliance with established requirements of such prescriptions and the comparisons between correct and incorrect prescriptions. METHODS: This was a cross-sectional study of prescriptions for transdermal patches using data from a population-based drug dispensing database between December 1 and 31, 2019. Medical prescriptions were randomly reviewed, establishing whether the drugs were appropriately prescribed by the manufacturer's indications or national regulations. Descriptive and bivariate analysis was performed. RESULTS: A total of 415 prescriptions were reviewed; the prescription was provided to 412 patients with a median age of 76.9 years, and 63.3% were women. Rivastigmine was the most prescribed transdermal patch (57.8%). 66.3% of all prescriptions did not meet the minimum appropriate prescribing standards, especially those for rivastigmine (97.1%). The 7.0% of all prescriptions had posology errors, especially prescriptions for buprenorphine (43.8%). Older patients (84.4% vs 52.5%), from the Pacific region (34.4% vs 23.7%), with manual formulations (22.1% vs 0.8%), dementia (49.0% vs 6.8%), and in management with lipid-lowering drugs (41.8% vs 30.5%), presented incorrect transdermal patch formulations more frequently (p < 0.05). CONCLUSION: The high proportion of inappropriately prescribed transdermal patches should draw the attention of those responsible for health care to improve the training of physicians and create prescription quality verification systems.

Parches transdérmicos anticonceptivos: evaluación de tecnología sanitaria / Contraceptive transdermal patches: health technology assessment

INTRODUCCIÓN: La anticoncepción es un derecho, y es obligación del Estado garantizar el acceso a métodos anticonceptivos efectivos, seguros y de calidad. Se realizó una evaluación de tecnología sanitaria sobre los parches anticonceptivos transdérmicos. MÉTODOS: Un equipo multidisciplinario e independiente designado por el Comité Provincial de Biotecnologías de Neuquén buscó información epidemiológica, regulatoria y evidencias científicas sobre eficacia, seguridad y adherencia. Se analizó y sistematizó siguiendo metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) y CASPe (Critical Appraisal Skills Programme Español). RESULTADOS: El único parche autorizado en Argentina para su comercialización libera 33,9 µg/día de etinilestradiol y 203 µg/día de norelgestromina. Su prospecto en Argentina, EE.UU. y Europa lo asocia al doble de riesgo de enfermedad tromboembólica venosa si se compara con las píldoras anticonceptivas que provee el Estado. Esto coincide con resultados de estudios de cohortes de alta calidad. Los parches proveen similar eficacia anticonceptiva a corto plazo, pero con altas tasas de abandono en el seguimiento. La Organización Mundial de la Salud no los ha incluido en su listado de medicamentos esenciales. Los parches son más costosos que otros métodos disponibles. DISCUSIÓN: Sobre la base de los principios de beneficencia, no maleficencia, de precaución y de proporcionalidad, no se recomienda la incorporación de parches.(AU)

INTRODUCTION: Contraception is a right, being an obligation of the State to guarantee access to effective, safe and quality contraceptive methods. A health technology assessment was carried out on transdermal contraceptive patches. METHODS: A multidisciplinary and independent team appointed by the Provincial Biotechnology Committee of Neuquén searched for epidemiological and regulatory information and scientific evidence on efficacy, safety and adherence. It was analyzed and systematized following the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and CASPe (Critical Appraisal Skills Programme Español) methodology. RESULTS: The only patch authorized for commercialization in Argentina releases 33.9 µg/day of ethinylestradiol and 203 µg/day of norelgestromin. Its package insert in Argentina, the US and Europe highlights that the risk of venous thromboembolic disease is twice as high compared to the contraceptive pills provided by the State. This is consistent with results from high-quality cohort studies. Patches provide similar short-term contraceptive efficacy, but with high dropout rates at follow-up. The World Health Organization has not included them in its list of essential medicines. Patches are more expensive than other available methods. DISCUSSION: Based on the principles of beneficence, non-maleficence, precaution and proportionality, the incorporation of patches is not recommended.(AU)

Exploración de la eficacia analgésica de dos parches transdérmicos analgésicos de opioides, buprenorfina y fentanilo, según sus variaciones de dosis en el control del dolor en pacientes paliativos oncológicos / Exploration of the analgesic efficacy of two-transdermal analgesic patches of opioids, buprenorphine and fentanyl, according to their dose variations in pain control in palliative cancer patients

Objetivo: El presente trabajo de investigación tuvo como objetivo explorar la eficacia analgésica mediante la comparación de la respuesta analgésica de los parches transdérmicos (PTD) de buprenorfina y fentanilo en dolor oncológico y patrón de uso. Material y Método: Se obtuvieron los datos y variables desde los registros clínicos de pacientes ingresados a la Unidad de Cuidados Paliativos (UCP) del Instituto Nacional del Cáncer (INC) que estaban bajo tratamiento en mayo del 2017. Se incluyó en este estudio a 78 pacientes con PTD, que representan el 13% de los pacientes en control mensual. De estos, 66 estaban bajo tratamiento con buprenorfina y 8 bajo tratamiento con fentanilo. Resultados: Los resultados mostraron que el PTD de buprenorfina se utiliza más frecuentemente que el de fentanilo. El principal motivo de rotación fue dolor no controlado, seguido por imposibilidad de contar con la administración por vía oral. En pacientes con mayores intensidades de dolor somático o visceral se indicó fentanilo y en aquellos con componente neuropático se prefirió el uso de buprenorfina. PTD de fentanilo fue indicado en dosis mayores que buprenorfina, incluso al comparar sus dosis equianalgésicas, siendo la variación de dosis alta para ambos parches: aumentó en promedio 257%. Se logró una mejor respuesta analgésica con buprenorfina, con una variación de intensidad de escala numérica verbal (ENV) de 2,94 y 1,88 puntos de promedio para buprenorfina y fentanilo, respectivamente. Adicionalmente, se presentó mayor reacción local dérmica con fentanilo. Conclusiones: Se evidenció diferencias en patrón de uso y, a diferencia de lo esperado, se obtuvo una mejor eficacia analgésica con buprenorfina. Datos que deben ser corroborados en estudios con mayor número de pacientes bajo tratamiento con fentanilo.

Objective: This study aims to explore analgesic efficacy comparisons of buprenorphine and fentanyl transdermal patches (TDP) in cancer pain and it's usage pattern. Material and Method: Data and variables were collected from patient's clinical reports who were admitted in the National Cancer Institute's (NCI) Palliative Care Unit (PCU) and were under treatment with TDP in May 2017. 78 TDP patients were studied and represented 13% of the monthly control patients in the PCU. Of these, 66 were under buprenorphine treatment and 8 under fentanyl treatment. Results: The results showed that buprenorphine TDP is more frequently used than fentanyl TDP, and the main reason for exchange between them was uncontrolled pain, followed by oral administration impossibility. Fentanyl TDP was indicated in patients with higher somatic or visceral pain intensities and Buprenorphine TDP was preferred in patients with neuropathic pain. Fentanyl TDP was indicated in higher doses than buprenorphine, even when comparing its equianalgesic doses, the dose variation was high for both patches throughout the treatment: it increased on average by 257%. A better analgesic response was achieved with buprenorphine, with a variation of intensity of the Verbal Numerical Scale (VNS) of 2.94 and 1.88 average points, for buprenorphine and fentanyl respectively. Additionally, there was a higher local dermal reaction with fentanyl TDP. Conclusions: Differences in usage patterns were evidenced and, unlike what was expected, better analgesic efficacy was obtained with buprenorphine TDP. This data should be corroborated in receiving fentanyl treatment.

Chitosan-based films containing nanoemulsions of methyl salicylate: Formulation development, physical-chemical and in vitro drug release characterization.

Transdermal patches for analgesic purposes are widely used, however, their occlusive characteristics can often cause allergic reactions, irritating contact dermatitis, and allergic contact dermatitis upon extended use. Chitosan is a natural positively charged bioadhesive polysaccharide with several biological properties, being promising templates for sustained and controlled topical or transdermal drug delivery. Methyl salicylate (MS) is a non-steroidal topical anti-inflammatory drug (NSAID). MS is a lipophilic oily drug commonly found in transdermal patches, being difficult to incorporate into hydrophilic formulations such as Chitosan-based films. Thus, MS is a good candidate to be encapsulated into nanoemulsions (NE). This work reports the formulation development, physical-chemical characterization, and in vitro drug release of NE-loaded Chitosan films formulated with MS, as a novel substitute for transdermal analgesic patches. MS was encapsulated into NE, which were prepared by ultrasonication and presented 29.3 nm ± 0.1 and PdI 0.167 ± 0.005. The incorporation of MS into NE prevented phase separation and provided a homogeneous physical blending formulation, as confirmed by FTIR, TGA. NE-loaded films provided high drug incorporation in the films 94.08% ± 6.63%), and a smaller crystallinity degree in comparison with physical mixture films, suggesting a plasticizing effect of nano-sized droplets. Besides, mean weight, thickness, and moisture content were increased in NE-loaded films in comparison with chitosan-based control films. In vitro drug release from NE-loaded films was significantly higher than for physical mixture films, following Weibull and Korsmeyer-Peppas release kinetics models. The results suggest that NE-loaded chitosan film can increase the drug loading capacity of oil drugs and successfully control in vitro release, constituting a novel approach for transdermal drug delivery of NSAIDs.

Transdermal patches of lidocaine/aspirin ionic liquid drug-loaded gelatin/polyvinyl alcohol composite film prepared by freeze-thawed procedure.

The objectives of this study are to prepare a 5 wt% lidocaine/aspirin ionic liquid drug-loaded gelatin/polyvinyl alcohol composite film using a freeze-thaw procedure and to evaluate their physicochemical characteristics, in vitro drug release, and stability. Lidocaine/aspirin ionic liquid drugs can be prepared by an ion-pair reaction between the hydrochloride salts of lidocaine and the sodium salts of aspirin, which showed a significant change in their thermal properties when compared to those pure drugs. The results showed that a transdermal patch could feasibly be used in pharmaceutical transdermal patches with good physicochemical properties. A chemical interaction between the drug and polymer base was not found. Decomposition of the lidocaine/aspirin ionic liquid drug was found in the patch; however, the properties of the patch were not changed after drug loading. The patch controlled the drug release and showed good stability during the studied period of three months when kept at 4°C more than at ambient temperature and 45°C.

Eficacia analgésica del EMLA en procedimientos transcutáneos. Revisión sistemática / Analgesic efficacy of EMLA in transcutaneous procedures. Systematic review

Los parches de EMLA son frecuentemente utilizados como anestésicos locales durante la realización en procedimientos invasivos. Con el fin de valorar su eficacia y compararla con la de otros analgésicos y anestésicos disponibles, se realizó una revisión sistemática de todos los estudios realizados que cumplieran criterios de inclusión entre los años 1990 y 2019. Población y métodos: la búsqueda bibliográfica de la evidencia disponible fue realizada en las bases de datos de Cochrane Medline y Lilacs. Se incluyeron todos los ECA y revisiones sistemáticas en pacientes menores de 16 años entre los años 1990 y 2019. Resultados: Fueron hallados 31 artículos de los cuales 21 cumplían con los criterios de inclusión. De dichos 21, solamente 8 estudios resultaron de muy buena y excelente calidad metodológica (JADAD). Conclusiones: El EMLA demostró mayor eficacia como analgésico en el 100% de los estudios donde se comparaba respecto del placebo. Sin embargo, no se encontraron diferencias significativas respecto de otros analgésicos farmacológicos y no farmacológicos.(AU)

EMLA patches are commonly used as local anesthetics in minor invasive procedures. To assess efficacy and compare the patches with other available analgesics and anesthetics, a systematic review was conducted evaluated all studies that met the inclusion criteria published between 1990 and 2019. Population and methods: A literature search of the available evidence was conducted in the Cochrane, Medline, and Lilacs databases. All RCTs and systematic reviews in patients younger than 16 years published between 1990 and 2019 were included. Results: 31 articles were identified of which 21 met the inclusion criteria. Of these 21, of only 8 studies the methodology was of very good and excellent quality (JADAD). Conclusions: EMLA better efficacy as an analgesic in 100% of the studies comparing EMLA patches with placebo. However, no significant differences were found when comparing the patches with other pharmacological and non-pharmacological analgesics.(AU)

Efficacy and safety of loxoprofen sodium topical patch for the treatment of pain in patients with minor acute traumatic limb injuries in Brazil: a randomized, double-blind, noninferiority trial.

Posttraumatic injury pain is commonly treated with oral nonsteroidal anti-inflammatory drugs. However, oral nonsteroidal anti-inflammatory drugs cause several adverse events, with topical formulations arising as an important alternative. Therefore, we aimed at evaluating the efficacy and safety of loxoprofen patch (LX-P) in the treatment of patients with posttraumatic pain. This phase III, randomized, double-blind, noninferiority study enrolled Brazilian patients aged 18 to 65 years diagnosed with lower and upper limb posttraumatic injury who were experiencing moderate or severe pain. Patients were assigned to active LX-P or to loxoprofen tablet (LX-T), and pain intensity was measured based on a visual analog scale score variation after 7 days of treatment. Data on clinical symptoms, rescue medication use, and adverse events were also collected. Visual analog scale score variation was compared using a 10% noninferiority margin. Two hundred forty-two patients were randomly assigned to LX-P (n = 123) or to LX-T (n = 119). The results showed a reduction in pain after 7 days of treatment: -49.96 (n = 118; SE 1.7) in the LX-P and -47.71 (n = 117; SE 1.6) in the LX-T groups (difference of -2.25; 95% CI: -5.97 to 1.47; P = 0.23). On the safety analysis, the LX-T group presented twice as many patients with treatment-emergent adverse events as the LX-P group (30.8% and 14.2%, respectively). A sensitivity analysis demonstrated that rescue medication use has not affected the primary end point. This study showed that LX-P has a comparable efficacy to LX-T, but with a better safety profile, being a therapeutic option for the treatment of posttraumatic injury pain.

Management of contraceptives and menstrual complaints in patients with Down syndrome.

Enhanced health care for patients with Down syndrome (DS) results in improved overall quality of life and longer life expectancy. The main gynecologic complaints of patients with DS and their caregivers relate to menstrual cycles, hygiene and reproductive issues. Certain aspects, such as age of menarche, menstrual cycles, internal genitalia, and hormone profile are similar to those observed in the general population. However, individuals with DS may have a higher incidence of other disorders related to menstruation, such as hypothyroidism, epilepsy and use of anticonvulsants. Contraceptive measures for individuals with DS can be used for both contraception and control of menstrual symptoms. The physician must be to make an individualized recommendation aimed at offering the most efficient and least invasive method with the fewest side effects. Among medical options are oral contraceptives, quarterly injectable medroxyprogesterone acetate, oral progesterone, a levonorgestrel-releasing intrauterine system, transdermal patch and vaginal rings. Surgical methods, including hysterectomy, endometrial ablation, or tubal ligation, are rarely considered because they raise ethical and legal questions. This article reviews the literature and basic guidelines to assist physicians who attend adolescent girls and women with DS to provide guidance on the appropriate management of the main gynecologic complaints of this population.

Semisynthetic Derivative of Artemisia annua-Loaded Transdermal Bioadhesive for the Treatment of Uncomplicated Malaria Caused by Plasmodium falciparum in Children.

According to the most recent World Health Organization statistics, malaria infected approximately 219 million people in 2017, with an estimate of 435,000 deaths (World Health Organization, 2018). Communities isolated from cities are the most deprived of access to the necessary hospital facilities. Herein we report the development of a transdermal bioadhesive containing artemether (ART), an alternative, potentially lifesaving, treatment regimen for malaria in low-resource settings. Bioadhesives were prepared from an aqueous blend of hydroxyethylcellulose (4.5% w/w), ART, propoxylated-ethoxylated-cetyl-alcohol, polysorbate 80, propyleneglycol, glycerine, mineral oil, and oleic acid. In this study, the average pore size of bioadhesive 5.5b was 52.6 ± 15.31 µm. Differential scanning calorimetry and thermogravimetric analyses confirm the thermal stability of ART bioadhesives at room temperature. Tensile tests indicated good mechanical properties for bioadhesive 5.5b, when compared to 5.5a, where 5.5b showed elastic modulus 0.19 MPa, elongation at break 204%, tensile stress 0.31 MPa, tensile strength at break 0.23 MPa. Bioadhesion assays suggested that formulations containing surfactants had higher detachment forces. Permeation studies demonstrated that the best outcome was achieved with a bioadhesive containing 25 mg ART (5.5b) that after 24 h released 6971 ± 125 µg, which represents approximately 28% of drug permeation. Data reported presents a promising candidate for a new antimalarial transdermal formulation.

Influence of different formulation variables on the performance of transdermal drug delivery system containing tizanidine hydrochloride: in vitro and ex vivo evaluations

The present study was aimed at preparation of transdermal patches of tizanidine HCl, evaluation of the effect of polymers on in vitro release pattern of the drug, and the effect of permeation enhancers on the penetration of the drug through the rabbit skin. Various proportions of hydrophilic (HPMC) and hydrophobic (Eudragit L-100) polymers were used with PEG 400 as film-forming agent, and Span 20 or DMSO as permeation enhancer. The formulations were assessed for physicochemical characteristics and in vitro drug release studies using USP paddle over disc method in phosphate buffered saline (pH 7.4) at 32.0±1°C. On the basis of in vitro studies and physicochemical evaluations, S03-A and S04-A were selected at Eudragit : HPMC ratios of 8 : 2 and 7 : 3, respectively, for further ex vivo analysis. The effects of different concentrations of Span 20 and DMSO were evaluated on excised rabbit skin using Franz diffusion cell. Cumulative drug permeation, flux, permeability coefficient, target flux, and enhancement ratio were calculated and compared with the control formulations. Kinetic models and Tukey's multiple comparison test were applied to evaluate the drug release patterns. Formulation SB03-PE containing Eudragit L-100:HPMC (7:3) with Span 20 (15% w/w) produced the highest enhancement in drug permeation, and followed zero order kinetic model with super case-II drug release mechanism.

Effectiveness of lidocaine patches for pain treatment after total knee arthroplasty / Eficácia do tratamento adjuvante da dor pós-artroplastia total do joelho utilizando emplastros com lidocaína

BACKGROUND: Effective analgesic therapy in the postoperative period of total knee arthroplasty is essential for good surgical outcomes. The current trend is to use multimodal treatment, in which the use of patches with lidocaine as adjuvant therapy has an increasingly relevant role. OBJECTIVE: To investigate the potential benefits of lidocaine patch association with the basic analgesia regimen for pain relief during the postoperative period of total knee arthroplasty. METHOD: A retrospective cohort study was performed , with a total of 24 patients in each group, who underwent total knee arthroplasty. Pain levels using a visual analogue scale and opioid intake were controlled from the immediate postoperative to the end of a 28-day interval. RESULTS: During the postoperative period, pain was less intense in patients who used lidocaine patches. In these same patients, the doses of opioids needed to control pain were lower in 15 of the 28 days analyzed. The relative frequency of nausea was higher in the group that did not use adjuvant therapy. Patients older than 70 years and females predominated. CONCLUSION: Adjuvant treatment after total knee arthroplasty using lidocaine patches was effective in reducing pain and decreasing the use of opioids in the period analyzed, and represents a good addition to multimodal analgesic therapy.

OBJETIVO: A terapia analgésica eficaz no pós-operatório de artroplastia total do joelho é imprescindível para bons resultados cirúrgicos. A tendência atual é a de se utilizar o tratamento multimodal, no qual a utilização de emplastros com lidocaína como terapia adjuvante tem papel crescente e relevante. Investigar os potenciais benefícios da associação do emplastro com lidocaína ao esquema terapêutico básico de analgesia para o alívio da dor durante o período pós-operatório de artroplastia total de joelho. MÉTODO: Foi realizado um estudo de coorte retrospectivo cuja população foi a de pacientes submetidos a artroplastia total do joelho, divididos em dois grupos com 24 integrantes em cada, acompanhados por um período de 28 dias. RESULTADOS: Durante o pós-operatório analisado a dor foi menos intensa nos pacientes que utilizaram os emplastros com lidocaína. Nesses mesmos pacientes, as doses de opióides necessárias para controlar a dor foram menores em 15 dos 28 dias analisados. A frequência relativa de náuseas foi maior no grupo que não utilizou a terapia adjuvante. Predominaram os pacientes com mais de 70 anos e o gênero feminino. CONCLUSÃO: O tratamento adjuvante após a artroplastia total do joelho utilizando emplastros com lidocaína mostrou ser eficaz na redução da dor e diminuição do uso de opióides no período analisado, constituindo um bom incremento para a terapia analgésica multimodal.

Terapia de reemplazo de nicotina / Nicotine replacement therapy

Resumen Todas las formas comercialmente disponibles de terapia de reemplazo de nicotina (TRN) (chicles, parche transdérmico, aerosol nasal, inhalador y tabletas sublinguales / lozenges) pueden ayudar a de dejar de fumar con éxito. TRN aumenta la tasa cesación en un 50 a 70%. La combinación de un parche de nicotina con una forma de administración rápida de TRN es más eficaz que un solo tipo de NRT. No hay diferencia en la eficacia entre TRN y bupropión, la combinación de NRT y bupropión es más efectiva que bupropión solamente. Los efectos de TRN son en gran parte independientes de la duración de la terapia, la intensidad del apoyo prestado o lugar en el que se ofreció. Según expertos chilenos, se puede usar TRN en adolescentes, en forma de chicles de 2 mg asociado a terapia conductual. Si una embarazada expresa un claro deseo de recibir TRN, se sugiere (i) discutir con ella los riesgos y beneficios asociados, (ii) utilizarla sólo si falla la cesación con medidas no farmacológicas y (iii) utilizar el criterio profesional al decidir si ofrecer la prescripción de TRN, tomando en cuenta el nivel de adicción de la embarazada y la presencia de comorbilidades. Estos fármacos existen en Chile, pero no están hasta el momento disponibles en el sistema público de salud.

All commercially available forms of nicotine replacement therapy (NRT) (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/pills) can help to quit smoking successfully. NRT increases the cessation rate by 50 to 70%. The combination of a nicotine patch with a rapid dosage form of NRT is more effective than a single type of NRT. There is no difference in efficacy between NRT and bupropion, the combination of NRT and bupropion is more effective than bupropion alone. The effects are largely independent of the duration of therapy, the intensity of the support provided or the setting in which the NRT was offered. According to Chilean experts, NRT can be used in adolescents, as chewing gum 2 mg adding behavioral therapy. If a pregnant woman expresses a clear desire to use NRT, it is suggested (i) discuss the associated risks and benefits with her, (ii) use it only if the cessation fails with non-pharmacological measures and iii) use the professional approach when deciding whether to offer the prescription of NRT, considering the level of addiction of the pregnant woman and the presence of comorbidities. TRN exists in Chile, but is not currently available in the public health system.

Molécula 1 de Adhesión Intercelular Soluble en menopáusicas tratadas con estradiol oral o transdérmico / Soluble Intercellular Adhesion Molecule 1 In Postmenopausal Women Treated With Oral Or Transdermal Estradiol

El objetivo de la investigación fue comparar las modificaciones de las concentraciones plasmáticas de la molécula 1 de adhesión intercelular soluble en menopáusicas tratadas con estradiol oral o transdérmico después de 3 meses de uso. Se realizó una investigación con una muestra de 140 pacientes menopáusicas que asistieron a la consulta de Medicina Interna, Endocrinología y Menopausia del Hospital Central Dr. Urquinaona, Maracaibo, Venezuela. Se asignó a 70 pacientes tratamiento con estradiol oral (grupo A) y a 70 pacientes tratamiento con estradiol transdérmico (grupo B). Se evaluaron las concentraciones plasmáticas de molécula 1 de adhesión intercelular soluble antes y después de 3 meses de tratamiento. (p = ns). Las concentraciones plasmáticas de la molécula 1 de adhesión intercelular soluble demostraron una reducción después de 3 meses de tratamiento en ambos grupos (grupo A: 279,1 +/- 76,5 ng/ml al inicio comparado con 241,7 +/- 68,4 ng/ml después del tratamiento y grupo B: 251,9 +/- 73,2 ng/ml después del tratamiento comparado con el valor promedio inicial de 288,7 +/- 62,7 ng/ml; p < 0,05). Se concluye que el uso de estradiol transdérmico puede ser una alternativa eficaz al uso de estradiol oral después de 3 meses de uso, debido a que ambos tratamientos producen disminuciones en las concentraciones plasmáticas de molécula 1 de adhesión intercelular soluble.

The objective of research was: to compare modifications of plasma concentrations of solubleintercellular adhesion molecule 1 in postmenopausal women treated with oral or estradiol after 3 months of use. This study included 140 postmenopausal women attending the Internal Medicine, Endocrinology and Menopause Departments at the Hospital Central "Dr. Urquinaona", Maracaibo, Venezuela. Seventy patients were assigned to be treated with oral estradiol (group A) and 70 patients were treated with transdermal estradiol (group B). Plasma concentrations of soluble intercellular adhesion molecule 1 were measured before and after 3 months of treatment. There were no statically significant differences in general characteristics between the two treatment groups (p = ns). In both groups, soluble intercellular adhesion molecule 1 was reduced after 3 months of treatment (group A: 279.1 +/- 76.5 ng/ml before treatment compared with 241.7 +/- 68.4 ng/ml after treatment and group B: 251.9 +/- 73.2 ng/ml after treatment compared with initial mean value of 288.7 +/- 62.7 ng/ml; p < 0.05). It is concluded that transdermal estradiol could be an effective alternative to oral estradiol after 3 months of use since both treatments decreased plasma concentrations of soluble intercellular adhesion molecule 1. KEYWORDS: Estradiol; Menopause; Transdermal; soluble intercellular adhesión.

Eficacia y seguridad del uso de buprenorfina parche transdérmico en pacientes con dolor neuropático / Efficacy and safety of the use of buprenorphine transdermal patch in patients with neuropathic pain

INTRODUCCIÓN: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad del uso de buprenorfina 35mcg/hr parche transdérmico para el tratamiento del dolor neuropático. El dolor neuropático es consecuencia de un "daño" al sistema somato sensorial, que puede ocurrir por una variedad de etiologías entre las que se encuentran traumatismo vertebro medular, neuropatía diabética, neuralgia post-herpética, neuropatía post-quirúrgica, radiculopatía lumbar, dolor neuropático asociado a cáncer, neuropatía relacionada al virus de inmunodeficiencia humana, dolor fantasma, neuralgia del trigémino, entre otros. A nivel global, la prevalencia del dolor neuropático oscila entre 7% y 10% en población general. El dolor neuropático posee particularidades que implican un desafío para su manejo. Así, éste puede desencadenarse por algún estímulo sensorial o producirse espontáneamente; también puede presentar variaciones de acuerdo al tipo de paciente y la condición específica de fondo, debido a los diferentes mecanismos que operan en cada individuo. Todo ello, dificulta la elección del analgésico, por lo que existe más de un algoritmo de tratamiento para el dolor neuropático, que incluye el uso de medicamentos antiepilépticos, antidepresivos y opioides. En EsSalud, se dispone de medicamentos antiepilépticos y antidepresivos para el tratamiento del dolor neuropático como gabapentina y amitriptilina, entre otros. En caso de requerir el uso de opioides para el control del dolor neuropático se cuenta con tramadol y en el caso de dolor neuropático oncológico, se cuenta además con oxicodona y morfina. Sin embargo, los pacientes que suscitaron la solicitud de uso de buprenorfina transdérmica a ser evaluada en el presente dictamen, poseen condiciones clínicas particulares que dificultan el uso de las opciones de tratamiento incluidas actualmente en el Petitorio Farmacológico de la institución. Por lo que, existe la necesidad de contar con una alternativa eficaz y segura, dentro del grupo de medicamentos opioides, para el tratamiento del dolor neuropático en dicho grupo de pacientes. METODOLOGÍA: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de buprenorfina en parche transdérmico para el dolor neuropático. La búsqueda se inició revisando la información sobre el uso del medicamento de acuerdo con entidades reguladoras como la Food and Drug Administration (FDA), la European Medicines Agency (EMA) y la Dirección General de Medicamentos y Drogas (DIGEMID). Posteriormente, se revisaron las bases de datos de PubMed, TRIPDATABASE y www.clinicaltrials.gov. Adicionalmente, se realizó una búsqueda de evaluaciones de tecnologías y guías de práctica clínica en las páginas web de grupos dedicados a la investigación y educación en salud en general como The National Institute for Health and Care Excellence (NICE). RESULTADOS: De acuerdo con la pregunta PICO, se llevó a cabo una búsqueda de evidencia científica relacionada al uso de buprenorfina transdérmica para el tratamiento de dolor neuropático. En la presente sinopsis se describe la evidencia disponible. CONCLUSIONES: El presente dictamen tuvo como objetivo evaluar la eficacia y seguridad del uso de buprenorfina transdérmica en parches para el tratamiento del dolor neuropático. Como parte de la evaluación se prestó especial atención a los pacientes con enfermedad renal crónica concomitante o que no tienen una vía de administración alternativa para el medicamento analgésico. De acuerdo a lo revisado, no hay evidencia disponible que sugiera que la buprenorfina transdérmica sea más eficaz, comparado con otras opciones de tratamiento incluidas en el Petitorio Farmacológico de EsSalud, para el tratamiento del dolor neuropático. Sin embargo, existe alguna evidencia del uso de buprenorfina transdérmica en pacientes que presentan eventos adversos, los cuales llevan a la suspensión o disminución de la dosis del opioide, o que presentan pobre acceso a la vía de administración del medicamento analgésico, condiciones que incluyen a la insuficiencia renal concomitante y dificultad para otras vías de administración (i.e. vía oral, vía de acceso para bloqueo neural). Así, dentro de la búsqueda realizada se identificó un estudio observacional que evaluó el uso de buprenorfina transdérmica para dolor neuropático, publicado por Filitz et al. Adicionalmente, también se identificó evidencia indirecta en torno al uso de buprenorfina transdérmica en pacientes que presentan dificultad para otras vías de administración. Esta evidencia proviene de dos guías de práctica clínica en pacientes con dolor oncológico, las guías de Scottish Intercollegiate Guidelines Network del 2013 y la guía de European Society for Medical Oncology 2012. Asimismo, debido a la escasez de evidencia científica sólida proveniente de ensayos clínicos aleatorizados y controlados; se incluyó también la opinión de expertos, cuya opinión se condice con la evidencia encontrada. En conclusión, la evidencia encontrada en torno a la eficacia y seguridad del uso de buprenorfina transdérmica como opción de analgésico para pacientes con dolor neuropático no ha probado que este sea más eficaz que otros tratamientos analgésicos actualmente aprobados en el Petitorio Farmacológico de la institución. Sin embargo, existe un grupo de pacientes, los cuales presentan insuficiencia renal concomitante o dificultan para otras vías de administración que requieren una alternativa de analgésico distinta. La evidencia de uso de buprenorfina transdérmica en estos pacientes proviene de estudios observacionales o evidencia indirecta, que de acorde con la opinión de expertos supondría una opción de tratamiento valida. Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación- IETSI, aprueba el uso de buprenorfina transdérmica en pacientes con dolor neuropático que presentan insuficiencia renal concomitante o dificultad para otras vías de administración, y que por lo tanto no puedan utilizar las alterativas incluidas en el Petitorio Farmacológico de EsSalud; según lo establecido en el Anexo N° 1. La vigencia del presente dictamen preliminar es de un año, la continuación de dicha aprobación estará sujeta a los resultados obtenidos de los pacientes que se beneficien con dicho tratamiento y a nueva evidencia que poda surgir en el tiempo.

Risedronate transdermal delivery system based on a fumaric copolymer for therapy of osteoporosis.

Transdermal drug delivery system (TDDS) could be seen as alternative to the oral administration which avoids several adverse effects. In this study a novel TDDS for risedronate (RI), a bisphosphonate used for osteoporosis treatment, based on a vinyl acetate-dioctylfumarate copolymer, poly(VA-co-DOF), previously synthetized, was developed. Two membranes including 6 and 12% (w/w) of drug were obtained, which exhibited good transparence and homogeneous drug distribution, as evaluated by optical microscopy. FTIR spectroscopy and differential scanning calorimetry (DSC) analysis showed no significant drug/polymer interactions, only a plasticizer effect. A new reverse phase high-performance liquid chromatography (RP-HPLC) method for quantification of RI was development and validated, which demonstrate good linearity, reproducibility and accuracy with limits of detection (LOD) and quantification (LOQ) of 0.38µg/mL and 1.17µg/mL, respectively. High drug load efficiency and great drug stability were found. The analysis of the drug release kinetics, fitting to Ritger-Peppas model, leads to values of the diffusion coefficient (n) of 1.37 and 1.05, for 6 and 12% (w/w) RI, respectively. These results correspond to super case transport II and suggest a complex transport mechanism, regulated by the mobility of the polymer chains. Together, these results indicate that this new TDDS could be useful for osteoporosis treatment without adverse effect.

Development of a Discriminative In Vitro Release Test for Rivastigmine Transdermal Patches Using Pharmacopeial Apparatuses: USP 5 and USP 6.

The aim of this study was to develop and validate a discriminating in vitro release test to evaluate rivastigmine transdermal patches. The Exelon® Patch was chosen as a model transdermal product. The studies of in vitro release were designed to determine the impact of the official apparatus chosen (USP apparatus 5 and USP apparatus 6), the rotation speed, and the dissolution medium characteristics on the rivastigmine release profile from transdermal patches. Patches with different drug release profiles were tested in order to evaluate the discriminating power of the in vitro release test developed and validated. Variables such as the apparatus type, the dissolution medium, and the rotation speed have a significant influence on the drug release characteristics from a transdermal patch. The in vitro release methodologies using the USP apparatus 5 at 50 rpm and USP apparatus 6 at 25 rpm using the medium phosphate-buffered saline pH 7.4 were considered discriminative and adequate to characterize the rivastigmine (RV) release from a commercial transdermal patch, Exelon® Patch.

Chemical Leukoderma Associated with Methylphenidate Transdermal System: Data From the US Food and Drug Administration Adverse Event Reporting System.

OBJECTIVE: To identify and characterize cases of chemical leukoderma, an underrecognized adverse event, associated with the methylphenidate transdermal system (MTS) reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS). STUDY DESIGN: We searched the Food and Drug Administration Adverse Event Reporting System for reports of chemical leukoderma associated with MTS, received by the Food and Drug Administration from April 6, 2006 to December 23, 2014. RESULTS: We identified 51 cases of chemical leukoderma reported with the use of MTS. The median age was 11 years; 43 cases reported leukoderma at or near the application site only, and 7 reported leukoderma at other parts of the body in addition to the application site; 1 case did not provide enough information to confirm the affected site. The time to onset ranged from 2 months to 4 years after the initiation of MTS. MTS was discontinued in 31 cases. Thirteen patients were prescribed treatment for repigmentation. Three cases reported continued spread of leukoderma after MTS was discontinued. Nineteen cases were diagnosed as vitiligo, including 5 cases reporting histologic features consistent with vitiligo. Leukoderma was persistent in all cases. The median follow-up interval after the discontinuation of MTS in 23 cases was 14 months. CONCLUSIONS: As outlined in recent changes to the prescribing information for MTS, health care professionals need to be aware of the potential risk of chemical leukoderma caused by MTS, especially given that chemical leukoderma is often misdiagnosed as idiopathic vitiligo. MTS should be discontinued at the earliest sign of pigment loss and other treatment options considered.

Rivastigmina via transdérmica (adesivo) para o tratamento de pacientes com demência leve e moderadamente grave do tipo Alzheimer / Rivastigmine via transdermal (patch) for the treatment of patients with mild and moderately severe Alzheimer's dementia

Contexto: A doença de Alzheimer (DA) é um distúrbio neurodegenerativo progressivo crônico caracterizado por uma deterioração global e não reversível no funcionamento do cérebro, implicando perda de memória e déficit motor e discursivo. No Brasil, a prevalência de demência na população com mais dos 65 anos foi de 7,1%, sendo que a DA foi responsável por 55% dos casos. A taxa de incidência foi 7,7 por 1.000 pessoas-ano no estudo de São Paulo e 14,8 por 1.000 pessoas-ano no estudo do Rio Grande do Sul. Os fármacos considerados de primeira escolha são os inibidores da colinesterase. Dentre esses, encontra-se a rivastigmina, disponível no SUS na sua apresentação por via oral. Atualmente, a rivastigmina como tratamento por via transdérmica está registrada no País, mas não está disponível no SUS. Pergunta: O uso de rivastigmina adesivo transdérmico é eficaz e seguro no tratamento de pacientes com doença de Alzheimer quanto comparado com rivastigmina oral? Evidências científicas: Um ensaio clínico randomizado, duplo cego, com quatro braços: placebo, Exelon Patch 10, Exelon Patch 20 e cápsula oral 6mg 2xdia, que estudou mais de 1000 voluntários, foi apresentado como evidência científica. Os resultados do estudo demonstram que a apresentação via transdérmica (Exelon Patch 10) se mostrou superior ao placebo e tão eficaz quanto a apresentação via oral e que os adesivos poderiam apresentar redução de efeitos adversos gastrointestinais. Os dados corroboram outros estudos que avaliaram o adesivo transdérmico e que também demonstraram eficácia e segurança comparável entre as duas formas farmacêuticas (oral e transdérmica) do medicamento. Mais atenção deve ser dada ao tamanho do efeito que estas drogas tem gerado de eficácia no tratamento da doença de Alzheimer. Conclusão: Os resultados apresentados nos ensaios clínicos sugerem que a rivastigmina via transdérmica é tão eficaz e segura quanto a rivastigmina via oral. Entretanto, o tamanho do efeito apresentado é de difícil mensuração, sendo baseado em variações pontuais de pequena magnitude de uma escala específica. O impacto orçamentário para a incorporação da tecnologia diminui significativamente caso seja adotado um preço para o Patch 5 equivalente a Rivastigmina 1,5mg (duas vez ao dia) e para o Patch 10 equivalente a Rivastigmina 3mg (duas vez ao dia), que seriam as doses equivalentes de tratamento inicial e de manutenção. Decisão: Incorporar a rivastigmina adesivo transdérmico para o tratamento de demência para Doença de Alzheimer, conforme Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde, no âmbito do Sistema Único de Saúde ­ SUS, dada pela Portaria SCTIE-MS nº 31 publicada no Diário Oficial da União (DOU) nº 183, de 22 de setembro de 2016.

Comparative evaluation of rivastigmine permeation from a transdermal system in the Franz cell using synthetic membranes and pig ear skin with in vivo-in vitro correlation.

In the present study, in vitro permeation experiments in a Franz diffusion cell were performed using different synthetic polymeric membranes and pig ear skin to evaluate a rivastigmine (RV) transdermal drug delivery system. In vitro-in vivo correlations (IVIVC) were examined to determine the best model membrane. In vitro permeation studies across different synthetic membranes and skin were performed for the Exelon(®) Patch (which contains RV), and the results were compared. Deconvolution of bioavailability data using the Wagner-Nelson method enabled the fraction of RV absorbed to be determined and a point-to-point IVIVC to be established. The synthetic membrane, Strat-M™, showed a RV permeation profile similar to that obtained with pig ear skin (R(2)=0.920). Studies with Strat-M™ resulted in a good and linear IVIVC (R(2)=0.991) when compared with other synthetic membranes that showed R(2) values less than 0.90. The R(2) for pig ear skin was 0.982. Strat-M™ membrane was the only synthetic membrane that adequately simulated skin barrier performance and therefore it can be considered to be a suitable alternative to human or animal skin in evaluating transdermal drug transport, potentially reducing the number of studies requiring human or animal samples.