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Antagonistas de Receptores Adrenérgicos beta 1/efectos adversos , Bisoprolol/efectos adversos , Preparaciones de Acción Retardada/efectos adversos , Dermatitis Alérgica por Contacto/diagnóstico , Erupciones por Medicamentos/diagnóstico , Parche Transdérmico/efectos adversos , Administración Cutánea , Dermatitis Alérgica por Contacto/etiología , Erupciones por Medicamentos/etiología , HumanosRESUMEN
HISTORY AND CLINICAL FINDINGS: We present the case of an 89-year-old patient with impaired consciousness for whom the emergency services were called. She was soporose and showed a pronounced generalized muscle rigidity. Due to a third-party history the incorrect use of a fentanyl patch was found out to be at cause. TREATMENT AND CLINICAL COURSE: The antidote administration of naloxone led to restoration. The need for repetitive administration confirmed the clinical hypothesis. CONCLUSION: The application of fentanyl via the skin in the form of transdermal therapeutic systems (TTS) has become more popular over the years. Incorrect administration causes intoxication with the leading symptoms of loss of consciousness and respiratory depression. This case report extends the spectrum of symptoms to include skeletal muscle rigidity otherwise only described in connection with intravenous administration, especially in anaesthetic settings.
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Analgésicos Opioides , Trastornos de la Conciencia/inducido químicamente , Sobredosis de Droga , Antagonistas de Narcóticos , Parche Transdérmico/efectos adversos , Anciano de 80 o más Años , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Sobredosis de Droga/tratamiento farmacológico , Sobredosis de Droga/etiología , Femenino , Fentanilo/administración & dosificación , Fentanilo/efectos adversos , Humanos , Naloxona/administración & dosificación , Naloxona/uso terapéutico , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéuticoRESUMEN
Two open-label, single-dose, randomized crossover studies were conducted in healthy Japanesemen to (1) assess dose proportionality of 5 doses (1.38, 2.75, 5.5, 8.25, and 11.0 mg) of Lafenta, a novel matrix-type transdermal fentanyl patch with a rate-controlling membrane; and (2) compare patch bioequivalence (11.0 mg) with a commercially available reference patch (Durotep MT Patch [16.8 mg]). Pharmacokinetics, adhesion performance, residual fentanyl, and safety parameters were assessed. Increases in mean AUC0-t and Cmax after application of the test patch were dose proportional. The test patch (11.0 mg) was bioequivalent to the 16.8-mg reference patch in terms of mean AUC0-inf , AUC0-t , and Cmax . Residual fentanyl levels 72 hours postapplication were lower in the test than in the reference patch. Differences in adhesion performance between the test and the reference patch did not affect delivery efficacy and reliability of the novel matrix patch. Safety findings were in line with previous experiences with fentanyl. Both studies showed low variation in fentanyl exposure and delivery via the test patch. The test patch provided equivalent fentanyl exposure at a lower dose than the reference patch formulation with lower variability and the potential to lower medicinal waste.
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Analgésicos Opioides/farmacocinética , Tolerancia a Medicamentos/etnología , Fentanilo/farmacocinética , Administración Cutánea , Adulto , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Área Bajo la Curva , Disponibilidad Biológica , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos , Fentanilo/administración & dosificación , Fentanilo/efectos adversos , Voluntarios Sanos/estadística & datos numéricos , Humanos , Japón/epidemiología , Naltrexona/administración & dosificación , Antagonistas de Narcóticos/administración & dosificación , Reproducibilidad de los Resultados , Seguridad , Equivalencia Terapéutica , Parche Transdérmico/efectos adversosRESUMEN
A transdermal patch formulation of a non-steroidal anti-inflammatory drug (NSAID) used by a 44-year-old man resulted in acute interstitial nephritis and acute tubular injury. This patient also had a history of mild kidney dysfunction and osteoporosis. The NSAID patch had been prescribed after a traffic accident. He was also receiving a vitamin D analog and taking over-the-counter calcium supplements. Two months later, renal dysfunction and hypercalcemia were discovered. A renal biopsy showed acute interstitial nephritis and acute tubular injury. Once these agents were withdrawn, the renal function recovered. This is the first reported occurrence of biopsy-proven acute interstitial nephritis attributable to NSAID patch usage.
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Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/fisiopatología , Antiinflamatorios no Esteroideos/efectos adversos , Enfermedades Renales/tratamiento farmacológico , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/fisiopatología , Fenilpropionatos/efectos adversos , Parche Transdérmico/efectos adversos , Adulto , Humanos , Japón , MasculinoRESUMEN
RATIONALE: Paroxysmal autonomic instability with dystonia (PAID) is an underdiagnosed syndrome that describes a collection of symptoms following diverse cerebral insults, such as traumatic brain injury, hydrocephalus, hemorrhagic stroke, or brain anoxia. It is manifested by systemic high blood pressure, hyperthermia, tachycardia, tachypnea, diaphoresis, intermittent agitation, and certain forms of dystonia. PATIENT CONCERNS: A semi-comatose 46-year-old man was transferred from the regional rehabilitation hospital with various complaints involving fluctuating vital signs, including uncontrolled hyperthermia, hypertension, tachycardia, and tachypnea, and dystonia in all extremities. The patient underwent brain surgery for astrocytoma in 1996. The patient also had a history of first ischemic stroke on the basal ganglia in 2008 and a second one in the same area in 2017. DIAGNOSIS: The laboratory, electrocardiography, and radiologic findings were normal. Brain imaging indicated an old infarction on the basal ganglia with hydrocephalus. Tractography using diffusion tensor imaging showed discontinuity of multiple tracts, and electrophysiologic tests, such as evoked potentials, displayed an absent response. Based on the dysautonomic symptoms and brain evaluations, the physiatrist diagnosed the patient with PAID. INTERVENTIONS: Bromocriptine, propranolol, and clonazepam were administered sequentially, but autonomic instability persisted. Then, intravenous opioid was administered, and fluctuations in body temperature, heart rate, and respiratory rate, as well as decerebrate-type dystonia were improved. However, simultaneously, drug-induced severe hypotension developed (systolic blood pressure, 57âmm Hg). Subsequently, a transdermal opioid (fentanyl) patch for PAID was applied once every 3 days. OUTCOMES: Ultimately, all vital signs and dystonia were managed without further complications, and the patient was discharged. LESSONS: A patient diagnosed with PAID following multiple cerebral insults was observed, whose condition was controlled by application of opioid patch rather than by intravenous or oral routes. A transdermal opioid patch, such as fentanyl patch, can thus be effective in the treatment of patients with PAID following multiple cerebral insults.
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Analgésicos Opioides/uso terapéutico , Enfermedades del Sistema Nervioso Autónomo/tratamiento farmacológico , Distonía/diagnóstico , Fentanilo/uso terapéutico , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Ganglios Basales/patología , Isquemia Encefálica/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Distonía/etiología , Fiebre/diagnóstico , Fiebre/etiología , Humanos , Hidrocefalia/etiología , Hipertensión/diagnóstico , Hipertensión/etiología , Hipotensión/inducido químicamente , Masculino , Persona de Mediana Edad , Síndrome , Taquicardia/diagnóstico , Taquicardia/etiología , Taquipnea/diagnóstico , Taquipnea/etiología , Parche Transdérmico/efectos adversos , Resultado del TratamientoRESUMEN
The development of microarray patches for vaccine application has the potential to revolutionise vaccine delivery. Microarray patches (MAP) reduce risks of needle stick injury, do not require reconstitution and have the potential to enhance immune responses using a fractional vaccine dose. To date, the majority of research has focused on vaccine delivery with little characterisation of local skin response and recovery. Here we study in detail the immediate local skin response and recovery of the skin post high density MAP application in 12 individuals receiving 3 MAPs randomly assigned to the forearm and upper arm. Responses were characterised by clinical scoring, dermatoscopy, evaporimetry and tissue viability imaging (TiVi). MAP application resulted in punctures in the epidermis, a significant transepidermal water loss (TEWL), the peak TEWL being concomitant with peak erythema responses visualised by TiVi. TEWL and TiVi responses reduced over time, with TEWL returning to baseline by 48 h and erythema fading over the course of a 7 day period. As MAPs for vaccination move into larger clinical studies more variation of individual subject phenotypic or disease propensity will be encountered which will require consideration both in regard to reliability of dose delivery and degree of inherent skin response.
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Epidermis , Eritema , Parche Transdérmico/efectos adversos , Vacunación/efectos adversos , Vacunas , Adolescente , Adulto , Anciano , Epidermis/inmunología , Epidermis/patología , Eritema/etiología , Eritema/inmunología , Eritema/patología , Humanos , Masculino , Persona de Mediana Edad , Vacunas/administración & dosificación , Vacunas/inmunologíaRESUMEN
BACKGROUND: Melasma is an acquired disorder of hyperpigmentation that is often recalcitrant to current therapies. Microneedling is used to treat scars, striae, and rhytides and has a relatively low risk of post-treatment dyspigmentation. Several studies have examined its use in melasma. OBJECTIVE: To review the published evidence on the efficacy and safety of microneedling in the treatment of melasma. METHODS: A systematic review was performed. A meta-analysis could not be performed because of methodological differences across studies and data heterogeneity. RESULTS: Eight studies were included for analysis. Most studies assessed the utility of microneedling in combination with other topical therapies and detected some success. However, microneedling-mediated transdermal delivery of medications is not superior to microinjections of medications. There is less evidence supporting the use of microneedling as monotherapy. Microneedling, when used with a 1064-nm Q-switched Nd:YAG laser, may provide additional benefit, although with a risk of post-treatment dyspigmentation. CONCLUSION: Based on low-quality evidence, microneedling may play a role in the treatment of melasma, with the mechanism of action likely being the facilitation of delivery of topical therapies to the epidermis and dermis, and one ancillary benefit of this approach being the very low risk of postinflammatory hyperpigmentation.
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Fármacos Dermatológicos/administración & dosificación , Punción Seca/métodos , Melanosis/terapia , Administración Cutánea , Terapia Combinada/efectos adversos , Terapia Combinada/instrumentación , Terapia Combinada/métodos , Fármacos Dermatológicos/efectos adversos , Punción Seca/efectos adversos , Punción Seca/instrumentación , Humanos , Microinyecciones/efectos adversos , Microinyecciones/métodos , Agujas/efectos adversos , Parche Transdérmico/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: The hypothesis is to augment the bioavailability and therapeutic potential of low bioavailable Carvedilol (25-35%) through Nanostructured Lipid Carrier (NLC) loaded Transdermal patch (Nanolipid Transferosomes). METHODS: Box-Behnken design was designed to formulate NLC through a hot homogenization technique. About 17 formulations (C1-C17) were formulated by varying the critical material attribute and critical process parameter. Optimization was done based on its critical quality attributes like particle size, zeta potential and entrapment efficiency. Selected NLC (C16) has been fabricated into a transdermal patch through solvent evaporation technique and estimated for thickness, weight variation, moisture content, folding endurance, drug content, in vitro drug release, ex vivo skin permeation studies 48 hrs, in vitro drug release kinetic studies and skin irritation studies. In vivo pharmacokinetics and pharmacodynamic study parameters were compared between carvedilol loaded NLC transdermal patch and a conventional formulation (Coreg CR). RESULTS: NLC (C16) was selected as the best formulation based on desirable, less particle size (201.1 ± 2.02 nm), more zeta potential (-37.2 ± 1.84mV) and maximum entrapment efficiency (87.54 ± 1.84%). Experimental investigations of in vivo dermatopharmacokinetic data shown statistically significant changes (p<0.05) in the parameter (increased AUC0-α, MRT with decreased Cmax, Tmax) when administered through the transdermal patch and on compared to the conventional dosage form. It was observed that there was a significant change with p<0.05 among the pharmacokinetic factors of conventional Carvedilol formulation, Carvedilol NLC and Carvedilol NLC loaded Transdermal patch with a maximum time of peak plasma concentration (Tmax) of 4 hrs, 8 hrs and 8 hrs; maximum peak plasma concentration (Cmax) of 0.258 µg/ml, 0.208 µg/ml and 0.108 µg/ml. Area Under Curve (AUC0-α) was established to be 125.127 µg/ml/h, 132.576 µg/ml.h and 841.032 µg/ml.h. Mean Residence Time (MRT0- α) of the drug was established to be 17 hrs, 19 hrs and 82 hrs, respectively. This data reveals the impact of NLC on the enhancement of bioavailability through a transdermal patch. In vivo pharmacodynamic studies confirm that NLC loaded transdermal patch (Nanolipid Transferosomes) shows a significant control in blood pressure for 48 hrs when compared to the conventional dosage form. CONCLUSION: This research data concludes that NLC loaded transdermal patch (Nanolipid Transferosomes) was a suitable candidate to enhance the bioavailability of low bioavailable drug-like Carvedilol. Lay Summary: It was inferred from the literature that NLC filled transdermal patches were a novel strategy to increase the solubility and permeability of Carvedilol, which has less bioavailability. It reveals that there was no reproducible preparation for the NLC. It also reveals that the option of formulation and process parameters for the formation of NLC is not clearly justified. On account of this, an uniquely validated and optimized formulation technique was developed for NLC with low soluble and poorly bioavailable carvedilol, tested in Albino wistar rats for enhancement of bioavailability, the same study has been performed and proved.
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Antagonistas Adrenérgicos beta/farmacocinética , Carvedilol/farmacocinética , Sistemas de Liberación de Medicamentos/métodos , Liposomas/farmacocinética , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/farmacología , Animales , Disponibilidad Biológica , Presión Sanguínea/efectos de los fármacos , Carvedilol/administración & dosificación , Carvedilol/farmacología , Portadores de Fármacos/administración & dosificación , Composición de Medicamentos/métodos , Liberación de Fármacos , Cinética , Liposomas/metabolismo , Liposomas/farmacología , Masculino , Modelos Animales , Modelos Estadísticos , Nanoestructuras/administración & dosificación , Tamaño de la Partícula , Permeabilidad/efectos de los fármacos , Ratas , Ratas Wistar , Absorción Cutánea/efectos de los fármacos , Solubilidad/efectos de los fármacos , Parche Transdérmico/efectos adversosRESUMEN
BACKGROUND: The efficacy and safety of buprenorphine transdermal patch (BTP) has been well established in chronic pain, but data regarding acute postoperative pain relief is still very limited. Therefore, we design a prospective, randomized, controlled study to evaluate the effectiveness and safety of the BTP for postoperative analgesia in total hip arthroplasty. METHODS: This study is designed as a single-center, prospective, double-blind, randomized controlled trial. Group A receives a 10âmg patch of buprenorphine at the conclusion of surgery which is continued for 14 days. Group B receives a conventional analgesic regimen, that is, IV paracetamol 1âmg every 8âhours alternating with parenteral tramadol 50âmg every 8âhours for the first 2 postoperative days followed by oral administration of the same drug still the end of 2 weeks. A total of 160 patients are needed with an allowance for 10% drop-out. The primary outcome of this noninferiority study is opioid consumption within the first 24âhours following surgery. The secondary outcomes included numerical rating scale scores at rest, postoperative complications, length of hospital stay, and patient satisfaction. RESULTS: This trial is expected to be the largest randomized trial assessing the efficacy of BTP after primary total hip arthroplasty and powered to detect a potential difference in the primary outcome. TRIAL REGISTRATION NUMBER: This study protocol was registered in Research Registry (researchregistry5524).
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Analgésicos Opioides/uso terapéutico , Artroplastia de Reemplazo de Cadera/efectos adversos , Buprenorfina/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Parche Transdérmico/efectos adversos , Acetaminofén/administración & dosificación , Acetaminofén/uso terapéutico , Administración Intravenosa , Administración Oral , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/uso terapéutico , Analgésicos Opioides/administración & dosificación , Buprenorfina/administración & dosificación , Estudios de Casos y Controles , Método Doble Ciego , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Dimensión del Dolor/estadística & datos numéricos , Dimensión del Dolor/tendencias , Satisfacción del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Tramadol/administración & dosificación , Tramadol/uso terapéuticoAsunto(s)
Acrilatos/efectos adversos , Adhesivos/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Anciano de 80 o más Años , Inhibidores de la Colinesterasa/administración & dosificación , Humanos , Masculino , Rivastigmina/administración & dosificación , Parche Transdérmico/efectos adversosRESUMEN
Hydrogel-forming microneedle array patches (MAPs) have been proposed as viable clinical tools for patient monitoring purposes, providing an alternative to traditional methods of sample acquisition, such as venepuncture and intradermal sampling. They are also undergoing investigation in the management of non-melanoma skin cancers. In contrast to drug or vaccine delivery, when only a small number of MAP applications would be required, hydrogel MAPs utilised for sampling purposes or for tumour eradication would necessitate regular, repeat applications. Therefore, the current study was designed to address one of the key translational aspects of MAP development, namely patient safety. We demonstrate, for the first time in human volunteers, that repeat MAP application and wear does not lead to prolonged skin reactions or prolonged disruption of skin barrier function. Importantly, concentrations of specific systemic biomarkers of inflammation (C-reactive protein (CRP); tumour necrosis factor-α (TNF-α)); infection (interleukin-1ß (IL-1ß); allergy (immunoglobulin E (IgE)) and immunity (immunoglobulin G (IgG)) were all recorded over the course of this fixed study period. No biomarker concentrations above the normal, documented adult ranges were recorded over the course of the study, indicating that no systemic reactions had been initiated in volunteers. Building upon the results of this study, which serve to highlight the safety of our hydrogel MAP, we are actively working towards CE marking of our MAP technology as a medical device.
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Biomarcadores/análisis , Microinyecciones/instrumentación , Administración Cutánea , Adulto , Diseño de Equipo , Femenino , Voluntarios Sanos , Humanos , Hidrogeles , Masculino , Microinyecciones/efectos adversos , Agujas , Parche Transdérmico/efectos adversosRESUMEN
OBJECTIVE: To evaluate the bioequivalence of norelgestromin and ethinyl estradiol (NGMN-EE) and adhesion of a transdermal contraceptive patch containing a newly sourced adhesive component (test) compared with the marketed (reference) patch. STUDY DESIGN: In this randomized, double-blind, 2-way crossover study, healthy women received single 7-day application of both test and reference patches. Treatment phase included two treatment periods of 11 days each separated by a 21-day washout period starting from day of patch removal (day 8) of treatment period 1. Assessments included NGMN and EE pharmacokinetics (PK), adhesion using European Medicines Agency (EMA) 5-point scale, irritation potential and application-site reactions, and safety. Patches were bioequivalent if 90% CIs of ratios of means of test/reference for AUC168h, AUCinf, and Css fell within 80-125%. Patch adhesion was comparable if ratios of mean cumulative adhesion percentage values of test/reference were ≥90.0%. RESULTS: Seventy women were randomized; 57 completed both treatments with ≥80% adhesion (score 0-1). Bioequivalence of test and reference patches was demonstrated as 90% CI of ratio of geometric means for AUC168h, AUCinf, and Css for NGMN and EE fell within 80-125%. Both patches had similar adhesion properties (geometric mean ratio was 100.3% [90% CI, 93.2-107.9]). Similar rates of mild-to-moderate itching (11% vs 10%) and erythema events (79% vs 74%) were reported for test and reference patches, respectively, on day 8. CONCLUSIONS: The test patch with the newly sourced adhesive component is bioequivalent to the currently marketed NGMN-EE transdermal patch and has similar adhesion and irritation potential. IMPLICATIONS STATEMENT: The norelgestromin and ethinyl estradiol transdermal patch containing a newly sourced adhesive component is bioequivalent to the currently marketed patch for both active moieties. Both patches had similar adhesion, irritation potential, and safety profiles.
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Adhesivos/efectos adversos , Agentes Anticonceptivos Hormonales/farmacocinética , Etinilestradiol/farmacocinética , Norgestrel/análogos & derivados , Parche Transdérmico/efectos adversos , Adhesivos/administración & dosificación , Adulto , Agentes Anticonceptivos Hormonales/administración & dosificación , Agentes Anticonceptivos Hormonales/efectos adversos , Estudios Cruzados , Método Doble Ciego , Combinación de Medicamentos , Etinilestradiol/administración & dosificación , Etinilestradiol/efectos adversos , Femenino , Humanos , Norgestrel/administración & dosificación , Norgestrel/efectos adversos , Norgestrel/farmacocinética , Equivalencia Terapéutica , Parche Transdérmico/normasRESUMEN
A rasagiline transdermal patch can be used to offer continuous rasagiline to patients with Parkinson's disease who cannot take their usual oral medications. This was the first study to investigate the pharmacokinetics, pharmacodynamics, and safety of the rasagiline transdermal patch in healthy Chinese subjects. Thirty subjects were randomized to 3 groups with 10 subjects in each group. The 10 subjects of group 1 received a single 1-mg dose of rasagiline as a tablet; the 20 subjects of groups 2 and 3 received a single transdermal patch (48-hour patch-on period) containing 1.25 mg and 2.5 mg rasagiline, respectively. After a 2-week washout period, the subjects of group 1 were assigned to receive 1 mg of rasagiline tablets every 24 hours for 7 days, and the subjects of group 2 were assigned to receive 1.25-mg rasagiline transdermal patches (48-hour patch-on period) every 72 hours for 5 time periods. The absorption of rasagiline from the transdermal patch was significantly improved, although the peak plasma concentration was obviously reduced. There was slight accumulation of rasagiline dose after multiple administrations. Inhibition of platelet monoamine oxidase-B (MAO-B) activity was dose dependent. The 80% inhibition maintained for at least 48 hours after multiple-dose administration of 1 mg tablets, and for 72 hours after multiple-dose administration of 1.25 mg/48 h patch. Compared with rasagiline tablets, the transdermal patch had a prolonged duration of 80% inhibition and increased maximal inhibition of MAO-B activity. These characteristics permitted an interval of 3 days of dosing, which was convenient for patients to use.
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Indanos/farmacocinética , Inhibidores de la Monoaminooxidasa/farmacocinética , Enfermedad de Parkinson/tratamiento farmacológico , Parche Transdérmico/efectos adversos , Administración Cutánea , Administración Oral , Adulto , Pueblo Asiatico/etnología , Pueblo Asiatico/estadística & datos numéricos , Índice de Masa Corporal , Relación Dosis-Respuesta a Droga , Voluntarios Sanos , Humanos , Indanos/administración & dosificación , Indanos/efectos adversos , Indanos/farmacología , Masculino , Persona de Mediana Edad , Inhibidores de la Monoaminooxidasa/administración & dosificación , Inhibidores de la Monoaminooxidasa/efectos adversos , Inhibidores de la Monoaminooxidasa/farmacología , SeguridadRESUMEN
BACKGROUND: Blonanserin transdermal patch therapy is now available in Japan for the treatment of schizophrenia and may provide several advantages over the tablet formulation. OBJECTIVE: The aim was to evaluate the long-term safety and efficacy of blonanserin transdermal patches in Japanese patients with schizophrenia. METHODS: An open-label study was conducted in adults with schizophrenia at 37 sites in Japan. Patients were enrolled in either cohort 1 or 2. Patients in cohort 1 received 8-16 mg/day blonanserin tablets for 6 weeks and then 40-80 mg/day blonanserin patches for 52 weeks. The dose of blonanserin patches was determined according to the dose of the tablets. In cohort 2, every patient started from 40 mg/day and then 40-80 mg/day blonanserin transdermal patches for 52 weeks. Both cohorts had 1-2 weeks of follow-up. Safety endpoints included the incidence of adverse events (AEs), treatment-related AEs, extrapyramidal AEs [also assessed using the change in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) score], the use of any concomitant antiparkinsonian drugs, and skin-related AEs, including skin irritation. Patients also underwent assessment of laboratory values including for serum prolactin concentration, vital signs, body weight, electrocardiographic (ECG) changes, and the corrected QT (QTc) interval. Suicidal ideation was assessed via the Columbia-Suicide Severity Rating Scale (C-SSRS) score. Efficacy was assessed via duration of blonanserin transdermal patch treatment, Positive and Negative Syndrome Scale (PANSS) total and subscale scores, and Clinical Global Impression-Severity (CGI-S) scores. Other endpoints included total Drug Attitude Inventory 10 (DAI-10) scores, EuroQol-5 Dimension (EQ-5D) effect values, and a patient questionnaire about the dosage form. RESULTS: A total of 223 patients with consents, 117 in cohort 1 and 106 in cohort 2 were included in the study. Of the 117 patients in cohort 1, 108 were treated with blonanserin tablets, and 97 received blonanserin patches and were included in the safety analysis set. In cohort 2, 103 of the 106 patients were treated with blonanserin transdermal patches and were included in the safety analysis set. In total, 91 patients were male (45.5%). The mean age was 43.8 years. Discontinuation occurred in 40 patients (41.2%) in cohort 1 and 44 patients (42.7%) in cohort 2. Discontinuation resulted from AEs in 18.6% (cohort 1) and 11.7% (cohort 2) and from withdrawal of consent in 13.4% (cohort 1) and 20.4% (cohort 2), and seven patients overall discontinued due to skin reactions. AEs were reported in 174 patients (87.0%), and 13 serious AEs occurred in 12 patients (6.0%), of which six patients were in cohort 1 and six patients were in cohort 2. Serious AEs were six schizophrenia (n = 6) and seven other AEs (n = 6), which included impulse-control disorder, fracture, epistaxis, asthma, pneumonia aspiration, pneumonia hemophilus, and pneumonia. The most common AEs were nasopharyngitis (n = 62, 31.0%), application site erythema (n = 45, 22.5%), application site pruritus (n = 23, 11.5%), and akathisia (n = 20, 10.0%). AE incidence was similar in cohort 1 (84.5%) and cohort 2 (89.3%). Extrapyramidal and skin-related AEs were reported in 51 patients (25.5%) and 83 patients (41.5%), respectively. None of these AEs were serious. The mean change from baseline in total DIEPSS score at Week 52 {last observation carried forward [LOCF] (standard deviation [SD])} was -0.1 (1.55), indicating no marked effect. In terms of concomitant medications used in cohort 1 and cohort 2, 33.0% (32/97) and 22.3% (23/103) used antiparkinsonian drugs, respectively. The majority of skin-related AEs occurred early in treatment and were appropriately managed with topical therapies. Of the patients who answered "No" to all C-SSRS categories at baseline (n = 129), 13 patients (10.1%) were evaluated as having emergence of suicidal ideation. Among patients who answered "No" to all C-SSRS suicidal behavior categories at baseline (n = 172), one (0.6%) was evaluated as having suicidal behavior during blonanserin transdermal patch treatment. There were no clinically significant changes in laboratory tests or examinations, including prolactin level, vital signs, body weight, ECG, metabolism-related parameters, and QTc interval. The mean (SD) change in body weight was - 0.04 (4.561) kg and - 0.67 (6.841) kg in cohort 1 and cohort 2, respectively. The mean changes from baseline in PANSS total score at Week 52 (LOCF [SD]) were - 0.1 [11.6] and - 3.4 [15.3] in cohort 1 and 2, respectively. PANSS scores did not change after switching from tablet to patch formulation in cohort 1 and decreased over the 52 weeks of treatment with the blonanserin patches. The mean change from baseline in CGI-S score at Week 52 (LOCF [SD]) was - 0.2 [1.03] in both cohorts combined. After 52 weeks of blonanserin patch treatment, the total DAI-10 score increased or remained unchanged compared with baseline in 82 of the 129 patients (63.6%) for whom these data were available. In the intention-to-treat population of the combined cohorts (n = 200), the mean (SD) change from baseline in EQ-5D score at the last assessment was - 0.0365 (0.17603). Patients' attitudes to the blonanserin transdermal patches were generally positive. CONCLUSIONS: Blonanserin transdermal patches are safe and effective in the long-term treatment of schizophrenia. CLINICALTRIALS. GOV REGISTRATION: NCT02335658.
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Piperazinas/efectos adversos , Piperazinas/uso terapéutico , Piperidinas/efectos adversos , Piperidinas/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Parche Transdérmico/efectos adversos , Administración Cutánea , Adulto , Anciano de 80 o más Años , Pueblo Asiatico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: Aging skin is a gradual physiological process associated with functional and structural changes of the skin. Both intrinsic and extrinsic factors influence skin aging by the involvement of multiple pathways. Restoring natural skin conditions requires a multi-targeted approach. Recent developments in both bioactive peptides and microneedle delivery system have presented an opportunity for tackling premature skin aging. AIMS: This study was aimed at evaluating the dermal tolerability and efficacy of hyaluronic acid-based microneedle patches loaded with bioactives for restoration of the skin properties including hydration, wrinkle reduction, density, and thickness. PATIENTS/METHODS: The test product of HA-MNs comprises arginine/lysine polypeptide, acetyl octapeptide-3, palmitoyl tripeptide-5, adenosine, and seaweed extracts. In the monocentric 12-week clinical trial, the HA-MNs patches were applied to the outer corner of the right and left eye and a defined area on the volar forearm on healthy subjects with aged skin. Instrumental analysis of skin properties was determined. RESULTS: The product was tolerated excellently; none of the subjects reported any primary or cumulative skin reactions. Assessment of measurable skin properties provides insight into the general effectiveness: The fine lines/wrinkles showed 25.8% noticeable decrease; the skin hydration measurements demonstrated 15.4% improvement; the skin density and thickness in the dermis increased 14.2% and 12.9%, respectively. CONCLUSIONS: The composition of the microneedle patches works in a multi-targeted manner and all ingredients might possibly be acted synergistically for the improvement of skin structure, function, and appearance. The study has demonstrated the overall usefulness of the HA-MNs with careful formulation for skin care applications.
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Portadores de Fármacos/farmacología , Ácido Hialurónico/farmacología , Péptidos/administración & dosificación , Envejecimiento de la Piel/efectos de los fármacos , Parche Transdérmico/efectos adversos , Administración Cutánea , Adulto , Anciano , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Sinergismo Farmacológico , Estudios de Factibilidad , Femenino , Humanos , Ácido Hialurónico/química , Persona de Mediana Edad , Agujas/efectos adversos , Péptidos/farmacocinética , Piel/efectos de los fármacos , Resultado del TratamientoRESUMEN
The most common side effects of transdermal patches are mechanical reactions caused by applying or removing the transdermal patch, or by excessive perspiration under the patch. Allergic contact dermatitis (type IV allergic reaction) is the most commonly occurring hypersensitivity reaction and can be caused by the active substance or by excipients. Type I allergic reactions such as urticaria, bronchospasm and angioedema are rare and usually caused by the active substance in the patch. Allergy testing to determine the allergen is indicated following a type I allergic reaction, or after a type IV allergic reaction that requires an alternative for the patch. It is important to document hypersensitivity reactions in the electronic patient records in order to prevent a hypersensitivity reaction in the future.
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Dermatitis Alérgica por Contacto/etiología , Excipientes/efectos adversos , Parche Transdérmico/efectos adversos , Angioedema/etiología , Dermatitis Alérgica por Contacto/diagnóstico , Femenino , Humanos , Masculino , Pruebas Cutáneas , Urticaria/etiologíaRESUMEN
Fentanyl is a potent synthetic opioid with a variety of possible applications. Transdermal fentanyl patches are regularly prescribed for patients with severe chronic or cancer-related pain. The potential for abuse is well-known and cases associated with illicit fentanyl intake are common. Fentanyl related fatalities due to unintentional misuse are relatively rare. This study focused on those instances and their identification in forensic examinations and adds new cases and consolidates the existing femoral blood concentrations in the event of fatal fentanyl patch misapplications. A total of 35 cases between 2010 and 2018 in which transdermal fentanyl patches were detected during forensic autopsies were identified and reviewed for the frequency of unspecific macroscopic signs of opioid intoxication. Furthermore, a detailed examination is presented for 11 cases in which toxicological results were available. The cause of death was eventually considered to be related to fentanyl patch misuse in 5 of these 11 cases. Co-administered drugs and signs of opioid intoxication, especially pulmonary edema, were frequently found. Lastly, it is advised to include norfentanyl and hair analysis in the interpretation of post-mortem fentanyl concentrations.
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Analgésicos Opioides/efectos adversos , Fentanilo/efectos adversos , Trastornos Relacionados con Opioides/complicaciones , Mal Uso de Medicamentos de Venta con Receta , Parche Transdérmico/efectos adversos , Adolescente , Adulto , Anciano , Analgésicos Opioides/análisis , Analgésicos Opioides/envenenamiento , Cromatografía Liquida , Femenino , Fentanilo/análogos & derivados , Fentanilo/análisis , Fentanilo/envenenamiento , Cabello/química , Humanos , Masculino , Espectrometría de Masas , Edema Pulmonar/patología , Estudios Retrospectivos , Retención Urinaria/patologíaRESUMEN
PURPOSE OF REVIEW: The administration of a transdermal fentanyl patch can be complicated with different pharmacokinetics than other fentanyl preparations. RECENT FINDINGS: The medical condition and baseline opioid requirements must all be carefully considered when dosing a fentanyl patch. An advantage of the fentanyl patch is its ability to bypass the gastrointestinal tract and in many patients, provide effective analgesia with minimal side effects. Fentanyl patches must be carefully administered since morbidity and/or mortality can result from the following: Giving higher doses than a patient needs, combining the medication with potent sedatives, or heating a fentanyl patch. The use of a transdermal fentanyl patch for the treatment of acute postoperative pain is not recommended and any patient undergoing a surgical procedure should have the fentanyl patch removed preoperatively. The current manuscript discusses the history of fentanyl and the fentanyl patch, as well as perioperative considerations, contraindications, current clinical efficacy, and clinical adversities related to the transdermal fentanyl patch. Regarding the heating of a transdermal fentanyl patch, which significantly increases blood levels of fentanyl, it is of the utmost importance that the patch be removed prior to surgery.
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Analgésicos Opioides/administración & dosificación , Consenso , Fentanilo/administración & dosificación , Dolor Postoperatorio/cirugía , Parche Transdérmico , Analgésicos Opioides/uso terapéutico , Fentanilo/uso terapéutico , Humanos , Morfina/uso terapéutico , Dimensión del Dolor , Parche Transdérmico/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVE: Loxoprofen (LOX) is a nonsteroidal anti-inflammatory drug (NSAID). Although oral administration of LOX has been widely prescribed, clinical guidelines for osteoarthritis generally recommend topical rather than oral NSAIDs in specific patients. However, there is limited information on the effects of loxoprofen sodium oral (LOX-O) versus loxoprofen sodium hydrogel transdermal patch (LOX-T) in myalgia patients. Hence, this non-inferiority study was designed to compare the efficacy and safety of LOX-O versus LOX-T in Chinese patients with myalgia. METHODS: In this double-blind, double-dummy, parallel-group, randomized controlled trial, 182 Chinese patients were enrolled and randomized equally to either LOX-T or LOX-O treatment for 2 weeks. Patients in the LOX-T group applied one sheet of the active LOX-T once a day on the affected site and took one placebo tablet three times a day immediately after meals, whereas patients in the LOX-O group applied one sheet of the placebo patch once a day and took one active LOX-O three times a day. Primary endpoint was the proportion of patients with 50% overall improvement or higher at the final visit. The cutoff value of a non-inferiority difference was set as - 10%. RESULTS: In the full analysis set, the primary endpoint of final efficacy rate was 81.3% (n = 91) in the LOX-T group and 72.2% (n = 88) in the LOX-O group. The difference between the two groups was 9.1% [95% confidence interval (CI) - 3.1 to 21.3%], which showed that LOX-T was non-inferior compared with LOX-O. No serious adverse events occurred in either group. CONCLUSIONS: This trial showed the non-inferiority of LOX-T compared with LOX-O in efficacy and safety in Chinese patients with myalgia. Also, the characteristic features of topical LOX-T, such as better compliance and lower risk-benefit ratio, make it more favorable for clinical practice. TRIAL REGISTRATION: The study was registered in the isrctn.com registry (ISRCTN trial ID: ISRCTN16227145).
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Antiinflamatorios no Esteroideos/administración & dosificación , Hidrogeles/administración & dosificación , Mialgia/tratamiento farmacológico , Mialgia/epidemiología , Fenilpropionatos/administración & dosificación , Parche Transdérmico , Administración Oral , Adulto , Anciano , Antiinflamatorios no Esteroideos/efectos adversos , China/epidemiología , Método Doble Ciego , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/epidemiología , Humanos , Hidrogeles/efectos adversos , Masculino , Persona de Mediana Edad , Mialgia/diagnóstico , Fenilpropionatos/efectos adversos , Comprimidos , Parche Transdérmico/efectos adversos , Resultado del TratamientoRESUMEN
PURPOSE: Countries worldwide are developing a variety of strategies to combat the opioid epidemic, such as restricting access to high-strength opioid formulations. We aimed to examine the dispensing patterns of strong opioids by dose units (DUs), age, and sex. METHODS: We used Australian population-level dispensing data from January 2003 to December 2015 and categorised strong opioids by DU: very low, low, moderate, and high, corresponding to total daily doses of less than or equal to 25, 26 to 50, 51 to 100, and greater than 100 morphine milligramme equivalents, respectively. We measured trends in strong opioid use as dispensings/1000 population/year and stratified dispensing in 2015 by patient age and sex. RESULTS: From 2003 to 2015, strong opioid dispensing of very low, low, moderate, and high DU increased 6.7-, 6.2-, 2.2-, and 1.8-fold, respectively. The increase in very low and low DU dispensing was driven primarily by oxycodone (5, 10, and 15 mg tablets and capsules) and buprenorphine transdermal patches. In 2015, the number of dispensings/1000 population for very low, low, moderate, and high DU were 180.3, 77.0, 52.7, and 34.8, respectively. Females aged greater than or equal to 85 years had the highest opioid use, ranging from 157.1 dispensings/1000 population for high DU to 2104.5 dispensings/1000 population for very low DU. In contrast, the high DU dispensings in males aged 25 to 64 years exceeded their female counterparts by approximately 1.3-fold. CONCLUSION: Relative to moderate and high DU strong opioids, dispensing of very low and low DU strong opioids increased dramatically during the study period in Australia. Future studies investigating opioids use and harms in elderly females and males between 25 to 64 years are warranted.