Transdermal Medication Research Articles

Unmet Needs for Transdermal Patch Management in Electronic Medication Administration Records: An Analysis of Data from 66 Aged Care Facilities.

Transdermal medication patches have caused serious adverse events in residential aged care facilities (RACFs). Preliminary research suggests that facilities are using a workaround consisting of manually entered reminders in their electronic medication administration records (eMARs) to prompt staff to check and remove patches, because the eMAR does not support these tasks. However, the prevalence and factors associated with use of this workaround among facilities is unknown. The objectives of this study were to (1) examine the frequency and consistency with which manual reminders to check and remove transdermal patches were used in facility eMARs, and (2) identify resident and facility factors associated with reminder use, to inform eMAR redesign. This was a retrospective cross-sectional analysis of eMAR data from 66 Australian RACFs including 4,787 permanent residents, aged ≥65 years in January 2017. Prevalence of the use of reminders to check and remove patches, and consistency in their application within facilities were examined. Generalized estimating equations were used to determine factors associated with use of manual reminders. One in five (n = 937) residents used a patch, and 83.6% of patches contained opioids, a high-risk medicine. 56.9% of facilities implemented manually entered check patch reminders in the eMAR, and 72.3% implemented remove reminders. The reminders were applied inconsistently, with only half of these facilities having reminders for all residents with patches. Residents in facilities in regional areas were more likely to have a check reminder compared with those in major cities (adjusted odds ratio = 4.72 [95% confidence interval: 1.69-13.20]). Transdermal patches containing high-risk medicines are frequently used in RACFs, but their safe administration is not supported by a widely implemented eMAR. The frequent, but inconsistent use of a workaround to manually enter reminders indicates an unmet need for new eMAR functionality to improve safety.

Development of self-care textile wearables with thermally stimulated drug delivery function via biological and physical investigations

Previous studies have examined and verified the drug loading and releasing functionality from the interior channels of hollow fibers. An integrated design for self-care textile wearables with a thermally stimulated drug delivery function was proposed. To progress the in-depth development of the proposed self-care wearables, physical and biological investigations, including i) liquid release with thermal stimulation and ii) drug release upon thermal stimulation, were conducted. Physical investigation revealed that the concentration of dyes released from the heated specimens increased with higher temperature during the initial first hour of delivery. Moreover, higher cytotoxic effect could be induced with drugs delivered through heated specimens under higher thermal stimulated energy through biological examination. These results set up milestones for demonstrating the influence of thermal energy on different therapeutic requirements, such as rapid-onset transdermal medication.

Identifying risks areas related to medication administrations - text mining analysis using free-text descriptions of incident reports

BackgroundSome medications carry increased risk of patient harm when they are given in error. In incident reports, names of the medications that are involved in errors could be found written both in a specific medication field and/or within the free text description of the incident. Analysing only the names of the medications implicated in a specific unstructured medication field does not give information of the associated factors and risk areas, but when analysing unstructured free text descriptions, the information about the medication involved and associated risk factors may be buried within other non-relevant text. Thus, the aim of this study was to extract medication names most commonly used in free text descriptions of medication administration incident reports to identify terms most frequently associated with risk for each of these medications using text mining.MethodFree text descriptions of medication administration incidents (n = 72,390) reported in 2016 to the National Reporting and Learning System for England and Wales were analysed using SAS® Text miner. Analysis included text parsing and filtering free text to identify most commonly mentioned medications, followed by concept linking, and clustering to identify terms associated with commonly mentioned medications and the associated risk areas.ResultsThe following risk areas related to medications were identified: 1. Allergic reactions to antibacterial drugs, 2. Intravenous administration of antibacterial drugs, 3. Fentanyl patches, 4. Checking and documenting of analgesic doses, 5. Checking doses of anticoagulants, 6. Insulin doses and blood glucose, 7. Administration of intravenous infusions.ConclusionsInterventions to increase medication administration safety should focus on checking patient allergies and medication doses, especially for intravenous and transdermal medications. High-risk medications include insulin, analgesics, antibacterial drugs, anticoagulants, and potassium chloride. Text mining may be useful for analysing large free text datasets and should be developed further.

Patches

Transdermal delivery is an alternative to oral routes of drug administration and has made considerable contributions to the treatment of various medical diseases. With the advent of new transdermal delivery technologies, higher numbers of medications are being approved for use as transdermal formulations. This route of administration has several innate advantages that have the potential to benefit various patient populations, including those with central nervous system disorders. The current review briefly outlines the history of transdermal medications, discusses the advantages and disadvantages of transdermal formulations, and examines the challenges and opportunities present for the use of transdermal treatments in psychiatry. Patients with psychiatric illnesses have many unmet needs that may be filled through the benefits gained from transdermal treatments, such as reduced dosing frequency, effective control of plasma medication concentrations, improved tolerability, ability to check compliance visually, and avoidance of first-pass hepatic metabolism. Established transdermal treatments for various psychiatric diseases are discussed followed by an introduction to therapies that are being developed as the first patch formulations for the treatment of schizophrenia. Hypothetical schizophrenia patient profiles are also outlined to aid providers in considering how transdermal treatments for this disease may fill unmet needs for specific patients. The evidence demonstrating the potential benefits of transdermal treatments in psychiatry presented in the current review should both encourage health care providers to consider how patients may benefit from transdermal alternatives and promote future innovation in the area of transdermal drug delivery for psychiatric disorders.

Interventional treatments for metastatic bone cancer pain.

Metastatic bone cancer pain may cause significant morbidity among the cancer patient population. Painful bone lesions are challenging to manage due to the aggressive pathophysiology of the pain generator involved. The WHO's approach to cancer pain treatment involves the use of a three-step ladder which provides a guideline for clinicians to treat patients who struggle from cancer pain syndromes. It is possible that this ladder is no longer helpful for patients who continue to fail oral or transdermal medication options. A fourth step in the cancer pain ladder has been proposed to include interventional approaches to cancer pain management. This review will discuss opioid therapy, radium-223, denosumab and bisphosphonate therapy, but will primarily review the available interventional treatment options for metastatic bone cancer pain.

Advances in pharmacotherapies for movement disorders in children: current limitations and future progress.

In childhood, movement disorders are generated by a very large number of disorders of the nervous system, and the very different developmental ages at which these occur make studies of pharmacotherapy efficacy extremely difficult. In most clinical practices, medication used in management is by trial and error, and limited by lack of efficacy and/or adverse drug reactions leading to drug intolerance. Nevertheless, symptom reduction using polypharmacy must be balanced against any accompanying comorbidities such as poor attention and concentration, constipation, ileus, urinary retention, blurred vision sedation and respiratory depression. A 'personalised medicine' approach may lead to specific management breakthroughs that are beneficial to a wider number of children. At present, neuromodulation with implantable devices offers greater proven efficacy for dystonia, myoclonus and dystonic-choreoathetosis, but enteral, intravenous and, more recently, transdermal medication strategies with clonidine patches and enteral gabapentin may provide important relief for both home management and critical care settings. The current review brings the clinician up-to-date with the latest, albeit limited, thinking on the pharmacological management of movement disorders in children by focussing on goal-directed outcome measures to improve clinical decision-making in an evidence-light clinical setting.

Levodopa/carbidopa intestinal gel (LCIG) infusion as mono- or combination therapy.

Levodopa/carbidopa intestinal gel (LCIG) infusion is an effective escalating therapy in patients with Parkinson disease (PD) suffering from motor fluctuations and dyskinesia. Levodopa/carbidopa given continuously as infusion provides an optimized application of the most effective and best tolerable antiparkinsonian drug. It has been proven to have a superior motor effect compared with oral levodopa and to improve also non-motor symptoms. However, invasiveness, discomfort resulting from carrying an external device, and side effects associated with the way of administration limit its application in PD patients. At present, there are no guidelines that delineate to which patients LCIG should be offered as monotherapy, in combination with oral and/or transdermal medication, or as additional therapy to deep brain stimulation (DBS). Based on clinical studies, we propose an expert consensus for neurologists addressing the question when LCIG therapy should be recommended and in which cases LCIG infusion is suggested in combination with other antiparkinsonian drugs and/or DBS. We describe how LCIG should be initiated and what we consider necessary for clinical follow-up. We suggest an algorithm facilitating decision-making with respect to the currently available invasive PD therapies, namely infusion with subcutaneous apomorphine, LCIG, and DBS.

Caregiver Preference and Treatment Compliance in Patients with Mild-to-Moderate Alzheimer's Disease in South Korea: RECAP Study Results.

The aim of this study was to assess caregiver preference and treatment compliance with oral and transdermal medications in a "real-world" setting in patients with mild-to-moderate Alzheimer's disease (AD) in South Korea. Real-world evaluation of compliance and preference in Alzheimer's disease treatment (RECAP) was a 24-week, multicenter, prospective, non-interventional study in patients with AD treated with oral or transdermal therapy. Here, we report data from patients living in South Korea. Eligible patients were grouped into one of two treatment cohorts: oral (donepezil, galantamine, rivastigmine, or memantine) or transdermal (rivastigmine patch). Caregiver preference, patient compliance, and physician preference were assessed at week 24 (end of the study). Safety was assessed by reported adverse events (AEs). A total of 398 patients were enrolled (oral 51.8%; transdermal 48.2%) and 79.4% completed the study. Caregivers of patients that were exposed to either the oral or transdermal monotherapy showed a preference for the treatment to which the patients were exposed (both p<0.0001). However, caregivers of patients that were exposed to both forms of treatments reported a higher preference for transdermal monotherapy (65.9%; p<0.0041). Patients in both treatment cohorts showed good compliance, with an overall mean (SD) score of 8.84 (1.514) (a median of 9). Of the 15 participating physicians, eight indicated their preference for transdermal therapy and seven preferred oral therapy at week 24. A total of 133 (33.4%) patients reported at least one AE during the study period (oral: 60 patients; transdermal: 73 patients). The study showed higher caregiver preference for transdermal monotherapy over oral monotherapy when patients with AD were exposed to both forms of treatment and good patient compliance for both oral and transdermal treatments.

Commentary on: Micro-Needling Depth Penetration, Presence of Pigment Particles, and Fluorescein-Stained Platelets: Clinical Usage for Aesthetic Concerns.

Micro-needling is a relatively novel technique that uses needles ranging from 0.5 mm to 2.5 mm in order to create micro-wounds or channels in the skin. The microneedles are designed to penetrate the stratum corneum without traveling into the nerve fibers of the skin. In doing so, micro-needling can create micro channels in the skin relatively painlessly. The channels allow for delivery of macromolecules through the skin, and, while healing, promote collagen production in the skin. As a result, micro-needling is an effective tool for treating aesthetic skin concerns such as wrinkling, as well as delivering transdermal medications and vaccines. The author aimed to determine average depth penetration of microneedles, as well as the optimal time of topical application to achieve maximum depth of macromolecule dissemination through the skin after micro-needling treatment.1 In studies I, II, and III, the study utilized low sample sizes of only facial skin excised from Caucasian patients aged 72, 73, and 62, respectively. The use of only these pre-auricular skin strips from a narrow ethnic background limits the study's broader applications. …

Real-world evaluation of compliance and preference in Alzheimer's disease treatment: an observational study in Taiwan.

PurposeAmong the medications approved for Alzheimer’s disease (AD), rivastigmine is the only one available as transdermal patch. The aim of this study was to evaluate compliance and caregivers’ preference with oral and transdermal (rivastigmine) monotherapy in patients with mild-to-moderate AD from Taiwan.MethodsReal-world Evaluation of Compliance And Preference in Alzheimer’s disease treatment (RECAP) in Taiwan was a prospective, noninterventional, observational study with a 24-week (±8 weeks) observational period for each participant. Eligible patients were grouped into one of the two treatment cohorts based on the baseline AD therapy: oral (donepezil, galantamine, rivastigmine, or memantine) or transdermal (rivastigmine patch). The primary end points were caregiver preference and caregiver assessment of patients’ compliance to the current medication (oral or transdermal medication) at Week 24 (end of the study). Safety was assessed by recording any adverse events.ResultsA total of 301 patients (age: 77.6±7.19 years) were enrolled from nine centers in Taiwan, of whom 138 (45.8%) patients were in the transdermal monotherapy cohort. Caregivers of patients who were exposed to both forms of therapies demonstrated a higher preference for transdermal rivastigmine monotherapy than the oral monotherapy (82.4% [n=61] versus 17.6% [n=13], P<0.0001); for patients treated with only one therapy, the caregivers’ preference was significantly in favor of the treatment to which the patient was exposed (both P<0.0001). In both cohorts, patients showed good compliance, with an overall score of 8.65±1.38 on an 11-point scale. Of 301 enrolled patients, 102 (33.9%) reported at least one adverse event during the study (51 patients each in the two cohorts).ConclusionWith the higher caregiver preference and a good patient compliance, the trans-dermal rivastigmine patch is a suitable treatment choice for patients with mild-to-moderate AD, especially for patients intolerant to oral therapies.

Splanchnic neurolysis for gallbladder cancer pain

Abdominal sympathetic blockade is a safe, minimally invasive and proven measure for pain control in intra-abdominal malignancies. Hereby, we report a case of severe abdominal and back pain due to advanced carcinoma gall bladder refractory to oral and transdermal medications, managed successfully by bilateral splanchnic neurolysis using 50% alcohol under fluoroscopy. Pain was significantly relieved immediately after the procedure with a gradual reduction in analgesics consumption. The effect was sustained during follow-up with improved quality of life.

Real-world evaluation of compliance and preference in Alzheimer's disease treatment.

PurposeRivastigmine transdermal patch has shown higher caregiver satisfaction and greater preference than oral formulation in patients with Alzheimer’s disease. However, there is limited literature available related to caregiver preference or treatment compliance in real-world clinical settings. To date, no such data are available from Asia and the Middle East, which account for a sizeable proportion of patients with Alzheimer’s disease. The objective of this study was to evaluate treatment preference and compliance with oral and transdermal medications in daily clinical practice in an ethnically diverse patient population from Asia and the Middle East with mild-to-moderate Alzheimer’s disease.Patients and methodsRECAP (Real-world Evaluation of Compliance And Preference in the treatment of Alzheimer’s disease) was a 24-week, multicenter, prospective, noninterventional study. Two treatment cohorts were observed during the study: oral (cholinesterase inhibitors or memantine) and transdermal (rivastigmine patch). Caregiver preference, physician preference, and patient compliance were evaluated at week 24.ResultsA total of 978 of 1,931 enrolled patients (mean age: 72.8 years; 50.5% female) were in the transdermal cohort. For patients with exposure to both oral and transdermal monotherapy (n=330), a significant caregivers’ preference for the transdermal monotherapy was observed (82.7%; P<0.0001). Of the 89 participating physicians, 71 indicated preference for transdermal monotherapy. Patient compliance was also significantly higher for transdermal than oral monotherapy (P<0.0001).ConclusionOur study showed higher caregiver and physician preference and greater patient compliance with transdermal monotherapy in daily practice.

Caregivers’ and physicians’ attitudes to rotigotine transdermal patch versus oral Parkinson’s disease medication: an observational study

Objective:To provide real-world data on caregiver and physician perceptions of the advantages and disadvantages of rotigotine transdermal patch (Neupro) versus oral Parkinson’s Disease (PD) medication.Methods:Cross-sectional, non-interventional study in routine clinical practice in Germany (NCT01330290). Patients had PD with documented need for care, and had received rotigotine transdermal patch as add-on to oral PD treatment for ≥1 month. Caregivers/nurses and physicians assessed rotigotine transdermal patch versus oral PD medications using questionnaires. Specific questions regarding the possible benefits of transdermal application were asked and comprised questions on: swallowing dysfunction, nausea/vomiting, monitoring therapy, once daily application, application independently from meals, application to sleeping patients, caregiving efforts (caregivers only) and clinical aspects (physicians only). Each question was assessed on a 5 point scale ranging from -2 (major disadvantage) to 2 (major advantage) compared with oral treatment. Primary outcomes were mean total scores of all questions for caregivers/nurses and physicians who provided responses for ≥4 questions. As there are no validated tools to assess physician/caregiver preference in the PD setting, there is no reference against which the current findings can be compared; this study serves to pilot the questionnaires.Results:Questionnaire responses from 128 caregivers/nurses and 41 physicians were documented for 147 patients. One hundred (68%) patients had a caregiving family member; 40 (27%) were cared for by a nurse. Mean PD duration was 8.2 (SD 6.3) years; 136 (93%) patients were taking levodopa. Mean total score of caregivers’/nurses’ questionnaires was 1.32 (SD 0.67) and of physicians’ questionnaires was 1.46 (0.32) indicating a perceived advantage of rotigotine transdermal patch over oral PD therapy. Mean scores for individual questions were in the range 1.03–1.54 for caregivers/nurses and 1.15–1.87 for physicians. When given a choice about rationale to prescribe, physicians cited pharmaceutical form (patch) in 139 (95%) cases and active agent (rotigotine) in 89 (61%) cases.Conclusion:Caregivers/nurses and physicians perceived advantages with rotigotine transdermal patch compared to an oral PD medication as add-on therapy in patients with PD; advantages were observed in aspects of medical treatment as well as in everyday situations of caregiving of PD patients.

Percutaneous absorption of methimazole: an in vitro study of the absorption pharmacokinetics for two different vehicles

The use of transdermal medications in cats has become popular in veterinary medicine due to the ease of administration compared to oral medication. However, the research to support systemic absorption of drugs applied to the pinna after transdermal administration in cats is limited. The aim of this study was to characterize the percutaneous absorption pharmacokinetics of methimazole in a lipophilic vehicle compared to methimazole in Pluronic(®) lecithin organogel (PLO) using a finite dose applied to feline ear skin in an in vitro Franz cell model. The two formulations of methimazole (10mg) were applied to the inner stratum corneum of six pairs of feline ears. The receptor medium was sampled up to 30h post-administration, and methimazole concentrations were measured using high-performance liquid chromatography (HPLC). Histological examination of all ears was undertaken as small differences in the thickness of ear skin may have contributed to inter-individual differences in methimazole absorption between six cats. Methimazole was absorbed more completely across the pinnal skin when administered in the lipophilic vehicle compared to administration in the PLO gel (P<0.001).

The transdermal formulation of rivastigmine improves caregiver burden and treatment adherence of patients with Alzheimer's disease under daily practice conditions

BackgroundRivastigmine is the only cholinesterase inhibitor (ChEI) available as transdermal patch. The patch was developed to improve gastrointestinal tolerability and treatment adherence to higher dosages as compared with oral medication. Preferences of patients and caregivers for the patch were reported; however, neither patient compliance nor caregiver burden has yet been measured under routine practice conditions.MethodsThis was a prospective, multi-centre, observational study in patients with Alzheimer's disease treated with rivastigmine patch in Germany. To compare the transdermal with oral dosage forms, physicians were asked to enrol patients who recently switched from oral to transdermal medication. Beyond effectiveness and tolerability, outcome measures were drug adherence evaluated by the Morisky questionnaire, and caregiver burden, measured as the daily time expenditure for dressing the patient, controlling appearance and administration of medication.ResultsIn total, 1104 outpatients (57.5% female gender; mean age 77 ± 7 years) were enrolled in 220 sites. After 6 months of treatment, 67.5% of patients had an improved Clinical Global Impression and the Mini-Mental State Examination score increased from 19.0 ± 5.1 to 20.0 ± 5.2 (p < 0.001); 84.1% of patients were still on treatment, 64.6% on the target dose of 9.5 mg/day. Compliance and patient satisfaction with therapy continuously increased over the study period and average time savings of caregivers added up to 20 min/day. In general, tolerability was deemed good and there were no unexpected adverse events.ConclusionsTransdermal rivastigmine is an effective treatment alternative, which may improve adherence and treatment satisfaction of the patient and relieve the caregiver. Controlled parallel-group trials are warranted.Clinical trials registration: none (observational study).

Pain Management Therapy: The Benefits of Compounded Transdermal Pain Medication

The high worldwide incidence of both acute and chronic pain leads to widespread consequences for both the healthcare system and the economy. First-line pain treatment options are typically oral pain medications; however, concerns regarding side effects, prescription drug abuse, risk of overdose, patient non-adherence to treatment regimens, and lack of efficacy in certain conditions provide a number of challenges for both healthcare providers and patients. As a result, healthcare providers have become increasingly interested in new ways to manage pain and develop customized treatment plans for their patients. Compounded transdermal pain medication may offer benefits such as customizable dosages and formulations, the ability to combine multiple drugs with various mechanisms of action, the likelihood of lower systemic absorption with minimization of side effects, more convenience and consequent improved adherence to treatment regimens, and minimization of risk of abuse and addiction. This review offers an overview of examples to provide evidence of the benefits of transdermal compounded pain medication in the treatment of a number of pain-related conditions, including neuropathic, musculoskeletal, arthritis-related, and postoperative pain, among other conditions.

Interventional Modalities to Treat Cancer-Related Pain

Cancer-related pain is a significant cause of morbidity in those affected by both primary and metastatic disease. Although oral, transdermal, and parenteral opioid medications are an integral part of the World Health Organization's analgesic ladder, their use may be limited by side effects. Fortunately, there are advanced interventional pain management strategies effective in reducing pain in the cancer patient while mitigating the aforementioned side effects. Celiac plexus blocks and neurolysis have been proven effective in treating cancers of the abdominal viscera (ie, pancreas). Transversus abdominis plane blocks, neurolysis, and catheter placement can be used to treat cancer pain associated with the abdominal wall. Peripheral nerve blocks and catheter placement at the brachial and lumbosacral plexus or peripheral nerves treat cancer pain associated with the upper and lower limbs, whereas paravertebral and intercostal blocks treat cancer pain associated with the chest wall and ribs. Finally, alternate drug delivery methods such as intrathecal drug delivery systems concentrate medication at central opioid receptors without affecting the peripheral receptors implicated in unwanted side effects. This article provides an overview of these interventions, including indications, contraindications, and potential complications of advanced interventional pain management options available for the treatment of intractable cancer-related pain.

SAT0427 S- and R-flurbiprofen pharmacokinetics following repeated transdermal medication to healthy subjects

BackgroundFlurbiprofen (fbp) is a chiral non-steroidal anti-inflammatory drug (NSAID) used as racemate in the treatment of rheumatism & non-arthritic pain. Topical formulations of NSAIDs have become popular for treatment of...

The Irritant Effects of Pharmaceutically Applied Surfactants

AbstractDermal or transdermal medication may lead to irritant contact dermatitis. However, little information is available on the irritant effect of surfactants which are applied in topical formulations. Our aim was to examine the irritant effect of the most frequent compounds in topical products. A murine model was applied. The following compounds were examined: sodium lauryl sulphate (SLS), polyethoxylated (40EO) hydrogenated castor oil and sucrose laurate. SLS led to severe erythema, increase in transepidermal water loss (TEWL) and induced necrosis and accumulation of neutrophylic granulocytes and lymphocytes. Exposure to sucrose laurate resulted in an elevation of TEWL, but histology did not reveal impairment of the skin structure. Application of polyethoxylated (40EO) hydrogenated castor oil was not accompanied by tissue damage. Special attention should be paid to the irritant effect of SLS. Polyethoxylated (40EO) hydrogenated castor oil seems to be a non‐irritant agent and sucrose laurate is also a promising candidate for application in topical preparations.

Abstracts from the TOXINS 2012

Abstracts from the TOXINS 2012