fesoterodine and Urinary-Bladder--Overactive

The choice of the most efficacious drug for patients with idiopathic overactive bladder (IOAB) remains challenging.. The aim of this network meta-analysis was to determine the most efficacious oral antimuscarinic or β-adrenoceptor agonist accounting for adverse events for the management of IOAB.. A comprehensive electronic search was done in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Ovid for studies in any language in February 2021 considering the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. We included all randomized controlled trials assessing oral antimuscarinics or β-adrenoceptor agonists for the treatment of IOAB. We determined the effect of specific bothersome symptoms separately.. Fifty-four articles were included in our analysis. The most efficacious agents considering the evaluated outcomes were oxybutynin 15 mg/d in reducing incontinence episodes, imidafenacin 0.5 mg/d together with solifenacin 10 and 5 mg/d in reducing micturition episodes, fesoterodine 4 and 8 mg/d as well as solifenacin 10 mg/d in reducing urgency episodes, imidafenacin 0.5 mg/d and solifenacin 10 mg/d in reducing urgency urinary incontinence episodes, and solifenacin 10 mg/d, vibegron 50 mg/d, and fesoterodine 8 mg/d in improving the voided volume. Gastrointestinal problems, especially due to antimuscarinic agents, were the most prevalent adverse events.. Taken together, there is only minimal difference between the efficacy of oral antimuscarinics and that of β-adrenoceptor agonists. Although finding the best medication for all is impossible, finding the best treatment for every individual patient can be done by considering the efficacy of a medicine for the most bothersome symptom(s) in balance with drug-specific adverse events.. This study aimed to find the most efficient oral medication to treat overactive bladder, taking into consideration the adverse events. Based on our study, there is a minimal difference in the efficacy between the two major drug classes used to treat overactive bladder. Gastrointestinal problems were the most common adverse events in medical treatment of overactive bladder. Selection of the best treatment is possible through shared decision-making between the doctor and the patient based on the patient's most bothersome symptom. We provide a framework for physicians to facilitate shared decision-making with each individual patient.

Topics: Benzhydryl Compounds; Humans; Muscarinic Antagonists; Network Meta-Analysis; Receptors, Adrenergic; Solifenacin Succinate; Urinary Bladder, Overactive; Urinary Incontinence

This is a summary of a study originally published in. Although complete resolution of all symptoms was rare with fesoterodine treatment, a resolution of accidental urination was more common, which is the most important treatment goal for many patients. After taking fesoterodine, episodes of accidental urination were more likely to be reduced or completely absent than episodes of an urgent need to urinate.. These results can help patients with overactive bladder understand their own chances of treatment success with fesoterodine and can help doctors support their patients on what to expect regarding their specific symptoms and concerns. ▪Toviaz (fesoterodine) is approved to treat the condition that is discussed in this summary. Approval varies from country to country; please check with your local health provider for more details. ▪This summary reports the combined results of 6 studies. The results of individual studies may vary from the combined study results presented here. Individuals should make treatment decisions based on all available evidence. ClinicalTrials.gov NCT number: NCT01302054, NCT01302067, NCT00444925, NCT00611026, NCT00220363, and NCT00138723.

Topics: Benzhydryl Compounds; Humans; Language; Treatment Outcome; Urinary Bladder, Overactive

Overactive bladder (OAB) is often treated with medications that block the cholinergic receptors in the bladder (known as anticholinergics). The effect of this medication class on cognition and risk of dementia has been increasingly studied over the past 40 years after initial studies suggested that the anticholinergic medication class could affect memory. Short-term randomized clinical trials demonstrated that the administration of the anticholinergic oxybutynin leads to impaired memory and attention, and large, population-based studies showed associations between several different anticholinergic medications and dementia. However, trials involving anticholinergics other than oxybutynin have not shown such substantial effects on short-term cognitive function. This discordance in results between short-term cognitive safety of OAB anticholinergics and the long-term increased dementia risk could be explained by the high proportion of patients using oxybutynin in the OAB subgroups of the dementia studies, or a study duration that was too short in the prospective clinical trials on cognition with other OAB anticholinergics. Notably, all studies must be interpreted in the context of potential confounding factors, such as when prodromal urinary symptoms associated with the early stages of dementia lead to an increase in OAB medication use, rather than the use of OAB medication causing dementia. In patients with potential risk factors for cognitive impairment, the cautious use of selected OAB anticholinergic agents with favourable physicochemical and pharmacokinetic properties and clinical trial evidence of cognitive safety might be appropriate.

Topics: Benzhydryl Compounds; Benzofurans; Cholinergic Antagonists; Cognition; Cognitive Dysfunction; Dementia; Humans; Mandelic Acids; Prodromal Symptoms; Pyrrolidines; Risk Assessment; Risk Factors; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive

Cumulative exposure to one or more anticholinergic medications ("anticholinergic burden") is associated with an increased risk of adverse outcomes, particularly among older individuals. Mirabegron, an oral selective β3-adrenergic receptor agonist, has demonstrated efficacy in managing the symptoms of overactive bladder without contributing to anticholinergic burden. However, it is not known whether the favorable safety profile of mirabegron relative to antimuscarinics varies with increasing age among a patient population who may have a high anticholinergic burden.. The primary objective of this study was to indirectly compare the safety and efficacy profile of mirabegron relative to antimuscarinics in older adults with overactive bladder.. A systematic literature review was conducted to identify randomized controlled trials that reported safety and efficacy endpoints among patients aged ≥ 65 years. Identified randomized controlled trials were subsequently synthesized via a network meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines in designing, performing, and reporting the literature review were followed. In line with current best practices, the network meta-analysis was conducted using a Bayesian approach and according to the overall general guidance for evidence synthesis developed by the National Institute for Health and Care Excellence decision support unit. Estimates of relative safety were assessed via the odds ratio and estimates of relative efficacy were assessed via means and credible intervals.. A total of 3078 abstracts, 300 of which underwent full-text screening, were identified using the search criteria. Twenty articles reporting on 21 randomized controlled trials were eligible for data extraction and synthesis. Following review, five safety and five efficacy endpoints were considered for inclusion in the network meta-analysis. Regarding findings typical of anticholinergic exposure in older adults, mirabegron was not associated with an increased odds of dry mouth (odds ratio 95% credible interval 0.76 [0.26-2.37]) or constipation (1.08 [0.39-3.02]) relative to placebo, whereas antimuscarinics were strongly associated with these events (odds ratio range 3.78-7.85 and 2.12-4.66, respectively). In this older population, mirabegron was associated with a similar odds of experiencing adverse event-related treatment discontinuations relative to placebo (0.99 [0.57-1.70]), while the odds of experiencing an adverse event-related treatment discontinuation for antimuscarinics had a range of 1.14-3.03 (in most cases, the association was mild). No increased odds of experiencing overall treatment-emergent adverse events was observed for mirabegron or antimuscarinics (odds ratio range 1.25-1.55), apart from fesoterodine (2.23 [1.37-3.37]). Finally, a similar treatment effect was observed across all efficacy endpoints between mirabegron and antimuscarinics in this older population.. This study indicates that the safety and efficacy profile of mirabegron remains favorable compared with antimuscarinics among older adults. This includes safety outcomes typically associated with anticholinergic burden, which were less frequently observed in patients treated with mirabegron.

Topics: Acetanilides; Aged; Benzhydryl Compounds; Constipation; Female; Humans; Male; Muscarinic Antagonists; Network Meta-Analysis; Odds Ratio; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

To carry out a network meta-analysis of randomised controlled trials (RCTs) of anticholinergic drug treatment for people with overactive bladders.. Comprehensive searches for relevant RCTs were carried out starting with RCTs included in previous systematic reviews with the last search in February 2017. Searches included terms for the anticholinergic drugs tolterodine, oxybutynin, trospium, propiverine, solifenacin, darifenacin, imidafenacin, and fesoterodine. Data was extracted from the systematic reviews or reports of studies for cure or improvement, voids per 24 hr, leakage episodes per 24 hr and dry mouth. Data was analysed using frequentist network meta-analysis.. 128 studies were found. There was no clearly best treatment for cure or improvement. The differences between treatments for voids and leakages were small and unlikely to be of clinical importance. Transdermally delivered oxybutynin was clearly the best treatment for dry mouth but was still worse than placebo.. All the anticholinergic drugs were better than placebo but apart from dry mouth were similar in effect. Transdermal oxybutynin caused less dry mouth than the other treatments, so may be worth considering as the first treatment.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Cholinergic Antagonists; Humans; Imidazoles; Mandelic Acids; Network Meta-Analysis; Pyrrolidines; Solifenacin Succinate; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

To compare efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents for the treatment of overactive bladder (OAB).. Literature searches of MEDLINE, Embase, and the Cochrane Library were undertaken to identify randomized controlled trials in OAB (2000-2015) for antimuscarinic agents. A network meta-analysis (NMA) was performed to estimate efficacy and tolerability outcomes for solifenacin 5 mg/day relative to other antimuscarinics.. The NMA included 53 eligible trials (published, n = 48; unpublished on search date, n = 5). Solifenacin 5 mg/day was significantly more effective than tolterodine 4 mg/day for reducing incontinence and urgency urinary incontinence (UUI) episodes, but significantly less effective than solifenacin 10 mg/day for micturition; no other statistically significant differences were noted for efficacy. Solifenacin 5 mg/day had a statistically significant lower risk of dry mouth compared with darifenacin 15 mg/day, fesoterodine 8 mg/day, oxybutynin extended-release 10 mg/day, oxybutynin immediate-release (IR) 9-15 mg/day, tolterodine IR 4 mg/day, propiverine 20 mg/day, and solifenacin 10 mg/day. There were no significant differences between solifenacin 5 mg/day and other antimuscarinics for risk of blurred vision, or for 11 of 17 active comparators for risk of constipation.. This NMA suggests that the efficacy of solifenacin 5 mg/day is at least similar to other common antimuscarinics across the spectrum of OAB symptoms analyzed, and is more effective than tolterodine 4 mg/day in reducing incontinence and UUI episodes. Solifenacin 5 mg/day has a lower risk of dry mouth compared with several agents.

Topics: Benzhydryl Compounds; Benzilates; Humans; Mandelic Acids; Muscarinic Antagonists; Network Meta-Analysis; Solifenacin Succinate; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

Fesoterodine (as one of three drugs: dutasteride, finasteride and fesoterodine) was classified B (beneficial) by LUTS-FORTA 2014, indicating that it is a medicinal product with proven or obvious efficacy in the elderly, with limited side effects and/or safety concerns. A systematic literature review was undertaken in January 2018 using the PubMed and Google Scholar databases with the following individual and combined keywords: "fesoterodine", "pharmacology", "overactive bladder" and "antimuscarinics". The aim of the review was to determine which of fesoterodine's pharmacological properties explains its clinical benefits in general patient populations with OAB and the elderly in particular. The articles in the results were then selected by publication language (English and French only), methodology (off-topic studies, reported cases and literature reviews were excluded), relevance to the subject matter and publication date prior to 31 January 2018. A total of 205 articles was initially obtained, with 115 read and 45 selected. It appears that the association of four pharmacological properties specific to fesoterodine can explain that this drug has a good balance between efficacy and tolerability. These properties are namely the drug's high and nearly equal affinity for both the M2 and M3 muscarinic receptors, poor penetration of the blood-brain barrier, lack of hepatic first-pass activation -fesoterodine being rapidly and extensively converted to its active metabolite, 5-hydroxymethyl tolterodine, by ubiquitous esterases-, and its extended-release formulation. Fesoterodine's pharmacological profile is optimal for the treatment of overactive bladder. It is now recognized as one of the leading first-line treatment for this indication.

Topics: Animals; Benzhydryl Compounds; Humans; Muscarinic Antagonists; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Urinary Bladder, Overactive; Urological Agents

Overactive bladder (OAB) is a particular challenge to treat in older adults with co-morbid conditions taking multiple medications. Antimuscarinics (e.g., solifenacin, fesoterodine) and β3-adrenergic receptor agonists (mirabegron) are similarly efficacious; however, antimuscarinics may be associated with side effects that result in poor persistence and contribute to anticholinergic burden, particularly in those taking other medications with anticholinergic properties. With a mechanism of action distinct from antimuscarinics, mirabegron has a different tolerability profile and does not contribute to anticholinergic burden. The objective of this review was to compare and contrast the tolerability profiles of antimuscarinics and mirabegron in older patients to inform practice.. Prospective trials or retrospective subgroup analyses of antimuscarinics for the treatment of OAB in older patients were identified through a search of PubMed. Tolerability data and results of subgroup analyses of mirabegron in patients aged ≥65 and ≥75 years from a pooled analysis of three trials each of 12 weeks and a 1 year trial are described.. Anticholinergic adverse events (AEs) including dry mouth and constipation were more frequent with antimuscarinics versus mirabegron. In patients aged ≥65 years, dry mouth occurred with a six-fold higher incidence with tolterodine extended-release (ER) 4 mg than with mirabegron 25 mg or 50 mg over 12 weeks, and a three-fold higher incidence with tolterodine ER than mirabegron 50 mg over 1 year. Mirabegron had a low incidence of central nervous system effects. A systematic review of the cardiovascular safety profile of mirabegron has not identified any clinically significant effects on blood pressure or pulse rate at therapeutic doses amongst patients aged ≥65 years.. Mirabegron has a more favorable tolerability profile than antimuscarinics amongst older patients and may provide an improved benefit-to-risk ratio and therefore be considered as an alternative to antimuscarinics for older patients.

Topics: Acetanilides; Administration, Oral; Adrenergic beta-Antagonists; Aged; Benzhydryl Compounds; Blood Pressure; Clinical Trials as Topic; Constipation; Female; Heart Rate; Humans; Male; Middle Aged; Muscarinic Antagonists; Prospective Studies; Retrospective Studies; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

Overactive bladder (OAB) is a common condition, with prevalence rates increasing with advancing age. Symptoms of OAB, including urgency urinary incontinence (UUI), are associated with various co-morbidities in elderly individuals (e.g., falls and fractures, functional impairment, and depression). The current mainstay of pharmacological therapy for OAB is antimuscarinic agents. Until recently, few studies had specifically evaluated the efficacy and safety of antimuscarinics in the treatment of OAB symptoms in elderly patients. This review summarises available evidence from the medical literature on the efficacy and safety of fesoterodine in elderly patients with OAB symptoms, including UUI. The data from unique placebo-controlled fesoterodine trials of elderly and vulnerable elderly patients, together with age-stratified data from post hoc analyses of fesoterodine trials, demonstrate that treatment with fesoterodine 4 or 8 mg results in statistically and clinically significant improvements in OAB symptoms and patient-reported outcomes in many elderly patients. The data indicate that the efficacy of fesoterodine in elderly patients is comparable with that in younger patients. Fesoterodine is generally well tolerated in elderly and vulnerable elderly patients, with low rates of urinary retention and little evidence of central nervous system events or impaired cognition. The data support a favourable benefit-to-risk ratio for fesoterodine in elderly and medically complex vulnerable elderly patients with OAB.

Topics: Aged; Benzhydryl Compounds; Humans; Muscarinic Antagonists; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

To summarize published evidence on the pharmacology, efficacy, and safety of fesoterodine for the treatment of overactive bladder (OAB) symptoms in relation to patient clinical and demographic profiles.. A systematic review of published articles on fesoterodine was conducted via a PubMed search. Articles were identified using the search term fesoterodine, with limits of human species and abstract available. Review and meta-analysis articles, validation studies, articles focused on treatment compliance/adherence, meeting abstracts, and articles not focused on oral fesoterodine administration in human subjects were excluded. Data from retained articles were summarized descriptively.. Of 137 articles identified, 61 (15 articles on the pharmacology and 46 articles on the efficacy and/or safety of fesoterodine) met inclusion criteria. Superiority trials demonstrated the additional efficacy of fesoterodine 8 mg versus fesoterodine 4 mg and tolterodine extended release 4 mg in treating OAB. Prospective trials in specific patient populations indicated beneficial effects of fesoterodine in elderly patients, vulnerable elderly patients, patients dissatisfied with or with a suboptimal response to previous antimuscarinic therapy, patients with urge urinary incontinence (UUI) or nocturnal urgency, and men with persistent LUTS during alpha-blocker treatment. With two effective doses, the fesoterodine dose can be adjusted to achieve optimal efficacy and tolerability in individual patients. The most common adverse events during fesoterodine treatment are dry mouth and constipation.. Extensive evidence demonstrates the efficacy and safety of fesoterodine in relieving OAB symptoms, including urgency, urinary frequency, UUI, and nocturnal urgency, in patients with various clinical and demographic profiles. Trial results provide valuable information on fesoterodine treatment in specific patient populations, including both elderly and vulnerable elderly patients. Potential limitations of this review are that only English language articles in PubMed were searched and included.

Topics: Administration, Oral; Aged; Benzhydryl Compounds; Constipation; Humans; Male; Medication Adherence; Muscarinic Antagonists; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge

Overactive bladder (OAB) is a common constellation of lower urinary tract storage symptoms that causes a significant impact on a person's quality of life. The elderly may be disproportionally impacted by these symptoms due to concomitant poor mobility, comorbid conditions such as diabetes and heart failure, and polypharmacy. While behavioral modification and pelvic floor muscle training should be considered first-line treatment options, pharmacotherapy remains the backbone of the therapeutic regimen. Trospium, oxybutynin, fesoterodine, and darifenacin all have unique properties that may confer certain advantages in the elderly population. The hydrophilicity and quaternary amine structure of trospium may limit its ability to cross the blood-brain barrier and thus minimize impact on cognition in the elderly. In its oral form, oxybutynin may have the most significant effect on cognition; however, the transdermal preparations may be favorable in the elderly population due to the ability to avoid first-pass metabolism and its limited antimuscarinic adverse effects. Fesoterodine may be the most extensively studied OAB medication in the elderly population. Darifenacin has a strong affinity for the M3 receptor in the bladder, while having a weak affinity for the M1 receptor commonly found in the brain. It must be noted that all muscarinic receptor antagonists are associated with common adverse effects to some degree, and frequent re-evaluation of the elderly patient is necessary to confirm the proper benefit-to-risk profile.

Topics: Aged; Aging; Benzhydryl Compounds; Benzofurans; Blood-Brain Barrier; Cognition; Female; Humans; Mandelic Acids; Pyrrolidines; Quality of Life; Urinary Bladder, Overactive

Urinary incontinence (UI) is a prevalent condition among women of all ages. It can have a significant negative impact on women's quality of life causing not only physical but also psychological distress.. This article aims to provide a review of the pharmacology, efficacy, safety and tolerability of fesoterodine fumarate (the newest anticholinergic launched in the UK) and the oxybutynin vaginal ring (the newest route of drug delivery in development) in the treatment of urgency UI.. Fesoterodine is now a well-established treatment option; however, as with all oral anticholinergic agents its use is hindered by side effects. The efficacy of the oxybutynin ring has only been demonstrated in small studies. Larger clinical trials assessing the efficacy, tolerability and acceptability are required before appropriate recommendations can be made.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Contraceptive Devices, Female; Drug Delivery Systems; Female; Humans; Mandelic Acids; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

Overactive bladder (OAB), a clinically defined symptom complex comprising urinary urgency, usually accompanied by urinary frequency and nocturia, with or without urgency incontinence, is common and has a markedly negative impact on the sufferer's quality of life. Following conservative and lifestyle management, the current pharmacological mainstay of treatment is antimuscarinic therapy. This review explores the role of fesoterodine, a relatively recently introduced antimuscarinic agent, in the treatment of patients who may have had a suboptimal response to initial therapy, who have switched treatment from tolterodine, or may be at risk of receiving poor treatment because of either multimorbidity or complex polypharmacy.

Topics: Benzhydryl Compounds; Humans; Muscarinic Antagonists; Urinary Bladder, Overactive

Overactive bladder is a prevalent condition worldwide that is associated with a considerable burden, both on the patient and on society.. Our objective was to assess the economic value of fesoterodine compared with tolterodine extended release (ER) for the treatment of overactive bladder (OAB) with urge urinary incontinence (UUI) in Spain and Finland.. A decision-tree economic model estimated the 52-week costs and quality-adjusted life-years (QALYs) of OAB/UUI patients initiating treatment with fesoterodine 4 mg/day or tolterodine ER. Individuals were evaluated for treatment response (UUI fewer than one episode/day) and persistence at weeks 4, 12, and 24. Titration from fesoterodine 4 mg/day to 8 mg/day was permitted at week 4. At week 12, non-responders discontinued treatment permanently. Efficacy, discontinuation, and utility data were derived from four clinical trials of fesoterodine. OAB-related costs, including physician visits, laboratory tests, incontinence pads, and comorbidities (fracture, skin infection, urinary tract infections, depression, and nursing home) were also included.. A total of 19.5 % and 18.0 % of fesoterodine and tolterodine ER patients remained on treatment until week 52, respectively. QALYs were higher with fesoterodine than tolterodine ER (0.762 vs. 0.760). In Spain, fesoterodine treatment had higher total costs than (generic) tolterodine ER (€6,697 vs. 6,597), resulting in a cost of €15,633/QALY gained. In Finland, fesoterodine was cost saving relative to (non-generic) tolterodine ER (€7,885 vs. 8,024). Sensitivity analysis confirmed that these findings were robust to the expected price decrease for generic tolterodine ER in Finland.. Fesoterodine is cost effective or cost saving relative to tolterodine ER for the treatment of OAB with UUI in two European countries. Payers and prescribers should consider a broad scope of costs to make informed cost-conscious choices of antimuscarinic treatment.

Topics: Benzhydryl Compounds; Cost-Benefit Analysis; Cresols; Finland; Humans; Phenylpropanolamine; Spain; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence, Urge

Topics: Animals; Benzhydryl Compounds; Clinical Trials as Topic; Female; Humans; Molecular Targeted Therapy; Muscarinic Agonists; Muscle Contraction; Muscle, Smooth; Organ Specificity; Patient Satisfaction; Quality of Life; Rats; Receptors, Muscarinic; Tablets; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urodynamics; Urological Agents

To systematically review dose-escalation data from flexible-dose studies of fesoterodine and summarise factors associated with dose-escalation decisions.. A PubMed search was conducted using the terms (fesoterodine AND flexible dose), with no limits. Articles were included if they contained fesoterodine dose-escalation data for efficacy or safety outcomes or factors associated with dose-escalation decisions.. Of 13 articles identified by the search, 10 articles (six clinical studies) met inclusion criteria. In flexible-dose trials of fesoterodine, 51-63% of subjects initially receiving fesoterodine 4 mg opted for dose escalation to fesoterodine 8 mg. Escalators generally reported significantly more severe overactive bladder (OAB) symptoms, greater OAB symptom bother and worse health-related quality of life at baseline than non-escalators. Escalators demonstrated less treatment benefit with fesoterodine 4 mg than non-escalators. Non-escalators generally had a higher rate of dry mouth and constipation with fesoterodine 4 mg than escalators. The decision to escalate appeared to be determined by the efficacy/tolerability responses; fesoterodine escalators demonstrated a lower sensitivity (less efficacy and fewer adverse events) before their decision to escalate. By study end (8-11 weeks after escalation decision), the efficacy and tolerability profiles were similar in escalators and non-escalators.. Data from flexible-dose studies provide strong evidence that fesoterodine provides treatment benefit to individual subjects with OAB because of its true dose-response effect. In clinical practice, it can be worthwhile to escalate to fesoterodine 8 mg in individual subjects who require additional efficacy benefit.

Topics: Benzhydryl Compounds; Female; Humans; Male; Muscarinic Antagonists; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder, Overactive

Fesoterodine fumarate is an approved drug for overactive bladder. The aim of this study is to review the preclinical and most up to date clinical data on fesoterodine, with a special emphasis on its unique pharmacokinetic features and its implications on safety and tolerability in various patient populations.. In this review, the authors extensively reviewed available literature via PubMed search regarding fesoterodine, covering its mechanism of action, pharmacodynamics and pharmacokinetics, clinical efficacy, safety, and tolerability.. Fesoterodine is an anti-muscarinic agent with a unique pharmacokinetic profile. It is a prodrug that is rapidly metabolized to its active form by nonspecific plasma esterases. Its metabolism is independent of the cytochrome P450 enzyme system. This along with its dual excretion pathways and minimal central nervous system penetration leads to less variability in drug exposure and allowance of administration in those with mild to moderate renal and hepatic insufficiency and in the geriatric population.

Topics: Administration, Oral; Animals; Benzhydryl Compounds; Clinical Trials, Phase III as Topic; Disease Models, Animal; Drug Evaluation, Preclinical; Humans; Muscarinic Antagonists; Prodrugs; Randomized Controlled Trials as Topic; Urinary Bladder, Overactive; Urological Agents

• To evaluate the effects of long-term fesoterodine treatment on health-related quality of life (HRQL) and treatment satisfaction in subjects with overactive bladder (OAB) symptoms. • To determine the impact of gender and age on these effects.. • This is a post hoc analysis of data pooled from identically designed open-label extensions of two randomized, double-blind, 12-week fesoterodine studies. • Initial treatment was once-daily fesoterodine 8 mg; subjects had the opportunity to receive open-label fesoterodine for ≥24 months. • After 1 month, subjects could elect dose reduction to 4 mg and subsequent re-escalation to 8 mg; dose reduction and re-escalation were each allowed once annually. • Changes in scores on the King's Health Questionnaire (KHQ), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and a Likert scale evaluating severity of bladder-related problems were assessed at open-label baseline and months 12 and 24; treatment satisfaction was assessed at open-label baseline and at months 4, 12 and 24.. • A total of 864 enrolled subjects were included (men, n= 182; women, n= 682; aged <45 years, n= 134; 45-64 years, n= 432; 65-74 years, n= 204; ≥75 years, n= 94); most subjects (77%) who continued treatment maintained the 8-mg dose. • Among subjects in the overall population, there were significant improvements in all KHQ domains, ICIQ-SF scores, and bladder-related problems at open-label baseline vs double-blind baseline (P < 0.05); additional significant improvements were observed at months 12 and 24 vs open-label baseline in all outcomes (P < 0.05) except for the KHQ General Health Perception domain. • When data were stratified by gender or age, significant improvements at open-label baseline vs double-blind baseline were further significantly enhanced or sustained at months 12 and 24 for most KHQ domains, and for ICIQ-SF scores and bladder-related problems for all groups. Women had significantly greater improvements than men in the KHQ Emotion (P= 0.0173) and Severity/Coping (P= 0.0112) domains and ICIQ-SF scores (P= 0.0276) during open-label treatment. Subjects aged <45 years had significantly greater improvement in the Personal Relationships domain compared with those aged 45-64 years (P= 0.0357) and in the Sleep/Energy domain compared with all other groups (all P < 0.02). • Treatment satisfaction was high (≥92%) throughout open-label treatment regardless of gender or age.. • Long-term fesoterodine treatment was associated with sustained improvement in measures of health-related quality of life and bladder-related problems and with high treatment satisfaction in subjects with overactive bladder symptoms. • Effects of gender and age were minimal.

Topics: Aged; Benzhydryl Compounds; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Satisfaction; Quality of Life; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder, Overactive

This is a systematic review of clinical data assessing the safety, efficacy and tolerability of fesoterodine in randomised control trials (RCTs) in the treatment of overactive bladder (OAB).. We performed a MEDLINE literature search of articles published between 2005 and 2010 regarding the efficacy and safety of fesoterodine. The US Food and Drug Administration Web site was also searched for RCTs.. Two studies demonstrated significant improvement of OAB symptoms with fesoterodine compared with placebo. Two phase III studies showed both doses of fesoterodine to be more effective than placebo for most symptoms. Another phase III trial confirmed the superiority of 8 mg fesoterodine compared with tolterodine ER 4 mg. Dry mouth was the commonest side effect.. Fesoterodine is effective for treating OAB symptoms. Its once-daily dosing regime and the flexibility to increase the dose are appealing factors.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Treatment Outcome; Urinary Bladder, Overactive

Antimuscarinics (AMs) are the mainstay of pharmacological treatment of overactive bladder (OAB), a symptom complex defined by the presence of urinary urgency, usually associated with frequency and nocturia, with or without urgency urinary incontinence. The AMs used to treat OAB differ in their pharmacological profiles, which may affect their potential for causing adverse effects (AEs).. The present article aims to review the literature about pharmacokinetics (PK) of the different AMs used in the treatment of OAB. Furthermore, the AEs related to the use of these drugs and their incidence are presented. This systematic review is based on material searched and obtained via Medline, Pubmed and EMBASE up to March 2012 using the search terms "adverse events, pharmacokinetics, tolerability" in combination with "darifenacin, fesoterodine, imidafenacin, oxybutynin, propiverine, solifenacin, tolterodine, and trospium.". Antimuscarinics are the first-line pharmacological treatment for OAB. Despite the development of new molecules that improve their efficacy/safety profile, there are some drugs that are pharmacokinetically more appropriate to be prescribed in specific populations such as patients with neurological disease or the elderly. Moreover, research should be encouraged in evaluating antimuscarinics in conjunction with other drugs such as estrogens or beta-agonists. The identification of prognostic criteria for pharmacological therapy would be helpful.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Chronic Disease; Cresols; Drug Combinations; Female; Humans; Imidazoles; Mandelic Acids; Muscarinic Antagonists; Nocturia; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence

Anticholinergic drugs are commonly prescribed for symptomatic treatment of overactive bladder (OAB). While recent meta-analyses have characterized the prevalence of dry mouth among patients utilizing OAB medications, prevalence of constipation has not been systematically reviewed.. To provide an effect measure for constipation associated with anticholinergic OAB drugs versus placebo.. A meta-analysis of trials with darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, and trospium was conducted. All randomized, placebo-controlled studies of anticholinergic OAB drugs published in English language and identified in Medline and Cochrane databases were considered for inclusion in this meta-analysis. Those meeting predetermined design characteristics and having sufficient duration (≥2 weeks) were included. Constipation-related data from all included studies were abstracted.. One hundred two English-language, randomized, placebo-controlled trials were originally identified. Thirty-seven studies were ultimately included in the analysis, involving 19,434 total subjects (12,368 treatment+7,066 placebo patients). The odds ratios for constipation compared with placebo were as follows: overall [odds ratio (OR) 2.18, 95% confidence interval (CI)=1.82-2.60], tolterodine (OR 1.36, 95% CI=1.01-1.85), darifenacin (OR 1.93, 95% CI=1.40-2.66), fesoterodine (OR 2.07, 95% CI=1.28-3.35), oxybutynin (OR 2.34, 95% CI=1.31-4.16), trospium (OR 2.93, 95% CI=2.00-4.28), and solifenacin (OR 3.02, 95% CI=2.37-3.84).. Our results demonstrate that patients prescribed anticholinergic OAB drugs are significantly more likely to experience constipation. Differences in muscarinic receptor affinities among individual agents may possibly account for the modest variation in constipation rates observed; however, such a determination warrants additional research.

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Benzofurans; Cholinergic Antagonists; Constipation; Female; Humans; Male; Middle Aged; Pyrrolidines; Randomized Controlled Trials as Topic; Risk Factors; Urinary Bladder, Overactive

Overactive bladder syndrome is a common condition that adversely affects the quality of life. It is mainly treated with a combination of bladder retraining and antimuscarinics. In a quest to reduce the side effect profile of these drugs, whilst improving their efficacy, more bladder-selective antimuscarinics were developed. One of the more recent of these antimuscarinics which has come to the market is fesoterodine. This review examines the evidence of the safety and efficacy of this drug.. A literature search performed identified two main multi-center trials which highlight the safety, efficacy and tolerability of fesoterodine. These together with the pharmacologic properties of the drug are discussed at length throughout the review. An expert opinion is then formulated based on the current evidence available and on comparison with other antimuscarinics.. It is concluded that fesoterodine has the added advantage of flexible dosing over some other antimuscarinics. It does, however, have a similar tolerability and side effect profile to other antimuscarinics and is, therefore, unlikely to revolutionize the treatment of the overactive bladder.

Topics: Benzhydryl Compounds; Clinical Trials, Phase III as Topic; Humans; Multicenter Studies as Topic; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Urinary Bladder, Overactive

To assess the effect of age on fesoterodine efficacy and tolerability in subjects with an overactive bladder.. The data from 2 randomized, 12-week studies of 1681 subjects treated with fesoterodine 4 or 8 mg or placebo were pooled and stratified by age. The subjects completed 3-day bladder diaries at baseline and weeks 2 and 12, the King's Health Questionnaire at baseline and week 12, and the Treatment Benefit Scale at week 12.. Of the subjects aged <65 years, fesoterodine 4 and 8 mg was associated with statistically significant improvements in the diary variables at week 12 versus placebo. Greater improvement in urgency urinary incontinence was seen with fesoterodine 8 mg versus 4 mg. For those aged ≥65 to <75 years, fesoterodine 4 and 8 mg significantly improved all diary variables, except for the mean voided volume and micturition frequency, respectively, [corrected] versus placebo. In subjects aged ≥75 years, fesoterodine 8 mg significantly improved all diary variables, except for mean voided volume, versus placebo. No significant improvements were observed with fesoterodine 4 mg versus placebo. Fesoterodine significantly improved several King's Health Questionnaire domains versus placebo in all age groups. Fesoterodine 4 mg did not significantly improve any domains in subjects aged ≥75 years. In all age groups, the treatment response rates were significantly greater with both fesoterodine doses versus placebo. Dry mouth and constipation occurred more frequently in subjects aged ≥75 years receiving fesoterodine 8 mg than in those receiving fesoterodine 4 mg or placebo, although the discontinuation rates because of dry mouth and constipation were not increased.. Fesoterodine 4 and 8 mg effectively treated overactive bladder symptoms in subjects aged <75 years. Fesoterodine 8 mg was effective in subjects aged ≥75 years.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Benzhydryl Compounds; Constipation; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Dropouts; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Xerostomia; Young Adult

black triangle Fesoterodine is a muscarinic receptor antagonist that is rapidly and extensively converted to the active and more potent metabolite 5-hydroxymethyltolterodine. The drug is approved for once-daily oral administration in patients with overactive bladder syndrome (OAB). black triangle In two large, 12-week, randomized, double-blind, multicentre, phase III trials, oral fesoterodine 4 or 8 mg once daily improved the symptoms of OAB (frequency of micturition, urgency and urge incontinence) significantly more than placebo. black triangle Furthermore, significantly more patients receiving fesoterodine 4 or 8 mg once daily had a positive response to therapy than those receiving placebo, as determined by a treatment questionnaire. black triangle Health-related quality of life was improved to a significantly greater extent in patients with OAB who received fesoterodine 4 or 8 mg once daily than in those who received placebo in a post hoc analysis of pooled data from the phase III trials. black triangle Fesoterodine 4 or 8 mg once daily was generally well tolerated in patients with OAB; the most frequent adverse event was dry mouth, which was generally mild to moderate in severity.

Topics: Benzhydryl Compounds; Humans; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Treatment Outcome; Urinary Bladder, Overactive

To review pharmacologic, pharmacokinetic, efficacy, and safety data for fesoterodine and determine its role in the treatment of overactive bladder.. A MEDLINE search (1966-July 2009) was conducted using the key words fesoterodine, tolterodine, muscarinic receptor antagonist, anticholinergic, overactive bladder, urge incontinence, efficacy, safety, adverse effect, pharmacology, pharmacokinetic, and receptor binding.. All articles written in English that were identified from the data sources were evaluated, prioritizing randomized, controlled trials with human data. The references of published articles that we identified were examined for any additional studies appropriate for the review.. Fesoterodine, a competitive muscarinic receptor antagonist, is converted to its active metabolite, 5-hydroxymethyltolterodine, by nonspecific esterases, bypassing the cytochrome P450 system. Two randomized controlled Phase 3 trials examined the safety and efficacy of fesoterodine in the treatment of overactive bladder. Fesoterodine was found to produce significant improvements in the treatment of overactive bladder symptoms compared with placebo. Post hoc analysis of these trials demonstrated significant improvements in health-related quality of life in patients with overactive bladder. Only one study included tolterodine, and direct comparisons between fesoterodine and tolterodine were not conducted. The most common treatment-emergent adverse effects associated with fesoterodine included dry mouth, constipation, urinary tract infection, and headache.. Fesoterodine appears to be effective and generally safe for the treatment of overactive bladder. The efficacy and safety of fesoterodine in overactive bladder treatment seem to be at least similar to that of tolterodine. Although additional comparative trials are needed, based on available data, it does not appear that fesoterodine provides a substantial advantage over extended-release tolterodine in either efficacy or safety.

Topics: Animals; Benzhydryl Compounds; Cresols; Humans; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Bladder, Overactive

To evaluate the effect of fesoterodine on health-related quality of life (HRQoL) in patients with overactive bladder (OAB) syndrome.. Pooled data from two randomized placebo-controlled phase III studies were analysed. Eligible patients with frequency and urgency or urgency urinary incontinence were randomized to placebo or fesoterodine 4 or 8 mg for 12 weeks; one trial also included tolterodine extended release (tolterodine-ER) 4 mg. HRQoL was assessed using the King's Health Questionnaire (KHQ), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), a six-point Likert scale measuring the severity of bladder-related problems, and treatment response.. By the end of treatment, all active-treatment groups had significantly improved HRQoL compared with those on placebo, as shown by an improvement in the KHQ and ICIQ-SF scores, treatment response rate, and a major improvement in self-reported bladder-related problems. The fesoterodine 8-mg group had statistically significant improvements over placebo in eight of nine KHQ domains. Fesoterodine 4 mg and tolterodine-ER produced statistically significant improvements in seven of nine KHQ domains. Fesoterodine 8 mg gave better results than 4 mg in two domains; Emotions and Symptom Severity (P < 0.05). A major improvement (>or=2 points) in bladder-related problems was reported by 33% of patients on fesoterodine 4 mg, 38% on fesoterodine 8 mg, and 34% on tolterodine-ER, vs 21% on placebo (P < 0.001).. Fesoterodine significantly improved HRQoL in patients with OAB. Both fesoterodine 4 and 8 mg produced significant improvements on most KHQ domains, the ICIQ-SF, treatment response rate, and a Likert scale measuring bladder-related problems.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Clinical Trials, Phase II as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Satisfaction; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder, Overactive

Fesoterodine is a newly approved drug for the treatment of overactive bladder syndrome.. The aim of this study was to review the preclinical and clinical data on fesoterodine.. The study involved a search of the Medline database and the proceedings volumes of urological congresses.. Fesoterodine functions as an orally active prodrug that is converted to the active metabolite 5-hydroxymethyltolterodine by non-specific esterases. 5-Hydroxymethyltolterodine is a muscarinic receptor antagonist. Fesoterodine is primarily eliminated as inactive metabolites along with significant renal excretion as the unchanged active metabolite 5-hydroxymethyltolterodine. Fesoterodine is indicated for use at doses of 4 and 8 mg once daily. In clinical studies both doses of fesoterodine were consistently superior to placebo in improving the symptoms of overactive bladder syndrome, with 8 mg/day having significantly greater effects than 4 mg/day.

Topics: Benzhydryl Compounds; Clinical Trials as Topic; Drug Interactions; Humans; Muscarinic Antagonists; Syndrome; Urinary Bladder, Overactive

The aim of this prospective phase IIa, open-label exploratory, pre-post study was to determine the efficacy of fesoterodine (i.e., 12-week treatment period) to ameliorate autonomic dysreflexia (AD) in individuals with chronic SCI (> 1-year post-injury) at or above the sixth thoracic spinal segment, with confirmed history of AD and neurogenic detrusor overactivity (NDO). Twelve participants (four females, eight males; median age 42 years) completed this study and underwent urodynamics, 24-h ambulatory blood pressure monitoring (ABPM), and urinary incontinence-related quality of life (QoL) measures at baseline and on-treatment. The Montreal Cognitive Assessment (MoCA) and Neurogenic Bowel Dysfunction (NBD) score were used to monitor cognitive and bowel function, respectively. Compared with baseline, fesoterodine improved lower urinary tract (LUT) function, that is, increased cystometric capacity (205 vs. 475 mL,

Topics: Adult; Autonomic Dysreflexia; Blood Pressure Monitoring, Ambulatory; Female; Humans; Male; Prospective Studies; Quality of Life; Spinal Cord Injuries; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urinary Incontinence

Neurogenic detrusor overactivity (NDO) can damage the upper urinary tract leading to chronic renal impairment. Antimuscarinic therapy is used to improve urinary incontinence and protect the upper urinary tract in patients with NDO.. This study investigated safety and efficacy of fesoterodine, a muscarinic receptor antagonist, in 6‒<18-year-old patients with NDO (NCT01557244).. This open-label phase 3 study included 2 pediatric cohorts. Patients in Cohort 1 (bodyweight >25 kg) were randomized to fesoterodine 4 or 8 mg extended-release tablets or oxybutynin XL tablets administered over the 12-week active comparator-controlled phase. The safety extension phase evaluated fesoterodine 4 and 8 mg for a further 12 weeks, with patients in the oxybutynin arm allocated to fesoterodine 4 or 8 mg. Patients in Cohort 2 (bodyweight ≤25 kg) were randomized to fesoterodine 2 or 4 mg extended-release beads-in-capsule (BIC) administered over a 12-week efficacy phase and 12-week safety extension phase. Patients with stable neurologic disease and clinically or urodynamically proven NDO were included. The primary endpoint was change from baseline to Week 12 in maximum cystometric bladder capacity (MCC). Secondary efficacy endpoints included detrusor pressure at maximum bladder capacity, bladder volume at first involuntary detrusor contraction, bladder compliance, and incontinence episodes. Safety endpoints included adverse event incidence, and specific assessments of cognition, behavior and vision. The pharmacokinetics of 5-hydroxymethyl tolterodine (5-HMT; fesoterodine's active metabolite) was determined using population-pharmacokinetic analysis.. In Cohort 1 (n = 124), fesoterodine 4 and 8 mg treatment resulted in significant increases from baseline in the primary endpoint of MCC at Week 12. In Cohort 2 (n = 57), fesoterodine 2 and 4 mg BIC treatment resulted in improvements in MCC from baseline. Fesoterodine 4 and 8 mg and fesoterodine 4 mg BIC led to improvements in some secondary efficacy endpoints. The most common treatment-related adverse reactions were gastrointestinal effects, such as dry mouth, which occurred more frequently with oxybutynin than fesoterodine. No detrimental effects on visual accommodation or acuity, or on cognitive function or behavior were observed.. These safety and efficacy results are consistent with limited published data on fesoterodine treatment in pediatric populations with overactive bladder or NDO. Study limitations include the lack of placebo control and the small sample size, which limits the ability to make formal efficacy comparisons and detect rare adverse reactions.. Fesoterodine has a favorable benefit-risk profile in 6‒<18-year-old patients with NDO and may represent an additional option for pediatric NDO treatment.

Topics: Adolescent; Child; Humans; Mandelic Acids; Muscarinic Antagonists; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence; Urodynamics

Fesoterodine is a muscarinic receptor antagonist approved for the treatment of overactive bladder (OAB) in adults and neurogenic detrusor overactivity (NDO) in pediatric patients. This work aimed to characterize the population pharmacokinetics of 5-hydroxymethyl tolterodine (5-HMT, the active metabolite of fesoterodine) and its pharmacokinetic/pharmacodynamic relationship in pediatric patients with OAB or NDO following administration of fesoterodine.. 5-HMT plasma concentrations from 142 participants of age ≥ 6 years were analyzed, and a nonlinear mixed-effects model was developed. Weight-based simulations of 5-HMT exposure and maximum cystometric capacity (MCC) were conducted using the final models.. A one-compartment model with first-order absorption and a lag time, which included the effects of body weight, sex, cytochrome (CYP) 2D6 metabolizer status and fesoterodine formulation on pharmacokinetic parameters, best described the 5-HMT pharmacokinetics. An E. Population models were developed for 5-HMT and MCC in pediatric patients. Weight-based simulations indicated that 4 mg QD for pediatric patients weighing 25-35 kg and 8 mg QD for those weighing > 35 kg provided similar exposures to those in adults following 8 mg QD and a clinically meaningful CFB MCC.. NCT00857896, NCT01557244.. Fesoterodine is a muscarinic receptor antagonist approved for the treatment of overactive bladder (OAB) in adults and neurogenic detrusor overactivity (NDO) in pediatric patients in the US. Population pharmacokinetic and pharmacokinetic/pharmacodynamic models were developed for 5-HMT based on data from two pediatric clinical trials that included 142 patients of age ≥ 6 years with OAB or NDO. Weight-based simulations of 5-HMT exposure and maximum cystometric capacity were conducted using the final models to examine the impact of covariates on 5-HMT exposure and the exposure–response profile. The results of these simulations indicate that 4 mg QD for pediatric patients weighing 25–35 kg and 8 mg QD for those weighing > 35 kg provide similar exposures to those in adults following 8 mg QD.

Topics: Adult; Child; Cytochrome P-450 CYP2D6; Humans; Muscarinic Antagonists; Urinary Bladder, Overactive

We aimed to compare on-demand and continuous use of fesoterodine 4 mg concerning efficacy and adverse effects.. A total of 100 patients who were diagnosed with non-neurogenic overactive bladder (OAB) syndrome were included in the study. All patients were evaluated with MMSE, ICIQ-SF, SEAPI quality of health and OAB-V8 questionnaires, at the beginning, 1st month and 4th month. Fesoterodine 4 mg was started for treatment. At the end of the 1st month, patients who obtained benefit from the treatment were 1:1 randomized into two groups. In group 1, fesoterodine 4 mg was given 1 × 1 in a standard manner whereas in group 2 patients took the pills on demand. Both groups were evaluated for efficacy and adverse events at 4 months.. Final analyses included 69 patients. At 4-month follow-up, OAB-V8 scores were significantly improved compared to 1 month in both groups. Again at h months, no difference was detected between the two groups for MMSE, ICIQ-SF and SEAPI scores. In continuous usage group, 4th month MMSE scores were significantly lower than 1st month scores. At 4 months, dry mouth and constipation were lower in the on-demand group compared to continuous usage group.. Compared to standard continuous usage, on-demand usage of fesoterodine showed similar efficacy with fewer adverse events.

Topics: Benzhydryl Compounds; Humans; Muscarinic Antagonists; Treatment Outcome; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-3 Receptor Agonists; Aged; Aged, 80 and over; Benzhydryl Compounds; Humans; Indoles; Lower Urinary Tract Symptoms; Male; Middle Aged; Prospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To evaluate short-term efficacy and safety of fesoterodine fumarate in Parkinson's disease (PD) patients with overactive bladder (OAB) symptoms.. This is a randomized, double-blind, placebo-controlled study. It also has an open-label extension phase. From May 2016 to May 2018, 63 patients were randomized to receive fesoterodine 4 mg or placebo for 4 weeks. At the end of 4 weeks of randomization phase, patients were received fesoterodine fumarate 4 mg daily for another 4 weeks at the open-label extension phase. The change in the mean number of micturition episodes per 24 h period was the primary outcome measure of the study.. The number of micturition episodes per 24 h period significantly improved with the use of fesoterodine fumarate in the double-blind phase (p < 0.001). Also the mean number of nocturia and urgency episodes decreased in the fesoterodine group. In the open-label phase, the mean number of micturition, urgency and urgency urinary incontinence episodes were improved significantly. The number of nocturia episodes did not change in the open-label phase. Cognitive functions were stable after 4 weeks of fesoterodine 4 mg treatment.. OAB symptoms were significantly improved in older adults with PD under fesoterodine fumarate treatment, and this advantage continued in the open-label portion in the short term. In this randomized controlled study, the cognitive functions of the participants were not affected by fesoterodine 4 mg treatment compared with placebo.

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Parkinson Disease; Treatment Outcome; Urinary Bladder, Overactive

We sought to determine whether baseline characteristics predict which overactive bladder (OAB) patients benefit from fesoterodine 8 mg versus 4 mg.. In double-blind, placebo-controlled, flexible-dose trials, baseline characteristics of OAB patients with ≥ 1 urgency urinary incontinence (UUI) episodes/24 h who escalated from fesoterodine 4 mg to 8 mg were evaluated. Possible dose-escalation predictors (age; sex; previous antimuscarinic use; UUI, micturitions, and urgency episodes/24 h; race; body mass index; time to dose escalation; OAB duration) were compared in escalators versus non-escalators. Patients from fixed-dose trials with dose-escalator characteristics were identified (matched dose-escalator sample) to assess changes from baseline with fesoterodine 4 mg, 8 mg, and placebo.. In flexible-dose trials, significant predictors of fesoterodine dose escalation were younger age (≤ 65.8 years), greater number of baseline micturitions (≥ 13.1) and urgency episodes/24 h (≥ 10.9), greater OAB duration (≥ 9.1 years), and more frequent previous antimuscarinic use (58.3%), but not baseline UUI episodes/24 h. In the matched dose-escalator sample (fesoterodine 4 mg: n = 215; 8 mg: n = 198; placebo: n = 217), change from baseline in UUI episodes significantly improved with fesoterodine 8 mg versus 4 mg (P = 0.043) and with both doses versus placebo (P < 0.001). Dry mouth and constipation rates were higher with fesoterodine 8 mg.. Dose-escalator patients had a significantly greater UUI response with fesoterodine 8 mg versus 4 mg. Given the potential for adverse events, fesoterodine 4 mg is recommended to start; however, patients with UUI and identified predictors may benefit from initial treatment with fesoterodine 8 mg or rapid dose escalation.

Topics: Age Factors; Aged; Benzhydryl Compounds; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Propensity Score; Time Factors; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To compare the heart rate increase side effect of different antimuscarinic drugs used in overactive bladder (OAB).. Overall 341 patients were consecutively randomized to take seven different antimuscarinic drugs between January 2014 and June 2016 at three institutions, and 250 patients who completed the follow-up visits were accepted into this study. Ninety-one patients who never came to visits were excluded. Drugs were classified into two groups as selective (darifenacin hydrobromide, solifenacin succinate and oxybutynin hydrochloride) and non-selective (fesoterodine fumarate, tolterodine tartrate, trospium chloride and propiverine hydrochloride) antimuscarinic drugs. The cardiac pulse rates and the blood pressures were recorded during the baseline, first visit (1 week) and second visit (1 month). Data were compared for drugs and two groups (selective versus non-selective) by using ANOVA test.. Baseline characteristics were similar among the patients using different antimuscarinic drugs. Statistically significant increase in heart rate occurred in patients treated with non-selective antimuscarinic drugs compared to those treated with selective drugs (p < 0.001), and this increase was especially evident in patients treated with trospium chloride, tolterodine tartrate, fesoterodine fumarate and propiverine hydrochloride (p < 0.001, 0.003, 0.011 and 0.37, respectively). There was no statistical difference for the other side effects.. Our results showed that heart rate significantly increased in OAB patients treated with non-selective antimuscarinic drugs. Trospium chloride, tolterodine tartrate, fesoterodine fumarate and propiverine hydrochloride seem to have the most unfavorable properties with regard to increased heart rate side effect when compared to the other antimuscarinic drugs (darifenacin hydrobromide, solifenacin succinate and oxybutynin hydrochloride).

Topics: Adult; Aged; Benzhydryl Compounds; Benzilates; Benzofurans; Blood Pressure; Female; Heart Rate; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Nortropanes; Prospective Studies; Pyrrolidines; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive

To compare the efficacy of fesoterodine or mirabegron add-on therapy for persistent overactive bladder (OAB) symptoms despite silodosin monotherapy in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, in both subjective and objective aspects.. A total of 120 patients with persistent OAB symptoms despite silodosin monotherapy were randomized to receive add-on therapy with fesoterodine (4 mg/day) or mirabegron (50 mg/day) for 12 weeks. At week 12, changes from baseline in patients' subjective symptoms and voiding/storage functions, as assessed using the International Prostate Symptom Score (IPSS), OAB symptom score (OABSS), and urodynamic studies, were compared between the groups.. The final analysis included 50 and 52 patients in the fesoterodine and mirabegron groups, respectively. Although the IPSS and OABSS significantly improved in both groups, the fesoterodine (vs mirabegron) group showed significantly greater improvements in the OABSS-total (-2.8 vs -1.5, P = 0.004), IPSS-QOL (-1.5 vs -1.1, P = 0.04), and OABSS-urgency score (-1.5 vs -0.9, P = 0.008) at 12 weeks. Regarding storage functions, although both groups showed significant improvements, the fesoterodine group demonstrated greater improvements in the detrusor overactivity alleviation rate (52.6% vs 28.9%, P = 0.03). Voiding functions did not deteriorate in either group at 12 weeks; no significant inter-group differences were observed. Post-void residual urine significantly increased by 16 mL only in the fesoterodine group.. Add-on therapy of fesoterodine to silodosin was more effective than adding mirabegron to silodosin for improving OAB symptoms and storage functions, without deteriorating voiding symptoms or functions.

Topics: Acetanilides; Aged; Aged, 80 and over; Benzhydryl Compounds; Drug Therapy, Combination; Humans; Indoles; Male; Middle Aged; Prospective Studies; Prostatic Hyperplasia; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics; Urological Agents

To evaluate the association between pharmacologic therapy for urgency urinary incontinence (UUI) and sleep quality.. We conducted a planned secondary data analysis of sleep outcomes in a previously conducted multicenter, double-blind, 12-week randomized trial of pharmacologic therapy for urgency-predominant incontinence among community-dwelling women self-diagnosed using the 3-Incontinence Questions questionnaire. Participants (N=645) were assigned randomly to 4-8 mg antimuscarinic therapy daily or placebo. At baseline and 12 weeks, participants completed a validated voiding diary to evaluate incontinence and voiding symptoms, the Pittsburgh Sleep Quality Index to evaluate sleep quality, and the Epworth Sleepiness Scale to evaluate daytime sleepiness.. Mean (SD) age was 56 (±14) years, 68% were white, and 57% had poor sleep quality (Pittsburgh Sleep Quality Index score greater than 5). Mean frequency of any urinary incontinence and UUI was 4.6 and 3.9 episodes/d, respectively. After 12 weeks, women randomized to the antimuscarinic group reported greater decrease compared with the placebo group in UUI frequency (0.9 episodes/d; P<.001) and diurnal and nocturnal voiding frequency (P<.05). As compared with the placebo group, women in the antimuscarinic group also reported greater improvement in sleep quality (total Pittsburgh Sleep Quality Index score 0.48; P=.02) with greater improvement in sleep duration and sleep efficiency subscales (P<.05). The intervention did not affect daytime sleepiness.. Pharmacologic treatment of UUI is associated with decreased incontinence frequency and nocturia and improvement in overall sleep quality, sleep duration, and sleep efficiency.. ClinicalTrials.gov, NCT00862745.

Topics: Adult; Aged; Benzhydryl Compounds; Double-Blind Method; Female; Humans; Middle Aged; Muscarinic Antagonists; Self Report; Sleep; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge

Managing and preventing risk factors associated with cardiovascular and cerebrovascular impairment is well studied in able-bodied individuals. However, individuals with spinal cord injury (SCI) at or above the spinal segment T6 are prone to experience autonomic dysreflexia (AD) but also to suffer from neurogenic detrusor overactivity (NDO). Treatment of NDO would not only improve lower urinary tract function but could also reduce the severity and frequency of life-threatening episodes of AD. Fesoterodine, an antimuscarinic drug, has been successfully employed as a first-line treatment for detrusor overactivity in individuals without an underlying neurological disorder. Thus, our aim is to investigate the efficacy of fesoterodine to improve NDO and ameliorate AD in individuals with SCI.. This phase II, open-label exploratory, non-blinded, non-randomised, single-centre study will investigate the efficacy of fesoterodine to improve NDO and ameliorate AD in individuals with chronic SCI at or above T6. During screening, we will interview potential candidates (with a previous history of NDO and AD) and assess their injury severity. At baseline, we will perform cardiovascular and cerebrovascular monitoring (blood pressure (BP), heart rate and cerebral blood flow velocity) during urodynamics (UDS) and 24-hour ambulatory BP monitoring (ABPM) during daily life to assess severity and frequency of AD episodes (ie, maximum increase in systolic BP). The primary outcome is a reduction of artificially induced (during UDS) and spontaneous (during daily life) episodes of AD as a display of treatment efficacy. To answer this, we will repeat UDS and 24-hour ABPM during the last cycle of the treatment phase (12 weeks overall, ie, three cycles of 4 weeks each). At the end of each treatment cycle, participants will be asked to answer standardised questionnaires (AD symptoms and quality of life) and present bladder and bowel diaries, which will provide additional subjective information.. The University of British Columbia Research Ethics Boards (H15-02364), Vancouver Coastal Health Research Institute (V15-02364) and Health Canada (205857) approved this study. The findings of the study will be published in peer-reviewed journals and presented at national and international scientific meetings. This protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials and CONsolidated Standards Of Reporting Trials statements.. NCT02676154; Pre-results.

Topics: Adult; Autonomic Dysreflexia; Benzhydryl Compounds; Blood Flow Velocity; Blood Pressure; Cerebrovascular Circulation; Heart Rate; Humans; Muscarinic Antagonists; Quality of Life; Spinal Cord Injuries; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics

A recent study demonstrated improvement in nocturnal urgency in patients with overactive bladder when treated with fesoterodine. In the current study we aimed to determine which bladder diary parameters predict the response to fesoterodine in these patients.. Patients with nocturnal urgency completed a 2-week, single-blind placebo run-in followed by 1:1 double-blind randomization to 12 weeks of fesoterodine or placebo. We analyzed bladder diary parameter changes from baseline to week 12, including the actual number of night voids (total number of nocturia episodes), maximum voided volume, nocturnal bladder capacity, Nocturnal Bladder Capacity Index (NBCi) (actual number of night voids - nocturnal urine volume/maximum voided volume - 1), nocturnal urine volume, the nocturia index (nocturnal urine volume/maximum voided volume) and the nocturnal polyuria index (nocturnal urine volume/24-hour volume). Additionally, we analyzed OAB-q (Overactive Bladder Questionnaire) changes.. There was a linear relationship between the likelihood of being a responder for NBCi and the nocturia index. Responders had a significant decrease in nocturnal urine volume relative to baseline (-181.7 ml, p <0.01). Neither group showed a significant change in maximum voided volume relative to baseline. There was a significant decrease in NBCi and the nocturia index in responders (-0.82 and -0.61, respectively, each p <0.01). Responders demonstrated improvement in the OAB-q concern, coping, sleep, bother and total score metrics.. Patients with nocturnal urgency secondary to overactive bladder syndrome and low nocturnal bladder capacity with a mismatch between nocturnal urine production and bladder capacity may benefit from fesoterodine. Symptom improvement appears to be mediated by increases in typical rather than maximum nocturnal voided volumes. Symptom improvement was associated with improved quality of life.

Topics: Adult; Aged; Benzhydryl Compounds; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nocturia; Quality of Life; Retrospective Studies; Single-Blind Method; Treatment Outcome; Urinary Bladder, Overactive; Urination; Urological Agents

To assess the characteristics of tolterodine extended-release (ER) 4 mg responders and suboptimal responders (≤50% decrease in UUI episodes/24 h) among patients with overactive bladder (OAB), including urgency urinary incontinence (UUI), and identify predictors of a >50% UUI response with fesoterodine 8 mg in tolterodine suboptimal responders.. Adult patients with OAB symptoms for ≥6 months and ≥8 micturitions, and ≥2 and <15 UUI episodes/24 h at week -2 received open-label tolterodine ER 4 mg during a 2 week run-in. Suboptimal responders after tolterodine treatment (week 0) were randomized to fesoterodine (4 mg for 1 week, 8 mg for weeks 2-12) or placebo once daily. Post-hoc analyses compared the percentage change from week -2 to week 0 in UUI episodes/24 h in tolterodine responders versus suboptimal responders and identified significant predictors of a UUI response at week 12 with fesoterodine 8 mg among tolterodine suboptimal responders.. Of 897 patients, 610 (68%) were UUI suboptimal responders during the run-in period. UUI episodes/24 h at week -2 were similar in tolterodine responders and suboptimal responders (4.2 vs. 4.3), but responders showed a significantly greater median percentage decrease in UUI episodes/24 h after tolterodine treatment at week 0 (80.0% versus 15.3%; p < .0001). During double-blind treatment, the percentage of patients with a UUI response at week 12 was significantly greater with fesoterodine (69.9%) than placebo (57.0%; p = .0027). Fesoterodine (vs. placebo), no previous antimuscarinic use before tolterodine run-in, and less UUI severity at baseline were significant predictors of a UUI response.. For patients with OAB, including UUI, who were treated initially with tolterodine and showed a suboptimal UUI response, nearly 70% demonstrated a UUI response with second-line fesoterodine 8 mg. No antimuscarinic use before tolterodine and fewer baseline UUI episodes were significant predictors of a UUI response with fesoterodine.

Topics: Adult; Aged; Benzhydryl Compounds; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence

In clinical practice and in research patient-centred outcomes are often utilised to help improve communication between patients and clinicians and to help manage expectations from treatment. However, many of these goals are generic and do not adequately capture the details of day to day life that bother patients the most and that they hope will improve with therapy. This study aimed to understand what are the goals of patients with overactive bladder symptoms in the UK who were taking part in a clinical trial and to assess goal achievement.. This was a qualitative analysis of the patients goals recorded using the Self-Assessment Goal Achievement (SAGA) Questionnaire during the UK study assessing flexible dose fesoterodine in adults (SAFINA) trial. Free text patient goals were completed at baseline and an assessment of achievement was performed at the end of treatment. Grounded theory was used to develop themes and sub themes.. Three hundred and thirty-one patients completed the trial and 1137 open ended goals were set. Six themes emerged from the data including, OAB, other LUTS and finishing the task in hand with multiple subthemes noted.. By assessing and understanding what is important to the patient, it may help to tailor patient care and treatment and improve patient satisfaction.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Female; Goals; Humans; Male; Middle Aged; Patient Outcome Assessment; Patient Satisfaction; Quality of Life; Surveys and Questionnaires; Treatment Outcome; United Kingdom; Urinary Bladder, Overactive; Urological Agents; Young Adult

To evaluate the short-term and long-term effects of fesoterodine fumarate treatment which is used for overactive bladder (OAB) on pupil diameter (PD), intraocular pressure (IOP) and accommodation amplitude (AA).. Ophthalmic examination was performed before and after receiving medication (on the 30th and 90th day) on 120 eyes of 120 women whom were planned to begin anticholinergic treatment (fesoterodine fumarate, 4 mg/day, peroral) for OAB, prospectively. The changes in PD, IOP and AA were analyzed statistically.. The mean age of 120 women was 52.06 ± 9.39 years (30-70 years). The mean PD, IOP and AA values were 4.12 ± 0.61 mm (3.00-5.70 mm), 15.58 ± 1.74 mmHg (11-20 mmHg) 2.28 ± 1.26 Diopter (D) (0.50-5.50 D) at baseline; 4.68 ± 0.65 mm (3.20-5.80 mm), 16.11 ± 1.72 mmHg (11-20 mmHg), 1.68 ± 1.04 D (0.25-4.50 D) at 30th day; and 4.28 ± 0.58 mm (3.10-5.70 mm), 16.09 ± 1.96 mmHg (11-19 mmHg), 2.18 ± 1.19 D (0.50-5.00 D) at 90th day, respectively. Although increases in PD values and decreases in AA values were statistically significant (p < 0.001 for each), the changes in IOP values were not as such (p = 0.642). Visual complaint was not observed in any patient.. The newest anticholinergic medication in women with OAB increased the PD and decreased the AA statistically significantly. Clinically, it seems to be well-tolerated by the patient.

Topics: Accommodation, Ocular; Adult; Aged; Benzhydryl Compounds; Eye; Female; Humans; Intraocular Pressure; Middle Aged; Muscarinic Antagonists; Single-Blind Method; Tonometry, Ocular; Urinary Bladder, Overactive; Urological Agents

We investigated the long-term relationships between dry mouth, fluid intake and overactive bladder symptoms in women undergoing treatment with fesoterodine. We hypothesized that women who experienced dry mouth would increase their fluid intake and worsen their urinary symptoms.. We conducted a prospective ancillary study to a 9-month open-label trial of fesoterodine for women with urgency urinary incontinence. Fluid intake was measured and compared according to reported dry mouth. Multivariable analysis was used to study the interaction between dry mouth, fluid intake and urinary symptoms.. During the study 407 women without dry mouth significantly reduced their fluid intake (mean decrease 172.1 ml, median 118.3 ml, p = 0.02), while 91 women with dry mouth did not (mean decrease 95.8 ml, median 118.3 ml, p = 0.54). On univariable analysis a greater proportion of women who experienced dry mouth reported improvement in their urinary symptoms compared to women without dry mouth (60.5% vs 47.2%, p = 0.03). On multivariable analysis black women were less likely to report dry mouth (OR 0.4, 95% CI 0.2-0.9, p = 0.03) and older women were less likely to report improvement in urinary symptoms (OR 0.98, 95% CI 0.96-0.99, p = 0.003). Factors not associated with improvement in urinary symptoms on multiple regression were dry mouth, baseline fluid intake volume, change in fluid intake volume and caffeine intake volume.. In women with overactive bladder receiving fesoterodine dry mouth may prevent restriction of fluid intake but does not diminish treatment efficacy.

Topics: Benzhydryl Compounds; Dose-Response Relationship, Drug; Drinking; Female; Follow-Up Studies; Humans; Middle Aged; Mouth Diseases; Muscarinic Antagonists; Prospective Studies; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Treatment Outcome; Urinary Bladder, Overactive; Urination

The objective of this study is to investigate the combination effect of anti-muscarinic medication and topical vaginal estrogen in the treatment of overactive bladder (OAB) and female sexual dysfunction in postmenopausal women.. After IRB approval, 23 female subjects who met the entry criteria were randomized into two groups: (1) fesoterodine (Toviaz®, Pfizer, NY) with topical vaginal estrogen (Premarin®, Pfizer, NY) once daily or (2) fesoterodine once daily alone. If 4 mg fesoterodine was tolerated at 1-week, the dose was increased to 8 mg.. Primary endpoints were improvement in OAB symptom severity (Overactive Bladder Questionnaire, OAB-Q SF), improvement in OAB health-related quality of life (HRQL) (OAB-Q SF), and sexual function (Sexual Quality of Life-Female, SQOL-F) after 12 weeks. Secondary endpoint was change in total number of micturitions.. After 12-weeks, the combination group had a significant improvement in OAB symptom severity (p = 0.006), HRQL (p = 0.029), and SQOL-F (0.0003). The fesoterodine alone group also had significant improvement in OAB symptom severity (p < 0.0001), HRQL (p = 0.0002), and SQOL-F (p = 0.02). When compared directly to the fesoterodine alone group, the combination group after 12-weeks had a reduced OAB symptom severity (10 versus 23.3; p = 0.35), higher HRQL (96.9 versus 84.6; p = 0.75), and higher SQOL-F (99 versus 81; p = 0.098). The total number of micturitions over 3 d was significantly reduced in the combination group (45-26, p = 0.03) between baseline and 12-weeks.. The combined effect of fesoterodine and topical vaginal estrogen improved OAB symptoms and sexual function in postmenopausal women.

Topics: Administration, Intravaginal; Adult; Aged; Benzhydryl Compounds; Drug Therapy, Combination; Estrogens; Female; Humans; Middle Aged; Muscarinic Antagonists; Postmenopause; Quality of Life; Severity of Illness Index; Sexual Dysfunctions, Psychological; Sexuality; Surveys and Questionnaires; Urinary Bladder, Overactive

To investigate factors which may influence dose escalation of antimuscarinics for overactive bladder (OAB) in older patients and how dose escalation affects treatment efficacy.. A post hoc analysis of data from the 12-week randomized, placebo controlled phase of the SOFIA study investigating treatment with fesoterodine in older people with OAB. Predictors and outcomes in patients aged ≥65 years with OAB who did or did not choose to escalate from fesoterodine 4 to 8 mg before the first dose-escalation choice point (week 4) and at the end of the study (week 12) were assessed.. Variables which significantly increased likelihood of dose escalation were, at baseline, body mass index (OR: 1.06, 95% CI 1.01, 1.12; P = 0.0222), and male gender (OR: 2.06, 95% CI 1.28, 3.32; P = 0.0028) and at week 4, change from baseline in urgency episodes (OR: 1.12, 95% CI 1.05, 1.20; P = 0.0008), patient perception of bladder control (PPBC) (OR: 1.44, 95% CI 1.12, 1.84; P = 0.004). At week 12, dose escalation was associated with slightly reduced treatment outcomes compared to week 4 non-escalators.. No baseline disease related factor associated with dose escalation was identified. Magnitude of change in urgency episodes and reduction in PPBC at 4 weeks were associated with dose escalation. These data may be of use to healthcare providers as they allow judgement to be made in individual patients, allowing treatment decisions to be made. At end of treatment, improvements in efficacy and quality of life were achieved in both escalators and non-escalators.

Topics: Aged; Benzhydryl Compounds; Body Mass Index; Dose-Response Relationship, Drug; Female; Humans; Male; Muscarinic Antagonists; Sex Factors; Treatment Outcome; Urinary Bladder, Overactive

To determine whether levels of nerve growth factor (NGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) can be used to objectively assess overactive bladder syndrome (OAB) treatment outcome and to evaluate the effects of fixed-dose fesoterodine on OAB symptoms.. This study included 124 participants (62 patients with OAB and 62 controls) in Severance Hospital between 2010 and 2012. In patients with OAB, 4 mg fesoterodine was administered once daily. Repeated evaluations of putative biomarker levels, urine creatinine (Cr) levels, and questionnaire responses, including the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire (OAB q), were performed from baseline to 16 weeks.. Urinary levels of NGF/Cr (OAB: 1.13±0.9 pg/mg; control: 0.5±0.29 pg/mg) and HB-EGF/Cr (OAB: 8.73±6.55 pg/mg; control: 4.45±2.93 pg/mg) were significantly higher in subjects with OAB than in controls (p<0.001). After 16 weeks of fixed-dose fesoterodine treatment, urinary NGF/Cr levels (baseline: 1.13±0.08 pg/mg; 16 weeks: 0.60±0.4 pg/mg; p=0.02) and HB-EGF/Cr levels significantly decreased (baseline: 8.73±6.55 pg/mg; 16 weeks: 4.72±2.69 pg/mg; p=0.03, respectively). Both the OABSS and OAB q scores improved (p<0.001). However, there were no a statistically significant correlations between these urinary markers and symptomatic scores.. Urinary levels of NGF and HB-EGF may be potential biomarkers for evaluating outcome of OAB treatment. Fixed-dose fesoterodine improved OAB symptoms. Future studies are needed to further examine the significance of urinary NGF and HB-EGF levels as therapeutic markers for OAB.

Topics: Adult; Benzhydryl Compounds; Biomarkers; Case-Control Studies; Creatinine; Female; Heparin-binding EGF-like Growth Factor; Humans; Male; Middle Aged; Nerve Growth Factor; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics

Several studies have suggested that phosphodiesterase type 5 inhibitors (5-PDEi) show a potential therapeutic use in the treatment of overactive bladder (OAB) and male lower urinary tract symptoms (LUTS). The aim of this study was to evaluating the efficacy on OAB symptoms, impact on quality of life and sexual function of tadalafil 5mg once daily in older patients versus fesoterodine 8 mg.. 108 consecutive patients diagnosed with OAB were divided into 2 groups: Group A: 56 patients treated with tadalafil 5 mg once daily; Group B: 52 patients treated with fesoterodine 8 mg, both groups treated for a period of 12 weeks. Eligible patients were men aged ≥ 65 years with OAB symptoms, including urgency and increased frequency during a period of ≥ 1 year and urgency urinary incontinence during a period of ≥ 6 months before enrolment. Patients were asked to complete the 3-day voiding diary prior each scheduled visit at weeks 0, 4 and 12. During these visits, they were administered: Overactive Bladder Symptom Score (OABSS), International Prostate Symptoms Score (IPSS), International Index of Erectile Function (IIEF-5) and Quality of life (QoL).. Not statistically significant differences emerged between the two groups at baseline, both patient groups had similar age and BMI; in each treatment group, the proportion of men ≥ 75 years was approximately 65%. From the results of our study, we can say that a treatment once a day with tadalafil improves not only significantly: micturition/24 hours (p < 0.001), urgency episodes/24 hours (p < 0.003), and urge incontinence episodes (p < 0.001) compared to fesoterodine treatment, but also the quality of life (p < 0.001) and sexual function (p < 0.001) in older patients.. These analyses demonstrate that tadalafil 5 mg once daily vs. fesoterodine 8 mg is efficacious in the treatment of the symptoms of OAB in older adults, improving also the quality of life and sexual and social life.

Topics: Aged; Benzhydryl Compounds; Humans; Male; Phosphodiesterase 5 Inhibitors; Quality of Life; Tadalafil; Urinary Bladder, Overactive; Urological Agents

Anticholinergics are currently the mainstay for the management of overactive bladder (OAB). However, low drug adherence has been noted with these medications. The aim of this study was to determine whether a health education intervention (HEI) could improve drug persistence with anticholinergics in OAB patients.. We enrolled 682 OAB patients who were randomly distributed into either the HEI plus fesoterodine (HEI) group or the fesoterodine alone (control) group. The HEI consists of four education sections: understanding OAB disease, dietary control, bladder training and understanding anticholinergics. The primary end-point was the difference in drug persistence between the HEI and control groups at 24 weeks. Persistence was defined as a gap ≤ 30 days between successive prescription pills.. Among the 682 patients, 210 (30.8%) completed 24 weeks of study. Persistence of the HEI group at 6 months was not statistically higher than that of the control group (40.4% vs. 34.9%, p = 0.181). Compliance at 6 months was also similar between the two groups (38.5% vs. 32.5%, p = 0.128). Using OAB symptom score questionnaire, the efficacy of the two groups was not different at each follow-up (p > 0.05). The global response was similar between the two groups. However, the HEI group was more satisfied with treatment than the control group (p = 0.034). The most common reason for discontinuation was satisfaction with the treatment so that they did not need to follow-up, followed by inadequate efficacy in both groups. Adverse events were reported in 12.3% of patients.. The health education intervention was not effective to increase drug persistence in OAB patients on anticholinergics.

Topics: Adult; Aged; Benzhydryl Compounds; Cholinergic Antagonists; Female; Humans; Medication Adherence; Middle Aged; Muscarinic Antagonists; Patient Education as Topic; Quality of Life; Surveys and Questionnaires; Urinary Bladder, Overactive

To compare the use of solifenacin and fesoterodine in treatment of overactive bladder (OAB).. This prospective study was conducted on patients diagnosed with OAB who presenting to the Department of Obstetrics and Gynecology and Urology, School of Medicine, Kahramanmaraş Sütçü İmam University, Kahramanmaraş, Turkey between October 2013 and August 2014. Patients were randomized into 2 groups. Group 1 (n=60) received 5 mg solifenacin per day, while Group 2 (n=59) received 4 mg fesoterodine per day. All the patients' OAB symptom scores (OABSS) in weeks 0, 4, and 12 were recorded. In addition, treatment costs and side effects of the drugs were evaluated.. Average OABSS (score 1) was determined as: 9.5 ± 2.8 for Group 1 and 10.7 ± 1.8 for Group 2 at week 0; 2.2 ± 1.2 (Group 1) and 2.4 ± 1.3 (Group 2) at week 4 (score 2); and 1.3 ± 0.5 for Group 1 and 1.3 ± 0.6 for Group 2 at week 12 (score 3). In addition, no statistically significant difference was found between the scores (p=0.062 (score 1), p=0.464 (score 2), and p=0.527 (score 3). The discontinuation rate of medication due to its side effects was 0 (0%) for Group 1, and 6 (10.2%) for Group 2. Intragroup changes in the scores 1-2, 1-3, and 2-3 values was statistically significant in both groups (p less than 0.001).. No significant difference was found between the OABSS of these 2 drugs. However, discontinuation of drugs due to side effects was more frequent in fesoterodine.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Middle Aged; Muscarinic Antagonists; Prospective Studies; Solifenacin Succinate; Treatment Outcome; Urinary Bladder, Overactive

To assess the long-term safety, tolerability, and efficacy of flexible-dose fesoterodine in elderly patients with OAB.. Patients aged ≥65 years who completed a 12-week, randomized, double-blind, placebo-controlled trial were eligible for the 12-week, open-label (OL) extension phase. Patients who received double-blind placebo started on fesoterodine 4 mg and could increase to 8 mg after 4 or 8 weeks of OL treatment, while fesoterodine-treated patients continued on their double-blind dose; only one dose escalation or de-escalation was permitted. Discontinuations and adverse events (AEs) were monitored, and patients completed 3-day bladder diaries and patient-reported outcomes at the beginning and end of the 12-week OL phase.. Six hundred fifty-four patients entered the 12-week OL extension (mean age 72 years; 52% women). AEs were reported by 30.7% and 48.1% of patients who had received double-blind fesoterodine and placebo, respectively; 1.9% and 9.4%, discontinued due to AEs, respectively. Patients who received double-blind fesoterodine maintained their efficacy response. After 12 weeks of OL treatment, efficacy outcomes in patients who received double-blind placebo were similar to those who had received double-blind fesoterodine. On average, the efficacy response was maintained for the duration of the study.. Fesoterodine was well tolerated and improvements in OAB symptoms and quality of life measures were not diminished with longer-term treatment of patients aged ≥65 years.

Topics: Age Factors; Aged; Aged, 80 and over; Benzhydryl Compounds; Double-Blind Method; Europe; Female; Humans; Male; Muscarinic Antagonists; Prospective Studies; Quality of Life; Time Factors; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urinary Incontinence; Urination

To investigate the efficacy of fesoterodine vs placebo on nocturia, sleep disturbance, and sleep-related quality of life (QoL) in patients with overactive bladder and nocturia.. This posthoc analysis used data from a 12-week, randomized, placebo-controlled trial of fesoterodine 4 and 8 mg per day in Asian adults reporting ≥8 micturitions and ≥1 urgency urinary incontinence episodes per 24 hours at baseline. Patients who reported ≥1 nocturnal micturition/24 h were included in this analysis. Efficacy variables included change from baseline to week 12/end of treatment in nocturnal micturitions/24 h, nocturnal voided volume/micturition, and hours of undisturbed sleep. Sleep-related QoL was assessed using King's Health Questionnaire Sleep/Energy domain. Treatment comparisons were made using analysis of covariance.. Among 555 patients, reductions in nocturnal micturitions with fesoterodine 4 mg (-0.63) and 8 mg (-0.77) were numerically greater vs placebo (-0.56), but differences were not significant (P >.05). When patients with a nocturnal polyuria index >33% were excluded, the decrease in nocturnal micturitions was significantly greater with fesoterodine 8 mg vs placebo (-0.24; P = .031). Increases in nocturnal voided volume/micturition were significantly greater with fesoterodine 4 (38.07 mL; P = .013) and 8 mg (42.05 mL; P <.001) vs placebo (14.89 mL). Hours of undisturbed sleep was significantly longer with fesoterodine 4 mg vs placebo (80 vs 54 minutes; P = .032); improvement in King's Health Questionnaire Sleep/Energy scores was significantly greater with fesoterodine 4 (P = .034) and 8 mg (P = .019) vs placebo.. These results suggest that fesoterodine may reduce nocturnal micturitions and improve sleep quality and QoL in overactive bladder patients with nocturia.

Topics: Adult; Aged; Aged, 80 and over; Asian People; Benzhydryl Compounds; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Nocturia; Quality of Life; Sleep; Sleep Wake Disorders; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents; Young Adult

To assess the superiority of fesoterodine 8 mg vs 4 mg for improvement in urgency urinary incontinence (UUI) episodes and other diary variables, diary-dry rate (proportion of patients with >0 UUI episodes on baseline diary and 0 UUI episodes on post-baseline diary), and improvements in measures of symptom bother, health-related quality of life (HRQL), and other patient-reported outcomes (PROs).. This was a 12-week, randomised, double-blind, placebo-controlled, multinational trial of men and women aged ≥18 years with overactive bladder (OAB) symptoms including UUI (ClinicalTrials.gov ID NCT01302067). Patients were randomised (2:2:1) to receive fesoterodine 8 mg, fesoterodine 4 mg, or placebo once daily; those randomised to fesoterodine 8 mg started with fesoterodine 4 mg once daily for 1 week, then 8 mg once daily for the remaining 11 weeks. Patients completed bladder diaries at baseline and weeks 4 and 12 and the Patient Perception of Bladder Condition (PPBC), Urgency Perception Scale (UPS), and Overactive Bladder Questionnaire (OAB-q) at baseline and week 12. The primary endpoint was change from baseline to week 12 in UUI episodes per 24 h.. At week 12, patients receiving fesoterodine 8 mg (779 patients) had significantly greater reductions from baseline in UUI episodes, micturitions, and urgency episodes than patients receiving fesoterodine 4 mg (790) or placebo (386); diary-dry rate was significantly higher in the fesoterodine 8-mg group vs the fesoterodine 4-mg and placebo groups (all P < 0.05). At week 12, patients receiving fesoterodine 8 mg also had significantly greater improvements in scores on the PPBC, UPS, and all OAB-q scales and domains than patients receiving fesoterodine 4 mg or placebo (all P < 0.01). Patients receiving fesoterodine 4 mg had significantly greater improvements in UUI episodes, urgency episodes, and micturitions; significantly higher diary-dry rates; and significantly greater improvement in PPBC scores and OAB-q scores than patients receiving placebo (all P < 0.05). Dry mouth was the most commonly reported adverse event (AE) in the fesoterodine groups (placebo group, 3.4%; fesoterodine 4-mg group, 12.9%; fesoterodine 8-mg group, 26.1%); most cases were mild or moderate in all treatment groups. Rates of serious AEs and discontinuations due to AEs were low in all groups.. In a 12-week, prospectively designed, superiority trial, fesoterodine 8 mg showed statistically significantly superior efficacy vs fesoterodine 4 mg and placebo, as measured by reductions in UUI episodes and other diary variables, diary-dry dry rate, and improvements in measures of symptom bother, HRQL, and other PROs; clear evidence of dose-dependent efficacy is unique to fesoterodine among antimuscarinics and other oral agents for the treatment of OAB. Fesoterodine 4 mg was significantly more effective than placebo on all outcomes except for improvements in UPS scores. These data support the benefit of having two doses of fesoterodine in clinical practice, with the recommended starting dose of 4 mg for all patients and the fesoterodine 8-mg dose available for patients who require a higher dose to achieve optimal symptom relief.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Double-Blind Method; Drug Administration Schedule; Female; Health Status; Humans; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urological Agents

To determine clinical and demographic characteristics associated with antimuscarinic treatment response using a regression model.. Adults with overactive bladder (OAB) symptoms for >3 months and ≥ 1 urgency urinary incontinence (UUI) episode and ≥ 8 micturitions per 24 hours at baseline were randomized to fesoterodine (8 mg), tolterodine extended-release (4 mg), or placebo in two 12-week, double-blind, head-to-head studies. Fesoterodine-treated patients received 4 mg/d during the first week and 8 mg/d thereafter. Patients completed 3-day bladder diaries and the Overactive Bladder Questionnaire at baseline and week 12. Pooled data for changes from baseline to week 12 in winsorized UUI episodes, micturitions, and urgency episodes per 24 hours and Overactive Bladder Questionnaire Symptom Bother and health-related quality of life scores were analyzed posthoc using a regression model that selects outcome predictors from baseline values and patient characteristics while retaining baseline values and treatment, with stepwise inclusion of significant covariates and assessment of treatment interactions. Logistic regression was used for analysis of diary-dry rates.. Younger age, lack of previous antimuscarinic treatment, shorter duration of OAB diagnosis, and female gender were common predictors of larger changes in outcomes from baseline to week 12. Baseline measures often interacted with treatment, such that poorer baseline outcomes were predictive of larger treatment differences. Longer duration since OAB diagnosis predicted greater treatment differences for UUI episodes and in diary-dry rate, and increased age predicted greater treatment differences for micturitions.. Symptom severity and duration, age, gender, and previous antimuscarinic pharmacotherapy impact the response to antimuscarinic treatment.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; Logistic Models; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prognosis; Tolterodine Tartrate; Urinary Bladder, Overactive

This analysis was conducted to investigate factors that affect 5-hydroxymethyl tolterodine (5-HMT) pharmacokinetics after administration of fesoterodine sustained release tablets to Westerners and East Asians. Ten pharmacokinetic studies and three efficacy/safety studies in overactive bladder (OAB) patients were pooled for the population pharmacokinetic analysis. The plasma 5-HMT concentration data were described by a 1-compartment model with first order absorption and a lag time. Creatinine clearance (CLCR), hepatic impairment, CYP2D6 genotype, and concomitant medication with CYP3A inhibitor/inducer were identified as influential covariates. It was estimated that decreasing of CLCR from 80 to 15 mL/min resulted in a 39.5% reduction in 5-HMT apparent oral clearance (CL/F). Hepatic impairment, CYP2D6 poor metabolizer, and CYP3A inhibitor were estimated to reduce CL/F by about 60%, 40%, and 50%, respectively. CYP3A inducer resulted in about fourfold increase in CL/F. Although sex and Japanese ethnicity were selected as covariates on CL/F, each resulted in only about 10% decrease and increase of CL/F, respectively. Of the influential covariates of 5-HMT CL/F, CLCR, hepatic impairment, CYP2D6 genotype, and concomitant medication with CYP3A inhibitor/inducer were of significance, whereas sex and Japanese ethnicity covariates were considered not to have clinically significant impact on exposures of 5-HMT.

Topics: Adult; Aged; Aged, 80 and over; Asian People; Benzhydryl Compounds; Creatinine; Cresols; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Delayed-Action Preparations; Female; Genotype; Humans; Ketoconazole; Liver Diseases; Male; Middle Aged; Models, Biological; Muscarinic Antagonists; Rifampin; Tablets; Urinary Bladder, Overactive; Urological Agents; White People; Young Adult

To compare the effects of additional educational material on treatment satisfaction of overactive bladder (OAB) patients treated with a muscarinic receptor antagonist.. In an observational study of OAB patients being treated by their physician with fesoterodine for 4 months (FAKTEN study), sites were randomised to providing standard treatment or additional educational material including the SAGA tool. Patient satisfaction was assessed by three validated patient-reported outcomes including the Treatment Satisfaction Question. Because of premature discontinuation of the study, descriptive statistical analysis was performed.. A total of 431 and 342 patients received standard treatment or additional educational material, respectively. At study end, 76.1% [95% CI = 71.3, 80.4] of patients with standard care and 79.6% [95% CI = 74.4, 84.1] with additional SAGA tool were satisfied with treatment (primary end-point). Comparable outcomes with and without the additional educational material were also found in various patient subgroups, at the 1-month time point, and for the other patient-reported outcomes. A notable exception was the subgroup of treatment-naïve patients in which the percentage of satisfied patients was 77.2% vs. 89.5% with standard treatment and additional SAGA tool, respectively (post hoc analysis).. In an observational study, most overactive bladder patients were satisfied with fesoterodine treatment. Because of the small sample size, the study does not support or refute the hypothesis that adding the SAGA tool will improve patient satisfaction with treatment. The potential effect of additional educational material in treatment-naïve patients warrants further dedicated studies.

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Female; Humans; Male; Middle Aged; Observational Studies as Topic; Patient Medication Knowledge; Patient Satisfaction; Urinary Bladder, Overactive

To assess fesoterodine 8 mg efficacy over time and vs. placebo in subjects with overactive bladder (OAB) who responded suboptimally to tolterodine extended release (ER) 4 mg.. In a 12-week, double-blind trial, subjects with self-reported OAB symptoms for ≥ 6 months, mean of ≥ 8 micturitions and ≥ 2 to < 15 urgency urinary incontinence (UUI) episodes/24 h, and suboptimal response to tolterodine ER 4 mg (defined as ≤ 50% reduction in UUI episodes during 2-week run-in) were randomised to fesoterodine (4 mg for 1 week, 8 mg for 11 weeks) or placebo once daily. Change from baseline to week 12 in UUI episodes (primary end-point) was analysed in step-wise fashion: first, baseline vs. week 12 for fesoterodine; if significant, then change from baseline to week 12 for fesoterodine vs. placebo.. By week 12, subjects receiving fesoterodine 8 mg had significantly greater improvement from baseline vs. placebo in UUI episodes, urgency episodes and scores on the Patient Perception of Bladder Control, Urgency Perception Scale and OAB Questionnaire Symptom Bother and Health-Related Quality of Life scales and domains (all p < 0.05). 50% and 70% UUI responder rates were also significantly higher with fesoterodine 8 mg vs. placebo at week 12 (p < 0.05). Dry mouth (placebo, 4%, 12/301; fesoterodine, 16.6%, 51/308) and constipation (placebo, 1.3%, 4/301; fesoterodine, 3.9%, 12/308) were the most frequent adverse events.. Subjects who responded suboptimally to tolterodine ER 4 mg showed significant improvements in UUI and other OAB symptoms and patient-reported outcomes, with good tolerability, during treatment with fesoterodine 8 mg vs. placebo.

Topics: Adult; Aged; Benzhydryl Compounds; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Quality of Life; Surveys and Questionnaires; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

Adherence with oral medication for overactive bladder syndrome is suboptimal. To improve adherence, the YourWay plan was developed to assist patients and health care providers in defining treatment expectations and facilitating communication.. To evaluate medication adherence among patients with overactive bladder syndrome enrolled in the YourWay patient support plan, patient adoption of behavioral interventions, patient satisfaction with the plan, and physician experience with the plan.. In this 13-week, single-arm, open-label, multicenter, noninterventional study, fesoterodine-naïve patients received a prescription for fesoterodine 4 or 8 mg and a packet including a 14-day fesoterodine sample, educational materials, and progress tracker. Patients registered for the YourWay plan, which included an educational resource kit, interactive voice-response calls, and optional online and mail support. The primary end point was the proportion of patients who filled a prescription for a ≥ 90-day supply of fesoterodine within 90 days of enrollment. Secondary end points were the proportion of patients who filled ≥ 1 prescription and ≥ 2 prescriptions (post hoc), patient evaluation of their experience and satisfaction with the YourWay plan, and differences between prescription fillers and nonfillers in plan adoption and assessment (post hoc). We surveyed an independent sample of physicians to assess their experience with YourWay.. Of 500 study completers, 10.4% filled a prescription for a ≥ 90-day supply of fesoterodine. Of those filling a prescription, 26.2% filled ≥ 1 prescription and among those, 61.0% refilled their prescription at least once. Many behavioral recommendations were adopted by 82% to 94% of patients. Fillers were more likely to take fesoterodine as directed, whereas adoption of behavioral recommendations or plan satisfaction did not differ between fillers and nonfillers. Most patients reported that the plan was informative and feasible to implement, and that they were satisfied with various aspects of the plan. Physicians also reported positive experiences.. Most patients adopted YourWay components and viewed the plan positively, although adherence remained a challenge.

Topics: Aged; Attitude of Health Personnel; Benzhydryl Compounds; Drug Utilization; Humans; Medication Adherence; Middle Aged; Patient Education as Topic; Patient Satisfaction; Physicians; Practice Patterns, Physicians'; Urinary Bladder, Overactive; Urological Agents

To determine the course of overactive bladder (OAB) symptoms after 4 weeks of no treatment following a 12-week study of the efficacy and safety of flexible-dose fesoterodine in patients with OAB who were enrolled in the UK healthcare system. There are limited data available on the natural time course of OAB symptoms after the cessation of treatment.. In the open-label UK Study Assessing Flexible-dose Fesoterodine in Adults trial, patients aged ≥18 years with self-reported OAB symptoms for ≥3 months, a mean of at least eight micturitions per 24 h and three or more urgency episodes per 24 h on a 3-day bladder diary at baseline, and at least moderate bladder-related problems reported on the Patient Perception of Bladder Condition (PPBC) at baseline, were treated with fesoterodine for 12 weeks. All patients received fesoterodine 4 mg once daily for the first 4 weeks, at which time they could choose to increase the dose to 8 mg once daily, based on a discussion of treatment efficacy and tolerability with the investigator, or they could remain on fesoterodine 4 mg for the remaining 8 weeks. The 12-week treatment period was followed by a 4-week follow-up period of no fesoterodine treatment. Patients completed 3-day bladder diaries and the PPBC at baseline, week 4, end of treatment (week 12) and end of the follow-up period (week 16); the King's Health Questionnaire at baseline, end of treatment (week 12) and end of the follow-up period (week 16); and the Benefit, Satisfaction and Willingness to Continue questionnaire at week 12.. After 12 weeks of fesoterodine treatment, patients had clinically meaningful improvements in bladder diary variables and King's Health Questionnaire domains; 79% (254/322) of patients reported an improvement on the PPBC. After 4 weeks of no treatment, most patients deteriorated back to week 4 levels or worse on all bladder diary and patient-reported outcomes. Patients who expressed a benefit from fesoterodine treatment, satisfaction with their treatment or a willingness to continue treatment showed greater improvement from baseline to week 12 and greater deterioration from week 12 to week 16 than patients who did not respond positively on the Benefit, Satisfaction and Willingness to Continue questionnaire. Both men and women showed a meaningful deterioration in bladder diary variables and patient-reported outcomes at week 16; baseline symptom severity, age and week 4 dose escalation status did not appear to affect outcome deterioration at week 16.. At 4 weeks after fesoterodine was discontinued, patients showed an increase in the frequency of OAB symptoms, an increase in the severity of bladder-related problems and a reduction in health-related quality of life. Many patients with OAB who respond to antimuscarinics may require treatment for more than 12 weeks because symptoms recur as early as 4 weeks after the cessation of therapy.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Female; Follow-Up Studies; Humans; Male; Middle Aged; Quality of Life; Retrospective Studies; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics; Withholding Treatment; Young Adult

To assess the efficacy of fesoterodine 8 mg vs extended-release (ER) tolterodine 4 mg for overactive bladder (OAB) symptoms in terms of patient-reported outcomes in women and in men.. Pooled data from two 12-week, randomized, double-blind, double-dummy studies were analysed. Participants eligible for the studies were ≥18 years old, had self-reported OAB symptoms for ≥3 months in 3-day baseline diaries and had ≥8 micturitions and ≥1 urgency urinary incontinence (UUI) episode per 24 h. Individuals were randomized to fesoterodine (4 mg for 1 week then 8 mg for 11 weeks), ER tolterodine (4 mg), or placebo. Changes from baseline in 3-day bladder diary variables and scores from the Patient Perception of Bladder Condition (PPBC), Urgency Perception Scale (UPS), and Overactive Bladder Questionnaire (OAB-q), were assessed, as was the 'diary-dry' rate (the proportion of subjects with >0 UUI episodes according to baseline diary and no UUI episodes according to post-baseline diary). The primary endpoint was the change from baseline to week 12 in UUI episodes.. At week 12, women showed significantly greater improvement with fesoterodine 8 mg (n = 1374) than with ER tolterodine 4 mg (n = 1382) and placebo (n = 679) in UUI episodes (primary endpoint), micturition frequency, urgency episodes, and all other diary endpoints (except nocturnal micturitions versus ER tolterodine), and also in scores on the PPBC, UPS, and all OAB-q scales and domains (all P < 0.005). Diary-dry rates in women were significantly greater with fesoterodine (63%) than with tolterodine (57%; P = 0.002) or placebo (48%; P < 0.0001). In men, there were no significant differences in improvement in UUI episodes between any treatment groups at week 12. Improvements in men were significantly greater with fesoterodine 8 mg (n = 265) than with ER tolterodine (n = 275) for severe urgency and the OAB-q Symptom Bother domain and were also significantly greater with fesoterodine than with placebo (n = 133) for micturition frequency, urgency episodes, severe urgency episodes, PPBC responses and scores on all OAB-q scales and domains at week 12 (all P < 0.04). The most frequently reported treatment-emergent adverse events in both genders were dry mouth (women: fesoterodine, 29%; ER tolterodine, 15%; placebo, 6%; men: fesoterodine, 21%; ER tolterodine, 13%; placebo, 5%) and constipation (women: fesoterodine, 5%; ER tolterodine, 4%; placebo, 2%; men: fesoterodine, 5%; ER tolterodine, 3%; placebo, 1%). Urinary retention rates were low in women (fesoterodine, <1%; ER tolterodine, <1%; placebo, 0%) and men (fesoterodine, 2%; ER tolterodine <1%; placebo, 2%).. This analysis supports the superiority of fesoterodine 8 mg over ER tolterodine 4 mg on diary endpoints, including UUI, symptom bother and health-related quality of life in women. In men, fesoterodine 8 mg was superior to ER tolterodine 4 mg for improving severe urgency and symptom bother.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Tolterodine Tartrate; Urinary Bladder, Overactive; Young Adult

Our objective was to compare the efficacy and safety of imidafenacin over fesoterodine in patients with overactive bladder (OAB).. This study is a randomised, double-blind, parallel-group, fesoterodine-controlled study in patients with continuous OAB symptoms for ≥ 3 months, daily mean voiding frequency (DMVF) ≥ 8, and daily mean urgency or urgency incontinence frequency ≥ 2. A twice-daily 0.1 mg imidafenacin with placebo, or once-daily 4 mg fesoterodine with placebo were administered for 12 weeks. The primary efficacy end-point was the difference in DMVF at 12 weeks. The secondary efficacy end-points were differences in daily mean: (i) voiding frequency at 4 and 8 weeks; (ii) urgency frequency; (iii) urgency incontinence frequency; (iv) incontinence frequency; (v) nocturia frequency; and (vi) quality of life score. The variables for safety analysis were adverse events, vital signs, residual urine volume and clinical laboratory tests. An efficacy analysis was conducted in per-protocol patients and the safety analysis was conducted in all randomised patients.. The differences in DMVF at 12 weeks were -3.38 ± 3.63 and -2.45 ± 3.73 in the imidafenacin and fesoterodine groups, respectively, and the difference was not significant between the two groups. Imidafenacin was non-inferior to fesoterodine, and the lower limit of 95% two-sided confidence intervals was -0.53. The other six secondary end-points and variables for safety analysis showed no difference between the two groups.. Imidafenacin was non-inferior to fesoterodine in terms of efficacy, and showed no significant difference in terms of safety.

Topics: Analysis of Variance; Benzhydryl Compounds; Double-Blind Method; Drug Administration Schedule; Female; Health Status; Humans; Imidazoles; Male; Middle Aged; Muscarinic Antagonists; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Awakening from sleep to urinate is the hallmark of nocturia, a condition that impacts several facets of health related quality of life and for which current therapy is suboptimal. Given the paucity of prospective data on antimuscarinics for the management of nocturia, we investigated the efficacy and safety of flexible dose fesoterodine for the treatment of nocturnal urgency in subjects with nocturia and overactive bladder.. Subjects with 2 to 8 nocturnal urgency episodes per 24 hours began a 2-week, single-blind, placebo run-in followed by 1:1 randomization to 12 weeks of double-blind treatment with fesoterodine (4 mg daily for 4 weeks with an optional increase to 8 mg) or placebo using predefined criteria for nocturnal urgency episodes, nocturnal urine volume voided and total 24-hour urine volume voided. The primary end point was change from baseline to week 12 in the mean number of micturition related nocturnal urgency episodes per 24 hours.. Overall 963 subjects were randomized from 2,990 screened, and 82% of subjects treated with fesoterodine and 84% of those treated with placebo completed the study. Significant improvements in the primary end point (-1.28 vs -1.07), in nocturnal micturitions per 24 hours (-1.02 vs -0.85) and in nocturnal frequency urgency sum (-4.01 vs -3.42) were observed with fesoterodine vs placebo (all p ≤0.01). Health related quality of life measures (overactive bladder questionnaire Symptom Bother -20.1 vs -16.5, sleep 22.3 vs 19.9 and other domains; all p <0.05) were improved with fesoterodine.. To our knowledge this is the first prospective study to assess antimuscarinic efficacy for reducing nocturnal urgency. Flexible dose fesoterodine significantly reduced nocturnal urgency episodes vs placebo in subjects with overactive bladder.

Topics: Adult; Benzhydryl Compounds; Double-Blind Method; Female; Humans; Male; Nocturia; Prospective Studies; Urinary Bladder, Overactive

To assess the efficacy and safety of flexible-dose fesoterodine in elderly adults with overactive bladder (OAB).. Twelve-week, randomized, double-blind, placebo-controlled trial.. Sixty-one outpatient clinics in Europe, Israel, and Turkey.. Seven hundred ninety-four individuals aged 65 and older (47% male) with OAB symptoms for 3 months or longer, mean of eight or more micturitions and three or more urgency episodes per 24 hours, at least some moderate problems on Patient Perception of Bladder Condition (PPBC), and Mini-Mental State Examination (MMSE) score of 20 or greater.. Participants were randomized to fesoterodine or placebo for 12 weeks, with stratification according to age (>75 vs ≤ 75) and dosing time (morning vs evening). Participants receiving fesoterodine started on 4 mg and could increase to 8 mg at week 4 or 8 and de-escalate to 4 mg at week 8 (sham escalation for placebo).. Changes from baseline in bladder-diary variables (primary endpoint, urgency episodes) and patient-reported outcomes including OAB Questionnaire, Treatment Benefit Scale (TBS), PPBC, Urgency Perception Scale (UPS), and OAB Satisfaction Questionnaire (OAB-S); all observed or reported adverse events.. By week 8, 64% of fesoterodine-treated and 71% of placebo-treated participants opted for dose escalation. At week 12, the fesoterodine group had statistically significantly greater improvement than the placebo group in urgency episodes, micturitions, nocturnal micturitions, incontinence pad use, and OAB Questionnaire scores but not urgency urinary incontinence episodes. Responder rates on TBS, PPBC, UPS, and OAB-S were statistically significantly higher with fesoterodine. Improvements in most diary variables and participant-reported outcomes were greater with fesoterodine than placebo in participants in both age groups and when administered in the morning and evening. Rates of dry mouth and constipation were 34% and 9% with fesoterodine and 5% and 3% with placebo, respectively. Rates of adverse events and discontinuations were generally similar in participants in both age groups. There was no change in MMSE score.. Fesoterodine was associated with significantly greater improvements in most diary variables and participant-reported outcomes than placebo and was generally well tolerated in older people.

Topics: Aged; Aging; Benzhydryl Compounds; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Retrospective Studies; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder, Overactive; Urination

Study Type - Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Male lower urinary tract symptoms are often attributed to bladder outlet obstruction secondary to benign prostatic hyperplasia and treated with drugs targeting the prostate. However, many men with storage lower urinary tract symptoms may not respond adequately to these agents. Antimuscarinics, with or without an α-blocker, may be effective for the treatment of the storage symptoms of overactive bladder in some men. Flexible-dose fesoterodine as an add-on treatment significantly improved urinary frequency and symptom bother, but not urgency episodes (primary endpoint), versus add-on placebo and was well tolerated in men with persistent overactive bladder symptoms despite receiving α-blocker.. • To evaluate flexible-dose fesoterodine vs placebo in men with persistent overactive bladder (OAB) symptoms despite receiving α-blocker treatment. • This was a double-blind, 12-week, flexible-dose trial. • Men with persistent storage symptoms (≥ 8 micturitions and ≥ 3 urgency episodes per 24 h) after receiving an α-blocker for ≥ 6 weeks were randomized to add-on fesoterodine 4 mg or placebo, with optional dose escalation to 8 mg at week 4 and reduction back to 4 mg at week 8 (or matching placebo adjustments). • Subjects completed 3-day diaries, International Prostate Symptom Score (IPSS), Overactive Bladder Questionnaire (OAB-q), Patient Perception of Bladder Condition (PPBC), and Urgency Perception Scale (UPS) at baseline and weeks 4 and 12.. • A total of 943 men were randomized and received at least one dose of study treatment (fesoterodine, n= 471; placebo, n= 472). • Among these, 251 (53%) in the fesoterodine group and 300 (64%) in the placebo group requested dose escalation at week 4 and 35 (7%) and 15 (3%) requested dose reduction at week 8. Changes from baseline to week 12 in urgency episodes (primary endpoint) in the fesoterodine (-3.2) and placebo (-2.9) groups were not significantly different (P= 0.196), but improvements in micturitions (P= 0.009) and OAB-q symptom bother score (P= 0.007) were significantly greater with fesoterodine. • At week 4, significantly greater improvements in micturitions (P= 0.006), severe urgency episodes (P= 0.006), IPSS storage score (P= 0.022), OAB-q symptom bother score (P= 0.004), and OAB-q health-related quality of life (P= 0.041), but not urgency episodes (P= 0.062), were observed with add-on fesoterodine. • Dry mouth (fesoterodine, 21%; placebo, 6%) and constipation (fesoterodine, 6%; placebo, 2%) were the most common adverse events. Dysuria and urinary retention were reported by 3% and 2% of subjects, respectively, in the fesoterodine add-on group vs 1% and <1% of subjects, respectively in the placebo add-on group. One subject in each group had acute urinary retention requiring catheterization.. • Flexible-dose fesoterodine was well tolerated as an add-on treatment in men with persistent storage symptoms. • Changes in urgency episodes at week 12 (primary endpoint) and many secondary endpoints were not significantly different between fesoterodine and placebo add-on treatment; however, improvements in frequency and symptom bother were significantly greater with fesoterodine. • These data suggest that there remains a limited understanding of the optimal evaluation and treatment of men with LUTS.

Topics: Adrenergic alpha-Antagonists; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Double-Blind Method; Drug Therapy, Combination; Humans; Male; Middle Aged; Muscarinic Antagonists; Prostatic Hyperplasia; Treatment Outcome; Urinary Bladder, Overactive

Previous work has demonstrated the efficacy and safety of fesoterodine in older and younger subjects with overactive bladder (OAB) symptoms. The effect of long-term fesoterodine treatment in different age groups has not been assessed.. The aim was to determine the impact of age on the safety, tolerability and efficacy of long-term treatment with fesoterodine 8 mg in subjects with OAB syndrome.. This was a pooled analysis of two identically designed open-label extensions of 12-week, randomized, double-blind, placebo-controlled studies. The setting was urology and general practice offices. Subjects who participated in the 12-week, double-blind studies and opted to continue long-term, open-label treatment with fesoterodine were included. Subjects were initiated on fesoterodine 8 mg/day at open-label baseline. After 1 month, subjects could elect dose reduction to 4 mg/day and subsequent re-escalation to 8 mg; each was permitted once annually. Maximal duration of open-label treatment ranged from 24 to 36 months. Discontinuations, subject-reported treatment tolerance, and efficacy (3-day diaries) were assessed at open-label baseline and months 1, 4, 8, 12 and 24.. A total of 890 subjects were treated (age <45 years, n = 140; 45-64 years, n = 444; 65-74 years, n = 208; ≥75 years, n = 98); 49% continued treatment for ≥ 24 months (age <45 years, 43%; 45-64 years, 54%; 65-74 years, 50%; ≥75 years, 37%). Seventy-seven percent of subjects remained on fesoterodine 8 mg throughout treatment; this rate was highest among subjects aged ≥75 years (age <45 years, 72%; 45-64 years, 77%; 65-74 years, 73%; ≥75 years, 87%). Approximately 80% of continuing subjects were receiving fesoterodine 8 mg at each visit after open-label baseline up to 36 months. No new or unexpected safety signals were observed in any age group. Most subjects reported 'good' or 'excellent' treatment tolerance throughout the study (age <45 years, ≥90%; 45-64 years, ≥93%; 65-74 years, ≥85%; ≥75 years, ≥86%). Dry mouth, the most commonly reported treatment-emergent adverse event, was lowest among subjects aged ≥75 years (age <45 years, 31%; 45-64 years, 30%; 65-74 years, 32%; ≥75 years, 26%). Rates of discontinuation due to dry mouth were low in all age groups. Significant improvements in all diary variables, including urgency urinary incontinence episodes per 24 hours, micturitions per 24 hours, urgency episodes per 24 hours, and mean voided volume per micturition, observed between double-blind baseline and open-label baseline were sustained or increased during open-label treatment in the overall population and all age groups.. Long-term fesoterodine (administered primarily as 8 mg) was well tolerated and associated with sustained improvements in OAB symptoms, irrespective of age.

Topics: Adult; Age Distribution; Age Factors; Aged; Benzhydryl Compounds; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Safety; Time Factors; Treatment Outcome; Urinary Bladder, Overactive

To determine the pharmacokinetics, safety and tolerability of fesoterodine, and assess the utility of 3-day bladder diaries (exploratory objective) in pediatric subjects with neurogenic detrusor overactivity or idiopathic overactive bladder (OAB).. In this 8-week open-label study, subjects (8-17 years, >25 kg) received fesoterodine 4 mg for 4 weeks, then 8 mg for 4 weeks. Blood samples were obtained at weeks 4 and 8.. Of 21 subjects enrolled, 11 had neurogenic detrusor overactivity and 10 had idiopathic OAB; 1 discontinued (personal reasons). Mean age and weight were 13.2 years and 54.0 kg for boys (n = 12) and 13.1 years and 49.2 kg for girls (n = 9). 5-Hydroxy-methyltolterodine plasma concentrations did not differ by diagnosis and were consistent with predictions based on adult data. Treatment-related adverse events (all mild or moderate) included 1 event each of dry mouth, constipation, dry eyes and blurred vision, and 2 events each of nausea and increased post-void residual volume. Three-day bladder diaries proved feasible.. Oral administration of fesoterodine in pediatric subjects (>25 kg) with idiopathic OAB or neurogenic detrusor overactivity produced steady-state plasma 5-hydroxy-methyltolterodine exposures similar to those in adults. The doses given were well tolerated.

Topics: Administration, Oral; Adolescent; Anthropometry; Benzhydryl Compounds; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Maximum Tolerated Dose; Muscarinic Antagonists; Quality of Life; Severity of Illness Index; Single-Blind Method; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics

This study evaluated the efficacy and safety of flexible-dose fesoterodine and factors associated with dose escalation in subjects with overactive bladder (OAB).. In this 12-week, open-label study, 331 adults with OAB symptoms for ≥3 months, ≥8 micturitions and ≥3 urgency episodes per 24 h and who reported at least "some moderate" bladder-related problems were treated with fesoterodine 4 mg once daily for 4 weeks, with the option to escalate to 8 mg for the remaining 8 weeks based on discussion of efficacy and tolerability with the investigator. Factors influencing dose escalation were identified using stepwise logistic regression. Efficacy was assessed via 3-day bladder diaries and patient-reported outcomes.. Of the subjects, 59 % dose escalated at week 4; 93 % of escalators cited insufficient clinical response. The decision to escalate was most often made by the subject (alone or with the investigator). Improvements from baseline were observed in diary and patient-reported outcomes at weeks 4 and 12. Smaller improvements in micturition frequency and worse bladder-related problems at week 4 were significantly associated with increased likelihood of dose escalation; baseline micturition frequency, age, sex, body mass index, antimuscarinic-associated adverse events and OAB symptom duration were not. Non-escalators had greater improvement from baseline to week 4 than escalators; by week 12, improvement was similar among escalators and non-escalators. Fesoterodine was well tolerated.. Treatment with flexible-dose fesoterodine improved bladder diary and patient-reported outcomes. Lower clinical response was related to dose escalation; after escalation, response in escalators approached that of non-escalators.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Dose-Response Relationship, Drug; Female; Humans; Incidence; Logistic Models; Male; Middle Aged; Muscarinic Antagonists; Treatment Outcome; United Kingdom; Urinary Bladder, Overactive; Urinary Incontinence, Urge

Fesoterodine, a new antimuscarinic for the treatment of overactive bladder, is rapidly and extensively hydrolyzed by nonspecific esterases to its principal active moiety, 5-hydroxymethyl tolterodine (5-HMT). The elimination of 5-HMT involves metabolism and renal excretion. The plasma and urinary pharmacokinetics of 5-HMT and its inactive carboxy (SPM 5509), N-desisopropyl (SPM 7789), and carboxy-N-desisopropyl (SPM 7790) metabolites were investigated after a single oral dose of 8 mg of fesoterodine in 8 male subjects with moderate hepatic cirrhosis (Child-Turcotte-Pugh class B) and 8 matched healthy controls. The estimated mean ratios (95% confidence interval) of the area under the curve extrapolated to infinity after dosing (AUC(0-∞)), cumulative urinary excretion up to 48 hours after dosing (Ae(0-48)), maximum observed concentration (C(max)), and apparent terminal disposition half-life (t(1/2)) of 5-HMT for cirrhotic and healthy subjects were 2.2 (1.5-3.1), 2.5 (1.7-3.8), 1.4 (1.0-1.9), and 1.1 (0.8-1.3), respectively. In subjects with hepatic cirrhosis, AUC(0-∞) and Ae(0-48) of 5-HMT increased approximately 2-fold; the increase in C(max) was smaller, and t(1/2) was unaffected. AUC and C(max) of the inactive carboxy metabolites, SPM 5509 and SPM 7790, were reduced reciprocally by about 50%, whereas exposure to the dealkylated metabolite, SPM 7789, increased about 2-fold. Fesoterodine 8 mg was equally well tolerated in both groups. The results indicate that moderate hepatic cirrhosis reduces 5-HMT clearance, with an apparent effect on the carboxylation pathway and not on dealkylation.

Topics: Adolescent; Adult; Aged; Benzhydryl Compounds; Biotransformation; Cresols; Half-Life; Hepatic Insufficiency; Humans; Liver Cirrhosis; Male; Metabolic Clearance Rate; Middle Aged; Muscarinic Antagonists; Prodrugs; Severity of Illness Index; Urinary Bladder, Overactive; Young Adult

• To show the superior efficacy of fesoterodine over tolterodine extended release (ER) in a placebo-controlled overactive bladder (OAB) trial with predefined treatment comparisons for both diary measures and patient-reported outcomes.. • In this 12-week, double-blind, double-dummy trial, subjects reporting >1 urgency urinary incontinence (UUI) episode and ≥8 micturitions per 24 h at baseline were randomized to fesoterodine (4 mg for 1 week, 8 mg for 11 weeks), tolterodine ER 4 mg, or placebo. • Subjects completed 3-day bladder diaries, the Patient Perception of Bladder Condition (PPBC) and the Urgency Perception Scale (UPS) at baseline and weeks 1, 4 and 12 and the OAB Questionnaire at baseline and week 12.. • A total of 2417 subjects were randomized. At week 12, fesoterodine 8 mg showed superiority over tolterodine ER 4 mg and placebo on UUI episodes (primary endpoint), micturitions, urgency and most other diary endpoints, and on the PPBC, UPS and all OAB Questionnaire scales and domains (all P < 0.05). • Superiority of fesoterodine 8 mg over tolterodine ER 4 mg was seen as early as week 4 (3 weeks after escalation to fesoterodine 8 mg). At week 1, fesoterodine 4 mg was superior to placebo on most diary variables, the PPBC and the UPS (all P < 0.05). Dry mouth and constipation rates were 28% and 4% with fesoterodine, 13% and 3% with tolterodine ER, and 5% and 2% with placebo. • Discontinuation rates as a result of adverse events were 5%, 3% and 2% for fesoterodine, tolterodine ER and placebo, respectively.. • In this randomized study, which is the largest to compare antimuscarinic efficacy performed to date, fesoterodine 8 mg was superior to tolterodine ER 4 mg for UUI episodes, micturitions and urgency episodes, as well as for self-reported patient assessments of bladder-related problems, urgency, symptom bother and health-related quality of life. • The superiority of fesoterodine 8 mg over tolterodine ER 4 mg was observed as early as 3 weeks after escalation from fesoterodine 4 mg for most outcomes. These data may have important implications for the clinical management of OAB patients previously treated with tolterodine ER.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Young Adult

To assess the onset of efficacy of fesoterodine 4 mg once daily on overactive bladder (OAB) symptoms after 1 week of treatment.. This was a prespecified analysis of data collected during the first week of a 12-week, open-label, single-arm, flexible-dose study of fesoterodine. Eligible subjects were adult men and women (aged ≥ 18 years) who reported urinary frequency (eight or more micturitions per 24 h) and urgency (three or more episodes per 24 h) in 5-day bladder diaries at baseline, and dissatisfaction with previous tolterodine or tolterodine extended-release treatment received within 2 years of screening. All subjects received fesoterodine 4 mg once daily during the first 4 weeks of treatment (with an optional dose increase to fesoterodine 8 mg after week 4). Early onset of efficacy of fesoterodine 4 mg was assessed based on changes from baseline to week 1 in variables recorded in 5-day bladder diaries, including total micturitions, urgency episodes, urgency urinary incontinence (UUI) episodes and nocturnal micturitions. Urgency and severe urgency episodes were defined as those rated ≥ 3 and ≥ 4, respectively, on the five-point Urinary Sensation Scale (USS) (1 = no urgency, 5 = UUI); frequency-urgency sum (a combined measure of micturition frequency and urgency) was defined as the sum of all USS ratings.. All bladder diary variables, including total and nocturnal micturitions, UUI episodes, urgency episodes, severe urgency episodes and frequency-urgency sum per 24 h, were significantly improved (all P < 0.0001) after 1 week of treatment with fesoterodine 4 mg compared to baseline. The diary-dry rate at week 1 (i.e. subjects with at least one UUI episode at baseline who subsequently reported no UUI episodes on week 1 diary) was 38%.. In this open-label study of subjects with OAB who had been previously treated and dissatisfied with tolterodine, fesoterodine 4 mg showed a rapid onset of efficacy at 1 week.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Dose-Response Relationship, Drug; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Satisfaction; Treatment Outcome; Urinary Bladder, Overactive; Young Adult

To evaluate long-term safety, tolerability, and efficacy of fesoterodine for men and women with overactive bladder (OAB) symptoms.. This was a post hoc analysis of data pooled from two open-label extensions (NCT00220402, NCT00220376) of double-blind studies. All subjects began open-label treatment with fesoterodine 8 mg once daily, with voluntary dose reduction to 4 mg and re-escalation to 8 mg each permitted once annually. Maximum allowable duration of open-label treatment ranged from 24 to 36 months.. Safety and discontinuations were assessed throughout treatment; subject-reported treatment tolerability and 3-day bladder diaries were evaluated at open-label baseline and months 1, 4, 8, 12, and 24.. A total of 185 men and 705 women enrolled; 83 men (45%) and 356 women (50%) continued open-label treatment for ≥ 24 months. Most men (84%) and women (75%) remained on fesoterodine 8 mg throughout open-label treatment. No new or unexpected safety signals were observed. Dry mouth was the most common treatment-emergent adverse event (men, 24%; women, 32%), rates of discontinuation due to dry mouth were low (men, 1%; women, 2%). Most men and women (≥ 91%) reported at least 'good' tolerance. For men and women, statistically significant improvements in urgency urinary incontinence episodes, micturitions, urgency episodes, and mean voided volume per micturition achieved between double-blind baseline and open-label baseline were sustained or further improved through month 24; significant improvements in most OAB symptoms were observed between double-blind baseline and month 24 when subjects were stratified by double-blind treatment (placebo, tolterodine extended release 4 mg, fesoterodine 4 mg, fesoterodine 8 mg). Limitations include the lack of a placebo control and that subjects completing double-blind treatment may have been more likely to tolerate or respond to long-term fesoterodine treatment.. Long-term fesoterodine treatment was well tolerated and associated with sustained improvements in OAB symptoms in men and women.

Topics: Adult; Aged; Benzhydryl Compounds; Double-Blind Method; Female; Humans; Male; Middle Aged; Time Factors; Urinary Bladder, Overactive

To assess the onset of efficacy of fesoterodine 4 mg versus placebo in subjects with overactive bladder (OAB) symptoms.. Subjects who reported OAB symptoms for ≥ 3 months and recorded ≥ 8 micturitions and ≥ 1 urgency urinary incontinence (UUI) episode per 24 hours in 3-day baseline diaries were randomized to fesoterodine 4 mg, tolterodine extended release (ER) 4 mg, or placebo. This is an analysis of first week data from a 12-week, double-blind trial. ClinicalTrials.gov unique ID: NCT00444925.. Baseline to week 1 changes in 3-day bladder diary variables, Patient Perception of Bladder Condition (PPBC), and Urgency Perception Scale (UPS) scores reported by subjects receiving fesoterodine 4 mg or placebo.. By week 1, fesoterodine 4 mg (n = 679) was associated with significantly greater improvements compared with placebo (n = 334) in micturitions, urgency, severe urgency and UUI episodes, frequency-urgency sum, and MVV per 24 hours and 3-day diary-dry rate (all p < 0.05), but not nocturnal micturitions per 24 hours (p = 0.273). These differences were significant as early as day 5 of treatment (i.e., day 1 of the 3-day diary) for all diary endpoints except nocturnal micturitions and MVV. Changes in PPBC scores were significantly more favorable with fesoterodine 4 mg versus placebo (p = 0.0143); changes in UPS scores were not significantly different (p = 0.077).. The results provide evidence that patients receiving fesoterodine 4 mg for their OAB symptoms may expect to experience a response as early as 1 week after initiating treatment. One limitation is that, although 65% of subjects had received treatment with antimuscarinics before the study, whether subjects were dissatisfied with previous treatment and reasons for dissatisfaction were not collected. This might affect the magnitude of outcome improvements. Also, it is not known whether the UPS is sensitive enough to detect treatment differences as early as week 1.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Double-Blind Method; Female; Humans; Male; Middle Aged; Time Factors; Urinary Bladder; Urinary Bladder, Overactive; Young Adult

To characterize the response to fesoterodine treatment for overactive bladder (OAB) in subjects who did or did not choose to dose escalate in a flexible-dose study.. Subjects were randomized to fesoterodine 4  mg or placebo. At week 2, subjects could remain on 4  mg (non-escalators) or choose to increase to 8  mg (escalators) for the remaining 10 weeks (sham escalation for placebo). Subjects completed 3-day bladder diaries at baseline, week 2 and week 12 noting micturitions, urgency episodes, and urgency urinary incontinence (UUI) episodes.. Sixty-three per cent of 438 subjects randomized to fesoterodine and 73% of 445 randomized to placebo dose escalated. At baseline, fesoterodine escalators had significantly more micturitions and urgency episodes than fesoterodine non-escalators (P < 0.001); at week 2, before dose escalation, diary-dry rate and improvement in micturitions and urgency episodes were significantly greater among fesoterodine non-escalators versus escalators (P < 0.001); and by week 12, after dose escalation, diary-dry rate and improvements in micturitions and UUI episodes were similar between fesoterodine non-escalators and escalators (P > 0.05). The placebo escalator group did not demonstrate a similar response over placebo non-escalators following the dose escalation decision point.. A rapid and robust response to fesoterodine 4  mg was demonstrated in non-escalators. Subjects who chose to dose escalate to fesoterodine 8  mg at week 2 showed significant improvement by week 12 versus baseline and week 2 (prior to escalation), as well as versus placebo. Dose escalation to 8  mg fesoterodine provided subjects with efficacy and tolerability similar to those who were satisfied with the 4-mg dose.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Benzhydryl Compounds; Double-Blind Method; Female; Humans; Logistic Models; Male; Middle Aged; Muscarinic Antagonists; Placebos; Time Factors; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urodynamics; Young Adult

To determine whether the presence of detrusor overactivity (DO) in patients with overactive bladder (OAB) and urgency urinary incontinence (UUI) is a predictor of the response to treatment with fesoterodine.. This phase 2 randomized, multicentre, placebo-controlled trial consisted of a 1-week placebo run-in phase followed by an 8-week double-blind period. Eligible for the study were men and women aged 18-78 years with symptoms or signs of OAB with UUI; they were stratified into two balanced strata depending on the outcome of a baseline urodynamic assessment. By using this particular study design it was possible to investigate whether there were differences between the strata. The primary endpoint was the change from baseline to week 8 in mean voids/24 h. Secondary endpoints were the changes in UUI episodes/week, and for those patients with DO at baseline, the mean changes in volume at first involuntary contraction associated with a feeling of urgency, first desire to void, and strong desire to void, and change in maximum cystometric capacity. Because there were few patients the secondary analyses were considered exploratory.. Overall, there were linear dose-response relationships for placebo and the fesoterodine groups for the reduction in the number of voids/24 h and UUI episodes/week. Compared with the placebo group, the least squares mean changes from baseline to week 8 in both variables were significantly improved in patients receiving fesoterodine 4 mg (P = 0.045 and 0.040, respectively), 8 mg (P < 0.001 for both), and 12 mg (P < 0.001 for both). There were no significant differences in treatment responses, as measured by both variables between patients with and without DO. For patients with DO, the mean volume at the first desire to void improved in all fesoterodine treatment groups and worsened in the placebo group.. Regardless of the presence of DO, the response to fesoterodine treatment was dose-proportional and associated with significant improvements in OAB symptoms, indicating that the response to OAB pharmacotherapy in patients with UUI was independent of the urodynamic diagnosis of DO.

Topics: Adult; Aged; Benzhydryl Compounds; Dose-Response Relationship, Drug; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Quality of Life; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urodynamics; Young Adult

To assess the efficacy, safety, and tolerability of fesoterodine 4 and 8 mg in men with overactive bladder.. This was a subanalysis of pooled data from 358 men enrolled in 2 double-blind, placebo-controlled phase III trials. Subjects with frequency and urgency or urgency urinary incontinence (UUI) were randomized to fesoterodine 4 mg, fesoterodine 8 mg, or placebo for 12 weeks. Efficacy endpoints included bladder diary variables and subject-reported treatment response.. By week 12, men treated with fesoterodine 4 or 8 mg had significantly greater median percentage improvements in micturition frequency, urgency episodes, and UUI episodes versus placebo and significantly greater percentages reported a treatment response versus placebo. Significant increases in mean voided volume (MVV) per micturition versus placebo occurred with fesoterodine 8 mg only. At week 12, fesoterodine 8 mg was significantly more efficacious than fesoterodine 4 mg in improving UUI episodes and MVV per micturition. The most commonly reported adverse events with fesoterodine 4 and 8 mg were dry mouth (12.5% and 37.7% vs 5.6% with placebo) and constipation (2.5% and 8.8% vs 0.8% with placebo). Symptoms suggestive of urinary retention were reported in 0.8%, 0.8%, and 5.3% of men in the placebo, fesoterodine 4 mg, and fesoterodine 8 mg groups, respectively; only 1 subject, in the fesoterodine 8 mg group, was catheterized.. Fesoterodine 4 and 8 mg are generally safe, efficacious, and well tolerated for the treatment of overactive bladder symptoms in men. The 8 mg dose provides additional benefit and allows for treatment individualization.

Topics: Benzhydryl Compounds; Double-Blind Method; Humans; Male; Middle Aged; Urinary Bladder, Overactive

To evaluate the efficacy and tolerability of flexible-dose fesoterodine vs placebo in subjects with overactive bladder (OAB).. In a 12-week double-blind trial, subjects were randomized to fesoterodine 4 mg or placebo once daily, taken within 4 hours of bedtime. At week 2, subjects could increase the fesoterodine dose to 8 mg (sham escalation for placebo). Subjects completed 3-day bladder diaries, Patient Perception of Bladder Condition, and Urgency Perception Scale at baseline and weeks 2, 6, and 12 as well as OAB Questionnaire at baseline and week 12.. Of 883 subjects, 63% and 73% of the fesoterodine (n = 438) and placebo (n = 445) groups, respectively, opted for dose escalation. Week 12 improvements from baseline in total micturitions, urgency episodes, urgency urinary incontinence episodes, frequency-urgency sum, and all OAB Questionnaire scales and domains, but not nocturnal micturitions or nocturnal urgency episodes, were significantly greater with fesoterodine than placebo (all P <.05). Treatment differences in micturitions and frequency-urgency sum were significant by week 2 and in urgency urinary incontinence and urgency episodes by week 6. Significantly greater percentages of subjects taking fesoterodine had improved Patient Perception of Bladder Condition and Urgency Perception Scale scores at weeks 2, 6, and 12 (P <.05). Dry mouth (fesoterodine, 26%; placebo, 8%) and constipation (fesoterodine, 11%; placebo, 6%) were the most common adverse events. In both groups, 87% of the subjects completed the trial; 8% and 5% of the fesoterodine and placebo groups, respectively, discontinued because of an adverse event.. Flexible-dose fesoterodine was efficacious and generally well tolerated for treatment of OAB symptoms.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Double-Blind Method; Female; Humans; Male; Middle Aged; Urinary Bladder, Overactive; Young Adult

To compare the efficacy and tolerability of fesoterodine 8 mg with tolterodine extended-release (ER) 4 mg and placebo in a randomized clinical trial of patients with an overactive bladder (OAB).. In this 12-week double-blind, double-dummy, placebo-controlled, randomized clinical trial, eligible patients reported OAB symptoms for > or = 3 months and recorded > or = 8 voids and > or = 1 urgency urinary incontinence (UUI) episode per 24 h in 3-day bladder diaries at baseline. Patients were randomized in a 2:2:1 ratio to fesoterodine (4 mg for 1 week then 8 mg for 11 weeks); tolterodine ER 4 mg; or placebo (with sham dose escalation for tolterodine ER and placebo). Endpoints were changes from baseline to week 12 in UUI episodes (primary endpoint), total and nocturnal voids, urgency episodes, severe urgency episodes, and frequency-urgency sum per 24 h; mean voided volume per void (MVV); and the OAB questionnaire (OAB-q), Patient Perception of Bladder Condition (PPBC), and Urgency Perception Scale (UPS). Safety and tolerability were assessed and summarized over the 12-week study period.. Fesoterodine (636 patients) significantly improved UUI episodes at week 12 (primary endpoint) compared with tolterodine ER (641 patients; P = 0.017) and placebo (313 patients; P < 0.001). Fesoterodine also produced significantly greater improvements than tolterodine ER in MVV (P = 0.005). Fesoterodine significantly improved all diary endpoints compared with placebo (P < 0.001), except for nocturnal voids (P = 0.327). Tolterodine ER significantly improved all diary endpoints vs placebo (P < 0.001), except for nocturnal voids (P = 0.506) and MVV (P = 0.103). Diary dry rates (the proportion of patients reporting no UUI episodes at endpoint among those with one or more UUI episodes at baseline) were significantly higher with fesoterodine (64%) than with tolterodine ER (57%; P = 0.015) and placebo (45%; P < 0.001). Improvements in PPBC, UPS and OAB-q scale and domain scores at week 12 were all significantly better with fesoterodine than placebo (all P < 0.001) and tolterodine ER (all P < 0.05) except for the OAB-q Sleep domain vs tolterodine ER (P = 0.081). Dry mouth and constipation rates were 28% and 5% in the fesoterodine group, 16% and 4% in the tolterodine ER group, and 6% and 3% with placebo, respectively. Discontinuations due to treatment-emergent adverse events were 6%, 4% and 2% in the fesoterodine, tolterodine ER, and placebo groups, respectively.. In patients with OAB, fesoterodine 8 mg showed superior efficacy over tolterodine ER 4 mg and placebo in reducing UUI episodes (primary endpoint) and in improving most patient-reported outcome measures. Both active treatments were well tolerated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Satisfaction; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Young Adult

To determine whether baseline urgency urinary incontinence (UUI) episodes predict the need for increased doses of fesoterodine in patients with overactive bladder (OAB), as clinicians would benefit from data that help to predict which patients require higher doses of antimuscarinics to manage UUI episodes.. In this pooled analysis of data from two double-blind, placebo-controlled trials, patients were randomized to placebo or fesoterodine 4 or 8 mg for 12 weeks and stratified into tertiles (>0-<2, 2-<4, or > or =4) according to the number of UUI episodes/24 h as recorded in 3-day bladder diaries at baseline. The change in mean UUI episodes/24 h from baseline to end of study was assessed using analysis of covariance.. In a post hoc analysis of data from two clinical trials, there were significant reductions from baseline in UUI episodes for fesoterodine 4 and 8 mg vs placebo in patients (n) with >0-<2 (422), 2-<4 (424) and > or =4 (481) UUI episodes at baseline (all P < 0.01). In patients with 2-<4 and > or =4 UUI episodes at baseline, fesoterodine 8 mg gave significantly greater mean reductions (-1.92 and -4.17, respectively) vs fesoterodine 4 mg (-1.43 and -3.31) (P < 0.05). The most common adverse events were dry mouth (placebo, 8%; fesoterodine 4 mg, 19%; and 8 mg, 35%) and constipation (placebo, 2%; fesoterodine 4 mg, 5%; and 8 mg, 6%).. Fesoterodine 4 and 8 mg significantly reduced UUI episodes vs placebo; this effect appeared to be greater with fesoterodine 8 mg in patients with > or =2 UUI episodes/24 h at baseline. Fesoterodine was well tolerated, although higher doses increased the incidence of adverse events. These findings might aid the clinical identification of patients with OAB who would most benefit from increasing the dose of fesoterodine from 4 to 8 mg.

Topics: Aged; Benzhydryl Compounds; Dose-Response Relationship, Drug; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge

The aim of this study was to assess the long-term safety, tolerability and efficacy of fesoterodine treatment in subjects with overactive bladder (OAB) symptoms.. This was an open-label extension study of a 12-week, double-blind fesoterodine study. During open-label treatment, all subjects received fesoterodine 8 mg for an initial 4 weeks, after which subjects could elect dose reduction to 4 mg or subsequent reescalation to 8 mg during clinic visits (dose reduction and reescalation each permitted once annually). The maximum allowable duration of open-label fesoterodine treatment ranged from 24 to 32 months across study sites. Safety and tolerability were evaluated via discontinuations, fesoterodine exposure, treatment-emergent adverse events (TEAEs) and subject-reported treatment tolerance. Three-day bladder diaries and other patient-reported outcomes (PROs) were assessed during the first 24 months of open-label treatment. PROs included evaluations of health-related quality of life [HRQL; King's Health Questionnaire (KHQ), and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF)], severity of bladder-related problems and treatment satisfaction. Subjects completed 3-day diaries before open-label baseline and months 1, 4, 8, 12 and 24; the ICIQ-SF and measures of bladder-related problems and treatment satisfaction at open-label baseline and months 4, 12 and 24; and the KHQ at open-label baseline and months 12 and 24.. Of the 417 eligible subjects who enrolled in the open-label extension, 61% continued fesoterodine treatment for > or = 24 months and 71% elected to maintain the fesoterodine 8-mg dose throughout treatment. No unexpected safety signals were observed. Most subjects rated treatment tolerance as at least 'good' throughout the study (> or = 88%). Dry mouth was the most commonly reported TEAE (34%) during open-label treatment, resulting in discontinuation in 2% of subjects (n = 8). Improvements from open-label baseline in OAB symptoms, HRQL and bladder-related problems were statistically significant at the earliest point measured and maintained through month 24. Treatment satisfaction rates were high throughout the study (> or = 84%).. Long-term fesoterodine treatment was well tolerated and associated with sustained improvements in OAB symptoms and HRQL.

Topics: Adult; Aged; Attitude to Health; Benzhydryl Compounds; Double-Blind Method; Drug Administration Schedule; Female; Humans; Long-Term Care; Male; Middle Aged; Muscarinic Antagonists; Quality of Life; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Fesoterodine 4 mg and 8 mg once daily are indicated for the treatment of overactive bladder. A thorough QT study was conducted to investigate the effects of fesoterodine on cardiac repolarization.. In this parallel-group study, subjects were randomly assigned to receive double-blind fesoterodine 4 mg, fesoterodine 28 mg, or placebo or open-label moxifloxacin 400 mg (positive control) for 3 days. Electrocardiograms (ECGs) were obtained on Days -1 (baseline), 1, and 3. The primary analysis was the time-averaged changes from baseline for Fridericia's-corrected QT interval (QTcF) on Day 3.. Among 261 subjects randomized to fesoterodine 4 mg (n = 64), fesoterodine 28 mg (n = 68), placebo (n = 65), or moxifloxacin 400 mg (n = 64), 256 completed the trial. The least squares mean changes in QTcF from baseline were 21.1, 20.5, 18.5, and 31.3 ms (maximum), and -5.1, -4.2, -5.2, and 7.6 ms (time-averaged at Day 3) for placebo, fesoterodine 4 mg, fesoterodine 28 mg, and moxifloxacin, respectively. The lower limit of the 95% confidence interval exceeded 5 ms for moxifloxacin.. The results indicate that fesoterodine is not associated with QTc prolongation or other ECG abnormalities at either therapeutic or supratherapeutic doses.

Topics: Aza Compounds; Benzhydryl Compounds; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Fluoroquinolones; Humans; Least-Squares Analysis; Long QT Syndrome; Male; Middle Aged; Moxifloxacin; Muscarinic Antagonists; Quinolines; Urinary Bladder, Overactive

Fesoterodine is an antimuscarinic for the treatment of overactive bladder, a syndrome of urgency, with or without urgency urinary incontinence (UUI), usually with increased daytime frequency and nocturia. Our objective was to develop predictive models to describe the dose response of fesoterodine.. Data from subjects enrolled in double-blind, placebo-controlled phase II and III trials were used for developing longitudinal dose-response models.. The models predicted that clinically significant and near-maximum treatment effects would be seen within 3 to 4 weeks after treatment initiation. For a typical patient with 11 micturitions per 24 hours at baseline, predicted change was -1.2, -1.7, and -2.2 micturitions for placebo and fesoterodine 4 mg and 8 mg, respectively. For a typical patient with 2 UUI episodes per 24 hours at baseline, predicted change was -1.05, -1.26, and -1.43 UUI episodes for placebo and fesoterodine 4 mg and 8 mg, respectively. Increase in mean voided volume was estimated at 9.7 mL for placebo, with an additional 14.2 mL and 28.4 mL for fesoterodine 4 mg and 8 mg, respectively.. A consistent dose response for fesoterodine was demonstrated for bladder diary endpoints in subjects with overactive bladder, a result that supports the greater efficacy seen with fesoterodine 8 mg in post hoc analyses of clinical trial data. The dose-response models can be used to predict outcomes for doses not studied or for patient subgroups underrepresented in clinical trials.. The phase III trials used in this analysis have been registered at ClinicalTrials.gov (NCT00220363 and NCT00138723).

Topics: Aged; Benzhydryl Compounds; Computer Simulation; Dose-Response Relationship, Drug; Female; Humans; Male; Muscarinic Antagonists; Treatment Outcome; Urinary Bladder, Overactive

Fesoterodine is a new antimuscarinic agent developed for the treatment of overactive bladder. Fesoterodine itself is inactive and is rapidly and extensively converted by ubiquitous esterases to its principal active moiety, 5-hydroxymethyl tolterodine (5-HMT). 5-HMT is formed via biotransformation of both fesoterodine and tolterodine, albeit by different metabolising enzymes, viz. esterases and CYP2D6 respectively. Tolterodine is a potent muscarinic receptor antagonist and has been used for the treatment of overactive bladder for over ten years. The objective of this study was to establish the pharmacokinetic profile of fesoterodine and to highlight ist potential pharmacokinetic advantages over tolterodine.. Single-centre, open-label, randomised, 4-way crossover study in a total of 24 healthy male volunteers. Single oral doses of 4, 8, or 12 mg fesoterodine were administered after an overnight fast. In addition, the 8 mg dose was also administered after a standard high-fat and high-calorie breakfast. Blood and urine samples for the analysis of 5-HMT were collected before and multiple times after drug administration for pharmacokinetic analysis.. The mean peak plasma concentration (Cmax) of 5-HMT and the mean area under the time versus concentration curve (AUC) increased proportionally with the fesoterodine dose. These two parameters were some 2-fold higher in CYP2D6 poor metabolisers, whereas the time to peak plasma concentration (tmax) and half life (t1/2) were not influenced by the dose or the CYP2D6 metaboliser status. If fesoterodine was taken following a high-fat breakfast, we observed small increases in Cmax and AUC. In spite of these modest genetic influences and food effects on the pharmacokinetics of fesoterodine, the overall interindividual variability in Cmax levels was relatively little compared to previously published reports using tolterodine.. Due to the esterase-mediated cytochrome P450-independent formation of 5-HMT and involvement of multiple metabolic and renal excretion pathways in the elimination of 5-HMT, the effects of patient-intrinsic and -extrinsic factors on the pharmacokinetics of fesoterodine are only modest, with some 2-fold higher 5-HMT exposure. Therefore, in contrast to tolterodine, no reduction of fesoterodine dosage is required under conditions of reduced elimination. In most cases of drug interaction or renal/hepatic impairment, the fesoterodine dose may be increased to 8 mg/day based on individual patients' response, or patients may be required to remain at the initial recommended dose of 4 mg/day.

Topics: Administration, Oral; Adolescent; Adult; Benzhydryl Compounds; Chromatography, Liquid; Cresols; Cross-Over Studies; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Reference Values; Tolterodine Tartrate; Urinary Bladder, Overactive; Young Adult

To evaluate the efficacy and tolerability of flexible-dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment.. This was a 12-week, open-label, flexible-dose study of adults with OAB (> or = 8 micturitions and > or = 3 urgency episodes per 24 h) who had been treated with tolterodine (immediate- or extended-release) for OAB within 2 years of screening and reported dissatisfaction with tolterodine treatment. Subjects received fesoterodine 4 mg once daily for 4 weeks; thereafter, daily dosage was maintained at 4 mg or increased to 8 mg based on the subject's and physician's subjective assessment of efficacy and tolerability. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12 and rated treatment satisfaction at week 12 using the Treatment Satisfaction Question (TSQ). Safety and tolerability were assessed.. Among 516 subjects treated, approximately 50% opted for dose escalation to 8 mg at week 4. Significant improvements from baseline to week 12 were observed in micturitions, urgency urinary incontinence episodes, micturition-related urgency episodes and severe micturition-related urgency episodes per 24 h (all p < 0.0001). Approximately 80% of subjects who responded to the TSQ at week 12 reported satisfaction with treatment; 38% reported being very satisfied. Using the PPBC, 83% of subjects reported improvement at week 12 with 59% reporting improvement > or = 2 points. Significant improvements from baseline (p < 0.0001) exceeding the minimally important difference (10 points) were observed in OAB-q Symptom Bother and Health-Related Quality of Life (HRQL) scales and all four HRQL domains. Dry mouth (23%) and constipation (5%) were the most common adverse events; no safety issues were identified.. Flexible-dose fesoterodine significantly improved OAB symptoms, HRQL, and rates of treatment satisfaction and was well tolerated in subjects with OAB who were dissatisfied with prior tolterodine therapy.

Topics: Adult; Aged; Aged, 80 and over; Antimutagenic Agents; Benzhydryl Compounds; Dose-Response Relationship, Drug; Female; Humans; Male; Medical Records; Middle Aged; Patient Satisfaction; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urination; Young Adult

We assessed fesoterodine efficacy and tolerability in women with overactive bladder (OAB).. This post hoc analysis of pooled data from two clinical trials included 1,548 women with OAB randomized to placebo, fesoterodine 4 or 8 mg, or tolterodine extended release (ER) 4 mg (in 1 trial) for 12 weeks. Subjects completed 3-day bladder diaries at baseline and weeks 2 and 12 and rated Treatment Response at weeks 2 and 12.. By weeks 2 and 12, all active-treatment groups showed significant improvements in all five bladder diary variables assessed and greater Treatment Response rates vs placebo. Fesoterodine 8 mg was significantly more efficacious than fesoterodine 4 mg and tolterodine ER in improving urgency urinary incontinence episodes and continent days per week. The most common adverse events were dry mouth and constipation, which were predominately mild or moderate.. Fesoterodine is efficacious and well tolerated in women with OAB.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Constipation; Cresols; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

To compare, in a post hoc analysis of a phase III trial, the maximum recommended doses of fesoterodine (8 mg) and tolterodine (4 mg) for improving overactive bladder (OAB) symptoms and health-related quality of life (HRQoL), as fesoterodine effectively reduces OAB symptoms vs placebo.. Eligible patients with frequency (> or =eight voids/24 h) and either urgency (> or =six episodes over 3 days) or urgency urinary incontinence (UUI; > or =three episodes over 3 days) were randomized to placebo, fesoterodine 4 or 8 mg, or tolterodine extended-release (ER) 4 mg for 12 weeks; fesoterodine 4 mg data were published elsewhere. Patients completed a 3-day bladder diary in which they recorded the time of each void, voided volume (VV), and the severity of urgency. A post hoc inferential analysis was conducted on the primary endpoint (voids/24 h), the two co-primary endpoints (UUI episodes/24 h and treatment response), several secondary endpoints (severe urgency plus UUI per 24 h, mean VV (MVV)/void, and continent days/week), HRQoL, using the King's Health Questionnaire (KHQ) and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and self-reported bladder-related problems. A subanalysis also assessed all endpoints for patients who were incontinent at baseline. Tolerability and safety were assessed by evaluating adverse events, residual urine volume, laboratory variables and treatment withdrawals.. By week 12, patients with OAB in both active-treatment groups showed significant improvements in most bladder diary variables and treatment response rates compared with placebo. Fesoterodine 8 mg was statistically significantly better than tolterodine ER 4 mg for improving UUI episodes, severe urgency plus UUI, mean VV, and number of continent days/week. In addition, the fesoterodine and tolterodine ER groups showed significantly greater improvements in HRQoL than the placebo group, with positive changes in most domains of the KHQ and an improvement in ICIQ-SF score. The fesoterodine 8-mg group had statistically significant improvements over placebo in eight of nine KHQ domains. A major improvement in the severity of bladder-related problems was reported by 39% of the fesoterodine 8 mg and 34% of the tolterodine ER groups vs 25% of those on placebo (P < or = 0.01). Results for the subgroup of incontinent patients at baseline were similar to the overall results. Adverse events reported most commonly with active treatment included dry mouth, constipation, dry eye, dry throat, and nausea.. Both fesoterodine and tolterodine ER significantly improved OAB symptoms and HRQoL, with statistically significant advantages for fesoterodine 8 mg compared with tolterodine ER on several important endpoints.

Topics: Adolescent; Adult; Aged; Benzhydryl Compounds; Cresols; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Surveys and Questionnaires; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urination Disorders; Urodynamics; Young Adult

To compare the efficacy of fesoterodine 4 mg versus 8 mg in treating subjects with overactive bladder (OAB) syndrome.. This is a pooled analysis of data from 2 randomized placebo (PBO)-controlled phase III trials. Eligible subjects with frequency and urgency or urgency urinary incontinence (UUI) were randomized to PBO or fesoterodine 4 or 8 mg for 12 weeks. Subjects assessed efficacy using 3-day bladder diaries recording the time of each void, urgency, and incontinence episode. Endpoints included treatment response (based on a 4-point Treatment Benefit scale) and change from baseline in micturitions, UUI episodes, mean volume voided, urgency episodes, and continent days. We assessed tolerability and safety by evaluating adverse events, residual urine volume, laboratory parameters, and treatment withdrawals.. At the end of treatment, both doses of fesoterodine showed statistically significant improvements in all efficacy endpoints versus PBO (P <0.01). These effects were seen 2 weeks after initiation of treatment (the earliest evaluation point) and were sustained throughout the treatment period. Fesoterodine 8 mg performed significantly better than fesoterodine 4 mg in improving all diary variables (P <0.05) except micturition frequency, demonstrating a dose-response relationship. Adverse events reported more frequently with fesoterodine than with PBO included dry mouth, constipation, and urinary tract infection.. Both fesoterodine 4 and 8 mg are effective in improving OAB symptoms. The higher 8-mg dose provides additional benefit compared with the lower dose in improving most bladder diary variables, thus offering the possibility of dose flexibility and titration.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Urinary Bladder, Overactive

To determine the efficacy, tolerability, and safety of fesoterodine in subjects with overactive bladder (OAB).. This was a multicentre, randomised, double-blind, placebo- and active-controlled trial with tolterodine extended release (ER) to assess the efficacy and safety of fesoterodine. Eligible subjects (> or =18 yr) with increased micturition frequency and urgency and/or urgency urinary incontinence (UUI) were randomised to placebo, fesoterodine 4 mg, fesoterodine 8 mg, or tolterodine ER 4 mg for 12 wk. The primary efficacy variable was a change from baseline to week 12 in micturitions per 24 h. Co-primary end points included change from baseline to week 12 in UUI episodes per 24 h and Treatment Response ("yes" or "no," based on four-point treatment benefit scale). Secondary efficacy variables included mean volume voided per micturition, continent days per week, and number of urgency episodes.. At the end of treatment, subjects taking fesoterodine 4 and 8 mg had significant (p<0.05) and clinically relevant improvements versus placebo in the primary, co-primary, and most secondary efficacy variables. Tolterodine ER (active control) also provided significantly greater improvement than placebo for most efficacy variables, confirming the sensitivity of the study design. A more pronounced effect was observed with fesoterodine 8 mg at most end points.. Both doses of fesoterodine were significantly better than placebo in improving the symptoms of OAB and produced a significantly greater Treatment Response versus placebo. Efficacy was more pronounced with fesoterodine 8 mg compared with the other treatments. Active treatments were well tolerated.

Topics: Adult; Aged; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Selection; Phenylpropanolamine; Safety; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence; Urination

The differential risk of incident dementia associated with receiving various overactive bladder (OAB) drugs is unknown.. To estimate the association of antimuscarinic OAB drug (exposure), compared with a β-3 agonist (mirabegron), and incident dementia.. A population-based nested case-control study was conducted in patients treated with OAB medications in Ontario, Canada. A total of 11 392 patients aged ≥66 yr with a new diagnosis of dementia between 2010 and 2017, and 29 881 age- and sex-matched controls without dementia were included in the study.. Receipt of an antimuscarinic OAB drug or receipt of mirabegron, within the previous 6-12 mo.. Cases developed dementia and Alzheimer's disease. Controls were derived from the general population and matched to cases based on important baseline characteristics. Odds ratios (ORs) for incident dementia, adjusted for demographic and health-related characteristics, were determined.. Patients receiving solifenacin (OR 1.24; 95% confidence interval 1.08-1.43) and darifenacin (OR 1.30; 95% CI 1.08-1.56) in the prior 6 mo had increased odds of incident dementia compared with those receiving mirabegron. In the 6 mo to 1 yr prior to diagnosis, receipt of solifenacin (OR 1.34; 95% CI 1.11-1.60), darifenacin (OR 1.49; 95% CI 1.19-1.86), tolterodine (OR 1.21; 95% CI 1.02-1.45), and fesoterodine (OR 1.39; 95% CI 1.14-1.71) was associated with increased odds of incident dementia compared with receipt of mirabegron. No effect was seen with oxybutynin or trospium. Limitations included misclassification of the outcome and residual confounding associated with the use of health administrative databases.. Older adults receiving solifenacin and darifenacin in the 6 mo prior to diagnosis, and those receiving solifenacin, darifenacin, tolterodine, or fesoterodine in the year prior to diagnosis, have increased odds of incident dementia, compared with those receiving mirabegron. Oxybutynin and trospium were not associated with dementia, likely due to a protopathic bias. Careful drug selection is warranted when treating patients with OAB.. In a large Canadian cohort of patients who developed dementia after starting an overactive bladder (OAB) medication, those taking some anticholinergic medications for OAB have an increased risk of dementia compared with those taking mirabegron.

Topics: Aged; Canada; Case-Control Studies; Dementia; Humans; Muscarinic Antagonists; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive

Antimuscarinic (AM) and beta-3-agonist (B3A) treatment are the standard first-line pharmacological treatment used to manage overactive bladder (OAB) patients. Aim of our study was to analyze real-life data of adverse events related to AMs and B3A reported on Eudra-Vigilance (EV) Database.. EV database is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We recorded the number of AEs for antimuscarinic and beta-3-agonist per category and severity until January 2021.. Overall, 2313 AEs were reported for oxybutinin, 5129 for solifenacin, 2483 for tolterodine, 3523 for fesoterodine, 787 for trospium, 621 for propiverine and 7213 for mirabegron. Urinary retention was higher for fesoterodine (43%) and tolterodine (23%) when compared to solifenacin (10%), mirabegron (11%) and oxybutinin (4%). Cognitive disorder was uncommon for all the analyzed drugs analyzed. Regarding anticolinergic AEs: vision blurred, dry mouth and constipation were higher for AMs when compared to mirabegron. Their prevalence was higher in female patients. Mirabegron presented a higher risk of hypertension (7%) when compared to oxybutinin (2%, P<0.01), solifenacin (2%, P<0.01), tolterodine (2%, P<0.01) and fesoterodine (1%, P<0.01); the rate of hypertension was higher in females (63%) than males (29%) (P<0.01). The risk of acute urinary retention was also significantly higher (15% vs. 10%, P<0.01) in older patients (>85 years).. Real life data is consistent with registry studies regarding the rate of AEs related to antimuscarinic and beta-3-agonist. However some differences were observed. Female patients present higher rates of AEs when compared to male patients. The risk of acute urinary retention was particularly evident in the octogenarians.

Topics: Aged; Aged, 80 and over; Female; Humans; Hypertension; Male; Muscarinic Antagonists; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Retention

Antimuscarinic drugs are the first-line choice in the treatment of patients with neurogenic Detrusor Overactivity (nDO). Fesoterodine fumarate is the newest antimuscarinic drug. Limited data are published about the use of fesoterodine fumarate in patients suffering from neurogenic lower urinary tract dysfunction. Our study aims to determine the efficacy of fesoterodine fumarate on patients with nDO due to spinal cord lesion or multiple sclerosis (MS).. This is an open-label prospective interventional study. Eligible patients were 18-80 years old with SCL or MS and nDO confirmed by a urodynamic study (UDS). At baseline, patients underwent a UDS to confirm nDO. Quality of life (QoL) was assessed by the Short-Form (SF) Qualiveen questionnaire. Patients received fesoterodine 8 mg/day for 3 months and were re-evaluated with UDS and SF-Qualiveen. The primary endpoint was the confirmation of the maximum detrusor pressure (P. One hundred and twenty-four patients completed the study. Ninety-five of them (76.6%) had SCL, while 29 (23.4%) had MS. P. Fesoterodine fumarate (8 mg) is an efficacious drag in patients with SCL and MS, as it significantly decreases the detrusor pressure, increases the bladder capacity and compliance, and improves the QoL.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Botulinum Toxins, Type A; Humans; Middle Aged; Multiple Sclerosis; Prospective Studies; Quality of Life; Spinal Cord; Spinal Cord Injuries; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics; Young Adult

The aim of this study was to measure the effect of treatment with fesoterodine on physical function relevant to fall risk in older women with overactive bladder.. This was a prospective cohort study of women aged 65 years or older with overactive bladder. Urinary symptoms and physical function were measured at baseline and 8 weeks after treatment with fesoterodine. Physical activity and sedentary behavior were measured subjectively using questionnaires and objectively using an accelerometer. Physical function was measured using the Short Physical Performance Battery test.. We enrolled 75 women with a median age of 76 years. At baseline, bothersome urgency urinary incontinence and nocturia were reported by 55% and 81%, respectively. At baseline, participants were highly sedentary with a median of 2,118 steps daily. After treatment, urinary symptom severity and health-related quality of life subscale scores of the Overactive Bladder Questionnaire improved significantly (-22.3±24 and 17.5±19.7, respectively; P < 0.0001). The proportion of participants who self-reported a moderate-to-high level of physical activity increased from 27% to 35% after treatment (P = 0.86). However, daily steps decreased significantly (-420.2±949, P < 0.001), whereas daily sedentary time increased by 36.6±88 minutes (P < 0.001). There was no significant change in the Short Physical Performance Battery score (-0.3±2.3, P = 0.6).. In older women with overactive bladder, short-term treatment with fesoterodine decreased objectively measured physical activity with no significant change in physical function. Treatment with anticholinergics may need to be supplemented with other therapies to address fall risk in older women with overactive bladder.

Topics: Aged; Benzhydryl Compounds; Female; Humans; Prospective Studies; Quality of Life; Treatment Outcome; Urinary Bladder, Overactive

This study describes patients with different degrees and combinations of symptom resolution in response to fesoterodine exposure to aid physicians in counselling patients with overactive bladder (OAB) on the likelihood of treatment success.. Data came from 12-week fixed-dose studies of fesoterodine. The proportions of patients experiencing symptom resolution and change in patient-reported outcome measures (PROM) at 4, 8, and 12 weeks were calculated. Treatment-emergent adverse events (TEAE) were reported according to response in urinary urgency episodes (UUE). The relationship between PROM and response was examined.. Out of 6689 patients, 81.6% female, urgency urinary incontinence (UUI) episodes/24 h were more responsive to fesoterodine than UUE; with roughly 50% of patients reporting a 50% reduction and fewer than 10% reporting absence of UUE at 12 weeks compared to approximately 40%-50% reporting absence of UUI. TEAE was numerically lower in patients with greater response. There was a statistically significant relationship between improvement in urinary urgency and associated change in OAB-q symptom bother scores, r = 0.54, p < 0.001. At Week 4, 64.0%-76.7% of patients who had achieved a significant change in Patient Perception of Bladder Condition (PPBC) had a 50% reduction in UUI. At Week 12 this proportion was between 80% and 87.9%, with those being exposed to fesoterodine treatment reporting response in PPBC at numerically higher rates.. These data provide clinicians with information from which they may usefully communicate the likelihood of symptom resolution in response to pharmacotherapy for OAB and answer a key clinical question posed by many care providers. Roughly ⅓ of fesoterodine treated patients reported a 50% reduction urgency and ¾ reported 50% resolution of incontinence at 12 weeks. Total resolution of all symptoms was seldom achieved.

Topics: Benzhydryl Compounds; Female; Humans; Male; Muscarinic Antagonists; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

To examine the effect of combining a nonselective muscarinic receptor antagonist, 5-hydroxymethyl tolterodine (an active metabolite of fesoterodine), with a β3 adrenoceptor agonist, mirabegron, in a rat model of pelvic congestion.. The rat pelvic congestion model used female Sprague-Dawley rats with their bilateral common iliac and uterine veins ligated. Expressions of M2 and M3 receptor subtypes in the urothelium and detrusor were detected by real-time polymerase chain reaction assays. The effects of both drugs were investigated on isolated bladder strips contracted by electrical field stimulation. in vivo single cystometry was used to assess the effects of 5-hydroxymethyl tolterodine and mirabegron independently or in combination on bladder capacity, micturition pressure, and threshold pressure.. Pelvic congestion rats showed decreased bladder capacity compared with controls, but micturition pressure and threshold pressure were unchanged. Pelvic congestion model rats also demonstrated an approximately two-fold increase in expression of both M2 and M3 receptor subtypes in the urothelium. Additive relaxant effects of 5-hydroxymethyl tolterodine and mirabegron were observed in vitro in the electrical field stimulation-induced contractions of bladder strips from pelvic congestion rats. In vivo, bladder capacity was increased significantly by a combination of 5-hydroxymethyl tolterodine and mirabegron, with the combined effect exceeding the sum of the effects of monotherapies. Micturition pressure and threshold pressure did not significantly differ between groups.. The combination of 5-hydroxymethyl tolterodine with mirabegron suggests the potential of synergistic effects in a rat pelvic congestion model.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Benzhydryl Compounds; Cresols; Disease Models, Animal; Drug Monitoring; Drug Therapy, Combination; Female; Muscarinic Antagonists; Rats; Rats, Sprague-Dawley; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

We investigated the efficacy of Fesoterodine, in 51 patients who did not respond to treatment with Solifenacin from January 2017 to December 2018. We assessed the overactive bladder symptom score (OABSS), thirst, constipation, and residual urine at baseline, as well as at 3 and 6 months from the start of drug administration. The mean age of the patients was 83. 0±6. 55 years. The OABSS indicated significant improvement in urge urinary incontinence and residual urine at 6 months, and significant aggravation in urgency at 3 months. Thus, Fesoterodine is considered useful for patients who did not respond to treatment with Solifenacin.

Topics: Benzhydryl Compounds; Humans; Muscarinic Antagonists; Solifenacin Succinate; Treatment Outcome; Urinary Bladder, Overactive

Topics: Benzhydryl Compounds; Humans; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics

To examine the urodynamic effects of fesoterodine on neurogenic detrusor overactivity and/or low compliance bladder.. A total of 77 patients (52 men, 25 women; aged 61.6 ± 20.3 years) were given fesoterodine 4-8 mg/day and prospectively followed for 12 weeks. The primary end-point variable was change in the maximum cystometric capacity on urodynamic study. The secondary end-point was to assess the number of patients whose neurogenic detrusor overactivity disappeared, and the changes in the urodynamic parameters, lower urinary tract symptoms questionnaires and the 3-day frequency volume chart parameters after the treatment.. A total of 13 patients (16.9%) withdrew because of adverse events (dry mouth or blurred vision), and four patients dropped out for unknown reasons. Finally, 60 patients completed the study. Bladder capacity at first desire to void, maximum cystometric capacity and bladder compliance increased by 29.2 mL, 79.9 mL and 22.2 mL/cm H. Fesoterodine seems to be a valid treatment option for neurogenic detrusor overactivity and/or low compliance bladder in neurogenic bladder patients.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Female; Humans; Male; Middle Aged; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics

We investigated treatment satisfaction with flexible-dose fesoterodine in patients with overactive bladder (OAB) who were dissatisfied with previous anticholinergic therapy.. The subjects were prescribed fesoterodine 4 mg for 4 weeks and fesoterodine 4 mg or 8 mg for another 8 weeks. The primary end point of this study was patients' satisfaction after 12 weeks of fesoterodine treatment on a five-point Likert scale. Secondary end points included a change in the number of daytime micturition, urgency incontinence episodes, urgency episodes, and nocturnal micturition in a 24-hour period from baseline to final assessment.. Overall, 84 patients were assigned to the treatment group in this study and 63 patients completed the 12-week treatment course. A final fesoterodine dose of 4 mg and 8 mg was used by 45 (71.4%) and 18 (28.6%) patients, respectively. The satisfaction and dissatisfaction rates at 12 weeks were 69.9% and 14.2%, respectively. Mean changes in the daytime micturitions (9.73 ± 4.72 vs. 7.76 ± 2.86), urgency episodes (7.73 ± 5.68 vs. 3.71 ± 4.09), and nocturnal micturitions (2.13 ± 1.36 vs. 1.68 ± 1.12) in 24 hours improved significantly with flexible-dose fesoterodine treatment (P < .05). Most adverse events were mild and none were severe.. The flexible dose fesoterodine represents an alternative treatment modality in patients with OAB who are dissatisfied with previous anticholinergic therapy in Korea.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Nocturia; Patient Satisfaction; Prospective Studies; Retreatment; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urination; Urological Agents

To examine the efficacy and safety of non-ablative vaginal erbium:YAG laser (VEL) for the treatment of overactive bladder syndrome (OAB) compared with those of two other common pharmacotherapies, namely, anticholinergics and β3-adrenoceptor agonists.. Female subjects aged 60-69 years who presented with symptoms of OAB from 2015 to 2017 were assigned to three groups (n = 50) receiving treatment with an anticholinergic agent (4 mg fesoterodine), a β3-adrenoceptor agonist (25 mg mirabegron), or VEL (20 min/session of VEL performed thrice). The OAB symptom score (OABSS), Vaginal Health Index Scale (VHIS), and occurrence of adverse effects were examined prior to and at 1 year following treatment initiation.. The three groups showed significant improvement (p < 0.001) for all items of the OABSS questionnaire. Improved VHIS scores were observed only in the VEL group. Furthermore, after VEL treatment, a negative correlation was observed between questions 3 (urinary urgency) and 4 (urgency urinary incontinence) of the OABSS and VHIS. Regarding safety, no adverse events were observed in the VEL group. However, subjects in the other two groups complained of constipation, as indicated by the Constipation Assessment Scale scores, and mouth dryness. The therapeutic effects were inadequate for one and two subjects in the VEL and β3-adrenoceptor agonist groups, respectively.. VEL safely and effectively improved OABSS through a different mechanism than that involved in pharmacotherapy. We propose the use of VEL as a novel surgical treatment option in the field of urology.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Benzhydryl Compounds; Cholinergic Antagonists; Female; Humans; Lasers, Solid-State; Middle Aged; Prospective Studies; Syndrome; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urologic Surgical Procedures; Vagina

Topics: Aged; Benzhydryl Compounds; Female; Humans; Hypertension; Muscarinic Antagonists; Urinary Bladder, Overactive

5-Hydroxymethyl tolterodine (5-HMT; the active fesoterodine metabolite) is metabolized via the cytochrome P450 (CYP) 2D6 and CYP3A pathways. Mirabegron is a moderate CYP2D6 inhibitor and weak CYP3A inhibitor. Potential drug-drug interactions (DDIs) following coadministration of these 2 overactive bladder treatments were estimated using physiologically based pharmacokinetic models, developed and verified by comparing predicted and observed pharmacokinetic profiles from clinical studies. Models predicted and verified mirabegron and desipramine (CYP2D6 substrate) and 5-HMT and ketoconazole (strong CYP3A inhibitor) DDIs. Mirabegron model-predicted mean steady-state AUC and C

Topics: Acetanilides; Adult; Benzhydryl Compounds; Cresols; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Female; Humans; Ketoconazole; Male; Middle Aged; Rifampin; Thiazoles; Urinary Bladder, Overactive

The present study aimed to characterize muscarinic receptor binding of fesoterodine, 5-hydroxymethyl tolterodine (5-HMT), and tolterodine in bladder and other tissues of rats after their oral, intravenous, or intravesical administration. Muscarinic receptors in tissues were measured by using [N-methyl-

Topics: Administration, Intravenous; Administration, Intravesical; Administration, Oral; Animals; Benzhydryl Compounds; Cresols; Dose-Response Relationship, Drug; In Vitro Techniques; Male; Organ Specificity; Protein Binding; Rats, Sprague-Dawley; Receptors, Muscarinic; Tissue Distribution; Tolterodine Tartrate; Urinary Bladder; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Aged, 80 and over; Benzhydryl Compounds; Benzofurans; Denmark; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Norway; Practice Patterns, Physicians'; Prospective Studies; Pyrrolidines; Registries; Solifenacin Succinate; Sweden; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Brain; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Oxyhemoglobins; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics

To assess fesoterodine treatment in elderly women with overactive bladder with and without hypertension.. Data for 2527 elderly women with overactive bladder symptoms, including urgency urinary incontinence, were pooled from 10 double-blind, placebo-controlled fesoterodine studies.. A total of 1523 elderly women (60.3%) had a history of hypertension, and 1004 women (39.7%) had no hypertension history. Overactive bladder symptoms, mean bodyweight and mean body mass index at baseline were significantly higher in women with overactive bladder and hypertension versus those without hypertension (P < 0.05). Statistically significant improvements in overactive bladder symptoms at week 12 were observed for fesoterodine treatment versus placebo in women with hypertension and those without (P < 0.05). The diary-dry rate (no urgency urinary incontinence episodes), the proportion with less than eight micturitions/24 h, overactive bladder symptom bother and health-related quality of life were also statistically significantly improved by fesoterodine treatment in both populations. Incidence of treatment-related adverse events with fesoterodine was similar in women with hypertension (39.3%) and without hypertension (44.6%). Dry mouth and constipation were the most common treatment-related adverse events with fesoterodine in women with hypertension (26.2% and 5.2%, respectively) and without hypertension (30.5% and 8.0%).. A relationship among the severity of overactive bladder symptoms, hypertension and obesity in elderly women is suggested. Fesoterodine provides significantly greater improvements in overactive bladder symptoms and health-related quality of life versus placebo in women with or without hypertension. Hypertension does not appear to affect the efficacy and safety of fesoterodine in elderly women with overactive bladder symptoms, including urgency urinary incontinence.

Topics: Age Factors; Aged; Benzhydryl Compounds; Comorbidity; Constipation; Female; Humans; Hypertension; Incidence; Muscarinic Antagonists; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Xerostomia

To determine the impact of physicians' financial relationships with the pharmaceutical industry on prescribing marketed alpha-blockers and overactive bladder (OAB) medications. We also aim to examine if the number or total value of transactions is influential.. We linked the Open Payments Program database of industry payments to prescribers with Medicare Part D prescription data. We used binomial logistic regression to identify the association between receipt of industry payment and prescribing of marketed alpha-blockers (silodosin) and OAB medications (fesoterodine, solifenacin, and mirabegron). We also evaluated the impact of increasing total value and number of payments on prescribing of marketed drugs.. The receipt of industry payment was associated with increased odds of prescribing the marketed drug for all included drugs: silodosin (odds ratio [OR] 34.1), fesoterodine (OR 5.9), solifenacin (OR 2.7), and mirabegron (OR 6.8) (all P <.001). We also found that increasing value of total payment and increasing frequency of payments were both independently associated with increased odds of prescribing with a dose-response effect.. There is a consistent association between receipt of industry payment and prescribing marketed alpha-blockers and OAB medications. Both the total value and number of transactions were associated with prescribing.

Topics: Acetanilides; Adrenergic alpha-Antagonists; Benzhydryl Compounds; Databases as Topic; Drug Industry; Drug Prescriptions; Humans; Indoles; Medicare Part D; Practice Patterns, Physicians'; Solifenacin Succinate; Thiazoles; United States; Urinary Bladder, Overactive; Urological Agents; Urology

To examine early trends in the use of overactive bladder (OAB) agents across Canada, with a focus on initial uptake and reimbursement of two newer agents: fesoterodine, an anticholinergic, and mirabegron, a therapeutically novel beta-3 agonist.. We conducted a population-based cross-sectional study of outpatient prescriptions for long-acting oral OAB agents dispensed to individuals in Canada between May 2010 and April 2015 to examine the differences in the uptake of the newer agents and their reimbursement through cash, private, and public payers.. The national dispensing rate of OAB agents increased by 60% from May 2010 to April 2015 (from 924 to 1475 units per 10 000). We observed an increase in the dispensing rate of fesoterodine, solifenacin, and mirabegron, but a decrease in that of tolterodine and oxybutynin. Mirabegron was adopted rapidly after Health Canada approval, growing to a rate of 191 units per 10 000 by study completion, with its uptake being primarily funded through private payers (72.2%). Conversely, fesoterodine's uptake was minimal (8.3 units per 10 000) prior to its listing on public plans. This increased to 185 units per 10 000 by study completion, with the majority (65%) paid for by public insurers.. The differences in the uptake and reimbursement of two new OAB agents emphasize the impact of therapeutically novel agents on the prescription rates of older OAB agents with significant adverse effects. Further studies are needed to explain changes in the dispensing rates as more provinces list the newer drugs on their formulary.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Benzhydryl Compounds; Canada; Cholinergic Antagonists; Cross-Sectional Studies; Humans; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Benzhydryl Compounds; Canada; Humans; Thiazoles; Urinary Bladder, Overactive

Topics: Aged; Benzhydryl Compounds; Humans; Muscarinic Antagonists; Polypharmacy; Urinary Bladder, Overactive

The muscarinic receptors have been used as target in treatment of overactive bladder (OAB) for a long time. These patients have complaints of urgency, increased urinary frequency and nocturia, sometimes with urinary incontinence (involuntary urine leakage which is associated with abrupt and strong desire to void). Fesoterodine is a prodrug that is structurally and functionally associated with tolterodine and it is the novel drug for OAB treatment. As a result of fesoterodine cleavage by non-specific esterase, the active metabolite 5-hydroxymethyl tolterodine (5-HMT) is formed. Like other antimuscarinic drugs, fesoterodine allows to improve bladder storage function (reducing the frequency of urination) and urgency. For assessing an improvement of the quality of life after treatment by fesoterodine the KHQ questionnaire was used.

Topics: Benzhydryl Compounds; Cresols; Humans; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

The 33-item Overactive Bladder questionnaire (OAB-q; 1-week recall version) has been psychometrically validated in middle-aged, generally healthy patients with overactive bladder. The present analysis was conducted to determine the psychometric validity of the OAB-q in medically complex elderly patients.. OAB-q structure was evaluated using a second-order confirmatory factor analysis (CFA) model with five domains and one aggregated domain, using pooled data from two clinical trials (786 observations) for urgency urinary incontinence (UUI). Psychometric validity was evaluated with CFA, Cronbach coefficient α (CCA) for reliability, Spearman correlations for convergent validity, differences in OAB-q scores in relation to UUI severity and Patient Perception of Bladder Condition (PPBC) scores for known-groups validity, and effect size (ES) of differences in mean scores of OAB-q domains over time for treatment responsiveness.. Participants were predominantly female (82.2%) and white (85.9%); mean age was 75.0 years. The second-order CFA was confirmed with a Bentler's comparative fit index of 0.90, t values for path coefficients of >1.96, and standardized path coefficients of >0.40. OAB-q domains demonstrated good internal consistency (CCA >0.7). Convergent validity was supported by moderate correlations (0.4-0.7) between OAB-q domain and PPBC scores. Significant differences in OAB-q domain scores between groups with different symptom severity established known-groups validity. Significant changes in mean OAB-q scores from baseline to week 12 with moderate-to-large ES (0.50-0.80) demonstrated treatment responsiveness.. The OAB-q demonstrates reliability, concurrent and discriminant validity, and responsiveness to treatment. The evidence shows that the OAB-q is psychometrically sound for use in medically complex elderly patients with overactive bladder.

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Factor Analysis, Statistical; Female; Humans; Male; Patient Reported Outcome Measures; Psychometrics; Quality of Life; Reproducibility of Results; Statistics, Nonparametric; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

This technical update addendum reviews success rates and comparative evidence of the anticholinergic fesoterodine, as well as mechanism of action, safety profile, success rates, and comparative evidence of the β3 agonist mirabegron in the treatment of non-neurogenic overactive bladder syndrome (OAB). This adds to OAB pharmacotherapy recommendations initially published in 2012.. Residents and other trainees, primary care practitioners, gynaecologists, urologists, urogynaecologists, and other health care providers who assess, counsel, and treat women with OAB.. Adult women with symptomatic OAB.. This addition relates to fesoterodine, mirabegron, and anticholinergic-β3 agonist combination pharmacotherapy.. The outcomes of interest are clinical efficacy of fesoterodine compared with no treatment or other OAB therapies; mechanism of action and safety profile of mirabegron, clinical efficacy of mirabegron compared to no treatment or other OAB therapies; clinical efficacy of anticholinergic-β3 agonist combination pharmacotherapy for OAB.. PubMed, Medline, and the Cochrane Database were searched using the key words "fesoterodine" and "mirabegron." Results were restricted to English or French and human clinical and pharmacological research. Animal research and clinical studies including only male participants were excluded. Articles were included until the end of December 2016. Grey literature was not searched. Clinical practice guidelines, guidelines of specialty societies, and systematic reviews were included. RCTs and observational studies were included when evidence for the outcome of interest or in the target population was not available from systematic reviews. New studies not yet included in systematic reviews were also included. References of included articles were also searched to ensure comprehensive inclusion of relevant literature.. The content and recommendations were drafted and agreed upon by the principal author, as well as members of the Urogynaecology Committee. The Board of the SOGC approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework. The Summary of Findings is available upon request.. It is expected that this technical update will benefit patients with OAB by providing physicians and other interested health care providers with additional options for and knowledge of safe and effective OAB pharmacotherapy. The benefits clearly outweigh the potential harms or costs of implementation of this technical update, although there are no direct harms or costs identified. UPDATES: "Evidence will be reviewed 5 years after publication to decide whether all or part of the document should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations.". Not applicable.

Topics: Acetanilides; Benzhydryl Compounds; Drug Therapy, Combination; Female; Humans; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive; Urological Agents

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Benzhydryl Compounds; Contraindications, Drug; Drug Therapy, Combination; Female; Humans; Thiazoles; Urinary Bladder, Overactive; Urological Agents

The impact of formulary management strategies on utilization and expenditures in overactive bladder (OAB) treatment has not been extensively investigated. In 2013, step therapy (ST) policies for 2 branded OAB treatments, mirabegron and fesoterodine, were removed from Humana Medicare Advantage Prescription Drug (MAPD) plans and Medicare prescription drug plans (PDP), allowing for an examination of the effect of ST policies on OAB medication use patterns and costs.. To assess the impact of removal of formulary restriction policies for mirabegron and fesoterodine on medication utilization patterns and costs associated with OAB treatment in Medicare patients.. A retrospective cross-sectional study design was utilized. Subjects included individuals enrolled in Humana MAPD plans or PDPs, aged ≥ 65 years, with ≥ 1 prescription for an OAB medication in 2013. Patient demographic characteristics, OAB medication utilization, and pharmacy cost trends in 2013 were described. OAB medication use was calculated as the number of 30-day-supply equivalent medication claims and reported as a percentage of the total number of 30-day-supply equivalent claims across all OAB products. OAB medication expenditures were calculated as a percentage of the sum of pharmacy costs for OAB medications and reported separately for each month and drug during 2013. Temporal trends of OAB medication utilization and expenditures in 2013 were calculated using ordinary least squares regression.. Of 194,511 patients, trends in utilization of OAB medications indicated that on average, there was a statistically significant monthly increase in utilization of mirabegron (regression coefficient [B] = 274; P < 0.001; 95% CI: 218, 330), fesoterodine (B = 167; P < 0.001; 95% CI = 129, 205), oxybutynin extended release (ER; B = 357; P = 0.011; 95% CI = 99, 614), and trospium ER (B = 33; P = 0.001; 95% CI = 17, 50) and statistically significant decreases in utilization of solifenacin (B = -202; P = 0.048; 95% CI = -402, -2), tolterodine ER (B = -287; P = 0.002; 95% CI = -437, -137), darifenacin (B = -94; P < 0.001; 95% CI = -128, -61), and trospium immediate release (IR; B = -22; P = 0.001; 95% CI = -32, -12). Total OAB medication expenditures significantly increased an average of 0.12% for each month during the course of 2013 (B = 0.12; P = 0.026; 95% CI = 0.017, -0.223). While monthly oxybutynin IR utilization did not change significantly throughout 2013 (B = 228; P = 0.169; 95% CI = -114, -570), it demonstrated the largest average monthly expenditure increase (B = 0.082; P < 0.001; 95% CI = 0.056, 0.108). When removing oxybutynin IR costs from the total OAB medication costs, the trend in total OAB medication average monthly expenditures was not significant (B = 0.038; P = 0.365; 95% CI = -0.051, -0.126). An over 4-fold per-unit-cost increase for oxybutynin IR was noted.. Utilization of 2 branded OAB products increased in the months after ST removal with minimal cost impact. One of the possible reasons total OAB expenditures increased may have been due to the increased cost of the largest-volume generic product, oxybutynin IR.. This research was funded by Astellas Pharma Global Development and was conducted as part of the Astellas-Humana Research Collaboration. Ng, Kristy, Schermer, and Bradt are employees of Astellas. Astellas manufactures mirabegron (Myrbetriq) and solifenacin (VESIcare). Abbass, Caplan, Collins, and Suehs are employees of Comprehensive Health Insights, a subsidiary of Humana, which received funding from Astellas for this study. Suehs owns stock in Humana. Chan is an employee of Humana Pharmacy Solutions. Portions of this study were presented as a poster at Academy of Managed Care Pharmacy Nexus 2015; October 26-29, 2015; Orlando, Florida. Study concept and design were contributed by Ng, Chan, Suehs, and Abbass, along with Collins. Abbass took the lead in data collection, along with Collins and with assistance from Caplan, Chan, and Suehs. Data interpretation was provided by Kristy and Bradt, along with Abbass, Caplan, Ng, Suehs, Collins, and Chan. The manuscript was written primarily by Caplan, along with Schermer, Suehs, and Abbass, and revised by Caplan, Schermer, and Ng, along with the other authors.

Topics: Acetanilides; Aged; Benzhydryl Compounds; Cross-Sectional Studies; Drug Utilization; Female; Health Care Costs; Health Expenditures; Humans; Male; Managed Care Programs; Medicare; Muscarinic Antagonists; Retrospective Studies; Thiazoles; United States; Urinary Bladder, Overactive; Urological Agents

overactive bladder (OAB) is a common condition in older persons. Antimuscarinic treatment remains the mainstay of treatment of OAB but clinicians have been reluctant to prescribe this to older patients. This study examined efficacy and safety information from patients >65 in fesoterodine trials to reaffirm efficacy and to explore the relationships between treatment emergent adverse events (TEAEs), coexisting medication and co-morbidity.. data from 10 double-blind, placebo-controlled studies were analysed. A logistic regression analysis, where TEAE incidence was predicted by treatment, prior antimuscarinic treatment, number of coexisting medications, number of concomitant diseases and all possible combinations of two-way interaction terms with treatment was conducted.. of 4,040 patients who participated in trials; fesoterodine treatment was associated with statistically significant reductions in all disease-related and patient-reported outcomes compared to placebo. There was a significant increase in the likelihood of reporting a TEAE in association with the number of coexistent medications (odds ratio (OR) = 1.028, 95% CI: 1.0143-1.044, P < 0.003). The OR of having a TEAE with increase in the number of concomitant diseases was 1.058 (95% CI: 1.044-1.072, P < 0.0001). Central nervous system (CNS) events were few.. fesoterodine treatment led to clinically meaningful improvements across all included patient reported outcomes. The number of concomitant conditions had the greatest influence on the likelihood of an adverse event being reported. CNS TEAE were not associated with fesoterodine dose and were low across all categories of concomitant disease and coexisting medication.

Topics: Age Factors; Aged; Aged, 80 and over; Benzhydryl Compounds; Chi-Square Distribution; Comorbidity; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Least-Squares Analysis; Logistic Models; Male; Muscarinic Antagonists; Odds Ratio; Polypharmacy; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urodynamics; Urological Agents

In spinal cord injury, onset of detrusor overactivity (DO) is detrimental for quality of life (incontinence) and renal risk. Prevention has only been achieved with complex sophisticated electrical neuromodulation techniques.. To assess the efficacy of early fesoterodine fumarate (FF) administration in preventing bladder overactivity in a spinal cord transected (SCT) rat model.. 33 Sprague-Dawley rats were allocated to 6 groups-Group 1: 3 normal controls; Group 2: 6 SCT controls; Group 3: 6 SCT rats + FF 0.18 mg/kg/d; Group 4: 6 SCT rats + FF 0.12 mg/kg/d; Group 5: 6 SCT rats + FF 0.18 mg/kg/d + 72-h wash-out period; Group 6: 6 SCT rats + FF 0.12 mg/kg/d + 72-h wash-out period. SCT was performed at T10. FF was continuously administered. Cystometry was undertaken 6 weeks after SCT in awake rats recording intermicturition pressure (IMP), baseline pressure, threshold pressure (Pthres) and maximum pressure (Pmax). Normal controls and SCT controls were initially compared using the Mann-Whitney U tests in order to confirm the SCT effect on cystometric parameters. The comparisons in cystometric and metabolic cage parameters between SCT controls and treated rats were done using post-hoc Dunn's tests for Kruskal-Wallis analysis. Statistical testing was conducted at the two-tailed α-level of 0.05.. Pressure parameters were significantly higher in SCT control group compared to normal controls. Six weeks after SCT, IMP was significantly lower in low dose treated group than in SCT controls. Pmax was significantly lower in 3 treated groups compared to SCT controls. Pthres was significantly lower in full time treated groups than in SCT controls.. Early administration of FF modulates bladder overactivity in a SCT rat model. Whereas short-term prevention has been demonstrated, the long-term should be further analyzed. Clinical application of these results should confirm this finding through randomized research protocols.

Topics: Animals; Benzhydryl Compounds; Disease Models, Animal; Female; Muscarinic Antagonists; Pressure; Rats; Spinal Cord Injuries; Time Factors; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive

To determine the association between self-reported adherence to anticholinergic medication and clinical outcomes in women with overactive bladder (OAB).. A prospective study of women with OAB treated with fesoterodine for 8 weeks. Adherence to medication was measured using the Medication Adherence Self-report Inventory (MASRI). A self reported adherence rate of ≥80% was considered adherent. The association between self-reported adherence and clinical outcomes (Global Index of Improvement, Global impression of Severity, urinary symptom and quality of life scores) was examined. We hypothesized that adherent women would have greater improvement in urinary symptoms and quality of life than non-adherent women.. Based on the MASRI, 115 (62.5%) women were adherent and 69 (37.5%) were non-adherent to anticholinergic medication at 8weeks. Adherent women were more likely to report overall improvement in their symptoms compared to non-adherent women (84% vs. 24%, P < 0.001). Significantly more non-adherent women described their bladder symptoms as "moderate" or "severe" at 8 weeks compared to adherent women (74% vs. 44%, P = 0.03). At 8 weeks, adherent women reported significantly greater improvement (change) in urinary symptoms from baseline to 8 weeks than non-adherent women (-13.3 ± 25.8 vs. 2.5 ± 14.4, P = 0.04). Similarly, adherent women reported greater improvement in quality of life scores than non-adherent women (- 7.9 ± 24.0 vs. -1.8 ± 11.9, P = 0.003).. Self-reported non-adherence, as measured by the MASRI, is associated with clinically meaningful outcomes in women with OAB. This further validates the MASRI as a clinically useful tool for measuring adherence to anticholinergic medications in women with OAB. Neurourol. Urodynam. 35:738-742, 2016. © 2015 Wiley Periodicals, Inc.

Topics: Aged; Benzhydryl Compounds; Female; Humans; Medication Adherence; Middle Aged; Muscarinic Antagonists; Quality of Life; Self Report; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To assess the costs of treating overactive bladder (OAB) with fesoterodine compared to no OAB pharmacotherapy among vulnerable elderly from the US payer perspective.. A decision analytic cost model was developed to estimate the 52-week costs of a cohort of vulnerable elderly with OAB initiating treatment with fesoterodine or no OAB pharmacotherapy. Vulnerable elderly OAB patients were defined as those aged ≥65 years with self-reported urge urinary incontinence (UUI) symptoms for ≥3 months, 2-15 UUI episodes/day, and at risk of deteriorating health by a score of ≥3 on the Vulnerable Elders Survey (VES)-13. Patients were evaluated for fesoterodine treatment response (defined as no UUI episodes) and persistence at weeks 12, 26, and 52. The model included a hypothetical health plan with 100,000 elderly members. A total of 7096 vulnerable elderly subjects were identified as the model target population based on the percentage of vulnerable elderly and annual prevalence of OAB among vulnerable elderly. OAB-related costs included fesoterodine drug acquisition costs, healthcare resource use (inpatient hospitalization, outpatient visits, and physician office visits), and OAB-related co-morbidities (falls/fractures, urinary tract infections, depression, and nursing home admissions). All costs were inflated to 2013 US$ using the medical care component of the consumer price index (CPI).. When 7096 vulnerable elderly OAB patients were treated with fesoterodine, US healthcare payers could save $11,463,981 per year, or $1616 per patient vs no OAB pharmacotherapy. Univariate one-way sensitivity analyses supported the robustness of the findings and showed results were most sensitive to changes in fesoterodine efficacy followed by annual costs of inpatient hospitalization.. From a US payer perspective, treating vulnerable elderly OAB patients with fesoterodine was cost-saving compared to no OAB pharmacotherapy.

Topics: Aged; Benzhydryl Compounds; Cost Savings; Decision Support Techniques; Female; Geriatric Assessment; Hospitalization; Humans; Male; United States; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urological Agents; Vulnerable Populations

To assess therapeutic persistence and its relationship with concomitant medication in patients treated with fesoterodine versus tolterodine and solifenacin for overactive bladder (OAB) in standard clinical practice conditions.. An observational, multicentre retrospective study was performed based on medical registries of patients followed-up in primary care (PC). Three study groups were analysed. Persistence was defined as the time (in months) without withdrawing from the initial therapy or without changing to another medication for at least 30 days after the initial prescription. The concomitant medications were antidepressants, anxiolytic/hypnotic agents, antibiotics, antiseptic agents, laxatives and skin products. We employed the SPSSWIN program version 17 (statistical significance, P<.05).. We selected 3094 patients for the study. The median age was 54.0 years and 62.2% were women. The patients treated with fesoterodine shown greater treatment persistence (12 months) when compared with those who took solifenacin and tolterodine (40.2% vs. 34.7% and 33.6%, respectively; P=.008). They also showed a lower use of concomitant medication (1.1 vs. 1.2 and 1.2 drugs, respectively; percentages: 61.6% vs. 67.1% and 70.1%, respectively; P<.03).. The patients undergoing OAB treatment with fesoterodine, when compared with those taking solifenacin and tolterodine, were associated with greater treatment persistence and a reduced use of concomitant medication.

Topics: Benzhydryl Compounds; Female; Humans; Male; Medication Adherence; Middle Aged; Muscarinic Antagonists; Primary Health Care; Retrospective Studies; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive

To evaluate the cost-effectiveness of first-line treatment of Overactive Bladder (OAB) with fesoterodine relative to mirabegron, from the Spanish National Health System (NHS) perspective.. A decision tree model was developed to represent a typical clinical process of 52-week of treatment for an OAB patient with urge urinary incontinence (UUI) initiating first-line therapy with fesoterodine 4mg, including optional titration to 8mg, vs.mirabegron 50mg. Efficacy data were obtained from a Bayesian indirect treatment meta-analysis. Patients with UUI of less than one episode/day were defined as treatment responder and persistence was assessed at weeks 4, 12 and 24. At week 12, non-responders discontinued treatment permanently. Quality-adjusted life years (QALYs) were calculated based on time spent in responder and non-responder states. OAB-related drug and medical care costs including physician visits, laboratory tests, incontinence pads, and comorbidities (fracture, skin infection, urinary tract infections and depression) were modeled and expressed in €2015.. At week 52, the percentage of responders was 20.8% for patients starting on fesoterodine 4mg who optionally titrated to 8mg and 19.4% for patients treated with mirabegron. QALYs were slightly higher with fesoterodine than mirabegron (0.7703vs. 0.7668, difference=0.0035). Fesoterodine treatment also had slightly higher total costs than mirabegron (3,296€vs. 3,217, difference=79€), resulting in a cost of 22,523/QALY€ gained for fesoterodine versus mirabegron. Probabilistic sensitivity analysis confirmed the slight advantage of fesoterodine with a 61.1% probability of being cost-effective at the 30,000€ willingness-to-pay for 1QALY threshold.. Given the relatively small 1-year cost difference between the two treatments, fesoterodine can be considered a cost-effective option relative to mirabegron for the first-line management of OAB with UUI in Spain.

Topics: Acetanilides; Benzhydryl Compounds; Cost-Benefit Analysis; Delivery of Health Care; Female; Humans; Male; Middle Aged; Spain; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence, Urge

The aim of this study was to evaluate the safety and efficacy of fesoterodine fumarate (fesoterodine; Toviaz ) in Korean patients with overactive bladder (OAB) in routine clinical practice.. This was an open-label, non-interventional, prospective, post-marketing surveillance study submitted to the Korean Ministry of Food and Drug Safety. A total of 3109 patients aged ≥18 years with OAB symptoms were prescribed flexible doses of fesoterodine at the investigator's discretion. Safety was assessed based upon the reporting of adverse events (AEs). Efficacy was evaluated on the basis of patient self-assessment using a bladder diary as well as on the basis of investigator assessment in terms of overall clinical efficacy.. A final analysis was performed on 3107 (99.9%) and 2978 (95.8%) patients for safety and efficacy analysis, respectively. The mean treatment duration of fesoterodine was 83.2 days. The incidence of AEs was 8.5% (265/3107). Common AEs that accounted for more than 1.0% of the total AE incidence included dry mouth (5.4%, 168/3107), constipation (1.5%, 48/3107) and micturition disorder (1.1%, 35/3107). Mean episodes of urinary frequency, urgency, and urgency urinary incontinence (UUI) per 24 hours decreased by 4.0, 2.4, and 0.8, respectively (all p < 0.001). At the final follow-up visit, the investigators found improvement in clinical efficacy for the majority of patients (90.1%, 2684/2978). Limitations of this study include the observational study design and the relatively short treatment duration.. These results suggest that fesoterodine is a well tolerated and effective treatment for Korean patients with OAB in routine clinical practice.

Topics: Adult; Aged; Benzhydryl Compounds; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Product Surveillance, Postmarketing; Prospective Studies; Urinary Bladder, Overactive

To determine if treatment of overactive bladder (OAB) can improve self-reported limitations in physical activity in women.. This is a prospective study of women with OAB treated with flexible-dose fesoterodine therapy and standardized behavioral counseling. Subjects were evaluated at baseline and 8 weeks post-treatment. Physical activity scores were assigned using two questions of the Short Form 12 (SF-12) and categorized into three levels of physical activity (no limitations, moderate limitations, severe limitations). Response of urinary symptoms to treatment at 8 weeks was measured using the Patient Global Impression of Improvement. Physical activity limitations at baseline and 8 weeks were compared.. We recruited 137 women. At baseline, 71 (52%) women had no limitations, 34 (25%) had moderate, and 32 (23%) had severe physical limitations. Eight weeks after treatment, the proportion of women reporting severe limitations in physical activity was significantly lower with 71 (52%) women reporting no limitations, 50 (36%) reporting moderate, and 16 (12%) reporting severe limitations in physical activity (p = 0.001). At 8 weeks, the proportion of women with no limitations in physical activity was higher in responders than nonresponders (52% vs. 33%), and the proportion of women with severe restriction was lower in responders (13% vs. 17%), although there was no significant difference between the groups (p = 0.24), which both showed overall improvement in physical activity limitations.. Treatment of OAB is associated with a decrease in perceived physical activity limitations; however, this is not directly associated with improvement in urinary symptoms.

Topics: Adult; Aged; Benzhydryl Compounds; Cognitive Behavioral Therapy; Exercise; Female; Humans; Middle Aged; Prospective Studies; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder, Overactive

The ability to set realistic expectations of treatment response in patients with overactive bladder (OAB) can have an impact on patient engagement and adherence to study medication. In order to help set treatment expectations for OAB, a Physician Predictive Tool has been developed based on predictive modelling. Models have been developed utilizing data from eight Phase 3 and 4 fesoterodine clinical trials and these models enable the prediction of individual treatment response in subjects with OAB, based on various baseline characteristics. The data utilized and covariates that were hypothesized to influence treatment response are described. The model selection and development process are also outlined, and the final model and some example results utilizing this model are presented. Finally, we discuss the potential benefits and limitations of such a predictive tool.

Topics: Benzhydryl Compounds; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Humans; Muscarinic Antagonists; Risk Assessment; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge

To describe the profile of the overactive bladder (OAB) patient on treatment with flexible-dose antimuscarinic treatment in daily clinical practice.. This was an observational, retrospective and multicenter study, carried out at 88 public and private hospitals. Adult patients diagnosed with OAB who initiated flexible-dose antimuscarinic treatment. Type of antimuscarinic, dose, concomitant treatments, treatment benefit and treatment adherence were recorded.. This was a pluripathological (83.5% and polymedicated 73.4%) population, comprised of 846 patients, mostly women (74.5%) with a mean (SD) age of 61.3 (12.1) years and more than one year of OAB evolution. Main initially prescribed antimuscarinics were fesoterodine (66.5%) and solifenacine (30.0%). Overall, 68.2% of the patients started treatment with the low dosage; at the follow-up visit 47.0% changed the dosage (84.2% increased the dosage, 15.8% decreased the dosage). Patients who changed the dosage showed a significantly greater morbidity, worse OAB symptoms, greater health resources use, and worse adherence to treatment compared with those that maintained the high dosage all the time.. No differences were found regarding the demographic or clinical characteristics that allow us to identify which patients should receive the different options of available dose of antimuscarinic drugs, although greater benefits seem to be achieved with the use of the highest or the lowest dose from the outset than with the change of dose.

Topics: Benzhydryl Compounds; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Retrospective Studies; Solifenacin Succinate; Urinary Bladder, Overactive

To validate a self-administered instrument, the Medication Adherence Self-Report Inventory (MASRI) for measuring adherence to anti-cholinergic medication for overactive bladder (OAB).. Prospective study in 131 women with OAB treated with fesoterodine. Adherence was measured at 8 and 12 weeks using an interviewer administered brief medication questionnaire (BMQ) that assesses barriers to adherence (criterion standard), the MASRI, and pill count. Construct, concurrent and discriminant validity of the MASRI was assessed. We hypothesized that women who were non-adherent as measured by the MASRI would be more likely to have a belief barrier than women who were adherent to medication.. Women diagnosed as non-adherent by the MASRI were more likely to report a belief barrier to taking medication as compared to adherent women at 8 weeks (80% vs. 38%, P < 0.001) and at 12 weeks (70% vs. 40%, P = 0.003). Significant correlations were noted between adherence rates measured by the MASRI and the BMQ at 8 weeks (r = 0.87, P < 0.001) and 12 weeks (r = 0.90, P < 0.001). Moderate correlation was noted between the adherence rate as measured by the MASRI and pill count at 8 weeks (r = 0.49, P = 0.02) but not at 12 weeks (r = 0.05, P = 0.87). The MASRI correctly identified 93% and 96% of non-adherent women at 8 and 12 weeks, respectively. Sensitivity, specificity, and positive likelihood ratio of the MASRI for predicting non-adherence was 91%, 82%, and 5.1 at 8 weeks and 90%, 85% and 6.1 at 12 weeks.. The MASRI is a valid self-administered tool for measuring adherence to anti-cholinergic medication in women with OAB.

Topics: Aged; Attitude to Health; Benzhydryl Compounds; Cholinergic Antagonists; Cohort Studies; Female; Humans; Medication Adherence; Middle Aged; Muscarinic Antagonists; Prospective Studies; Reproducibility of Results; Surveys and Questionnaires; Urinary Bladder, Overactive

To assess the short-term compliance with fesoterodine treatment and to identify the reasons for lack of adherence and discontinuation in routine clinical practice. The secondary aim was to estimate the patient-reported outcomes.. This was an observational retrospective, multicenter study conducted in a sample of women with overactive bladder on fesoterodine treatment for at least three months. Adherence to medication was assessed using the Morisky-Green test. Patient-reported outcomes were assessed using the Incontinence Questionnaire Short Form (ICIQ-SF), Overactive Bladder Questionnaire Short Form (OAB-qSF), and Treatment Benefit Scale (TBS).. One hundred and twenty women with a mean age [standard deviation (SD)] of 62.2 (12.0) years with severe OAB [mean (SD) ICIQ-SF score 13.2 (4.0)] were included. 42.1% of the patients were considered compliant with fesoterodine treatment. The main causes for non-compliance/discontinuation stated by the remaining 57.9% of the patients were adverse events (62.2%) and lack of clinical benefits (20.0%). The illness status as well as the patient-perceived bother occasioned by the OAB symptoms and their impact on the quality of life improved significantly after three months on fesoterodine treatment (p<0.0001). Most of the patients stated that the current state of their urinary problems had greatly improved/ improved.. In routine clinical practice, a high percentage of patients were adherent to fesoterodine and perceived the benefit that the treatment provided them three months after starting treatment. However, more than half of the study population failed to comply or discontinued the treatment mainly due to intolerance or lack of efficacy.

Topics: Aged; Benzhydryl Compounds; Female; Humans; Medication Adherence; Middle Aged; Muscarinic Antagonists; Patient Satisfaction; Quality of Life; Retrospective Studies; Socioeconomic Factors; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder, Overactive

Overactive bladder (OAB) is a syndrome characterized by presenting symptoms of urgency, with or without urge incontinence, and normally accompanied by day and night frequency.. The aim of this study was to evaluate the impact of lost work productivity [number of days of sick leave] in patients treated with fesoterodine versus tolterodine and solifenacin to treat OAB in Spain.. A retrospective, observational study was carried out using the records (digital databases) of actively working patients (2008-2013). The study population comprised of patients from two autonomous communities; 31 primary care centres agreed to participate. Patients who began first treatment with antimuscarinics (fesoterodine, solifenacin or tolterodine) and who met certain inclusion/exclusion criteria were included in the study. Follow-up lasted for 1 year. The main outcome measures were comorbidity, medication possession ratio (MPR), treatment persistence, and number of days of sick leave and associated costs. Indirect costs were considered to be those related to lost work productivity (number of days of sick leave, exclusively), (1) due to OAB and (2) overall total. The cost was expressed as the average cost per patient (cost/unit). Multivariate analyses (Cox, ANCOVA) were used to correct the models.. A total of 3094 patients were recruited into the study; 43.0 % were treated with solifenacin, 29.2 % with tolterodine, and 27.8 % with fesoterodine. The average age of patients was 54 years (standard deviation 9.2), and 62.2 % were women. The comparison of fesoterodine versus solifenacin and tolterodine showed a higher MPR (90.0 vs. 87.0 and 86.1 %, respectively), higher treatment persistence (40.2 vs. 34.7 and 33.6 %), lower use of sick leave (22.8 vs. 52.9 and 36.7 %), total number of days of sick leave (5.1 vs. 9.7 and 9.3 days) and costs corrected for covariates (€371 vs. €703 and €683); p < 0.05.. Despite the possible limitations of this study, active patients who began treatment with fesoterodine to treat OAB (compared with solifenacin or tolterodine) had fewer days of sick leave, resulting in lower costs due to lost productivity.

Topics: Adult; Benzhydryl Compounds; Female; Follow-Up Studies; Humans; Male; Middle Aged; Muscarinic Antagonists; Primary Health Care; Retrospective Studies; Sick Leave; Solifenacin Succinate; Spain; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Work Performance

To explore in the daily clinical practice setting that antimuscarinic, Fesoterodine or Solifenacin, provides a greater clinical benefit after changing their prior Overactive Bladder (OAB) therapy with tolterodine extended-release (ER) to other novel antimuscarinic agents.. A post-hoc analysis of data from an observational multicenter, cross-sectional, retrospective study. Adult patients of both sexes, with OAB and OAB-V8 score≥8, who switched to fesoterodine or solifenacin within the 3-4 months before study visit from their prior tolterodine-ER-based therapy due to poor response were included. 92 patients were selected for each treatment group, matched (1:1) according to conditioned probability using the propensity score. Benefit of treatment change perceived by the physician and patient was evaluated by means of the Clinical Global Impression of Improvement subscale (CGI-I) and Treatment Benefit Scale (TBS), respectively. Degree of worry, bother and interference with daily living activities due to urinary symptoms, level of satisfaction, and preference for current treatment were also assessed.. Fesoterodine provided a significantly greater improvement than solifenacina in terms of therapeutic benefit perceived by the physician according to ICG-I. 96.7% of the patients on fesoterodine treatment vs. 81.6% of the solifenacin group showed a score of improvement in TBS (P<.05). Fesoterodine was also better rated than solifenacin with regard to satisfaction and preference for the new treatment (93.4 vs. 78.2% P<.05).. In daily clinical practice the switch from tolterodine LP to fesoterodine seems to provide greater benefits both from the physician's and the patient's point of view compared with those provided by solifenacin.

Topics: Activities of Daily Living; Adult; Aged; Benzhydryl Compounds; Comorbidity; Cresols; Cross-Sectional Studies; Drug Substitution; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Muscarinic Antagonists; Observational Studies as Topic; Patient Preference; Patient Satisfaction; Personal Satisfaction; Phenylpropanolamine; Physicians; Propensity Score; Quinuclidines; Retrospective Studies; Sample Size; Solifenacin Succinate; Tetrahydroisoquinolines; Therapeutic Equivalency; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents; Young Adult

To evaluate the use of resources and health costs in vulnerable elderly institutionalized patients with overactive bladder (OAB) treated with fesoterodine, tolterodine or solifenacin in routine medical practice.. A multicenter retrospective study, from the records of patients treated during 2008-2010 in three geographical locations and starting treatment with antimuscarinic (fesoterodine, solifenacin and tolterodine) for OAB. The attribute of vulnerability was based on collecting at least 3 of the Vulnerable Elders Survey criteria-13, age>75 years, poor/average age for health and difficulty in at least one daily physical activity.. morbidity, persistence and resource use and costs. Monitoring of patients was conducted over 52 weeks. A general linear model with covariates and bootstraping (1000) at random was used to construct the 95% CI of the cost differences between drugs.. Records of 552 patients (50.8% women, mean age: 80.2 years) were analyzed. Treated with fesoterodine (N=58), solifenacin (N=252) or tolterodine (N=212). The use of absorbent was 20.7%, 29.4% and 33.0% (P=.186), respectively. Persistence to treatment was slightly greater with fesoterodine. The patient healthcare costs/year were lower with fesoterodine, €1,775 (1550-2014) vs. solifenacin €2,062 (1911-2223) and tolterodine €2,149 (1,978-2,307), P=.042, as a result of lower utilization visits and concomitant medication.. Despite the potential limitations of the study, the vulnerable elderly non institutionalized patients with OAB treated with fesoterodine, compared to solifenacin or tolterodine were associated with lower resource utilization and healthcare costs.

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Female; Health Care Costs; Health Resources; Humans; Male; Muscarinic Antagonists; Retrospective Studies; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive; Vulnerable Populations

To investigate the pattern of use of anticholinergic drugs for overactive bladder among women in Norway with regard to persistence, adherence and switch rates.. Observational study.. Data from the Norwegian Prescription Database on prescriptions for tolterodine, solifenacin, darifenacin and fesoterodine filled in Norwegian pharmacies from 1 January 2004 to 31 December 2010.. Data from the database were analysed at an individual level, and drug persistence, discontinuation rates and switch rates during a follow-up period of 365 days after the first prescription were calculated.. Overall 1-year persistence for new users was 38.0%. Within the same period, a total of 10.3% switched from the index drug to another drug in the same group, whereas 51.7% discontinued without switching. Users of solifenacin and tolterodine were somewhat more persistent than users of darifenacin and fesoterodine. Persistence was lowest (20.9%) in the age group 18-39 years, increased with age and was highest in the age groups 70-79 years and 80 years and above (43.5 and 43.3%, respectively). In total, 31.9% filled only one prescription of the drug and, of these, only one of four women switched to another drug. The proportion who were adherent during treatment was 60.4%.. The discontinuation rate for anticholinergic drugs for overactive bladder in women is high. The reasons why patients stop using them remain obscure but could be related both to a limited clinical effect and an unacceptable adverse effect burden.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Benzofurans; Cholinergic Antagonists; Cresols; Databases, Pharmaceutical; Drug Substitution; Female; Follow-Up Studies; Humans; Medication Adherence; Middle Aged; Norway; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive; Young Adult

Topics: Benzhydryl Compounds; Cresols; Female; Humans; Male; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Overactive

Overactive bladder (OAB) is associated with high healthcare costs, which may be partially driven by drug treatment. There is little comparative data on antimuscarinic drugs with respect to resource use and costs. This study was conducted to address this gap and the growing need for naturalistic studies comparing health economics outcomes in adult patients with OAB syndrome initiating treatment with different antimuscarinic drugs in a primary care setting in Spain.. Medical records from the databases of primary healthcare centres in three locations in Spain were assessed retrospectively. Men and women ≥18 years of age who initiated treatment with fesoterodine, tolterodine or solifenacin for OAB between 2008 and 2010 were followed for 52 weeks. Healthcare resource utilization and related costs in the Spanish National Health System were compared. Comparisons among drugs were made using multivariate general linear models adjusted for location, age, sex, time since diagnosis, Charlson comorbidity index, and medication possession ratio.. A total of 1,971 medical records of patients (58.3% women; mean age, 70.1 [SD:10.6] years) initiating treatment with fesoterodine (n = 302), solifenacin (n = 952) or tolterodine (n = 717) were examined. Annual mean cost per patient was €1798 (95% CI: €1745; €1848). Adjusted mean (95% bootstrap CI) healthcare costs were significantly lower in patients receiving fesoterodine (€1639 [1542; 1725]) compared with solifenacin (€1780 [€1699; €1854], P = 0.022) or tolterodine (€1893 [€1815; €1969], P = 0.001). Cost differences occurred because of significantly fewer medical visits, and less use of absorbent products and OAB-related concomitant medication in the fesoterodine group.. Compared with solifenacin and tolterodine, fesoterodine was a cost-saving therapy for treatment of OAB in the primary care setting in Spain.

Topics: Aged; Benzhydryl Compounds; Cholinergic Agents; Cost-Benefit Analysis; Cresols; Female; Health Care Costs; Humans; Male; Phenylpropanolamine; Prevalence; Primary Health Care; Quinuclidines; Retrospective Studies; Solifenacin Succinate; Spain; Syndrome; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Evaluate the effect of the treatment with fesoterodine fumarate in patients with overactive bladder, as an alternative in case of failure of the usual anticholinergic treatment, due to either lack of therapeutic efficacy or due to intolerance to side effects.. A retrospective review of 158 patients with overactive bladder was carried out. The patients were divided into two groups; the first group; 56 patients where the anticholinergic treatment showed to be ineffective, and the second group; 102 patients who presented intolerance to anticholinergic side effects.. For the first group where fesoterodine fumarate was used to improve effectiveness of the anticholinergics, improvement in the components of urinary urgency (p=0.001), insufficient emptying (p=0.001), incontinence (p=0.009), and in the number of pads/day (p<0.001) was detected. As to the second group where fesoterodine fumarate was used as an alternative to anticholinergics to avoid side effects, a high reduction in the incidence of dry mouth (p<0.001) and constipation (p=0.015) was seen, as well as a significant clinical improvement.. Fesoterodine fumarate is an optimal treatment option when the clinical response to anticholinergics has not been satisfactory, either by the lack of therapeutic action or by intolerance to side effects, and especially when the treatment is expected to be long.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Female; Humans; Middle Aged; Muscarinic Antagonists; Retrospective Studies; Urinary Bladder, Overactive

Previous randomized studies have demonstrated that fesoterodine significantly improves the Overactive Bladder (OAB) symptoms and their assessment by patients compared with tolterodine extended-release (ER). This study aimed to assess the effect of aging and dose escalation on patient-reported treatment benefit, after changing their first Overactive Bladder (OAB) therapy with tolterodine-ER to fesoterodine in daily clinical practice.. A post-hoc analysis of data from a retrospective, cross-sectional and observational study was performed in a cohort of 748 OAB adults patients (OAB-V8 score ≥8), who switched to fesoterodine from their first tolterodine-ER-based therapy within the 3-4 months before study visit. Effect of fesoterodine doses (4 mg vs. 8 mg) and patient age (<65 yr vs. ≥65 yr) were assessed. Patient reported treatment benefit [Treatment Benefit Scale (TBS)] and physician assessment of improvement with change [Clinical Global Impression of Improvement subscale (CGI-I)] were recorded. Treatment satisfaction, degree of worry, bother and interference with daily living activities due to urinary symptoms were also assessed.. Improvements were not affected by age. Fesoterodine 8 mg vs. 4 mg provides significant improvements in terms of treatment benefit [TBS 97.1% vs. 88.4%, p < 0.001; CGI-I 95.8% vs. 90.8% p < 0.05)], degree of worry, bother and interference with daily-living activities related to OAB symptoms (p <0.05).. A change from tolterodine ER therapy to fesoterodine with dose escalation to 8 mg in symptomatic OAB patients, seems to be associated with greater improvement in terms of both patient-reported-treatment benefit and clinical global impression of change. Improvement was not affected by age.

Topics: Aged; Aging; Benzhydryl Compounds; Cohort Studies; Cresols; Cross-Sectional Studies; Delayed-Action Preparations; Drug Substitution; Female; Humans; Male; Middle Aged; Phenylpropanolamine; Retrospective Studies; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

To assess the efficacy and tolerability of fesoterodine 8 mg versus tolterodine extended release (ER) 4 mg in subjects with overactive bladder (OAB) stratified by age (<65, 65-74, and ≥75 years).. This was a post hoc analysis of data from two double-blind trials. Subjects reporting ≥1 urgency urinary incontinence (UUI) episode and ≥8 micturitions/24 hr at baseline were randomized to fesoterodine (4 mg for 1 week, 8 mg for 11 weeks), tolterodine ER 4 mg, or placebo. Subjects completed 3-day bladder diaries, Urgency Perception Scale (UPS), Patient Perception of Bladder Condition (PPBC), and OAB questionnaire (OAB-q) at baseline and week 12. The primary endpoint in both studies was change from baseline to week 12 in UUI episodes.. Among subjects <65 years (n = 2,670), improvements in UUI episodes, micturitions, urgency episodes, severe urgency episodes, frequency-urgency sum, UPS, PPBC, and all OAB-q scales and domains were significantly greater with fesoterodine versus tolterodine ER, and diary-dry rates were significantly higher. Among subjects 65-74 years (n = 990), improvements in mean voided volume per void, PPBC, and OAB-q Symptom Bother and Coping were significantly greater with fesoterodine versus tolterodine ER. Among subjects aged ≥75 years (n = 448), improvements in urgency episodes, severe urgency episodes, frequency-urgency sum, UPS, and OAB-q Symptom Bother were significantly greater with fesoterodine versus tolterodine ER. Both active treatments produced significant improvements in most outcomes versus placebo across age groups. Adverse event rates were similar among age groups.. Fesoterodine 8 mg consistently improved several OAB-related variables versus tolterodine ER 4 mg in subjects aged <65, 65-74, and ≥75 years, with some differences reaching statistical significance, and was generally well tolerated.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urination; Young Adult

To assess changes in overactive bladder (OAB) symptoms and patient-reported outcomes in a post hoc analysis in which subjects from a 12-week, open-label, flexible-dose fesoterodine study were stratified according to whether they opted for dose escalation.. Subjects with OAB (eight or more micturitions and three or more urgency episodes per 24 h) who reported dissatisfaction with tolterodine within 2 years of screening received fesoterodine 4 mg once daily for 4 weeks, with an optional dose increase to 8 mg after week 4 based on discussion of efficacy and tolerability between the subject and investigator. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and Urgency Perception Scale (UPS) at baseline and weeks 4 and 12, and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12. Subjects rated treatment satisfaction at week 12.. Dose escalation to 8 mg at week 4 was chosen by 255 (50%) of 513 subjects. At baseline, subjects who opted for dose escalation at week 4 (escalators) had significantly higher means for all diary variables except urgency urinary incontinence (UUI) episodes, significantly greater OAB-q Symptom Bother scores and significantly lower OAB-q health-related quality of life (HRQL) scores (all P < 0.05) compared to subjects who did not opt for dose escalation (non-escalators). There was no significant difference in the percentage of escalators (51%) and non-escalators (48%) who reported at least one UUI episode on baseline diary. At week 4 (before the decision to escalate was made), all outcomes were significantly improved vs baseline among both groups (all P < 0.0001), although non-escalators had significantly greater improvements in all diary variables and in PPBC and UPS scores than escalators (all P < 0.05), and the 5-day diary-dry rate (i.e. the percentage of subjects with at least one UUI episode on baseline diary and no UUI episodes on week 4 diary) was significantly higher (P = 0.0016) among non-escalators (62%) than among escalators (42%). At week 12, all outcomes were again significantly improved vs baseline among both groups (all P < 0.0001). There were no significant differences between non-escalators and escalators in week 12 improvements for most diary variables, UPS scores, OAB-q Symptom Bother scores, the diary-dry rate (68% vs 60%) or the percentage of subjects who reported treatment satisfaction (82% vs 78%). However, escalators still had significantly greater improvements from baseline in urgency episodes, PPBC scores and OAB-q total HRQL and Coping domains (P < 0.05). Adverse event rates were similar between non-escalators and escalators. Dry mouth was the most frequently reported adverse event; most cases were mild.. Flexible-dose fesoterodine significantly improved OAB symptoms and patient-reported outcomes in subjects who chose to remain on the initial 4-mg dose, as well as in the 50% of subjects who escalated to the 8-mg dose after 4 weeks. Non-escalators had significantly fewer OAB symptoms at baseline and significantly greater improvements than escalators before dose escalation. Escalators showed increased symptom relief after dose escalation; improvements in most outcomes were similar among non-escalators and escalators by week 12. Flexible-dose fesoterodine was well tolerated, with similar adverse-event profiles observed in the escalator and non-escalator groups. These results may help clinicians to identify patients more likely to require fesoterodine 8 mg to achieve maximum relief of OAB symptoms and thus facilitate dose escalation in these patients.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Dose-Response Relationship, Drug; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Satisfaction; Treatment Outcome; Urinary Bladder, Overactive; Young Adult

This study provides antimuscarinic agents for overactive bladder (OAB) display variable association with side effects mediated by the central nervous system (CNS), which may be of particular concern in the elderly. Adverse effects on CNS functioning are related to muscarinic receptor subtype selectivity and the ability of the agent to cross the blood-brain barrier, where P-gp plays a role in limiting permeability.. This study provides a parallel investigation of CNS penetration of antimuscarinic OAB agents in vivo and assessment of physical properties and permeability in cell monolayers in vitro. It adds further understanding of the roles of passive transcellular permeability and P-gp in determining CNS penetration of antimuscarinic OAB agents. It also enables a comparison of CNS side-effect profiles of OAB agents with preclinical CNS penetration data.. To assess and compare the mechanisms of central nervous system (CNS) penetration of antimuscarinic overactive bladder (OAB) agents.. Physical properties were computed or compiled from the literature. Rats were administered 5-hydroxymethyl tolterodine (HMT), darifenacin, oxybutynin, solifenacin, tolterodine or trospium subcutaneously. At 1 h postdose, plasma, brain and cerebrospinal fluid (CSF) concentrations were determined using LC-MS/MS assays. Brain and plasma protein binding were determined in vitro. Permeability in the presence and absence of the efflux transporter P-glycoprotein (P-gp) was assessed in RRCK and MDCK-MDR1 transwell assays.. Oxybutynin displayed extensive CNS penetration, with brain:plasma ratios (B:P), unbound brain:unbound plasma ratios (Kp,free) and CSF:free plasma ratios each >1. Tolterodine (B:P = 2.95, Kp,free = 0.23 and CSF:free plasma = 0.16) and solifenacin (B:P = 3.04, Kp,free = 0.28 and CSF:free plasma = 1.41) showed significant CNS penetration but with some restriction from CNS as indicated by Kp,free values significantly <1. 5-HMT, darifenacin and trospium displayed much lower B:P (0.03-0.16), Kp,free (0.01-0.04) and CSF:free plasma (0.004-0.06), consistent with poor CNS penetration. Permeability in RRCK cells was low for trospium (0.63 × 10(-6) cm s(-1) ), moderate for 5-HMT (11.7 × 10(-6) cm s(-1) ) and high for darifenacin, solifenacin, tolterodine and oxybutynin (21.5-38.2 × 10(-6) cm s(-1) ). In MDCK-MDR1 cells 5-HMT, darifenacin and trospium, were P-gp substrates, whereas oxybutynin, solifenacin and tolterodine were not P-gp substrates.. Brain penetration was low for antimuscarinics that are P-gp substrates (5-HMT, darifenacin and trospium), and significant for those that are not P-gp substrates (oxybutynin, solifenacin and tolterodine). CNS adverse events reported in randomized controlled clinical trials show general alignment with the preclinical data described in this study.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; Benzhydryl Compounds; Benzofurans; Blood-Brain Barrier; Brain; Cell Line; Chromatography, High Pressure Liquid; Cresols; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Randomized Controlled Trials as Topic; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Solifenacin Succinate; Tandem Mass Spectrometry; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive

As shorter recall periods are sometimes preferable to longer recall periods, the objective of this study was to evaluate the psychometric characteristics and measurement properties of the 1-week recall version of the Overactive Bladder Questionnaire (OAB-q).. Secondary analyses were performed on data for three 12-week clinical trials of fesoterodine. Patients completed the Patient Perception of Bladder Condition (PPBC), the Patient Perception of Urgency Scale (PPUS), and 3-day bladder diaries in addition to the OAB-q at baseline, 4 and 12 weeks. Analyses were conducted to evaluate the reliability, concurrent and discriminant validity and responsiveness of the OAB-q 1-week recall version.. The patients in the three studies (Study 1: N=516, Study 2: N=441; Study 3: N=882) had a mean age of 59.6, 59.4, and 59.9 years, respectively; and most of the patients were female (77.1%, 88.9%, and 82.9%) and White (76.6%, 90.0%, and 88.0%). Patients had been diagnosed with OAB for a mean of 5.2, 8.3, and 9.1 years, respectively. Cronbach's alpha values were greater than 0.85 across all samples and subscales. Correlations between the 1-week recall version of the OAB-q and the PPBC, PPUS, and most of the bladder diary variables were moderate to strong. Discriminant validity of the OAB-q was good, with significant differences in mean OAB-q scores across all response categories of the PPUS. The OAB-q was highly responsive to changes in patients' conditions as indicated by moderate to large effect sizes. The OAB-q 1-week recall version has a similar factor structure to the 4-week recall version with each subscale model demonstrating acceptable fit.. The 1-week recall version of the OAB-q appears to be reliable, valid, and responsive and is psychometrically equivalent to the 4-week recall version. The validation of the 1-week recall version offers researchers and clinicians an additional option for using the OAB-q.

Topics: Aged; Benzhydryl Compounds; Female; Humans; Male; Mental Recall; Middle Aged; Muscarinic Antagonists; Psychometrics; Quality of Life; Reproducibility of Results; Self Report; Surveys and Questionnaires; Time Factors; Treatment Outcome; Urinary Bladder, Overactive

Fesoterodine is an antimuscarinic agent indicated for the treatment of overactive bladder (OAB) symptoms. The objective of this study was to evaluate the efficacy of fesoterodine versus placebo over selected intervals during a 24-hour period in subjects with OAB.. In a post hoc analysis, data were analyzed from two randomized, double-blind, placebo-controlled 12-week phase III trials in which subjects with a history of OAB symptoms for >or=6 months were treated with morning doses of fesoterodine 4 mg, fesoterodine 8 mg, or placebo.. These trials are registered at ClinicalTrials.gov (NCT00220363 and NCT00138723).. Changes were evaluated in number of micturitions, urgency episodes, urgency urinary incontinence (UUI) episodes, and mean voided volume (MVV) divided into three 8-hour intervals: 08:00-15:59 (daytime), 16:00-23:59 (evening), and 00:00-07:59 (nighttime). Comparisons with placebo were made using analysis of covariance (for least squares mean changes) and Wilcoxon rank sum test (for median percent changes); differences were considered significant at p < 0.05.. Data from 1674 subjects, 80% of whom were women, were included in the analysis. At the end of treatment, the least squares mean change from baseline for all efficacy endpoints was significantly greater with fesoterodine 4 mg and fesoterodine 8 mg compared with placebo during each 8-hour time interval (all p < 0.05). Median percent change in number of micturitions, urgency episodes, and UUI episodes also was significantly greater with both fesoterodine doses compared with placebo during all time intervals (all p < 0.05).. Fesoterodine 4 mg and 8 mg given once daily demonstrated efficacy over placebo for OAB symptoms during all three 8-hour intervals of a 24-hour period, thus providing clinical support for once-daily dosing. Limitations include that this was a post hoc analysis.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Least-Squares Analysis; Male; Middle Aged; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Urinary Bladder, Overactive

To assess the cost-effectiveness of solifenacin vs other antimuscarinic strategies commonly used in UK clinical practice, based on the results of a recent published review.. Overactive bladder (OAB) syndrome is characterized by symptoms of urgency, frequency, incontinence and nocturia. Pharmacological treatment comprises oral antimuscarinic agents, which are divided into older-generation treatments, including oxybutynin, and new-generation treatments, comprising solifenacin, tolterodine, darifenacin and fesoterodine. The latter have reduced central nervous system penetration and have better selectivity for the M3 subclass of acetylcholine receptors, resulting in improved tolerability. A recent systematic review and meta-analysis of the efficacy and safety of antimuscarinics provided an opportunity for an economic evaluation of these agents using a rigorous assessment of efficacy. A cost-utility analysis was undertaken using a 1-year decision-tree model. Treatment success was defined separately for urgency, frequency and incontinence, with efficacy data taken from the recent review. Treatment persistence rates were taken from the Information Management System database. Utility values for the calculation of quality-adjusted life-years (QALYs) were taken from published sources. The analysis included costs directly associated with treatment for OAB, i.e. antimuscarinic therapy, consultations with general practitioners, and outpatient contacts. Resource use was based on expert opinion. Costs were reported at 2007/2008 prices. Extensive deterministic and probabilistic analyses were conducted to test the robustness of the base-case results.. Solifenacin was associated with the highest QALY gains (per 1000 patients) for all three outcomes of interest, i.e. urgency (712.3), frequency (723.1) and incontinence (695.0). Solifenacin was dominant relative to fesoterodine, tolterodine extended-release (ER) and tolterodine immediate-release (IR), and cost-effective relative to propiverine ER for urgency, frequency and incontinence. Solifenacin was not found to be cost-effective relative to oxybutynin IR for the frequency and incontinence outcomes, with an incremental cost-effectiveness ratio of > pound30,000/QALY threshold.. Solifenacin provided the greatest clinical benefit and associated QALYs for all three outcomes of interest across all therapies considered, and to be either dominant or cost-effective relative to all other new-generation agents, but not cost-effective relative to oxybutynin for frequency and incontinence.

Topics: Benzhydryl Compounds; Benzilates; Cost-Benefit Analysis; Cresols; Decision Trees; Delayed-Action Preparations; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

Overactive bladder (OAB) is a common condition that causes a profound impact on an individual's overall health and quality of life. Muscarinic antagonists are the mainstay of oral pharmacotherapy for OAB. The most-recently introduced muscarinic antagonist, fesoterodine fumarate, is unique in that the parent compound has no antimuscarinic efficacy due to its rapid and complete hydrolysis after oral administration. The active metabolite, 5-hydroxymethyl tolterodine, is responsible for all of the antimuscarinic effects. In two phase III studies, fesoterodine has been shown to significantly reduce mean urgency and urge urinary incontinence (UUI) episodes over placebo. As many as 60% of patients actively treated with fesoterodine reported no urge urinary incontinence episodes on a 3-day voiding diary, a significant improvement over placebo. Finally, several quality of life indices were significantly improved over placebo. There was a dose-related increase in antimuscarinic adverse events, such as dry mouth and constipation; however, few patients discontinued fesoterodine due to side effects.

Topics: Animals; Benzhydryl Compounds; Clinical Trials as Topic; Cresols; Humans; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Urinary Bladder, Overactive

Topics: Benzhydryl Compounds; Humans; Muscarinic Antagonists; Urinary Bladder, Overactive

Recent studies have described muscarinic receptors on the mucosa and the detrusor of the human urinary bladder. Muscarinic receptor antagonists are effective in the treatment of overactive bladder (OAB), but their site(s) of action and actual therapeutic target are unclear. Our aim was to compare, in human bladder mucosa and detrusor, the radioligand binding characteristics of newer, clinically effective agents: darifenacin, its hydroxylated metabolite UK-148,993, fesoterodine, solifenacin, tolterodine, and trospium. Specimens were collected from asymptomatic patients (50-72 years old) undergoing open bladder surgery. Radioligand binding studies with the muscarinic antagonist [3H]quinuclidinyl benzilate (QNB) were performed separately on detrusor and mucosal membranes. All antagonists displayed high affinity when competing for [3H]QNB binding in both detrusor and mucosa. Inhibition constants were also obtained for all antagonists against individual muscarinic receptor subtypes expressed in Chinese hamster ovary cells. Here, fesoterodine showed anomalous binding results, suggesting that some conversion to its metabolite had occurred. Global nonlinear regression analysis of bladder binding data with five antagonists demonstrated 82% low-affinity sites in mucosa and 78% low-affinity sites in detrusor, probably representing M(2)/M(4) receptors. There was an excellent correlation (r(2) = 0.99) of low-affinity global estimates between detrusor and mucosa, whereas the corresponding high-affinity estimates ( approximately 20% of sites) were dissimilar. In conclusion, commonly used and clinically effective muscarinic receptor antagonists bind to receptors located on the bladder mucosa and the detrusor, providing support for the hypothesis that muscarinic receptors in the mucosa may represent an important site of action for these agents in OAB.

Topics: Aged; Benzhydryl Compounds; Benzofurans; Cresols; Cystectomy; Female; Humans; Male; Middle Aged; Mucous Membrane; Muscarinic Antagonists; Phenylpropanolamine; Prostatectomy; Pyrrolidines; Quinuclidines; Quinuclidinyl Benzilate; Radioligand Assay; Receptors, Muscarinic; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder; Urinary Bladder, Overactive

To review the efficacy and safety of fesoterodine, a new antimuscarinic for treating overactive bladder (OAB) symptoms.. Review of efficacy and safety data from the pivotal phase 3 trials of fesoterodine for the treatment of OAB. Although there were a number of additional end points, they were not included in the US prescribing information for fesoterodine and thus are not included in this article.. OAB is a chronic condition affecting both men and women. The principal symptom is urgency, with or without urgency incontinence, with some patients experiencing increased daytime frequency and nocturia. In two 12-week, randomized, double-blind, phase 3 trials, fesoterodine 4 and 8 mg administered once daily were significantly better than placebo in alleviating OAB symptoms, as determined by changes in bladder diary variables. Both doses of fesoterodine were well tolerated.. Fesoterodine is an efficacious, well-tolerated treatment for OAB.

Topics: Benzhydryl Compounds; Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Humans; Multicenter Studies as Topic; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Urinary Bladder, Overactive

Topics: Benzhydryl Compounds; Drug Approval; Humans; Muscarinic Antagonists; United States; Urinary Bladder, Overactive

Topics: Benzhydryl Compounds; Humans; Muscarinic Antagonists; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urinary Incontinence, Urge

Topics: Benzhydryl Compounds; Contraindications; Drug Administration Schedule; Humans; Muscarinic Antagonists; Urinary Bladder, Overactive

Topics: Adult; Benzhydryl Compounds; Clinical Trials as Topic; Drug Approval; Drug Interactions; Drug Labeling; Humans; Muscarinic Antagonists; Quality of Life; Treatment Outcome; United States; United States Food and Drug Administration; Urinary Bladder, Overactive

To investigate the primary pharmacology of fesoterodine (a novel antimuscarinic drug developed for treating overactive bladder) and SPM 7605 (its active metabolite, considered to be the main pharmacologically active principle of fesoterodine in man) against human muscarinic receptor subtypes, and to investigate in vitro and in vivo functional activity of these agents on the rat bladder compared with existing standard agents.. The displacement of radioligand binding by fesoterodine, SPM 7605 and standard agents in membrane preparations of Chinese hamster ovary (CHO) cells expressing the different human muscarinic receptors (M1-M5) was characterized. Agonistic and antagonistic activities were studied using different CHO cell lines stably expressing the human recombinant muscarinic receptor subtypes. The effects of fesoterodine and SPM 7605 on isolated bladder strips contracted by carbachol or electrical field stimulation (EFS) were investigated. In vivo the effects of fesoterodine and SPM 7605 on micturition variables were assessed using continuous cystometry in conscious female Sprague-Dawley rats, and compared to those of oxybutynin and atropine.. In vitro SPM 7605 potently inhibited radioligand binding at all five human muscarinic receptor subtypes with equal affinity across all five. Fesoterodine had a similar balanced selectivity profile but was less potent than SPM 7605. Both substances were competitive antagonists of cholinergic agonist-stimulated responses in human M1-M5 cell lines and had a similar potency and selectivity profile to the radioligand-binding studies. In rat bladder strips, fesoterodine and SPM 7605 caused a rightward shift of the concentration-response curve for carbachol with no depression of the maximum, and concentration-dependently reduced contractions induced by EFS. The potency of both drugs was similar to that of atropine and oxybutynin. In the presence of the esterase inhibitor neostigmine, the concentration-response curve of fesoterodine was shifted to the right, suggesting that part of the activity was caused by metabolism to SPM 7605 by tissue enzymes. In vivo, low doses (0.01 mg/kg) of fesoterodine and SPM 7605 reduced micturition pressure and increased intercontraction intervals and bladder capacity, but did not affect residual volume.. Fesoterodine and its active metabolite, SPM 7605, are nonsubtype selective, competitive antagonists of human muscarinic receptors, but SPM 7605 has greater potency than the parent compound. Pharmacodynamic studies in the rat bladder in vitro confirm the competitive muscarinic antagonist profile of these agents in a native tissue preparation, and in vivo studies in the rat showed effects on bladder function consistent with a muscarinic antagonist profile.

Topics: Animals; Benzhydryl Compounds; Cricetinae; Cricetulus; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Female; Humans; Muscarinic Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Urinary Bladder, Overactive