Fesoterodine 8mg modified-release tablets

Anticholinergics (ACs) are among the most prescribed drugs. Investigating the impaired cognitive domains due to individual ACs usage is associated with controversial findings. Objective: The objective of this study was to investigate the effects of individual ACs on different aspects of cognitive function based on clinical trial studies. Methods: This systematic review was conducted following the PRISMA statement. A systematic search was performed in Embase, PubMed, Cochrane Library, Scopus, and Web of Science databases. Risk of bias (RoB) was assessed by the Joanna Briggs Institute checklists and the meta-analysis was performed using the CMA software. Results: Out of 3,026 results of searching, 138 studies were included. A total of 38 studies that assess the cognitive impacts of scopolamine were included in the meta-analysis. Included studies reported cognitive effects of scopolamine, mecamylamine, atropine, biperiden, oxybutynin, trihexyphenidyl, benzhexol, and dicyclomine; however, glycopyrrolate, trospium, tolterodine, darifenacin, fesoterodine, tiotropium, and ipratropium were not associated with cognitive decline. Based on the meta-analyses, scopolamine was associated with reduced recognition (SDM -1.84; 95%CI -2.48 to -1.21; p<0.01), immediate recall (SDM -1.82; 95%CI -2.35 to -1.30; p<0.01), matching to sample (SDM -1.76; 95%CI -2.57 to -0.96; p<0.01), delayed recall (SDM -1.54; 95%CI -1.97 to -1.10; p<0.01), complex memory tasks (SDM -1.31; 95%CI -1.78 to -0.84; p<0.01), free recall (SDM -1.18; 95%CI -1.63 to -0.73; p<0.01), cognitive function (SDM -0.95; 95%CI -1.46 to -0.44; p<0.01), attention (SDM -0.85; 95%CI -1.38 to -0.33; p<0.01), and digit span (SDM -0.65; 95%CI -1.21 to -0.10; p=0.02). There was a high RoB in our included study, especially in terms of dealing with possible cofounders. Conclusion: The limitations of this study suggest a need for more well-designed studies with a longer duration of follow-up on this topic to reach more reliable evidence.

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OBJECTIVE: To systematically compare the efficacy and safety of medications in elderly with overactive bladder. METHODS: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched from database inception to July 25, 2023, and randomized, controlled, double-blind trials for overactive bladder in the elderly were screened according to the protocol. Data were analyzed using Stata17.0. RESULTS: In terms of reducing Micturitions, the interventions were ranked: trospium chloride (TRO), fesoterodine (FES) 4/8 mg, vibegron (VIB), mirabegron (MIR) 25/50 mg, tolterodine ER (TOL) 4 mg, placebo (PBO), of which only TOL showed no significant difference compared to placebo; Forsafety, the TEAE of TOL 4/8 mg had the highest incidence and was significantly different from others; MIR, VIB, and FES 4mg were well-tolerated regarding dry mouth and constipation; TOL 4 mg, FES 4/8 mg, and VIB showed a statistically increase from placebo for headache and FES 4/8mg and MIR 25 mg showed a statistically increase for dizziness. CONCLUSIONS: TRO 60 mg has the best efficacy in reducing micturitions, but increases the incidence of dry mouth and constipation; VIB and MIR are well tolerated in dry mouth and constipation, but may increase the risk of headache or dizziness.

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bladder based on a systematic review and network meta-analysis approach. METHODS: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. RESULT: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. CONCLUSION: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.

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BACKGROUND: Patients with benign prostatic hyperplasia (BPH) receive α-blockers as first-line therapy to treat lower urinary tract symptoms; however, some individuals still experience residual storage symptoms. Antimuscarinics, β3-agonists, and desmopressin are effective add-on medications. Nevertheless, there is currently no evidence for the appropriate choice of the first add-on medication. This systematic review aimed to investigate the clinical benefits of antimuscarinics, β3-agonists, and desmopressin, in addition to α-blockers, for persistent storage symptoms in BPH patients. METHODS: A comprehensive literature search of randomized controlled trials (RCTs) comparing the efficacy of different add-on medications in BPH patients with persistent storage symptoms despite α-blocker treatment was conducted. Clinical outcomes included the International Prostate Symptom Score (IPSS), IPSS storage subscore, nocturia, micturition, and urgency. A network meta-analysis was performed to estimate the effect size. Surface under cumulative ranking curves (SUCRAs) were used to rank the included treatments for each outcome. RESULTS: A total of 15 RCTs were identified. Add-on imidafenacin and mirabegron resulted in significant improvement in all outcomes assessed. Other add-on medications such as desmopressin, tolterodine, solifenacin, fesoterodine, and propiverine showed positive benefits for most, but not all, outcomes. Based on the SUCRA rankings, add-on desmopressin was the best-ranked treatment for IPSS and nocturia, and add-on imidafenacin was the best for the IPSS storage subscore and micturition. CONCLUSIONS: BPH patients presenting with persistent storage symptoms despite α-blocker administration are recommended to include additional treatment. Desmopressin and imidafenacin may be considered high-priority add-on treatments because of their superior efficacy compared with other medications.

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This narrative review discusses the relationship between anticholinergic medications and cognitive change specifically in patients with neurogenic lower urinary tract dysfunction (NLUTD). NLUTD is prevalent in various conditions, including spinal cord injury (SCI), spina bifida (SB), multiple sclerosis (MS), Parkinson's, stroke, and dementia and often requires anticholinergic overactive bladder (OAB) medications. In the general population, and among those with OAB, several studies have found a significant association between this class of medications and cognitive side effects, mostly when used for > 90 days. These cognitive side effects may be particularly relevant to people with NLUTD due to their higher baseline risk of cognitive impairment. Two studies (one in people with SCI and another in MS) found evidence of cognitive impairment with the use of OAB anticholinergics (specifically oxybutynin and tolterodine). People with dementia commonly use OAB anticholinergics, and there is evidence that oxybutynin and tolterodine may impair cognition in this population. Two recent studies in children with SB studied 12 months of solifenacin and 6 months of fesoterodine/oxybutynin and found there was no significant change in neuropsychological testing. Clinical studies in people with Parkinson's disease and prior stroke have not shown that trospium, darifenacin, or fesoterodine have a significant impact on cognitive measures. In summary, oxybutynin and tolterodine may pose a higher risk of cognitive impairment than newer OAB anticholinergics in people with NLUTD; there is no evidence that children with SB experience cognitive impairment with OAB anticholinergics. Further study is necessary to confirm cognitive safety, particularly as the NLUTD population may have a high exposure to OAB anticholinergics. Advocating for potentially safer OAB medications is necessary if there is concern about cognitive risks.

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Background: Older patients (> 65 yr) suffering from overactive bladder (OAB) are more likely to have functional impairment and comorbidity than those without OAB. This article reviews available published studies and discusses how fesoterodine might meet the specific needs of the older OAB patient. Methods: A comprehensive literature search was undertaken in order to evaluate fesoterodine safety in older OAB patients. Results: Fesoterodine offers flexible dosing, allowing the clinician to balance risk and benefits according to the symptoms and preferences of the patient. Its balanced affinity for M2 and M3 muscarinic receptors may lead to its benefit on OAB symptoms. Its active metabolite is a P-gp substrate that is actively transported from the central nervous system (CNS), potentially avoiding adverse CNS effects. Fesoterodine can be used in mild or moderate hepatic or renal insufficiency and no dose adjustment is routinely required. Fesoterodine's benefit has been demonstrated in multiple clinical trials in older and medically vulnerable patients. Fesoterodine was rated as "beneficial" in the LUTS-FORTA classification due to its efficiency and tolerability in older patients. Conclusion: Here, the use of fesoterodine in older and vulnerable patients is summarized given the need to approach pharmacotherapy for OAB differently in older adults.

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Objective: To investigate whether different anticholinergic drug treatments for overactive bladder have differential risks for incident dementia, in a large representative population of older adults in England. Design: Nested case-control study. Setting: General practices in England providing data to the Clinical Practice Research Datalink (CPRD) GOLD database, with linked patient admission records from secondary care (Hospital Episode Statistics), 1 January 2006 and 16 February 2022. Participants: 170 742 patients aged ≥55 years, with a first reported diagnosis of dementia during the study period, matched by age, sex, and general practice with 804 385 individuals without dementia (controls). Interventions: Cumulative drug use (defined using total standardised daily dose) of different anticholinergic drugs used for the treatment of an overactive bladder, and a non-anticholinergic drug, mirabegron, in the period 3-16 years before a diagnosis of dementia (or equivalent date in matched controls). Main outcome measures: Odds ratios for onset of dementia associated with the different anticholinergic drugs used for the treatment of an overactive bladder, adjusted for sociodemographic characteristics, clinical comorbidities, and use of other anticholinergic drug treatments. Results: The study population comprised 62.6% women, and median age was 83 (interquartile range 77-87) years. 15 418 (9.0%) patients with dementia and 63 369 (7.9%) controls without dementia had used anticholinergic drugs for the treatment of an overactive bladder in the 3-16 years before diagnosis (or equivalent date for controls). The adjusted odds ratio for dementia associated with the use of any anticholinergic drug used to treat an overactive bladder was 1.18 (95% confidence interval (CI) 1.16 to 1.20), and was higher in men (1.22, 1.18 to 1.26) than women (1.16, 1.13 to 1.19). The risk of dementia was substantially increased with the use of oxybutynin hydrochloride (adjusted odds ratio 1.31, 95% CI 1.21 to 1.42 and 1.28, 1.15 to 1.43 for use of 366-1095 and >1095 total standardised daily doses, respectively), solifenacin succinate (1.18, 1.09 to 1.27 and 1.29, 1.19 to 1.39), and tolterodine tartrate (1.27, 1.19 to 1.37 and 1.25, 1.17 to 1.34). No significant increases in the risk of dementia associated with darifenacin, fesoterodine fumarate, flavoxate hydrochloride, propiverine hydrochloride, and trospium chloride were found. The association between mirabegron, a non-anticholinergic drug, and dementia was variable across the dose categories and might be caused by previous use of anticholinergic drugs for the treatment of an overactive bladder in these individuals. Conclusions: Of the different anticholinergic drugs used to treat an overactive bladder, oxybutynin hydrochloride, solifenacin succinate, and tolterodine tartrate were found to be most strongly associated with the risk of dementia in older adults. This finding emphasises the need for clinicians to take into account the possible long term risks and consequences of the available treatment options for an overactive bladder in older adults, and to consider prescribing alternative treatments that might be associated with a lower risk of dementia.

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Introduction: Fesoterodine is one of the most widely used antimuscarinic drugs to treat an overactive bladder. Fesoterodine is extensively hydrolyzed by esterases to 5-hydroxymethyl tolterodine (5-HMT), the major active metabolite. CYP2D6 and CYP3A4 mainly metabolize 5-HMT and are, therefore, the primary pharmacogenetic candidate biomarkers. Materials and Methods: This is a candidate gene study designed to investigate the effects of 120 polymorphisms in 33 genes (including the CYP, COMT, UGT, NAT2, and CES enzymes, ABC and SLC transporters, and 5-HT receptors) on fesoterodine pharmacokinetics and their safety in 39 healthy volunteers from three bioequivalence trials. Results: An association between 5-HMT exposure (dose/weight corrected area under the curve (AUC/DW) and dose/weight corrected maximum plasma concentration (Cmax/DW)), elimination (terminal half-life (T1/2) and the total drug clearance adjusted for bioavailability (Cl/F)), and CYP2D6 activity was observed. Poor/intermediate metabolizers (PMs/IMs) had higher 5-HMT AUC/DW (1.5-fold) and Cmax/DW (1.4-fold) values than the normal metabolizers (NMs); in addition, the normal metabolizers (NMs) had higher 5-HMT AUC/DW (1.7-fold) and Cmax/DW (1.3-fold) values than the ultrarapid metabolizers (UMs). Lower 5-HMT exposure and higher T1/2 were observed for the CYP3A4 IMs compared to the NMs, contrary to our expectations. Conclusions: CYP2D6 might have a more important role than CYP3A4 in fesoterodine pharmacokinetics, and its phenotype might be a better predictor of variation in its pharmacokinetics. An association was observed between different genetic variants of different genes of the UGT family and AUC, Cmax, and CL/F of 5-HMT, which should be confirmed in other studies.

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