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Urinary tract disorders
Published in Henry J. Woodford, Essential Geriatrics, 2022
The only bladder anticholinergic drug that has been tested in older people with moderate to severe frailty is oxybutynin. Three studies have shown it to be ineffective in people with a mean age in their 80s (two in nursing home settings).111–113 Currently in the UK, the National Institute of Health and Care Excellence recommends not prescribing oxybutynin for women ‘at higher risk of a sudden deterioration in their physical or mental health'.87 There is no evidence to support the safety or efficacy of any other anticholinergic in older people with moderate to severe frailty. A study of fesoterodine for mildly frail older people (n = 562; mean age 75 [range 60–91]; mean MMSE score 28; requiring some assistance with daily activities) showed a similar effect size to non-frail people (0.6 fewer UI episodes per 24 hours v placebo).114 Adverse effects in the active treatment group included dry mouth (24%), constipation (11%), urinary retention (3%) and cognitive impairment (1%), which caused 9% of participants to discontinue fesoterodine within the 12-week study period.
Neurourology
Published in Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed, MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
Which is TRUE regarding anticholinergic medications?Oxybutynin causes direct smooth muscle relaxation via calcium channel blockade.Tolterodine is M3 receptor specific.M3 receptors are more abundant in the detrusor but M2 receptors are functionally more important.The STAR study compared efficacy, side effect profile and discontinuation rates of solifenacin 5 mg with 10 mg.Fesoterodine is a prodrug that after oral administration is hydrolysed to the same active metabolite as oxybutynin.
Urinary Incontinence
Published in David M. Luesley, Mark D. Kilby, Obstetrics & Gynaecology, 2016
Dudley Robinson, Linda Cardozo
Fesoterodine is a novel derivative of 3,3–diphenylpropyl-amine which is a potent antimuscarinic agent that has more recently been developed for the management of OAB. A phase 11 dose-finding study was conducted in 728 patients in Europe and South Africa.124 Fesoterodine 4 mg, 8 mg and 12 mg were all found to show significantly greater decreases in micturition frequency than placebo. The most commonly reported side effect was dry mouth with an incidence of 25 percent in the 4 mg group, rising to 34 percent in the 12 mg group. Discontinuation rates were 6 percent and 12 percent respectively. Subsequently a phase III randomised placebo-controlled trial has been reported comparing fesoterodine 4 mg and 8 mg with tolterodine ER 4 mg in patients complaining of OAB in 1135 patients at 150 sites throughout Australia, New Zealand, South Africa and Europe.125 Both doses of fesoterodine demonstrated significant improvements over placebo in reduction of daytime frequency and number of urge incontinence episodes per day and were found to be superior to tolterodine. The current evidence from two large phase IV studies would support these findings and suggest that fesoterodine may offer some advantages over tolterodine in terms of efficacy and flexible dosing regimens.126,127
The safety and effectiveness of mirabegron in Parkinson’s disease patients with overactive bladder: a randomized controlled trial
Published in Scandinavian Journal of Urology, 2022
Mohamad Moussa, Mohamad Abou Chakra, Baraa Dabboucy, Youssef Fares, Athanasios Dellis, Athanasios Papatsoris
Other randomized controlled trials (RCT) were performed to assess the efficacy of antimuscarinics for the treatment of OAB in patients with PD. An RCT evaluated the efficacy of solifenacin succinate in this setting. Patients were randomized to receive solifenacin succinate 5–10 mg daily or a placebo for 12 weeks followed by an 8-week open-label extension. Results showed that there was an improvement in the number of micturitions per 24 hour period in the solifenacin succinate group compared to placebo at a mean dose of 6 mg/day (p = 0.01) with multiple side effects [20]. Yonguc et al. [21] performed another RCT to test the short-term efficacy and safety of fesoterodine fumarate in PD patients with OAB. Sixty-three patients were randomized to receive fesoterodine 4 mg or placebo for 4 weeks. OAB symptoms were significantly improved in older adults with PD under fesoterodine fumarate treatment, even in the open-label period. The cognitive function was not affected in the treatment group.
Choosing oral drug therapy for overactive bladder in older people
Published in Expert Opinion on Pharmacotherapy, 2018
The efficacy of fesoterodine 4 and 8 mg versus placebo in a 12-week placebo-controlled, randomized study in men and women over 65 years of age resulted in improvement from baseline in urgency episodes (−1.92 vs. −3.47, p < 0.001), micturition frequency (−0.93 vs. −1.91, p < 0.001), nocturnal micturition frequency (−0.27 vs. −0.51, p = 0.003), severe urgency episodes (−1.55 vs. −2.40, p < 0.001), and incontinence pad use (−0.48 vs. −1.07, p = 0.01) [35]. The responses on the patient-reported outcome measures, Treatment benefit Scale, Overactive Bladder-Satisfaction Scale, Patient Perception of Bladder Condition, and Urgency Perception Scale were also statistically significantly greater in those in the fesoterodine group versus placebo. The effect of fesoterodine has also been assessed in older people classified as at risk of decline or death by the Vulnerable Elders Survey [39], many of whom fulfilled the frailty phenotype. This 12-week double-blind, placebo-controlled study included 562 people of mean age 75 years and resulted in mean reductions in UUI episodes at week 12 versus placebo (−0.65 (0.21), p < 0.0018) and 24-h micturition frequency (−0.84 (0.23), p < 0.0003) [36]. Adverse effects in all fesoterodine trials were dominated by dry mouth, affecting up to a third of patients exposed to fesoterodine 8 mg, which was mostly mild in nature. Treatment discontinuations and central nervous system (CNS) AEs were few. A post hoc pooled analysis which examined the effect of coexistent comorbid conditions and number of medications at baseline on the probability of reporting treatment emergent adverse events (TEAEs) with fesoterodine also noted the relative rarity of CNS AEs which were only related to dose in patients >75 years [40].
The prodrug approach in the era of drug design
Published in Expert Opinion on Drug Delivery, 2019
Prodrugs can also be designed to overcome metabolic drawbacks. Tolterodine and fesoterodine are both indicated for overactive bladder disease and both metabolized to 5-hydroxymethyl tolterodine. The bioactivation of tolterodine is highly dependent on CYP2D6 activity which resulted in interpatient variability. Fesoterodine, on the other hand, is rapidly and completely hydrolyzed by non-specific esterases. Also, eslicarbazepine acetate solved the problem of its predecessors: carbamazepine and oxcarbazepine which produced toxic metabolites such as epoxides.