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Scott Martin Vouri, Mario Schootman, Seth A Strope, Stanley J Birge, Margaret A Olsen
BACKGROUND: Oral oxybutynin has been associated with the development of cognitive impairment. OBJECTIVE: The objective of this study was to describe the use of oral oxybutynin versus other antimuscarinics (e.g., tolterodine, darifenacin, solifenacin, trospium, fesoterodine, transdermal oxybutynin) in older adults with documented cognitive impairment. METHODS: This is a population-based retrospective analysis of antimuscarinic new users aged ≥ 66 years from January 2008 to December 2011 (n = 42,886) using a 5% random sample of Medicare claims linked with Part D data...
February 28, 2018: Drugs & Aging
Jesper Hallas, Andrea V Margulis, Anton Pottegård, Nina Sahlertz Kristiansen, Willem Jan Atsma, Kwame Appenteng, Stefan de Vogel, James A Kaye, Susana Perez-Gutthann, Alejandro Arana
The purpose of this study was to estimate the incidence rate (IR) of 10 common cancers in new users of antimuscarinic overactive bladder (OAB) medications. We conducted a cohort study using data recorded in Danish registers for patients newly exposed to the OAB drugs darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine or trospium in years 2004-2012, aged ≥18 years and without cancer before treatment initiation. We estimated IRs for each study cancer (bladder, breast, colorectal, lung, melanoma, non-Hodgkin lymphoma, pancreas, prostate, renal and uterine), standardised by age and sex and explored IR trends over time since treatment initiation...
January 17, 2018: Basic & Clinical Pharmacology & Toxicology
Masayo Oishi, Yuma Takano, Yutaka Torita, Bimal Malhotra, Koji Chiba
This study was conducted to estimate in vivo inhibition constant (Ki) of ketoconazole on renal P-glycoprotein (P-gp) using human drug-drug interaction (DDI) study result of fesoterodine and ketoconazole. Fesoterodine is a prodrug which is extensively hydrolyzed by non-specific esterases to the active metabolite 5-hydroxymethyl tolterodine (5-HMT). 5-HMT is then further metabolized via Cytochrome P450 (CYP) 2D6 and CYP3A4. It is reported that 5-HMT is a substrate of P-gp whereas fesoterodine is not. Renal clearance of 5-HMT is approximately two-times greater than renal glomerular filtration rate...
November 15, 2017: Drug Metabolism and Pharmacokinetics
Ali B Goodson, Matthew A Cantrell, Robert F Shaw, Brian C Lund
BACKGROUND: Limited data from short-term clinical trials suggest efficacy advantages of solifenacin and fesoterodine over other anticholinergic agents in the treatment of lower urinary tract symptoms. OBJECTIVES: To (a) determine the real-world comparative effectiveness of newer anticholinergic agents for lower urinary tract symptoms, as assessed by 1-year persistence, and (b) identify patient factors independently associated with persistence. METHODS: We conducted a retrospective cohort study of U...
January 2018: Journal of Managed Care & Specialty Pharmacy
Osamu Yokoyama, Hidetomi Yamagami, Shintaro Hiro, Shinichi Hotta, Masaki Yoshida
OBJECTIVE: To assess fesoterodine treatment in elderly women with overactive bladder with and without hypertension. METHODS: Data for 2527 elderly women with overactive bladder symptoms, including urgency urinary incontinence, were pooled from 10 double-blind, placebo-controlled fesoterodine studies. RESULTS: 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...
December 10, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
John Heesakkers, Montserrat Espuña Pons, Philip Toozs Hobson, Emmanuel Chartier-Kastler
Overactive bladder (OAB) syndrome is a common, complex, and challenging condition. To assist the management of these patients, the European Association of Urology (EAU) updates its guidelines annually. This review reports the presentations from the symposium titled "Dealing with complex OAB patient profiles: in or out of the EAU guidelines?" held at the 32nd EAU Annual Congress in March 2017 in London. The symposium focused on three groups of OAB patients: women who may also suffer pelvic organ prolapse, stress urinary incontinence, the genitourinary syndrome of menopause (GSM); patients at risk of cognitive impairment; and elderly patients...
2017: Research and Reports in Urology
Jameel Nazir, Con Kelleher, Samuel Aballéa, Khaled Maman, Zalmai Hakimi, Colette Mankowski, Isaac Odeyemi
AIMS: To compare efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents for the treatment of overactive bladder (OAB). METHODS: 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...
November 15, 2017: Neurourology and Urodynamics
Andrea V Margulis, Jesper Hallas, Anton Pottegård, Nina Sahlertz Kristiansen, Willem Jan Atsma, Billy Franks, Milbhor D'Silva, Cristina Varas-Lorenzo, Susana Perez-Gutthann, Alejandro Arana
PURPOSE: The purpose of this study is to explore the cardiovascular safety of antimuscarinic drugs to treat overactive bladder (OAB) in Denmark. METHODS: This was a cohort study using data recorded in Danish registries from patients newly exposed to darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium in 2004-2012. We estimated crude and standardized incidence rates (IRs) for acute myocardial infarction (AMI); stroke; cardiovascular mortality; major adverse cardiac events (MACE, a combined endpoint of the previous three outcomes); and all-cause death for the individual and combined drugs...
February 2018: European Journal of Clinical Pharmacology
Roxana Geoffrion
OBJECTIVE: 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. INTENDED USERS: Residents and other trainees, primary care practitioners, gynaecologists, urologists, urogynaecologists, and other health care providers who assess, counsel, and treat women with OAB...
December 2017: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
Jianping Qu, Günter Helmchen
Metal catalyzed allylic substitution is a cornerstone of organometallic and synthetic chemistry. Enantioselective versions have been developed with catalysts derived from transition metals, most notably molybdenum, nickel, ruthenium, rhodium, iridium, palladium, and copper. The palladium- and the iridium-catalyzed versions have turned out to be particularly versatile in organic synthesis because of the very broad scope of the nucleophile and great functional group compatibility. Assets of the iridium-catalyzed reaction are the formation of branched, chiral products from simple monosubstituted allylic substrates, high degrees of regio- and enantioselectivity, and use of modular, readily available chiral ligands...
October 17, 2017: Accounts of Chemical Research
Adrian S Wagg, Steve Foley, John Peters, Jameel Nazir, Leanne Kool-Houweling, Ludmila Scrine
INTRODUCTION AND OBJECTIVES: Persistence with antimuscarinic (AM) drugs prescribed for overactive bladder (OAB) is poor. This study aimed to compare persistence and adherence with the beta-3-adrenoceptor agonist mirabegron (MIR) vs AMs over 12 months. PATIENTS AND METHODS: This retrospective cohort analysis included patients aged ≥18 years who were prescribed MIR, or any AM. A 12-month look-back was used to assess inclusion eligibility. The primary end-point was persistence, defined as time to first discontinuation of index drug, during 1 year follow-up...
October 2017: International Journal of Clinical Practice
Daisuke Kato, Satoshi Uno, James Van Schyndle, Alan Fan, Tomomi Kimura
OBJECTIVES: To evaluate persistence and adherence to mirabegron and antimuscarinics in Japan using data from two administrative databases. METHODS: The present retrospective study evaluated insurance claims for employees and dependents aged ≤75 years, and pharmacy claims for outpatients. From October 2012 to September 2014, new users of mirabegron or five individual antimuscarinics indicated for overactive bladder in Japan (fesoterodine, imidafenacin, propiverine, solifenacin and tolterodine) were identified and followed for 1 year...
August 22, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
Lars Grenabo, Sender Herschorn, Steven A Kaplan, Linda Cardozo, David Scholfield, Daniel Arumi, Martin Carlsson, Douglass Chapman, Fady Ntanios
OBJECTIVE: 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. METHODS: 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...
October 2017: Current Medical Research and Opinion
Dominik Dahlinger, Sevinc Aslan, Markus Pietsch, Sebastian Frechen, Uwe Fuhr
BACKGROUND: The objective of this study was to examine the inhibitory potential of darifenacin, fesoterodine, oxybutynin, propiverine, solifenacin, tolterodine and trospium chloride on the seven major human cytochrome P450 enzymes (CYP) by using a standardized and validated seven-in-one cytochrome P450 cocktail inhibition assay. METHODS: An in vitro cocktail of seven highly selective probe substrates was incubated with human liver microsomes and varying concentrations of the seven test compounds...
July 2017: Therapeutic Advances in Urology
Didem Yilmaz-Oral, Nur Bayatli, Serap Gur
OBJECTIVE: To investigate the possible role of fesoterodine (a competitive muscarinic receptor antagonist) on erectile dysfunction in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: A total of 16 adult male Sprague-Dawley rats were equally divided into control and diabetic groups. Diabetes was induced by a single intravenous injection of streptozotocin (25-35 mg/kg). In vivo erectile responses were evaluated by the stimulation of cavernosal nerves, and measurements were repeated after the intracavernosal injection of fesoterodine (1 µM) in rats...
June 1, 2017: Urology
Johnathan A Khusid, Jeffrey P Weiss, Martin O Carlsson, Erin K Mangan
PURPOSE: 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. MATERIALS AND METHODS: 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)...
November 2017: Journal of Urology
James A Kaye, Andrea V Margulis, Joan Fortuny, Lisa J McQuay, Estel Plana, Jennifer L Bartsch, Christine L Bui, Susana Perez-Gutthann, Alejandro Arana
STUDY OBJECTIVE: To estimate the incidence of 10 common cancers among patients treated with antimuscarinic medications for overactive bladder (AMOABs). DESIGN: Retrospective cohort study. DATA SOURCE: United Kingdom's Clinical Practice Research Datalink. PATIENTS: A total of 119,912 adults with no previous cancer diagnosis who were new users of AMOABs-darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium-between January 2004 and December 2012...
June 2017: Pharmacotherapy
John E Casida
What are the advantages of bioactivation in optimizing drugs and pesticides? Why are there so many prodrugs and propesticides? These questions are examined here by considering compounds selected on the basis of economic value or market success in 2015. The 100 major drugs and 90 major pesticides are divided into ones acting directly and those definitely or possibly requiring bioactivation. Established or candidate prodrugs accounted for 19% of the total drug sales, with corresponding values of 20, 37, and 17% for proinsecticides, proherbicides, and profungicides...
May 15, 2017: Chemical Research in Toxicology
Sophie Ramsay, Stéphane Bolduc
Overactive bladder (OAB) is a highly prevalent disorder in the pediatric population. This condition is especially troublesome for pediatric patients and their families when associated with incontinence, since it negatively affects self-esteem and impairs children's development. From the patient's perspective, urgency and urge incontinence can have a significant impact, negatively affecting their quality of life. For a therapy to have true benefit, changes must not only be statistically significant, but must also be perceived as meaningful by the patient...
January 2017: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
Jeannie Medeiros Charbonneau, Rania Bisset, Patrick Viet-Quoc Nguyen
We describe the case of an 89-year-old man who developed delirium following the introduction of fesoterodine to treat his urgency incontinence. The patient started experiencing visual hallucinations approximately five days after starting fesoterodine 4 mg once daily. Delirium resolved after fesoterodine was stopped. Despite the apparent safe cognitive profile due to its pharmacodynamic properties, fesoterodine should be used with caution in the elderly, frail population.
July 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
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