Fesoterodine Research Articles

Electrochemical oxidation of fesoterodine and identification of its oxidation products using liquid chromatography and mass spectrometry

The electrochemical behavior of fesoterodine (FES), an antimuscarinic drug used for the treatment of urge incontinence and overactive bladder, was investigated using linear sweep and cyclic voltammetry at a stationary and rotating disc glassy carbon electrodes. A single two-electron anodic signal of FES was observed in neutral buffered aqueous methanolic solutions. Kinetics of alkaline hydrolysis of FES to its active metabolite 5-hydroxymethyl tolterodine was investigated by time dependent linear sweep voltammetry. Controlled potential electrolysis of FES solutions was performed at platinum gauze electrode in aqueous-methanolic media. Electrolyzed solutions were analyzed using ultra performance liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometry. Two main products of electrochemical oxidation of fesoterodine were identified as 5-formyl fesoterodine (isobutyric acid 2-(3-diisopropylamino-1-phenyl-propyl)-4-formyl-phenyl ester) and N-desisopropylated fesoterodine (isobutyric acid 4-hydroxymethyl-2-(3-isopropylamino-1-phenyl-propyl)-phenyl ester). The mechanism of the electrochemical oxidation of FES has been proposed and confirmed using on-line electrochemistry/mass spectrometry with porous glassy carbon electrode.

Monolithic LC method applied to fesoterodine fumarate low dose extended-release tablets: Dissolution and release kinetics

A dissolution test for fesoterodine low dose extended-release tablets using liquid chromatographic (LC) method equipped with a C18 monolithic column was developed and validated. LC system was operated isocratically at controlled temperature (40°C) using a mobile phase of acetonitrile:methanol:0.03M ammonium acetate (pH 3.8) (30:15:55, v/v/v), run at a flow rate of 1.5mL/min and detected at 208nm. The best dissolution conditions for this formulation were achieved using a USP apparatus 2 (paddle) at 100rpm and 900mL of phosphate buffer at pH 6.8 as the dissolution medium. Validation parameters such as the specificity, linearity, accuracy, precision, and robustness were evaluated according to international guidelines, giving results within the acceptable range. The kinetic parameters of drug release were also investigated using model-dependent methods and the dissolution profiles were best described by the Higuchi model. The validated dissolution test can be applied for quality control of this formulation.

Fesoterodine cost effective in Spain, cost saving in Finland

Fesoterodine cost effective in Spain, cost saving in Finland

Determination of Fesoterodine in a Pharmaceutical Preparation by a Stability-Indicating Capillary Zone Electrophoresis Method

A simple, stability-indicating capillary zone electrophoresis (CZE) method was developed and validated for the analysis of fesoterodine (FESO) in tablets. Optimal conditions for the separation of FESO and its degradation products were investigated. The method used 10 mM sodium phosphate buffer at pH 6.5 as the background electrolyte with an applied voltage of 30 kV (positive polarity).The capillary length was 80.5 cm (72 cm to the detector), and the detection wavelength was 208 nm. The method was validated in accordance with the International Conference on Harmonization requirements, which involved specificity, linearity, precision, accuracy, robustness, LOD, and LOQ. The stability-indicating capability of the method was established by stress degradation studies combined with peak purity assessment using photodiode array detection. The method was linear over the concentration range of 2-100 microg/mL (r2 = 0.9998) of FESO. Intraday and interday precision and accuracy evaluated by RSD, respectively, were all lower than 2%. The LOD and LOQ were 0.57 and 1.90 microg/mL, respectively. The method proved to be robust by a fractional factorial design evaluation. The proposed CZE method was successfully applied for the quantitative analysis of FESO in extended-release tablets to support its QC.

1962 AGE, GENDER AND NOCTURNAL URGENCY SEVERITY PREDICT RESPONSE TO ANTIMUSCARINIC TREATMENT

INTRODUCTION AND OBJECTIVES: Nocturnal urinary urgency significantly impacts quality of life in patients with overactive bladder. To date, only 1 prospective study has demonstrated antimuscarinic efficacy for reducing nocturnal urgency episodes. Data on predictors of positive treatment outcomes would help identify patients who would most likely benefit from antimuscarinic pharmacotherapy. We examined the impact of sex, age and baseline nocturnal urgency on the response to fesoterodine (FESO) in overactive bladder (OAB) subjects with nocturnal urgency. METHODS: Eligible subjects aged 18 years with self-reported OAB symptoms, including nocturnal urgency, were randomized to receive fesoterodine or PBO for 12 wk if they had 2-8 nocturnal urgency episodes/24 h at baseline and a 35% reduction of nocturnal urgency episodes during a 2-week, single-blind PBO run-in. Following 1:1 randomization, FESO 4 mg (n 463) or PBO (n 474) was administered once daily for 4 weeks, followed by optional escalation to 8 mg for the remaining 8 weeks at the discretion of the investigator. For this post-hoc analysis, a logistic regression model was used to assess whether treatment, sex, age and number of baseline nocturnal urgency episodes predicted the likelihood of response, defined as a reduction from baseline of 1 micturition-related nocturnal urgency episodes/24 h at week 12. Missing data were imputed with the last observation carried forward method. RESULTS: Nocturnal urgency episodes were significantly reduced following fesoterodine treatment (P 0.0034; Figure). Women (P 0.0225) were more likely to show a treatment response than men to respond to fesoterodine. Greater number of baseline nocturnal urgency episodes (P 0.0001) was also associated with an increased likelihood of treatment response. Older age (P 0.0123) was associated with a slightly decreased likelihood of treatment response. CONCLUSIONS: Treatment, sex, age, and number of nocturnal urgency episodes at baseline significantly predicted the likelihood of response in subjects with OAB and nocturnal urgency.

Photochemistry of a novel antimuscarinic drug fesoterodine and identification of its photodegradation products by LC–ESI–MS studies

Abstract Fesoterodine (FESO) is a novel muscarinic receptor antagonist for the treatment of overactive bladder syndrome. The aim of this work was to study the photodegradation of FESO, to determine its kinetics and to identify the photodegradation products. The photochemistry of FESO was investigated in sample solutions exposed to a UV-A (320–400 nm) and UV-C irradiation (100–280 nm) at room temperature. The photodegradation process was monitored by means of liquid chromatography method equipped with monolithic column and photodiode array detector. This drug is more photolabile under UV-C light. In methanol–water solution (1:1, v/v), approximately 62.5% of FESO decomposes after 60 min of UV-C irradiation, whereas under 6 h of UV-A light only 4.9% decomposes. FESO was shown to be photolabile and its photodegradation reaction followed the zero-order kinetics with the rate constant k = 0.5503 min −1 , and t 1/2 and t 90% obtained were 46.92 min and 9.38 min, respectively. The main degradation products were isolated by semi-preparative liquid chromatography and identified by liquid chromatography coupled to an electrospray ionization mass spectrometry. The powdered and intact tablets were also exposed to UV-C irradiation. Based on the obtained results, a complete drug photodegradation pathway was proposed.

New perspectives of treatment with fesoterodine fumarate in patients with overactive bladder

ObjectiveTo 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 intolerance to side effects. Material and methodA retrospective review of 158 patients with overactive bladder was carried out. The patients were divided into two groups: the first group consisting of 56 patients where the anticholinergic treatment was shown to be ineffective, and the second group; 102 patients who presented intolerance to anticholinergic side effects. ResultsFor 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. ConclusionFesoterodine 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.

Nuevas perspectivas de tratamiento con el fumarato de fesoterodina en pacientes con vejiga hiperactiva

ObjectiveEvaluate 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. Material and methodA 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. ResultsFor 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. ConclusionFesoterodine 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.

Isolation and Characterization of Fesoterodine Fumarate Related Impurity

Isolation and Characterization of Fesoterodine Fumarate Related Impurity

Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia: Combined Treatment with Fesoterodine Fumarate Extended-Release and Tamsulosin - A Prospective Study

Objective: To evaluate the efficacy and safety of fesoterodine extended-release (ER) plus tamsulosin in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Patients and Methods: Men aged ≥50 years, with LUTS, prostate volume ≤60 ml and International Prostate Symptom Score (IPSS) ≥13 were enrolled in this study. 173 consecutive patients were treated initially with tamsulosin (0.4 mg) for 1 week. At the second visit, 47 patients out of the sample of 173 who were still experiencing inconvenient LUTS were randomized into two groups. The first group received a therapy with tamsulosin and fesoterodine combination (group 1, n = 24) while the second continued the therapy with the single administration of tamsulosin (group 2, n = 23) for an additional 4-week period. Results: There was no statistically significant difference in age, prostate volume, Q_max, and postvoid residual urine between the two groups. A statistical significance appeared in the combination group regarding the storage and the total IPSS values among the second and third visits (10.5 ± 1.4 to 8.5 ± 1.3 and 16.1 ± 1.8 to 13.7 ± 1.5 respectively). Conclusion: Regarding bothersome LUTS and storage symptoms, fesoterodine ER and tamsulosin combination was significantly more effective than the single administration of tamsulosin.

Fesoterodine fumarate for the treatment of overactive bladder in the elderly – a review of the latest clinical data

Overactive bladder is a common and troublesome condition for many older people. Although the first-line treatment for the condition is with behavioral and lifestyle measures, many older people will require pharmacological therapy to successfully manage their condition. Fesoterodine, a relatively new antimuscarinic agent for the treatment of overactive bladder, has been extensively trialed in older people and is associated with a significant improvement in both disease related outcomes and in quality of life. Fesoterodine also appears to be well tolerated in this older group of patients. This review discusses the available evidence for fesoterodine in older people to date.

468 Efficacy and tolerability of fesoterodine fumarate in the treatment of overactive bladder symptoms in patients affected by Multiple Sclerosis: Long term follow up

468 Efficacy and tolerability of fesoterodine fumarate in the treatment of overactive bladder symptoms in patients affected by Multiple Sclerosis: Long term follow up

Treatment of Overactive Bladder Symptoms with Extended Release Fesoterodine Fumarate

Fesoterodine extended-release (brand name Toviaz) is a new competitive muscarinic receptor antagonist labeled for the treatment of overactive bladder (OAB). Here we have undertaken a substantial update to a systematic review evaluating the effects of fesoterodine in the treatment of OAB. Our results indicate that fesoterodine was found to have significant improvements in the management of OAB 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 and constipation. In summary, fesoterodine appears to be effective and generally safe for the treatment of overactive bladder. Nonetheless, additional comparative trials are required to evaluate whether fesoterodine provides a substantial advantage over extended-release tolterodine.

Determination of Fesoterodine in Pharmaceutical Formulations by Using Liquid Chromatography—Tandem Mass Spectrometry

A simple, fast, sensitive, and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the analysis of fesoterodine (FESO) in pharmaceutical formulations was developed and validated using manidipine as internal standard (IS). The LC-MS/MS method was carried out on a Luna C8(2) column (50 mm × 3.0 mm i.d., µm) with a mobile-phase consisting of methanol/0.1% formic acid (90:10, v/v). The mass spectrometry method was performed employing a positive electrospray ionization technique, operating in multiple reaction monitoring mode (MRM), monitoring the transitions of 412.2→223.0 and 611.1→167.0 for FESO and IS, respectively. The total analysis time was 2 min and it was linear in the concentration range of 5-1000 ng mL(-1). Placebo solution and mobile-phase components were evaluated on the specificity test and did not interfere with the analyte or the IS. Intra-day and inter- day precision and accuracy evaluated by RSDs and relative errors, respectively, were lower than 5% for all analytes. The method proved to be robust by a fractional factorial design evaluation. The proposed method was successfully applied for the quantitative analysis of FESO in tablet formulations to support the quality control.

Fesoterodine fumarate

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.

Fesoterodine holds on well in Spain

Fesoterodine holds on well in Spain

Toviaz approved for overactive bladder

FDA on October 31 announced the U.S. marketing approval of fesoterodine fumarate for the treatment of overactive bladder in adults. Fesoterodine, which Pfizer will market as Toviaz, is described in its FDA-approved labeling as a competitive muscarinic-receptor antagonist that relaxes smooth muscles