Pseudoephedrine and circadian rhythm interaction on neuromuscular performance.

This study analyzed the effects of pseudoephedrine (PSE) provided at different time of day on neuromuscular performance, side effects, and violation of the current doping cut-off threshold [World Anti-Doping Agency (WADA)]. Nine resistance-trained males carried out bench press and full squat exercises against four incremental loads (25%, 50%, 75%, and 90% one repetition maximum [1RM]), in a randomized, double-blind, cross-over design. Participants ingested either 180 mg of PSE (supra-therapeutic dose) or placebo in the morning (7:00 h; AM(PLAC) and AM(PSE)) and in the afternoon (17:00 h; PM(PLAC) and PM(PSE)). PSE enhanced muscle contraction velocity against 25% and 50% 1RM loads, only when it was ingested in the mornings, and only in the full squat exercise (4.4-8.7%; P < 0.05). PSE ingestion raised urine and plasma PSE concentrations (P < 0.05) regardless of time of day; however, cathine only increased in the urine samples. PSE ingestion resulted in positive tests occurring in 11% of samples, and it rose some adverse side effects such us tachycardia and heart palpitations. Ingestion of a single dose of 180 mg of PSE results in enhanced lower body muscle contraction velocity against low and moderate loads only in the mornings. These mild performance improvements are accompanied by undesirable side effects and an 11% risk of surpassing the doping threshold.

Influence of antimuscarinic therapy on cognitive functions and quality of life in geriatric patients treated for overactive bladder.

OBJECTIVES: Incidences of overactive bladder (OAB) and cognitive dysfunction increase with aging. Treatment of OAB with antimuscarinic agents may result in cognitive decline, especially in patients with Alzheimer's disease (AD). The aim of this study is to evaluate the effect of antimuscarinic treatment on cognitive functions, depression, and quality of life (QOL) of patients with OAB. METHODS: This non-interventional prospective observational study was conducted in a geriatric medicine outpatient clinic. Overall, 168 OAB patients were enrolled. Patients were followed up in five groups: oxybutynin, darifenacin, tolterodine, trospium, and control groups. Follow-up visits were done at second, third, and sixth months. Comprehensive geriatric assessment, cognitive and mood assessment, QOL scales (IIQ-7, UDI-6) were performed. RESULTS: Mean age of the patients was 73.5 ± 6.1. Of the 168 patients, 92.3% were female, 83.3% benefited from the treatment, and 37.1% discontinued the medication. Discontinuation rate and frequency of side effects were more frequent in the oxybutynin group. Mini Mental State Examination scores did not decline after treatment, even in AD patients. Geriatric Depression Scale scores, Activities of Daily Living scores, and QOL scores significantly improved after treatment. CONCLUSION: Antimuscarinic agents are effective in OAB treatment. They have a positive impact on daily life activities, depression, and QOL indices. Furthermore, they do not have a negative effect on cognitive function in older adults with or without AD.

Single uroflow study as a tool in predicting the possibility of abnormal voiding symptoms after the administration of antimuscarinic agents in treating overactive bladder syndrome.

PURPOSE OF STUDY: The aim of this study was to evaluate the efficacy of uroflowmetry in predicting the possibility of abnormal voiding symptoms following antimuscarinic treatment for overactive bladder syndrome (OAB) in Taiwanese women. MATERIALS AND METHODS: A retrospective study was conducted on women with OAB. Forty-five women with abnormal voiding patterns shown by urodynamic study comprised the main group and 38 women with normal voiding patterns comprised the control group. All patients were prescribed two mg tolterodine once daily for one week. Follow-up on complaints of abnormal voiding symptoms was done one week later. RESULTS: One woman in control group and 12 women in main group complained of abnormal voiding symptoms. There was a significant difference in the occurrence of abnormal voiding symptoms after antimuscarinic administration between main study group and control group (26.7 % vs 2.6 %, p = 0.02). CONCLUSIOn: Uroflowmetry is a non-invasive and simple tool to predict the occurrence of abnormal voiding symptoms after antimuscarinic use.

Tolterodine extended release in the treatment of male OAB/storage LUTS: a systematic review.

BACKGROUND: Overactive bladder (OAB)/ storage lower urinary tract symptoms (LUTS) have a high prevalence affecting up to 90% of men over 80 years. The role of sufficient therapies appears crucial. In the present review, we analyzed the mechanism of action of tolterodine extended-release (ER) with the aim to clarify its efficacy and safety profile, as compared to other active treatments of OAB/storage LUTS. METHODS: A wide Medline search was performed including the combination of following words: "LUTS", "BPH", "OAB", "antimuscarinic", "tolterodine", "tolterodine ER". IPSS, IPSS storage sub-score and IPSS QoL (International Prostate Symptom Score) were the validated efficacy outcomes. In addition, the numbers of urgency episodes/24 h, urgency incontinence episodes/24 h, incontinence episodes/24 h and pad use were considered. We also evaluated the most common adverse events (AEs) reported for tolterodine ER. RESULTS: Of 128 retrieved articles, 109 were excluded. The efficacy and tolerability of tolterodine ER Vs. tolterodine IR have been evaluated in a multicenter, double-blind, randomized placebo controlled study in 1529 patients with OAB. A 71% mean reduction in urgency incontinence episodes was found in the tolterodine ER group compared to a 60% reduction in the tolterodine IR (p < 0.05). Few studies evaluated the clinical efficacy of α-blocker/tolterodine combination therapy. In patients with large prostates (prostate volume >29 cc) only the combination therapy significantly reduced 24-h voiding frequency (2.8 vs. 1.7 with tamsulosin, 1.4 with tolterodine, or 1.6 with placebo). A recent meta-analysis evaluating tolterodine in comparison with other antimuscarinic drugs demonstrated that tolterodine ER was significantly more effective than placebo in reducing micturition/24 h, urinary leakage episodes/24 h, urgency episodes/24 h, and urgency incontinence episodes/24 h. With regard to adverse events, tolterodine ER was associated with a good adverse event profile resulting in the third most favorable antimuscarinic. Antimuscarinic drugs are the mainstay of pharmacological therapy for OAB / storage LUTS; several studies have demonstrated that tolterodine ER is an effective and well tolerated formulation of this class of treatment. CONCLUSION: Tolterodine ER resulted effective in reducing frequency urgency and nocturia and urinary leakage in male patients with OAB/storage LUTS. Dry mouth and constipation are the most frequently reported adverse events.

Are we shortchanging frail older people when it comes to the pharmacological treatment of urgency urinary incontinence?

Overactive bladder and urgency incontinence are common and distressing conditions in older people, for which the first-line pharmacological treatment is a bladder antimuscarinic agent. Of these, oxybutynin is often recommended in guidelines, but is associated with a higher incidence of adverse drug effects, and in particular has been suggested to have deleterious cognitive effects. Despite this, guidelines often suggest oxybutynin as first-line treatment, and insurance based healthcare systems often require oxybutynin to be used as a first-line therapy and fail before reimbursement for the cost of newer anticholinergics is authorised. We reviewed the literature of bladder antimuscarinics in older adults, using the headings overactive bladder, urinary frequency, urgency, urge, oxybutynin, antimuscarinic, older, older people, and frail. In general, oxybutynin had a similar efficacy to other anticholinergic drugs, but a higher incidence of adverse drug events, in particular significant yet unnoticed cognitive impairment. We conclude that oxybutynin should not be used in frail older people.

Factors influencing patient satisfaction with antimuscarinic treatment of overactive bladder syndrome: results of a real-life clinical study.

OBJECTIVES: To investigate patient satisfaction with antimuscarinic treatment of overactive bladder syndrome, and to identify factors having a significant influence on satisfaction. METHODS: A cross-sectional questionnaire survey was carried out to assess treatment satisfaction among male and female patients with overactive bladder (age ≥20 years) in the Hokuriku district of Japan. The overactive bladder symptom scores, treatment efficacies, adverse events (dry mouth and constipation), and patient satisfaction scores were investigated and compared among patients using different antimuscarinic therapeutics. RESULTS: In total, 977 survey respondents (52.6% men; mean age 73.6 years) received antimuscarinic treatment. The mean overactive bladder symptom score of these patients was 6.17; in addition, 32.3% patients were satisfied with their treatment, but 33.1% were dissatisfied. Factors having a significant influence on treatment satisfaction were sex (men were less satisfied), efficacy, adverse events and the overactive bladder symptom score. Constipation negatively influenced patient satisfaction to a greater extent than did dry mouth. Patient satisfaction varied according to the drug used. Constipation was less severe with the immediate-release-type agents (imidafenacin and oxybutynin) than with the extended-release-type (propiverine, solifenacin or tolterodine). CONCLUSIONS: Just one-third of Japanese Hokuriku patients with overactive bladder seem to be satisfied with their antimuscarinic treatment. Patient satisfaction is impaired by poor efficacy and the presence of adverse events; furthermore, constipation should be recognized as an adverse event that negatively influences patient satisfaction to a greater extent than dry mouth. Patient satisfaction differs according to the antimuscarinic agent used, with higher patient satisfaction being associated with less severe constipation.

[Treatment of overactive bladder in older women increased doses of antimuscarinic drugs safe and effective alternative to existing methods].

The study included 95 female patients of 65 to 74 years (average age 67,1 years), who previously (more than 6 months before this study) took a course of monotherapy with hydrochloride trospium in higher dosages with unstable or weak effect. In this study, all patients were divided into three groups and were treated with two antimuscarinic drugs. The majority of older women suffering from OAB and treatment-resistant taking one antimuscarinic drug in high doses showed a significant positive progress in a state by adding a second antimuscarinic agent. The received side effects do not exceed thereof in comparison with treatment with a single drug.

Medication use during pregnancy and the risk of gastroschisis: a systematic review and meta-analysis of observational studies.

OBJECTIVES: The aetiology of gastroschisis is considered multifactorial. We conducted a systematic review and meta-analysis to assess whether the use of medications during pregnancy, is associated with the risk of gastroschisis in offspring. METHODS: PubMed, EMBASE, and Scopus were searched from 1st January 1990 to 31st December 2020 to identify observational studies examining the association between medication use during pregnancy and the risk of gastroschisis. The Newcastle-Ottawa Scale was used for the quality assessment of the individual studies. We pooled adjusted measures using a random-effect model to estimate relative risk [RR] and the 95% confidence interval [CI]. I2 statistic for heterogeneity and publication bias was calculated. RESULTS: Eighteen studies providing data on 751,954 pregnancies were included in the meta-analysis. Pooled RRs showed significant associations between aspirin (RR 1.66, 95% CI 1.16-2.38; I2 = 58.3%), oral contraceptives (RR 1.52, 95% CI 1.21-1.92; I2 = 22.0%), pseudoephedrine and phenylpropanolamine (RR 1.51, 95% CI 1.16-1.97; I2 = 33.2%), ibuprofen (RR 1.42, 95% CI 1.26-1.60; I2 = 0.0%), and gastroschisis. No association was observed between paracetamol and gastroschisis (RR 1.16, 95% CI 0.96-1.41; I2 = 39.4%). CONCLUSIONS: These results suggest that the exposure in the first trimester of pregnancy to over the counter medications (OTC) such as aspirin, ibuprofen, pseudoephedrine and phenylpropanolamine as well as to oral contraceptives, was associated with an increased risk of gastroschisis. However, these associations are significant only in particular subgroups defined by geographic location, adjustment variables and type of control. Therefore, further research is needed to investigate them as potential risk factors for gastroschisis, to assess their safety in pregnancy and to develop treatment strategies to reduce the risk of gastroschisis in offspring. PROSPERO registration number: CRD42021287529.

Benefits and harms of pharmacologic treatment for urinary incontinence in women: a systematic review.

BACKGROUND: Urinary incontinence (UI) in women adversely affects quality of life. PURPOSE: To conduct a systematic literature review of drugs for urgency UI in women. DATA SOURCES: MEDLINE, the Cochrane Central Register of Controlled Trials, SCIRUS, and Google Scholar were searched for articles published from 1966 to November 2011. STUDY SELECTION: Randomized, controlled trials (RCTs) reported in English. DATA EXTRACTION: Rates of outcomes and risk of bias were extracted by using a standardized form to pool absolute risk differences and calculate the number of attributable events per 1000 patients treated, with 95% CIs. DATA SYNTHESIS: 94 RCTs were eligible. Pooled analyses showed that among drugs for urgency UI, per 1000 treated women, continence was restored in 130 with fesoterodine (CI, 58 to 202), 85 with tolterodine (CI, 40 to 129), 114 with oxybutynin (CI, 64 to 163), 107 with solifenacin (CI, 58 to 156), and 114 with trospium (CI, 83 to 144). Rates of treatment discontinuation due to adverse effects were 31 per 1000 treated with fesoterodine (CI, 10 to 56), 63 with oxybutynin (CI, 12 to 127), 18 with trospium (CI, 4 to 33), and 13 with solifenacin (CI, 1 to 26). The studies' inconsistent definitions of reduction in UI and quality of life hampered synthesis of evidence. LIMITATION: Evidence for quality-of-life improvements and comparative effectiveness with drugs was limited, and evidence for the effects of race, baseline severity of UI, and comorbid conditions on treatment success was insufficient. CONCLUSION: Overall, drugs for urgency UI showed similar small benefit. Therapeutic choices should consider the harms profile. Evidence for long-term adherence and safety of treatments is lacking.

Comparison of tolterodine with standard treatment in pediatric patients with non-neurogenic dysfunctional voiding/over active bladder: a systematic review.

To examine the efficacy, safety and tolerability of tolterodine in children with overactive bladder in comparison with standard treatment i.e. oxybutynin as demonstrated in randomized clinical trials and other studies. A systematic search was done to screen the studies evaluating the effect of tolterodine in children with non-neurogenic overactive bladder. Results of studies were pooled and compared. Efficacy was determined from micturition diaries and dysfunctional voiding symptoms score. Safety and tolerability were assessed from the reported treatment emergent adverse events. A total of six randomized clinical trials and 11 other studies of tolterodine in children with urinary incontinence were included in the present systematic review. The dose of tolterodine used in different settings ranged from '0.5 to 8 mg/day' instead of '0.5 to 8 mg/kg per day' and the duration of studies ranged from 2 weeks to 12 months. Both extended and immediate release preparations of tolterodine were shown to have comparable efficacy and tolterodine proved to have comparable efficacy with better tolerability than oxybutynin in these studies. It can be concluded that tolterodine is efficacious in treatment of urinary incontinence in children. Moreover, its efficacy is comparable to oxybutynin, the most commonly prescribed anticholinergic in this condition, while having better tolerability. Hence, it can be considered as first line therapy for the treatmentof urinary incontinence in children.

Unexpected frequent hepatotoxicity of a prescription drug, flupirtine, marketed for about 30 years.

AIMS: To determine efficacy of the analgesic flupirtine in the treatment of overactive bladder syndrome in a proof-of-concept study. METHODS: Double-blind, double-dummy, three-armed comparison of flupirtine extended release (400 mg/day, titrated to 600 mg/day), tolterodine extended release (4 mg/day) and placebo for 12 weeks. RESULTS: When major elevations of liver enzymes (more than three times the upper normal limit) were detected in several flupirtine-exposed patients, the study was prematurely discontinued. Based on study-end data, hepatotoxicity was detected in 31% of patients receiving flupirtine for ≥ 6 weeks. CONCLUSIONS: Unexpected frequent and relevant toxicity can occur when testing an established drug for a new indication.

Efficacy and tolerability of fesoterodine versus tolterodine in older and younger subjects with overactive bladder: a post hoc, pooled analysis from two placebo-controlled trials.

AIMS: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparative adherence to oxybutynin or tolterodine among older patients.

PURPOSE: To compare persistence of oxybutynin or tolterodine therapy among older patients newly prescribed one of these drugs. METHODS: We conducted a retrospective cohort study of Ontarians aged 66 years and older who were newly prescribed either drug between January 1, 2000 and December 31, 2007. Persistence with treatment was defined on the basis of refills for the drug within a grace period equal to 50% of the prescription duration. RESULTS: We identified 31,996 patients newly treated with oxybutynin and 24,855 newly treated with tolterodine. After 2 years of follow-up, persistence on oxybutynin (9.4%) was significantly lower than that on tolterodine (13.6%, p < 0.0001). The median time to discontinuation of oxybutynin and tolterodine was 68 and 128 days, respectively. CONCLUSIONS: Our findings suggest that the tolerability of these drugs differs substantially.

Solifenacin for overactive bladder: a systematic review and meta-analysis.

This study aims to evaluate the efficacy and safety of solifenacin for treating overactive bladder. Randomized controlled trials (RCTs) were identified and extracted from MEDLINE, Embase, and CENTRAL. The quality of the included RCTs was assessed using the Jadad score, and heterogeneity was analyzed using the chi-squared test. The data of the included RCTs were collected, extracted, and assessed by our protocol. A total of nine RCTs were identified from the search strategy. Compared with the placebo and tolterodine treatments, both short-term (mostly 12-week) trials indicated that solifenacin significantly reduced urgency episodes, micturitions, and incontinence episodes per 24 h. Compared with the solifenacin (5 mg) group, the solifenacin (10 mg) group was significantly better in terms of the number of micturitions per 24 h. With regard to adverse effects, the patients treated with solifenacin had significantly higher rates of constipation and blurred vision than patients treated with tolterodine. The solifenacin therapy was not inferior to tolterodine in terms of efficacy profiles and had a similar incidence of overall adverse events compared with tolterodine treatment. Solifenacin (5 mg) is thus a recommended dose because of its reported balance between efficacy and acceptable tolerability.

Which anticholinergic drug for overactive bladder symptoms in adults.

BACKGROUND: Around 16% to 45% of adults have overactive bladder symptoms (urgency with frequency and/or urge incontinence - 'overactive bladder syndrome'). Anticholinergic drugs are common treatments. OBJECTIVES: To compare the effects of different anticholinergic drugs for overactive bladder symptoms. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 8 March 2011) and reference lists of relevant articles. SELECTION CRITERIA: Randomised trials in adults with overactive bladder symptoms or detrusor overactivity that compared one anticholinergic drug with another, or two doses of the same drug. DATA COLLECTION AND ANALYSIS: Two authors independently assessed eligibility, trial quality and extracted data. Data were processed as described in the Cochrane Reviewers' Handbook. MAIN RESULTS: Eighty six trials, 70 parallel and 16 cross-over designs were included (31,249 adults). Most trials were described as double-blind, but were variable in other aspects of quality. Crossover studies did not present data in a way that could be included in the meta-analyses. Twenty nine collected quality of life data (the primary outcome measure) using validated measures, but only fifteen reported useable data.Tolterodine versus oxybutynin: There were no statistically significant differences for quality of life, patient reported cure or improvement, leakage episodes or voids in 24 hours, but fewer withdrawals due to adverse events with tolterodine (Risk Ratio (RR) 0.52, 95% confidence interval (CI) 0.40 to 0.66, data from eight trials), and less risk of dry mouth (RR 0.65, 95% CI 0.60 to 0.71, data from ten trials).Solifenacin versus tolterodine: There were statistically significant differences for quality of life (standardised mean difference (SMD) -0.12, 95% CI -0.23 to -0.01, data from three trials), patient reported cure/improvement (RR 1.25, 95% CI 1.13 to 1.39, data from two trials), leakage episodes in 24 hours (weighted mean difference (WMD) -0.30, 95% CI -0.53 to -0.08, data from four studies) and urgency episodes in 24 hours (WMD -0.43, 95% CI -0.74 to -0.13, data from four trials), all favouring solifenacin. There was no difference in withdrawals due to adverse events and dry mouth, but after sensitivity analysis the dry mouth (RR 0.69, 95% CI 0.51 to 0.94) was statistically significantly lower with solifenacin when compared to Immediate Release (IR) tolterodine.Fesoterodine versus extended release tolterodine: Three trials contributed to the meta analyses. There were statistically significant differences for quality of life (SMD -0.20, 95% CI -0.27 to -0.14), patient reported cure/improvement (RR 1.11, 95% CI 1.06 to 1.16), leakage episodes (WMD -0.19, 95% CI -0.30 to -0.09), frequency (WMD -0.27, 95% CI -0.47 to -0.06) and urgency episodes (WMD -0.44, 95% CI -0.72 to -0.16) in 24 hours, all favouring fesoterodine, but those taking fesoterodine had higher risk of withdrawal due to adverse events (RR 1.45, 95% CI 1.07 to 1.98) and higher risk of dry mouth (RR 1.80, 95% CI 1.58 to 2.05) at 12 weeks.Different doses of tolterodine: The standard recommended starting dose (2 mg twice daily) was compared with two lower (0.5 mg and 1 mg twice daily), and one higher dose (4 mg twice daily). The effects of 1 mg, 2 mg and 4 mg doses were similar for leakage episodes and micturitions in 24 hours, with greater risk of dry mouth with 2 and 4 mg doses at two to 12 weeks.Different doses of solifenacin: The standard recommended starting dose of 5 mg once daily was compared to 10 mg: while frequency and urgency were less (better) with 10 mg compared to 5 mg, there was a higher risk of dry mouth with 10 mg solifenacin at four to 12 weeks.Different doses of fesoterodine:The recommended starting dose of 4mg once daily was compared to 8 and 12 mg. The clinical efficacy (patient reported cure, leakage episodes, micturition per 24 hours) of 8 mg was better than 4 mg fesoterodine but with a higher risk of dry mouth with 8 mg.There was no statistically significant difference between 4 and 12 mg in the efficacy but the dry mouth was significantly higher with 12 mg at eight to 12 weeks.Extended versus immediate release preparations of oxybutynin and/or tolterodine: There were no statistically significant differences for cure/improvement, leakage episodes or micturitions in 24 hours, or withdrawals due to adverse events, but there were few data. Overall, extended release preparations had less risk of dry mouth at two to 12 weeks.One extended release preparation versus another: There was less risk of dry mouth with oral extended release tolterodine than oxybutynin (RR 0.75, 95% CI 0.59 to 0.95), but no difference between transdermal oxybutynin and oral extended release tolterodine although some people withdrew due to skin reaction at the transdermal patch site at 12 weeks. AUTHORS' CONCLUSIONS: Where the prescribing choice is between oral immediate release oxybutynin or tolterodine, tolterodine might be preferred for reduced risk of dry mouth. With tolterodine, 2 mg twice daily is the usual starting dose, but a 1 mg twice daily dose might be equally effective, with less risk of dry mouth. If extended release preparations of oxybutynin or tolterodine are available, these might be preferred to immediate release preparations because there is less risk of dry mouth.Between solifenacin and immediate release tolterodine, solifenacin might be preferred for better efficacy and less risk of dry mouth. Solifenacin 5 mg once daily is the usual starting dose, this could be increased to 10 mg once daily for better efficacy but with increased risk of dry mouth.Between fesoterodine and extended release tolterodine, fesoterodine might be preferred for superior efficacy but has higher risk of withdrawal due to adverse events and higher risk of dry mouth.There is little or no evidence available about quality of life, costs, or long-term outcome in these studies. There were insufficient data from trials of other anticholinergic drugs to draw any conclusions.

[Safety of solifenacin and tolterodine in the treatment of overactive bladder: a meta-analysis].

OBJECTIVE: To evaluate the safety of solifenacin and tolterodine in the treatment of overactive bladder (OAB). METHODS: Studies on the solifenacin, tolterodine and OAB were searched and those fulfilling the inclusion criteria were selected. RevMan 5.0 software was used to perform meta-analysis. Three studies were included with an overall sample size of 1013 cases. The experimental group of solifenacin contained 517 cases while the control group had 496 cases. RESULTS: The incidence rates of overall adverse event, dry mouth, constipation and blurred vision of the experimental group (solifenacin 5 mg once per day) was 26.69% (138/517), 10.64% (55/517), 5.42% (28/517) and 6.55% (26/397) while those of the control group (tolterodine 2 mg twice per day) 33.27% (165/496), 16.73% (83/496), 2.22% (11/496) and 4.20% (16/381) respectively. There was no statistically significant difference in overall adverse event (RR = 0.76, 95%CI: 0.52 - 1.12, P = 0.170) and blurred vision (RR = 1.59, 95%CI: 0.88 - 2.90, P = 0.130) between two groups. However, the incidence rate of key antimuscarinic adverse events such as dry mouth (RR = 0.63, 95%CI: 0.46 - 0.87, P = 0.005) and constipation (RR = 2.38, 95%CI: 1.21 - 4.66, P = 0.010) showed statistically significant difference. CONCLUSIONS: Dry mouth is the most common adverse event of solifenacin (5 mg once per day) and tolterodine (2 mg twice per day). Solifenacin has a lower incidence rate of dry mouth and a higher rate of constipation than tolterodine. A clinical physician should consider the incidence of adverse events during treating OAB, especially for those patients prone to constipation.

[The use of tolterodine in patients with recurrent chronic cystitis].

The article presents the results of evaluation of effect of M-cholinoblocer tolterodine on the symptoms of lower urinary tract diseases (LUTD) and quality of life of patients with recurrent chronic cystitis. The study included 47 patients with chronic recurrent cystitis at acute stage with non-obstructive type of urination and LUTS. Group 1 included 23 women aged 45 to 56 years, who received tolterodine on the background of antibacterial therapy, taking into account the sensitivity of the isolated strain. Control group included 24 patients who received standard antibacterial therapy, also taking into account the sensitivity of the pathogen, and spasmolytics. The groups were almost homogeneous and did not differ on the basic characteristics. Analysis of the results of the study showed that tolterodine as a symptomatic therapy can reduce the time of rehabilitation. Therapy with tolterodine has shown clinical efficacy for 85.7% of women, has improved the quality of life by 24.8% compared with the control group, and provided relief of urgent and irritative symptoms in the short time.

Risk of serious falls associated with oxybutynin and tolterodine: a population based study.

PURPOSE: We compared the short-term risk of falls among recipients of oxybutynin or tolterodine to treat urinary incontinence. MATERIALS AND METHODS: We conducted a population based, retrospective cohort study with propensity score matching among patients 66 years old or older who commenced treatment with oxybutynin or tolterodine in Ontario, Canada. The primary outcome was a hospital visit for a fall within 90 days of drug initiation. Secondary outcomes included hospital visits for fractures, delirium or all cause mortality. RESULTS: We found no difference in the risk of falls among users of oxybutynin vs tolterodine (adjusted hazard ratio 1.04, 95% CI 0.95 to 1.14). Secondary analyses revealed no differential risk of fractures (aHR 0.96, 95% CI 0.82 to 1.13) or delirium (aHR 0.90, 95% CI 0.66 to 1.23) associated with oxybutynin. However, statistically significant increases in the risk of all cause hospitalization (aHR 1.12, 95% CI 1.07 to 1.17) and death (aHR 1.20, 95% CI 1.07 to 1.35) were seen with oxybutynin. CONCLUSIONS: Oxybutynin was not associated with a short-term increased risk of hospital visit for falls, fractures or delirium compared to tolterodine. Further research is needed to confirm whether oxybutynin is associated with an increased risk of hospitalization or death.

Investigation of the clinical efficacy and safety of pregabalin alone or combined with tolterodine in female subjects with idiopathic overactive bladder.

AIMS: To assess the efficacy and safety of pregabalin alone or in combination with tolterodine extended release (ER) in subjects with idiopathic OAB. METHODS: This 26-week, multicenter, randomized, double-blind, placebo-controlled, three-period crossover study enrolled women aged ≥ 18 years that were diagnosed with OAB and reported ≥ 8 micturitions/24 hr and ≥ 4 urgency episodes/week on 5-day bladder diary at baseline. Subjects were randomized to 1 of 10 treatment sequences and received three of five treatments, each for 4 weeks with 4-week washout periods: standard-dose pregabalin/tolterodine ER (150 mg twice daily [BID]/4 mg once daily [QD], n=102), pregabalin alone (150 mg BID, n=105), tolterodine ER alone (4 mg QD, n=104), low-dose pregabalin/tolterodine ER (75 mg BID/2 mg QD, n=105), and placebo (n=103). Subjects completed 5-day diaries at the end of treatment and washout periods. The primary endpoint was change from baseline to week 4 in mean voided volume (MVV) per micturition. The primary comparison was standard-dose pregabalin/tolterodine ER versus tolterodine ER alone; secondary comparisons were pregabalin alone versus tolterodine ER alone and versus placebo. RESULTS: Baseline-adjusted changes in MVV were significantly greater after treatment with standard-dose pregabalin/tolterodine ER (39.5 ml) versus tolterodine ER alone (15.5 ml; P<0.0001), and with pregabalin alone (27.4 ml) versus tolterodine ER alone (P=0.005) and placebo (11.9 ml; P=0.0006). Treatments were generally well tolerated; discontinuation rates due to adverse events were 4%, 2%, 5%, 0%, and 1% with standard- and low-dose pregabalin/tolterodine ER, pregabalin, tolterodine ER, and placebo, respectively. CONCLUSIONS: Pregabalin, alone or with tolterodine ER may offer an alternative treatment option for idiopathic OAB in women.