tolterodine-tartrate and Xerostomia

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.. 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.. 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.. 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.

Topics: Adrenergic alpha-Antagonists; Benzhydryl Compounds; Constipation; Cresols; Delayed-Action Preparations; Drug Therapy, Combination; Humans; Lower Urinary Tract Symptoms; Male; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents; Xerostomia

To compare the clinical efficacy and safety of solifenacin versus tolterodine in patients with overactive bladder (OAB).. Literature searches were performed with PubMed, EMBASE, Ovid and Google Scholar databases, Wanfang and CNKI from inception to October 2013 for comparative studies assessing solifenacin and tolterodine for OAB. The data were extracted and evaluated by two reviewers independently according to the Cochrane Handbook for Systematic Reviews. Meta-analyses were conducted with RevMan 5.2.. A total of 7 studies involving 1 805 patients were retrieved. Compared with tolterodine immediate release (IR), the number of urgency episodes and urge incontinence episodes in 24 h and the rate of dry mouth were significantly lower in patients on solifenacin (RR = -0.34, 95% CI: -0.50--0.18, P = 0.00; RR = -0.29, 95% CI:-0.55--0.04, P = 0.03; RR = 0.58, 95% CI: 0.41-0.83, P = 0.00) and the rate of constipation was higher in those on solifenacin (RR = 2.72, 95% CI: 1.38-5.39, P = 0.00). No significant differences existed between tolterodine IR and solifenacin in mean micturition volume per voiding and micturitions episodes in 24 h (P = 0.05,0.08). Between solifenacin and tolterodine extended release (ER), the number of urgency episodes, micturition and urge incontinence episodes in 24 h and mean micturition volume per voiding were not statistically different (all P > 0.05). The incidence of major adverse events, such as dry mouth, constipation and blurred vision, was not significantly different (all P > 0.05). And most adverse events were mild.. Solifenacin is superior to tolterodine IR in treating OAB symptoms. However the rate of constipation is higher for solifenacin. Both solifenacin and tolterodine ER have similar therapeutic efficacies and adverse events.

Topics: Benzhydryl Compounds; Constipation; Cresols; Humans; Phenylpropanolamine; Quinuclidines; Safety; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Xerostomia

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence; Xerostomia

Drug therapy for overactive bladder (OAB) most commonly includes antimuscarinic agents, which work by relaxing bladder smooth muscle through inhibition of acetylcholine receptors in the bladder. The major adverse effects with existing antimuscarinic agents are anticholinergic in nature (e.g., dry mouth, constipation, blurred vision). Oxybutynin and tolterodine have been used for several years for treatment of OAB; both are available in immediate- and extended-release formulations. Fewer or less severe adverse effects are reported with the extended- versus the immediate-release formulations, with little or no difference in efficacy. Oxybutynin is also available as a transdermal patch. Trospium, which was recently approved for use in the United States, has efficacy and an incidence of dry mouth similar to existing agents but does not cross the blood-brain barrier. It requires twice-daily dosing. Two new antimuscarinic agents--darifenacin and solifenacin--are in development. Both show significantly better efficacy compared with placebo for key symptoms of OAB, including urgency. The incidence of dry mouth at the lowest effective dose is 19% for darifenacin and 8% and 14% for solifenacin (2 studies).

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Constipation; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Vision Disorders; Xerostomia

Two newer antimuscarinic anticholinergic drugs--tolterodine and extended-release oxybutynin--are approximately as effective in treating overactive bladder as immediate-release oxybutynin, but are more tolerable. I review clinical trial data on the newer agents.

Topics: Benzhydryl Compounds; Controlled Clinical Trials as Topic; Cresols; Delayed-Action Preparations; Dose-Response Relationship, Drug; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Time Factors; Tolterodine Tartrate; Urinary Incontinence; Xerostomia

This analysis reviews clinical trials of the efficacy and safety of tolterodine for use in overactive bladder. It also compares the safety and efficacy of tolterodine and previously available pharmacotherapy. The MEDLINE database (1966 to present) was searched for all English language randomized controlled trials with keyword tolterodine. The search retrieved 10 randomized controlled trials involving tolterodine. Studies ranged from 2 to 12 weeks in duration. Nine trials studied tolterodine vs. placebo, 6 compared tolterodine vs. oxybutynin, 6 compared different doses of tolterodine, and 1 compared immediate-release and extended-release tolterodine. Doses of tolterodine were 0.5-4 mg bid or 4 mg extended-release daily, and doses of oxybutynin were 5 mg bid or tid. All studies found a benefit of tolterodine over placebo in decreasing symptoms of overactive bladder. Parameters significantly improved by tolterodine include number of voids per day, urine volume per void, number of incontinent episodes per day, pad use, maximal cystometric capacity, residual volume, volume at first detrusor contraction, and volume at normal desire to void. Tolterodine 2 mg bid was consistently of equal efficacy as oxybutynin 5 mg tid. Adverse events with both medications were mostly dose-related autonomic nervous system events. The most common adverse event was dry mouth, which was both more frequent and more severe with oxybutynin 5 mg tid than with tolterodine 2 mg bid. Dry mouth did not generally result in discontinuation of medication with either drug. Most drug withdrawal was because of blurred vision or headache. Tolterodine 2 mg bid caused less dose reduction, patient withdrawal, and adverse events, especially dry mouth, compared with oxybutynin 5 mg tid. A single trial found tolterodine extended-release 4 mg/day to have improved efficacy for decreasing urge incontinence episodes along with lower frequency of dry mouth vs. immediate-release tolterodine 2 mg bid. At 4 mg bid, tolterodine caused urinary retention. Neither drug significantly altered any laboratory tests, nor was there clear evidence of electrocardiographic abnormalities induced by either drug. In all randomized controlled trials to date, tolterodine 2 mg bid is an equally effective alternative to oxybutynin 5 mg tid, while causing less intense and less frequent dry mouth or need for treatment withdrawal.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Dose-Response Relationship, Drug; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Incontinence; Xerostomia

To evaluate the long-term safety (primary objective) and efficacy (secondary objective) of antimuscarinic add-on therapy in patients receiving mirabegron.. During a 2-week screening period, patients (aged ≥20 years, mirabegron treatment for ≥6 weeks, residual overactive bladder symptoms) received mirabegron 50 mg once daily. These patients were subsequently randomized to 52 weeks' treatment with mirabegron 50 mg/day plus an antimuscarinic (solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg, or tolterodine 4 mg) with the potential to double the antimuscarinic dose (except for tolterodine) at week 8. Safety assessments included treatment-emergent adverse events, vital signs, 12-lead electrocardiograms, post-void residual volume, and laboratory evaluations. Efficacy was assessed using changes from baseline in overactive bladder symptom score total score; overactive bladder questionnaire short form score; micturitions, urgency episodes, urinary incontinence episodes, and urgency urinary incontinence episodes/24 h; mean volume voided per micturition; and number of night-time micturitions.. Overall, 80.2% of patients (88.1% women, mean age 65 years) experienced at least one treatment-emergent adverse event, with similar rates for all treatments. The adverse events most commonly reported were dry mouth, nasopharyngitis, and constipation. No marked change was observed in systolic or diastolic blood pressure for any treatment, although pulse rate increased slightly in the mirabegron and propiverine, and mirabegron and tolterodine groups. For all treatments, significant improvements were observed in all efficacy parameters, including overactive bladder symptom score total and questionnaire short form scores.. Antimuscarinic add-on therapy is well tolerated and effective after initial treatment with mirabegron in patients with overactive bladder symptoms.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Benzilates; Blood Pressure; Constipation; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Imidazoles; Japan; Male; Middle Aged; Muscarinic Antagonists; Nasopharyngitis; Severity of Illness Index; Solifenacin Succinate; Thiazoles; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Xerostomia

We evaluated the efficacy and safety of a combination of 2 mg tolterodine and 9 mg pilocarpine, vs tolterodine monotherapy in patients with overactive bladder.. We enrolled patients with overactive bladder symptoms in a multicenter, randomized, double-blind, parallel, active control study. Patients were randomized to the combination or 2 mg tolterodine twice daily for 12 weeks. After the double-blind period finished all patients were started on the combination for 12 weeks. Study co-primary end points were the change from baseline in the mean number of daily micturitions and cumulative incidence of dry mouth at the end of 12 weeks. Secondary end points were other overactive bladder symptoms, the total xerostomia inventory score and results of a visual analogue scale for dry mouth at the end of 12 and 24 weeks.. The mean change in the number of daily micturitions from baseline to 12 weeks was -1.49 and -1.74 in the combination and tolterodine monotherapy groups, respectively. The mean difference was -0.26 (95% CI -0.79-0.27), confirming noninferiority. At 12 weeks the incidence of dry mouth was lower in the combination group than in the tolterodine monotherapy group (30.0% vs 42.9%, p = 0.009). All secondary and other efficacy outcomes related to overactive bladder symptoms improved in each group with no significant differences between the groups at 12 weeks. Changes from baseline in the total xerostomia inventory score and the visual analogue scale for dry mouth were significantly lower in the combination group than in the tolterodine monotherapy group.. Tolterodine and pilocarpine alleviated dry mouth in patients with overactive bladder while maintaining anticholinergic efficacy similar to that of tolterodine.

Topics: Aged; Cholinergic Antagonists; Double-Blind Method; Drug Combinations; Female; Humans; Incidence; Male; Middle Aged; Muscarinic Agonists; Pilocarpine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urination; Xerostomia

The aim of the present review article was to summarize the efficacy and tolerability for mirabegron 50 mg over 12 weeks and 1 year versus placebo (SCORPIO) or tolterodine ER 4 mg (SCORPIO and TAURUS). After a 2-week placebo run-in, adults with overactive bladder symptoms for ≥3 months were randomized if, during a 3-day micturition diary period before baseline, they had an average of ≥8 micturitions/24 h and ≥3 urgency episodes. Efficacy end-points were change from baseline to each study visit and final visit in incontinence, micturitions, volume voided/micturition, urgency incontinence, urgency (grades 3 or 4), level of urgency and nocturia. Additional secondary efficacy variables included patient-reported outcomes. Safety variables included changes in treatment-emergent adverse events and vital signs. For SCORPIO, statistically significant improvements from baseline in efficacy variables and patient-reported outcomes were seen with mirabegron versus placebo from week 4, and were maintained over time. For TAURUS, numerical improvements in efficacy were evident from month 1, and were maintained throughout 12 months. Treatment-emergent adverse events incidence was similar between groups, except for dry mouth, which was reported by fourfold (SCORPIO) and threefold (TAURUS) more patients taking tolterodine than mirabegron. Mirabegron 50 mg for 12 weeks was associated with statistically significant improvements in objective measures of efficacy and patient-reported outcomes. At final visit, improvements with mirabegron 50 mg were statistically greater versus placebo. The efficacy profile of mirabegron 50 mg appears to be maintained over 12 months.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Benzhydryl Compounds; Cresols; Double-Blind Method; Drug Administration Schedule; Female; Headache; Humans; Hypertension; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Retention; Urinary Tract Infections; Urination; Xerostomia

Despite several antimuscarinic treatment options for overactive bladder (OAB), there is still a need for distinct treatment approaches to manage this condition. Mirabegron, a β(3)-adrenoceptor agonist, has demonstrated efficacy and tolerability for up to 12 wk in phase 3 trials.. To assess the 12-mo safety and efficacy of mirabegron.. Patients ≥ 18 yr of age with OAB symptoms for ≥ 3 mo.. After a 2-wk single-blind placebo run-in, patients with eight or more micturitions per 24h and three or more urgency episodes in a 3-d micturition diary were randomized 1:1:1 to once-daily mirabegron 50mg, mirabegron 100mg, or tolterodine extended release (ER) 4 mg for 12 mo.. Primary variable: incidence and severity of treatment-emergent AEs (TEAEs). Secondary variables: change from baseline at months 1, 3, 6, 9, and 12 in key OAB symptoms.. A total of 812, 820, and 812 patients received mirabegron 50mg, mirabegron 100mg, and tolterodine ER 4 mg, respectively. Baseline demographic and OAB characteristics were similar across groups. TEAEs were reported in 59.7%, 61.3%, and 62.6% of patients, respectively; most were mild or moderate. Serious TEAEs were reported in 5.2%, 6.2%, and 5.4% of patients, respectively. The most common TEAEs were similar across groups. Dry mouth was reported by 2.8%, 2.3%, and 8.6% of patients, respectively. Adjusted mean changes from baseline to final visit in morning systolic blood pressure were 0.2, 0.4, and -0.5mm Hg for mirabegron 50mg, 100mg, and tolterodine ER 4 mg, respectively. Mirabegron and the active control, tolterodine, improved key OAB symptoms from the first measured time point of 4 wk, and efficacy was maintained throughout the 12-mo treatment period. The study was not placebo controlled, which was a limitation.. The safety and tolerability of mirabegron was established over 1 yr, with sustained efficacy observed over this treatment period.. ClinicalTrials.gov identifier: NCT00688688.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Benzhydryl Compounds; Constipation; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Headache; Humans; Hypertension; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Single-Blind Method; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urinary Retention; Xerostomia

Antimuscarinics, used commonly to treat overactive bladder, may differ in their potential to increase heart rate via effects on cardiac muscarinic M2 receptors. This prospective, 3-way crossover, randomized, double-blind study assessed the heart rate effects of 7 days' exposure to a nonselective M2/M3 receptor blocker (tolterodine; 4 mg/d), a highly selective M3 receptor blocker (darifenacin; 15 mg/d), and placebo in 162 healthy participants > or = 50 years. Heart rate was measured by 24-hour Holter monitoring. Tolterodine significantly increased heart rate versus darifenacin and heart rate versus placebo, while darifenacin did not affect heart rate versus placebo. The proportion of participants with an increase in mean heart rate per 24 hours of > or =5 beats per minute was higher with tolterodine than with darifenacin (P = .0004) or with placebo (P = .0114) but did not differ between darifenacin and placebo. The results show that antimuscarinics exert differential effects on heart rate depending on their muscarinic receptor profile. This should be considered when selecting a treatment.

Topics: Age Factors; Aged; Aged, 80 and over; Benzhydryl Compounds; Benzofurans; Constipation; Cresols; Cross-Over Studies; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Pyrrolidines; Time Factors; Tolterodine Tartrate; Xerostomia

To evaluate the clinical efficacy and tolerability of tolterodine extended-release (ER) in continent patients with overactive bladder (OAB) and nocturia.. A post hoc analysis was conducted of data from a 12-week, double-blind study of 850 patients randomized to tolterodine ER (4 mg once daily) or placebo, taken within 4 h of going to bed. Patients with a mean of > or = 8 voids/24 h were enrolled, including a mean of > or = 2.5 voids/night. Patients completed 7-day voiding diaries, and for each void an urgency rating was assessed using a 5-point scale (1, none; 5, urgency incontinence); 24-h voids were categorized by urgency rating: total (1-5), non-OAB (1-2), OAB (3-4), and severe OAB (4-5) voids. All adverse events were recorded.. The post hoc analysis included 513 patients (243 placebo; 270 tolterodine ER; 58% men) who were continent at baseline; 47% of 24-h voids were classed as non-OAB, and 12% as severe OAB. After 12 weeks of treatment, tolterodine ER significantly reduced mean urgency rating and 24-h OAB, severe OAB, and total voids vs placebo. Tolterodine ER did not affect normal, non-OAB voids, and there were no significant adverse events related to voiding. Other than dry mouth (tolterodine ER, 9% vs placebo, 2%), all the adverse events were reported in <3% of patients; <2% of patients receiving tolterodine ER withdrew because of adverse events.. In continent patients with OAB, tolterodine ER significantly improved urgency rating and reduced 24-h OAB, severe OAB, and total voids, suggesting that it is an effective and well-tolerated treatment option for this subpopulation. More studies are needed to better understand the clinical efficacy of tolterodine ER in this under evaluated group of OAB patients without incontinence.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Constipation; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urination Disorders; Urodynamics; Xerostomia

The incidence, severity and tolerability of dry mouth was compared in 790 women with overactive bladder who were treated with extended-release oxybutynin chloride 10 mg/day or extended-release tolterodine tartrate 4 mg/day for 12 weeks in a multicenter, double-blind, parallel-group study. Dry mouth was the most common adverse event associated with treatment, with an incidence rate of 28.1% in the oxybutynin group and 21.6% in the tolterodine group (P = 0.039). The majority of dry mouth events were mild in both treatment groups. Severe dry mouth occurred in 1.5% and 0.5% of patients in the oxybutynin and tolterodine groups, respectively (P = 0.173). Seven patients on extended-release oxybutynin and 4 patients on extended-release tolterodine discontinued treatment due to dry mouth (P = 0.380). The results of this analysis showed that dry mouth was common with both treatments, but most events were mild; there was no difference in the rate of severe dry mouth or in the rate of withdrawal due to dry mouth.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Severity of Illness Index; Tolterodine Tartrate; Urinary Incontinence; Xerostomia

To examine the efficacy and tolerability of antimuscarinic therapy in women with urge-predominant mixed incontinence.. This was a double-blind, randomized, placebo-controlled trial comprising 854 women with urge-predominant mixed incontinence, including urge incontinence (five or more episodes per week), urinary frequency (eight or more micturitions on average in 24 hours), and urgency in combination with stress incontinence. Women received 8 weeks of treatment with tolterodine tartrate extended-release (ER) 4 mg or placebo once daily. The outcome measures included urge incontinence episodes per week, stress incontinence episodes per week, micturition frequency per 24 hours, urgency episodes per 24 hours, volume voided per micturition, patient perception of bladder condition, and assessment of treatment benefit.. After 8 weeks, tolterodine ER produced a statistically significant decrease in the weekly urge incontinence episodes compared with placebo (-12.3 versus -8.0; P <0.0001). Other micturition variables improved significantly more with tolterodine ER. No difference was found between treatment groups regarding the change in the number of stress incontinence episodes. A significantly greater proportion of patients receiving tolterodine ER than those receiving placebo reported improvement in bladder condition (61% versus 46%; P <0.001) and treatment benefit (76% versus 55%; P <0.001). After 8 weeks, the tolterodine ER group had experienced statistically significant improvements compared with the placebo group in 9 of 10 quality-of-life domains. The frequency of adverse events was similar between treatment groups.. Tolterodine ER is an effective treatment of urge urinary incontinence, frequency, and urgency in women with concomitant stress urinary incontinence. The efficacy of tolterodine ER in reducing urge incontinence episodes was unaffected by the presence of stress incontinence. The results of this study support the first-line use of antimuscarinic therapy to treat the urge incontinence component of urge-predominant mixed incontinence.

Topics: Adult; Aged; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Diuresis; Double-Blind Method; Female; Humans; Middle Aged; Muscarinic Antagonists; Patient Acceptance of Health Care; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urinary Incontinence, Stress; Urination; Xerostomia

To compare tolterodine with oxybutynin and placebo in people with neurogenic detrusor overactivity.. Prospective, randomized, double-blind, crossover trial plus open-label comparative stage.. Ten participants with neurogenic detrusor overactivity due to spinal cord injury or multiple sclerosis who used intermittent catheterization.. Bladder capacity on cystometrogram, a 10-day record of catheterization volumes, number of incontinent episodes per day, and perceived dry mouth using a visual analog scale (VAS) were measured for the following: (a) a blinded comparison: tolterodine, 2 mg twice daily, vs placebo, twice daily; and (b) an unblinded comparison: oxybutynin vs tolterodine, each at self-selected doses (SSDs).. Tolterodine, 2 mg twice daily, was superior to placebo in enhancing catheterization volumes (P < 0.0005) and reducing incontinence (P < 0.001), but was comparable with placebo in cystometric bladder capacity. Efficacy of tolterodine SSD was comparable with oxybutynin SSD with regard to catheterization volumes, degree of incontinence, and cystometric bladder capacity. The side effect profile (dry mouth) was comparable between tolterodine, 2 mg twice daily, and placebo, but differed significantly when comparing tolterodine SSD with oxybutynin SSD (P < 0.05).. Tolterodine, when used at SSDs, is comparable with oxybutynin at SSDs in enhancing bladder volume and improving continence, but with less dry mouth. Tolterodine at the recommended dosage of 2 mg twice daily improves incontinence and bladder volumes compared with placebo, and without significant dry mouth. Larger doses of tolterodine may be needed to achieve best effect in this population, but further studies are required.

Topics: Adult; Benzhydryl Compounds; Cresols; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Multiple Sclerosis; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Spinal Cord Injuries; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urinary Incontinence; Xerostomia

To observe the efficacy of electrical stimulation in treatment of overactive bladder (OAB).. Patients (n = 60) with overactive bladder were randomly divided into 2 groups. Electrical stimulation group (n = 35) used an instrument for electrical stimulation through a special vagina or rectum probe transfer current (8-70 mA), for 20 min, qd, for 20-30 times. Medical group (n = 25) received oral tolterodine 2 mg, bid, for 2-4 weeks.. The total effective rate and cure rate were 74%, 37% in electrical stimulation group and 76%, 40% in medical group, respectively, showing no significant difference between two groups (P > 0.05). While patients' satisfactory rate was significantly higher in electrical stimulation group than in medical group (P < 0.05). Side effects were more commonly seen with tolterodine.. Electrical nerve stimulation is effective and safe for overactive bladder. Further studies are needed to show the long term efficacy and cost-effectiveness.

Topics: Adult; Aged; Benzhydryl Compounds; Constipation; Cresols; Electric Stimulation Therapy; Female; Humans; Middle Aged; Pelvic Floor; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urination; Urination Disorders; Xerostomia

Oxybutynin binds to the M(3) muscarinic receptors on the detrusor muscle of the bladder, preventing acetylcholinergic activation and relaxing the muscle. The transdermal system delivers oxybutynin over a 3- to 4-day period after application to intact skin. Peak plasma concentrations of oxybutynin and the major active metabolite, N-desethyloxybutynin, are reached 24 - 48 hours after a single application and therapeutic concentrations are maintained throughout the dosage interval. In a large, randomised, double-blind trial, transdermal oxybutynin 3.9 mg/day significantly decreased the median number of incontinence episodes per week compared with placebo (-19 vs -15, p = 0.0165) in patients with overactive bladder. In addition, the micturition frequency was reduced and average voided volume was increased by transdermal oxybutynin treatment. Significant reductions in incontinence episodes following transdermal oxybutynin treatment were also observed in two further studies and the clinical efficacy was similar to that of oral tolterodine or oral oxybutynin. Transdermal oxybutynin was well tolerated in clinical trials. Application site reactions were the most common adverse effect; however, the majority were mild to moderate in severity. Adverse events associated with anticholinergic drugs (e.g. dry mouth) were less frequently reported in patients treated with transdermal oxybutynin than in those receiving orally administered oxybutynin or tolterodine.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Aged; Benzhydryl Compounds; Cresols; Double-Blind Method; Exanthema; Humans; Mandelic Acids; Middle Aged; Phenylpropanolamine; Time Factors; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence; Xerostomia

To evaluate the efficacy, safety, and tolerability of a new, once-daily extended-release (ER) formulation of tolterodine in treating overactive bladder in older (> or =65) and younger (<65) patients.. A 12-week double-blind, placebo-controlled clinical trial.. An international study conducted at 167 medical centers.. One thousand fifteen patients (43.1% aged > or =65) with urge incontinence and urinary frequency.. Patients were randomized to treatment with tolterodine ER 4 mg once daily (qd) (n = 507) or placebo (n = 508) for 12 weeks.. Efficacy, measured with micturition charts (incontinence episodes, micturitions, volume voided per micturition) and subjective patient assessments, safety, and tolerability endpoints were evaluated, relative to placebo, according to two age cohorts: younger than 65 and 65 and older.. Mean age in the older and younger patient cohorts was 74 (range 65-93) and 51 (range 20-64), respectively. Compared with placebo, significant improvements in micturition chart variables with tolterodine ER showed no age-related differences. Irrespective of age, significantly more tolterodine ER recipients than placebo recipients reported an improvement in urgency symptoms. After 12 weeks of treatment with tolterodine ER, a fivefold increase in the percentage of patients able to finish tasks before voiding in response to urgency was noted in both age groups (<65: from 6.5-32.8%, > or =65: from 5.1-26.2%). Tolterodine ER recipients, irrespective of age, also had significant improvements in their bladder condition than did placebo recipients. Overall, a greater percentage of patients, irrespective of age, perceived any benefit with tolterodine ER than with placebo (P <.001). Dry mouth (of any severity) was the most common adverse event in both the tolterodine ER and placebo treatment arms, irrespective of age (<65: ER 22.7%, placebo 8.1%; > or =65: ER 24.3%, placebo 7.2%). Few patients (<2%) experienced severe dry mouth. No central nervous system, visual, cardiac (per electrocardiogram), or laboratory safety concerns were noted. Withdrawal rates due to adverse events on tolterodine ER 4 mg qd were comparable in the two age cohorts (<65: 5.5%; > or =65: 5.1%; P =.87).. The new, once-daily ER formulation of tolterodine is efficacious, safe, and well tolerated in the treatment of patients with symptoms of overactive bladder, irrespective of age.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Benzhydryl Compounds; Cohort Studies; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence; Xerostomia

To compare the efficacy and tolerability of extended-release oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with overactive bladder.. The OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study was a prospective, randomized, double-blind, parallel-group study conducted between March and October 2000 at 37 US study sites. Participants who had between 7 and 50 episodes of urge incontinence per week and 10 or more voids in 24 hours received extended-release oxybutynin, 10 mg/d, or tolterodine, 2 mg twice daily. The outcome measures were the number of episodes of urge incontinence, total incontinence, and micturition frequency at 12 weeks adjusted for baseline.. A total of 315 women and 63 men were randomized and treated, and 332 participants (276 women, 56 men) completed the study. At the end of the study, extended-release oxybutynin was significantly more effective than tolterodine in each of the main outcome measures: weekly urge incontinence (P=.03), total incontinence (P=.02), and micturition frequency episodes (P=.02) adjusted for baseline. Both drugs improved symptoms of overactive bladder significantly from baseline to the end of the study as assessed by the 3 main outcome measures (P<.001). Dry mouth, the most common adverse event, was reported by 28.1% and 33.2% of participants taking extended-release oxybutynin and tolterodine, respectively (P=.32). Rates of central nervous system and other adverse events were low and similar in both groups.. Extended-release oxybutynin was more effective than tolterodine as measured by end-of-study urge incontinence, total incontinence, and micturition frequency episodes. Both groups had similar rates of dry mouth and other adverse events.

Topics: Aged; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Nervous System Diseases; Phenylpropanolamine; Probability; Prospective Studies; Reference Values; Severity of Illness Index; Statistics, Nonparametric; Tartrates; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Incontinence, Stress; Urination Disorders; Xerostomia

To investigate the clinical safety and efficacy of two dosages of tolterodine in older patients with symptoms attributable to overactive bladder.. Randomized, double-blind, placebo-controlled, parallel-group, multinational, phase III study.. Incontinence, older care, urological, and urogynecological clinics in the United Kingdom, France, and the Republic of Ireland.. One hundred and seventy-seven older patients (age > or =65 years) with symptoms of urinary urgency, increased frequency of micturition (> or =8 micturitions/24 hours), and/or urge incontinence (> or =1 episode/24 hours).. Tolterodine 1 mg or 2 mg twice daily (bid), or placebo, for 4 weeks.. Safety and tolerability were evaluated through spontaneously reported adverse events, electrocardiogram, and blood pressure measurements. Efficacy was assessed using micturition diary variables: mean change from baseline in frequency of micturition and number of incontinence episodes/24 hours.. The mean age of the patient population was 75 years. Overall, > or =87% of patients completed the study. Neither dosage of tolterodine was associated with serious drug-related adverse events during the study. No cardiac arrythmogenic events were noted. Dry mouth (mild to moderate intensity) was the most common adverse event in both the placebo and tolterodine treatment groups. Three percent of patients in the tolterodine 2 mg bid group discontinued treatment because of dry mouth, compared with 2% of placebo-treated patients. Compared with placebo, statistically significant decreases in micturition frequency were apparent in both tolterodine treatment groups. Furthermore, patients treated with tolterodine 2 mg bid had statistically significant decreases in urge incontinence episodes/24 hours and increases in volume voided per micturition compared with placebo.. Tolterodine (taken for 4 weeks) is safe and shows efficacy, particularly at a dosage of 2 mg bid, in the treatment of older patients with urinary symptoms attributable to overactive bladder.

Topics: Age Factors; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Double-Blind Method; Drug Monitoring; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Placebos; Safety; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urination Disorders; Xerostomia

Details on the therapeutic effects of long-term antimuscarinic therapy have not been reported. Thus, the aim of this study is to evaluate the detailed long-term therapeutic effect of antimuscarinic therapy.. All consecutive patients who visited the urologic outpatient clinics of a medical center for treatment of overactive bladder syndrome and received antimuscarinic therapy of 12 months or more were retrospectively reviewed. All medical records, including the Overactive Bladder Symptom score (OABSS), the modified Indevus Urgency Severity Scale and the International Prostate Symptoms score (IPSS) questionnaires, and uroflowmetry parameters were reviewed at each visit.. A total of 140 patients had received 12 months or more of antimuscarinic therapy. Sustained therapeutic effects were observed by persistent decreases of IPSS-storage score, IPSS-total score and OABSS score. Moreover, the maximum flow rate did not change over time. A temporary increase in postvoid residual volume and decrease in voiding efficiency were found, but these parameters improved over long-term visits. Side-effects were observed in 81 patients (57.9%) and included dry mouth (n = 58, 41.4%), constipation (n = 48, 34.3%) and blurred vision (n = 4, 2.9%); all side-effects were tolerable. Patients aged 75 years or more (n = 94) had a higher comorbidity rate (n = 46, 48.9%) before treatment but generally exhibited similar therapeutic effects as overall patients; elderly patients could also tolerate side-effects.. Sustained therapeutic effects were observed in patients who received 12 months or more of antimuscarinic therapy, even in elderly patients. In addition, side-effects in patients receiving long-term therapy were also common but tolerable.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Constipation; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Retrospective Studies; Severity of Illness Index; Solifenacin Succinate; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics; Vision Disorders; Xerostomia; Young Adult

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Patient Preference; Randomized Controlled Trials as Topic; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents; Xerostomia

The objective was to validate an in vivo model for evaluation of pharmacological effects on bladder function taking the most predominant anticholinergic side effect (hyposalivation) into account. Therefore, two anticholinergic properties (propiverine hydrochloride and tolterodine-L(+)-tartrate) were used to test the in vivo model. Sacral anterior root stimulation (SARS) was performed to induce reproducible and standardized bladder contractions. To evaluate hyposalivation standardised salivavary flow measurements by stimulating the lingual nerve was performed in addition to SARS.. 10 male mini pigs were anaesthetised. The carotid artery was cannulated for blood pressure measurement and the jugular vein for administration of propiverine 0.4 mg kg(-1) b.w. and tolterodine 0.06 mg kg(-1) b.w. For stimulation-induced salivary flow measurements both lingual nerves were exposed and a cuff electrode was placed around the nerves. The bladder was exposed and a cystostomy catheter was inserted to performed cystometrographic measurements during SARS.. In all experiments, for each animal reproducible intravesical pressure values (pves) and salivary flow rates were elicited during electrostimulation before administration of the drug. Bladder pressure: After administration of propiverine, neurostimulation-induced rise in pves had fallen by 60% from the initial value. After administration of tolterodine pves had fallen by about 50%. After additional administration of atropine pves decreased to about 15% of the initial value for both drugs. Salivation: After propiverine salivary flow had fallen by 61%. Inhibition of salivary flow under tolterodine was about 56%. Additional administration of atropine led in both drugs to a nearly complete blockade of salivation. Heart rate (HR) and blood pressure (BP): Directly following intravenous administration of both drugs, a short-term and reversible period of mild but significant fluctuations in HR was observed. There was also a slight but non-significant rise in blood pressure.. This model allows comparative investigations of various drugs with bladder inhibitory properties in terms of acute efficacy and side effects.

Topics: Animals; Atropine; Benzhydryl Compounds; Benzilates; Blood Pressure; Cholinergic Antagonists; Cresols; Drug Evaluation, Preclinical; Electric Stimulation; Heart Rate; Lingual Nerve; Male; Models, Animal; Muscle Contraction; Phenylpropanolamine; Reproducibility of Results; Salivary Glands; Salivation; Swine; Swine, Miniature; Tolterodine Tartrate; Urinary Bladder; Xerostomia

Topics: Administration, Cutaneous; Administration, Oral; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Xerostomia

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Clinical Trials as Topic; Cresols; Delayed-Action Preparations; Female; Headache; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Urination Disorders; Xerostomia

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Child; Child, Preschool; Cresols; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence; Xerostomia

Topics: Benzhydryl Compounds; Clinical Trials as Topic; Cresols; Double-Blind Method; Humans; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Urination Disorders; Xerostomia