Dose Of Oxybutynin Research Articles

Dose escalation improves therapeutic outcome: post hoc analysis of data from a 12-week, multicentre, double-blind, parallel-group trial of trospium chloride in patients with urinary urge incontinence

BackgroundFlexible dosing of anticholinergics used for overactive bladder (OAB) treatment is a useful strategy in clinical practice for achieving a maximum effective and maximum tolerated level of therapeutic benefit. In this post hoc analysis we evaluated the efficacy and tolerability of trospium chloride treatment for urinary urge incontinence (UUI) with focus on flexible dosing.MethodsThe data came from a 12-week, randomised, double-blind, phase IIIb study in which 1658 patients with urinary frequency plus urge incontinence received trospium chloride 15 mg TID (n = 828) or 2.5 mg oxybutynin hydrochloride TID (n = 830). After four weeks, daily doses were doubled and not readjusted in 29.2% (242/828) of patients in the trospium group, and in 23.3% (193/830) in the oxybuytnin group, until the end of treatment. We assessed the absolute reduction in weekly UUI episodes and the change in intensity of dry mouth, recorded in patients' micturition diaries. Adverse events were also evaluated. Statistics were descriptive.ResultsDose escalation of either trospium or oxybutynin increased reduction in UUI episodes in the population studied. At study end, there were no relevant differences between the "dose adjustment" subgroups and the respective "no dose adjustment" subgroups (trospium: P = 0.249; oxybutynin: P = 0.349). After dose escalation, worsening of dry mouth was higher in both dose adjusted subgroups compared to the respective "no dose adjustment" subgroups (P < 0.001). Worsening of dry mouth was lower in the trospium groups than in the oxybutynin groups (P < 0.001). Adverse events were increased in the dose adjusted subgroups.ConclusionsFlexible dosing of trospium was proven to be as effective, but better tolerated as the officially approved adjusted dose of oxybutynin.Trial registration (parent study)The study was registered with the German Federal Institute for Drugs and Medical Devices (BfArM, Berlin, Germany), registration number 4022383, as required at the time point of planning this study.

Efficacy, tolerability and safety of propiverine hydrochloride in comparison to oxybutynin in children with urge incontinence due to overactive bladder: Results of a multicentre observational cohort study

To compare, in a retrospective observational cohort study, the efficacy, tolerability and safety of propiverine and oxybutynin in children with urge incontinence (UI) due to overactive bladder. Medical records were scrutinized for children with UI. As a primary efficacy outcome variable the achievement of continence after treatment with variable doses of propiverine or oxybutynin was assessed. Weekly UI episodes and daily voiding frequency were evaluated as secondary efficacy outcomes. Tolerability was evaluated by the rate of adverse events, adverse drug reactions caused by antimuscarinics and premature treatment termination. At 16 study centres, 621 children aged 5-14 years with UI due to overactive bladder were enrolled. After anticholinergic treatment (437 propiverine, 184 oxybutynin) continence was achieved in 61.6% and 58.7% of the patients after 186 and 259 days, respectively. There were clinically relevant improvements in voiding frequency across treatment groups. Daily doses of propiverine were markedly below the recommendations (0.54 vs 0.8 mg/kg body weight), daily doses of oxybutynin were according to the recommendations (0.31 vs 0.2-0.4 mg/kg body weight) at treatment initiation. There was a significantly more favourable tolerability to propiverine than oxybutynin for the overall rate of adverse events (3.9% vs 16.3%, odds ratio 4.813), adverse drug reactions caused by propiverine or oxybutynin (2.8% vs 9.2%) and premature treatment termination due to adverse drug reactions (1.6% vs 4.4%). Propiverine and oxybutynin are effective in children with UI due to overactive bladder. Sufficient treatment periods of at least 2, preferably 3-4, months are the crucial factors for a successful treatment. The tolerability profile of propiverine is better than for oxybutynin.

Combined Behavioral and Individualized Drug Therapy Versus Individualized Drug Therapy Alone for Urge Urinary Incontinence in Women

We tested whether individualized drug therapy enhanced with behavioral training would result in better outcomes than individualized drug therapy alone. Participants were community dwelling women with urge predominant incontinence. Using a randomized clinical trial design women were randomized to 8 weeks (4 visits) of drug therapy alone (32) or drug therapy plus behavioral training (32). Drug therapy was individually titrated, extended release oxybutynin with proactive management of side effects. Behavioral training included pelvic floor muscle training and urge suppression techniques. The primary outcome measure was reduction in frequency of incontinence episodes on bladder diary at 8 weeks (with followup at 6 and 12 months). Secondary outcomes included patient satisfaction, global perception of improvement, Urogenital Distress Inventory and Incontinence Impact Questionnaire. In intent to treat analysis frequency of incontinence was reduced a mean of 88.5% in the drug alone group and 78.3% in the combined therapy group (p = 0.16). Outcomes were not significantly different between the groups in the analysis of completers (91.5% vs 86.2%, p = 0.34), or in either analysis at 6 or 12 months. The groups also did not differ significantly on secondary outcomes at any point. Participants in the drug alone group tended to be taking higher doses of oxybutynin at 8 weeks but the final dose did not differ significantly between the groups. Based on a conditional power calculation the trial was stopped early for futility. When drug therapy is implemented with frequent individualized dose titration, daily bladder diaries and careful management of side effects, initiating concurrent behavioral training does not enhance outcomes for urge incontinence in women.

Oxybutynin and Propiverine Suppress Adenosine Triphosphate-induced Bladder Overactivity Other Than Through Antimuscarinic Mechanisms

Adenosine triphosphate (ATP) is released from bladder urothelium in response to stretch and may act as a sensory neurotransmitter. ATP release from the bladder urothelium is augmented in many pathophysiologic conditions, resulting in bladder overactivity. Patients who have bladder overactivity are treated with antimuscarinics with symptom improvement. We investigated the effects of oxybutynin and propiverine on bladder overactivity induced by intravesical instillation of ATP. Under urethane anesthesia, cystometry was performed in female Sprague-Dawley rats. After a 2-hour baseline period, protamine sulfate (10 mg/mL) was instilled for 1 hour, and then ATP (60 mM, pH 6.0) was instilled intravesically. Oxybutynin, propiverine, pyridoxal-(5) phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), atropine, 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP), and methoctramine were given intravenously when ATP-induced bladder overactivity was stable. When protamine sulfate was infused intravesically, the intercontraction interval (ICI) did not decrease significantly, but intravesical instillation of ATP after protamine sulfate treatment decreased the ICI compared with baseline. Oxybutynin, propiverine, and PPADS given intravenously reversed the ATP-induced ICI reduction in a dose-dependent manner. In contrast, ATP-induced ICI reduction was not reversed by intravenous atropine, 4-DAMP, or methoctramine. Maximum voiding pressure did not change with ATP but decreased with antimuscarinics. Pressure threshold (PT) decreased with ATP and stayed reduced after dose of oxybutynin or propiverine. Bladder overactivity induced by intravesical instillation of ATP with protamine pretreatment was suppressed by oxybutynin, propiverine, and PPADS, and not by atropine, 4-DAMP, and methoctramine. Oxybutynin and propiverine suppress ATP-induced bladder overactivity other than through antimuscarinic mechanisms.

Role of Bladder Capacity in Assessing the Effectiveness of Antimuscarinic Agents on Nocturia in Patients with Overactive Bladders

Objective The aim of this study was to evaluate the effectiveness of oxybutynin in the treatment of nocturia in patients with overactive bladders (OAB) and to assess predictive factors for the responses to oxybutynin. Patients and Methods Patients with symptoms of OAB and nocturia for more than 3 months were enrolled. A 2.5 mg dose of oxybutynin was given twice daily for 1 week after a baseline study that included a self-administered nocturia questionnaire, uroflowmetry, and frequency/volume chart. Outcome analysis included changes in nocturia episodes, uroflowmetry, and post-void residual urine. Patients were stratified according to a nocturia index (Ni), nocturnal polyuria index (NPi), and nocturnal bladder capacity index (NBCi). Results A total of 59 patients were eligible for analysis. After 1 week of treatment with oxybutynin, the mean number of nocturia episodes had reduced from 2.7 ± 1.3 to 2.3 ± 1.1 ( p < 0.01). There were no statistically significant differences in the mean reduction of nocturia episodes between the subgroup of patients with NPi ≤ 0.35 and those with NPi > 0.35 (−0.4 vs. −0.3, p = 0.34, ANCOVA). Reduction in number of nocturia episodes was more significant in patients with Ni ≤ 1.5 than in those with Ni > 1.5 (−0.9 vs. −0.2, p = 0.03, ANCOVA), and in patients with NBCi > 2 than in those with NBCi ≤ 2 (−1.1 vs. −0.2, p = 0.01, ANCOVA). Conclusion Ni and NBCi are good predicting factors for the effects of antimuscarinic agents on nocturia in patients with OAB.

Effect of oxybutynin on exercise‐induced sweating in healthy individuals

Objectives: Oxybutynin has been proven to be effective in patients with generalized hyperhidrosis. Some dermatoses aggravate as a result of sweating. Therefore, oxybutynin might also be useful in such normohidrotic patients. The aim was to evaluate the efficacy and safety of different doses of oxybutynin on exercise‐induced sweating in healthy individuals. Methods: Two randomized, double‐blind, placebo‐controlled, cross‐over studies were performed, in which two different dosages (2.5 and 5 mg) of oxybutynin were tested. The degree of sweating was determined by transepidermal water loss (TEWL) measurement on the forearm and the hand during exercise. Furthermore, the effectiveness was evaluated by means of the individual's global assessment score, and side effects were noted. Results: No significant differences between oxybutynin and placebo were found on the forearm and the hand at both dosages of oxybutynin with respect to TEWL values and the individual's global assessment score. Side effects consisted of diarrhoea, dizziness, dry mouth and dry eyes. Conclusions: In this model, oxybutynin did not result in inhibition of exercise‐induced sweating in healthy volunteers.

Long-term urodynamics followup of bladder augmentation for neurogenic bladder.

Augmentation enterocystoplasty is well tolerated by patients with neurogenic bladder in whom conservative therapy has failed. However, few studies exist on long-term urodynamic evaluation of these patients. We assessed the clinical and urodynamic outcomes of patients with neurogenic bladder treated with augmentation enterocystoplasty with at least 4 years of followup. A total of 26 patients with neurogenic voiding dysfunction underwent augmentation enterocystoplasty alone or in conjunction with various continence or antireflux techniques. Clinical outcomes regarding incontinence, medications, catheterization schedule, subsequent interventions, bowel function and patient satisfaction were addressed. Urodynamic evaluation was performed to assess the long-term durability of bladder augmentation. Mean followup was 8.0 years (range 4 to 13). All but 1 patient (96%) in our series had near or complete resolution of urinary incontinence. Mean total bladder capacity +/- SD increased from 201 +/- 106 to 615 +/- 204 ml. (p <0.001) and mean maximum detrusor pressure decreased from 81 +/- 43 to 20 +/- 12 cm. H O (p <0.01). Mean interval between catheterizations was 5 hours, with volumes ranging from 314 to 743 ml. Only 2 patients (8%) needed a low dose of oxybutynin postoperatively to maintain continence consistently. Of the 26 patients 23 (88%) reported no significant change in bowel function and nearly all patients expressed extreme satisfaction with urological management. A subsequent urological procedure was required in 12 patients (46%) at a mean of 4.4 years after initial surgery.(2) Bladder augmentation provides durable clinical and urodynamic improvement for patients with neurogenic bladder dysfunction refractory to conservative therapy. Furthermore, there is a high level of patient satisfaction with bladder augmentation.

EFFICACY AND SAFETY OF EXTENDED RELEASE OXYBUTYNIN FOR THE TREATMENT OF URGE INCONTINENCE: AN ANALYSIS OF DATA FROM 3 FLEXIBLE DOSING STUDIES

We assessed the efficacy and safety of extended release (ER) oxybutynin at individualized doses for urge urinary incontinence. Data were combined from 3 flexible dosing studies of a total of 420 patients with urge urinary incontinence or mixed incontinence in whom ER oxybutynin dose adjustments were made to achieve the optimal balance between efficacy and tolerability, as judged by each participant. Individual doses were adjusted in 5 mg increments across a dose range of 5 to 30 mg daily. Efficacy was assessed during maintenance therapy using a 7-day diary. Data on 368 patients who completed dose adjustment were included in the analysis. In 47% of patients the preferred dose was greater than 10 mg daily. Individualized doses of ER oxybutynin produced a 79.3% decrease from baseline in the total of all incontinence episodes and an 83.2% decrease in urge episodes. Of patients 81% achieved a decrease of at least 70% in all incontinence episodes and 43% achieved total dryness. Moderate or severe dry mouth was reported by 23% of patients and it was cited as the cause for early withdrawal by 1.4% who completed dose adjustment. Therapy was well tolerated. In the pooled sample overall 6.7% of patients cited adverse events as the reason for discontinuing. Individualized dosing with ER oxybutynin was associated with highly effective and well tolerated control of urinary incontinence with more than 40% of patients achieving total dryness.

EFFECTS OF THE SELECTIVE ACETYLCHOLINESTERASE INHIBITOR TAK-802 ON THE VOIDING BEHAVIOR AND BLADDER MASS INCREASE IN RATS WITH PARTIAL BLADDER OUTLET OBSTRUCTION

We examined the effects of the selective acetylcholinesterase (AChE) inhibitor TAK-802 on voiding behavior and residual urine volume in rats with partial bladder outlet obstruction (BOO) vs rats treated with the nonselective AChE inhibitor distigmine and the muscarinic agonist bethanechol. In addition, the effect of repeat doses of TAK-802 on the bladder mass increase associated with BOO was also examined. Male rats with BOO were used. Six to 8 days after obstruction voiding behavior was observed in a metabolic cage. The animals were then treated orally with 1 drug, and voiding frequency and urine volume at each void were measured for 3 hours. Subsequently the volume of urine retained in the bladder (residual urine) was measured. In another experiment bladder weight in rats with BOO was measured after early repeat doses of TAK-802. BOO increased voiding frequency and decreased average voided volume. TAK-802 and distigmine increased average voided volume, while not causing any change in voiding frequency. On the other hand, bethanechol increased voiding frequency without affecting average voided volume. While all 3 drugs significantly decreased residual urine volume, TAK-802 was most efficacious. In addition, bladder weight in the control BOO group was greater (approximately 2.2-fold) than that in the sham operated group and early repeat administration of TAK-802 prevented the bladder mass increase. AChE inhibitors decreased residual urine volume by restoring voiding function in rats with BOO, although only the effect of TAK-802 was dose dependent. Bethanechol also decreased residual urine volume in a dose dependent manner but by increasing voiding frequency. The prevention of a bladder mass increase by TAK-802 treatment may be attributable to its effect on restoring voiding.

Long-term prospective randomized study comparing two different regimens of oxybutynin as a treatment for detrusor overactivity

Objective: Prospective randomized trial to compare two low starting doses of oxybutynin, using an incremental regimen to assess patient compliance and treatment efficacy in the long-term. Study design: Women with detrusor overactivity were included. Oxybutynin was randomly prescribed with a starting dose of either 2.5 mg bd or 5 mg nocte. Instructions were given to increase oxybutynin up to 5 mg tds over a period of 6 weeks fortnightly. After two years we re-contacted all the women, using a specific questionnaire to assess the efficacy, acceptability and compliance with these two different regimens. Twenty-two women in each group were calculated to show a 5% difference with a significance of 0.05 and a power of 0.9. The χ 2-test was used to compare the two groups and a P-value < 0.05 was considered significant. Results: Ninety-six women were included; 66 (68.75%) (mean age 57.5 years) responded to our questionnaire. Twenty-seven had a starting dose of 2.5 mg oxybutynin twice a day and 39 of 5 mg nocte. 34.8% complained of side effects. Only 19 (43.2%) out of the 44, not on medication anymore abandoned oxybutynin for adverse reactions. Most of the patients stopped oxybutynin within 4 months. 53.0% reported improvement or cure. 39.4% denied any benefit and 7.6% (none still on oxybutynin) did not answer. The two groups did not differ for duration of treatment, improvement with oxybutynin, maximum dose they reached, the present dose, and the present urinary symptoms. Conclusion: This study did not show any advantage in efficacy or compliance with oxybutynin when two different regimens of low starting were used. Two-thirds of patients discontinued the therapy within 4–6 months. Therefore, patients on anticholinergics should be reassessed after 6 months in clinical practice.

Poster 37: Individualized Dosing of Extended-release Oxybutynin is Associated With Improved Outcomes in the Treatment of Urge Incontinence

OBJECTIVE: To determine whether flexible dosing with the option to use the full range of approved doses of extended-release (ER) oxybutynin (5–30 mg daily) was associated with improvements in frequency of urge urinary incontinence (UUI) episodes, while maintaining treatment tolerability. METHODS: Data were combined from 3 flexible-dosing studies in which ER oxybutynin dose adjustments were made to achieve a maximal reduction in UUI episodes with acceptable tolerability. Doses were adjusted in 5 mg increments every 4–7 days, until the patient 1) reached complete continence, 2) achieved the highest level of continence attainable while still maintaining tolerability, as judged by each participant, or 3) reached the maximal dose of 30 mg. If the dose was deemed intolerable by the patient, it was reduced by 5 mg. Efficacy outcomes included mean reduction in UUI episodes and responder rate according to 2 definitions: a reduction of 70% or more in UUI episodes, and the attainment of complete continence. RESULTS: Data from 368 patients with UUI or mixed incontinence with urge predominating were pooled. For 30% of patients, the preferred dose was 10 mg daily, whereas 47% of patients were maintained at a dose of ER oxybutynin that was greater than 10 mg. Treatment with individualized doses produced an 83% decrease from baseline in UUI episodes, and 82.6% of patients achieved a decrease in UUI episodes of at least 70%. Complete continence was achieved by nearly 43% of participants overall. The cumulative percentage of patients achieving these goals increased with each dose increment. Therapy was well tolerated, with 7.6% of patients discontinuing because of adverse events. Moderate or severe dry mouth was reported by 23% of patients and was cited as the cause for early withdrawal by 5 (1.4%) patients. Incidence of dry mouth increased with dose (except at 30 mg daily), but no systematic increase in discontinuation rate for adverse events was observed. CONCLUSIONS: Almost half of the patients in this study increased their dose of ER oxybutynin beyond 10 mg. Individualized adjustments in ER oxybutynin dose resulted in effective and well tolerated management of urge incontinence.

Inhibition of Hyperreflexia by Vaginally Administered Oxybutynin: A Novel Rabbit Model

The rabbit has proved to be an excellent model in which to study lower urinary tract function and pathological mechanisms involved in specific forms of lower urinary tract dysfunctions, including those involved with partial outlet obstruction (benign prostatic hyperplasia), erectile dysfunction, bladder instability and ischemic bladder disease. The current study describes a model of bladder instability induced in female rabbits and its use in developing a novel form of vaginal treatment for this instability. A total of 18 female New Zealand White rabbits were used for this experiment. Each rabbit was anesthetized and the carotid artery was cannulated for blood pressure monitoring. The bladder dome was catheterized for monitoring bladder pressure and for cystometry. A ligature was placed around the urethra just distal to the bladder neck to prevent leakage through the urethra and generate unstable bladder contractions. After initial cystometry the bladder was emptied and then filled to 30 ml. Acetylcholine (Ach) was administered into the vesical artery at 15-minute intervals for 2 hours. Hyperreflexia usually developed within 30 minutes. Vaginal oxybutynin (low and high dose) was applied and the effect on cystometry, the response to Ach, and the amplitude and frequency of hyperreflexia was determined. Each dose of oxybutynin increased bladder capacity and improved compliance. The high oxybutynin dose completely inhibited the response to Ach and significantly decreased micturition pressure. The high dose decreased uninhibited bladder contraction peak pressure in a time dependent manner to a greater extent than it decreased uninhibited contraction frequency. The low dose of oxybutynin had no effect on micturition pressure, significantly inhibited the response to Ach and hyperreflexia amplitude to approximately 40% of control values, and had little effect on hyperreflexia frequency. Vaginally delivered oxybutynin was effective in improving bladder compliance, inhibiting intra-arterial Ach stimulated bladder contractions and significantly decreasing the amplitude of hyperreflexia. Vaginal oxybutynin had a more potent effect on the evoked response to Ach and on hyperreflexia than it did on micturition pressure.

Can Higher Doses of Oxybutynin Improve Efficacy in Neurogenic Bladder?

We evaluated the efficacy and tolerability of higher dose oxybutynin chloride in patients with neurogenic bladder and multiple sclerosis, spinal cord injury or Parkinson's disease. The study design was a prospective, 12-week dose titration trial of controlled release oxybutynin (OXY-XL). A 7-day washout period was used before initiation of the starting dose of 10 mg OXY-XL. Doses of OXY-XL were increased by 5 mg at weekly intervals to a maximum dose of 30 mg per day guided by patient perception of efficacy versus side effect. Voiding diaries were completed at baseline, and weeks 6 and 12. Post-void residuals were recorded. Criteria for study admission included post-void residual less than 200 ml. Of the 39 patients enrolled in the study 22 had multiple sclerosis, 10 had spinal cord injury and 7 had Parkinson's disease. There were 29 women (74%) and 10 men (26%). Within 1 week a decrease in the number of voids per day was seen in greater than 50% of the subjects. At the end of the study statistically significant decreases in the number of voids in 24 hours, episodes of nocturia and incontinence episodes were observed. Residual urine remained unchanged from 33.9 +/- 7.6 ml at baseline to 51.3 +/- 10.4 ml after 12 weeks at the final dose (p = 0.17). No patient experienced serious adverse events and none dropped out during the course of the 12-week study. At the end of the study 20.5% of subjects remained on 30 mg, 15.4% on 25 mg, 23.1% on 20 mg, 15.4% on 15 mg and 25.6% on 10 mg OXY-XL. Aggressive dosing of OXY-XL is safe and effective in patients with neurogenic bladder. Compared with nonneurogenic overactive bladder, higher doses of OXY-XL (15 mg daily or greater) were requested by 74.4% of the patients in our study. The onset of clinical efficacy can occur within 1 week, and doses up to 30 mg are well tolerated and effective in this population.

Effectiveness of vaginally administered oxybutynin on rabbit bladder function

ObjectivesTo demonstrate the effectiveness of vaginally delivered oxybutynin on bladder function. Oxybutynin has been used for treatment of urge urinary incontinence for more than 20 years. MethodsThirty female New Zealand White rabbits were used for this experiment. Each rabbit was anesthetized, and the carotid artery was cannulated for blood pressure monitoring. The bladder dome was catheterized for both monitoring of bladder pressure and cystometry. After initial cystometry, acetylcholine (ACh) was injected into the vesical artery at 15-minute intervals for 4 hours. Cystometry was performed at the 2-hour mark and at the end of each experiment (4 hours). After the third ACh administration, vaginal or oral oxybutynin was given and the effect on the response to ACh, blood pressure, and cystometry was observed. ResultsThe high dose of oxybutynin completely inhibited the response to ACh and significantly inhibited the micturition reflex. A 45% inhibition of micturition pressure occurred at the intermediate dose. Little effect on compliance after the low dose and a significant increase in compliance after the mid-dose occurred. Both the low and intermediate doses of oxybutynin reduced the response to ACh to approximately 50% of control. No blood pressure effects of vaginal oxybutynin were noted for any concentration. Oral oxybutynin showed very similar effects to that of the intermediate vaginal dose. ConclusionsVaginally delivered oxybutynin was effective in decreasing bladder compliance and inhibiting intra-arterial ACh-stimulated bladder contractions with little or no effect on the vascular effect of ACh.

Long-Term Urodynamics Followup of Bladder Augmentation for Neurogenic Bladder

Augmentation enterocystoplasty is well tolerated by patients with neurogenic bladder in whom conservative therapy has failed. However, few studies exist on long-term urodynamic evaluation of these patients. We assessed the clinical and urodynamic outcomes of patients with neurogenic bladder treated with augmentation enterocystoplasty with at least 4 years of followup. A total of 26 patients with neurogenic voiding dysfunction underwent augmentation enterocystoplasty alone or in conjunction with various continence or antireflux techniques. Clinical outcomes regarding incontinence, medications, catheterization schedule, subsequent interventions, bowel function and patient satisfaction were addressed. Urodynamic evaluation was performed to assess the long-term durability of bladder augmentation. Mean followup was 8.0 years (range 4 to 13). All but 1 patient (96%) in our series had near or complete resolution of urinary incontinence. Mean total bladder capacity +/- SD increased from 201 +/- 106 to 615 +/- 204 ml. (p <0.001) and mean maximum detrusor pressure decreased from 81 +/- 43 to 20 +/- 12 cm. H O (p <0.01). Mean interval between catheterizations was 5 hours, with volumes ranging from 314 to 743 ml. Only 2 patients (8%) needed a low dose of oxybutynin postoperatively to maintain continence consistently. Of the 26 patients 23 (88%) reported no significant change in bowel function and nearly all patients expressed extreme satisfaction with urological management. A subsequent urological procedure was required in 12 patients (46%) at a mean of 4.4 years after initial surgery.(2) Bladder augmentation provides durable clinical and urodynamic improvement for patients with neurogenic bladder dysfunction refractory to conservative therapy. Furthermore, there is a high level of patient satisfaction with bladder augmentation.

Randomised, Double-Blind Study??? of the Effects of Oxybutynin, Tolterodine, Trospium Chloride and Placebo on Sleep in Healthy Young Volunteers

Central nervous effects of oral anticholinergics may limit the success of incontinence therapy and patient compliance. Only a few studies investigating this topic are available. This study was conducted to determine whether oral anticholinergics alter sleep and psychometric test parameters. Randomised, double-blind, crossover, placebo-controlled study. 24 healthy volunteers (age 22-36 years) without sleeprelated problems. Polysomnographic recordings, sleep questionnaires and psychometric tests (the number combination test [Zahlen-Verbindungs Test; ZVT] and the d2 attention test) were performed following single doses of oxybutynin 15mg, tolterodine 4mg, trospium chloride 45mg or placebo, each separated by an 8-day washout period. Rapid eye movement (REM) sleep (relative to total sleep time) was the primary parameter of polysomnography. The REM sleep for oxybutynin was significantly lower than that for trospium chloride (18.4% vs 20.2%; p < 0.05) and lower than that for placebo (20.1%; ns). The number combination test (ZVT), the primary parameter of cognitive function, and the d2 test did not reveal any differences in reaction time. With regard to the other sleep parameters, the REM latency for oxybutynin was clearly higher than that for placebo, trospium chloride and tolterodine. Effects on non-REM sleep were observed only after administration of oxybutynin compared with placebo. Oxybutynin influenced sleep structure, as was reflected by REM suppression and mild sedation, while subjective parameters and psychometric tests remained unaffected. The sleep and psychometric test values for tolterodine and trospium chloride were comparable to those of placebo. The clinical relevance of these effects is small in healthy young volunteers, but these results cannot be extended to the elderly.

Tolterodine: a clinical review.

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.

TOLTERODINE: SUPERIOR TOLERABILITY THAN AND COMPARABLE EFFICACY TO OXYBUTYNIN IN INDIVIDUALS 50 YEARS OLD OR OLDER WITH OVERACTIVE BLADDER: A RANDOMIZED CONTROLLED TRIAL

We compared the tolerability and clinical efficacy of tolterodine with those of oxybutynin in patients with an overactive bladder using an upward oxybutynin dose titration strategy analogous to that used in routine clinical practice in the United Kingdom and Republic of Ireland. In a randomized double-blind trial 378 male and female patients 50 years old or older with symptoms of overactive bladder (a urinary frequency of 8 or more voids per 24 hours with urgency and/or urge incontinence, that is 1 or more urge incontinence episodes per 24 hours) received 10 weeks of treatment with 2 mg. tolterodine twice daily/or an initial dose of 2.5 mg. oxybutynin twice daily, increasing to 5 mg. twice daily after 2 weeks of treatment. The main outcome measures were changes in voiding diary variables combined with detailed tolerability-safety assessments. Patients treated with tolterodine had significantly fewer adverse events (69% versus 81%, p = 0.01), notably dry mouth (37% versus 61%, p <0.0001), as well as a lower incidence of dose reduction (6% versus 25%, p <0.0001) than those in the oxybutynin group. Each agent had comparable efficacy for improving urinary symptoms. Tolterodine and oxybutynin caused a significant decrease (p = 0.0001) in the mean number of voids per 24 hours (-1.7 or -15% and -1.7 or -15%, respectively), urge incontinence episodes per 24 hours (-1.3 or -54% and -1.8 or -62%, respectively) and mean voided volume per void (33 ml. or 22% and 34 ml. or 23%) after 10 weeks of treatment. Tolterodine is as effective as oxybutynin for improving the symptoms of overactive bladder but it has superior tolerability. The combination of these qualities makes tolterodine the preferred pharmacological therapy for the long-term treatment of this condition.

Low–Dose Oxybutynin for the Treatment of Urge Incontinence: Good Efficacy and Few Side Effects

Objective: Oxybutynin is an efficacious pharmacotherapeutic agent for the treatment of urge incontinence. However, many patients discontinue therapy because of the considerable side effects. This study aims at assessing the efficacy of a low–dose oxybutynin (2.5 mg three times daily) in relation to the concomitant profile of side effects.Methods: Unselected primary care practice patients with involuntary urine loss were eligible for this study. A specially designed questionnaire was used to establish the diagnosis of symptomatic urge incontinence. All patients started with an oral dose of oxybutynin of 2.5 mg three times daily, and the responses with regard to efficacy and side effects were assessed after 2 and 6 weeks. Efficacy was evaluated using subjective patients’ impression as well as data extracted from their voiding diaries. Adverse events possibly related to the use of oxybutynin were specifically asked for. Patients who experienced little or no symptomatc relief and who experienced no side effects were given a higher dose (5 mg three times daily). Results: General practitioners recruited 416 patients with symptomatic urge incontinence. Increasing the dose to 5 mg three times was preferred by 115 patients (28%). After 6 weeks 393 patients reported a partial or complete symptomatic cure (positive responder rate 95%). The average number of micturitions per 24 h decreased from 9.9±(SD)3.7 to 6.0±2.5 (p<0.001), and the average number of episodes of urine loss per 24 h decreased from 6.0±3.6 to 1.7±1.8 (p<0.001). A total of 123 patients (30%) reported side effects attributable to the use of oxybutynin; 42 patients (10%) had to stop the medication because of the severity of these side effects. Conclusion: Successful pharmacological treatment of symptomatic urge incontinence can be given in a primary care setting using oxybutynin. Starting with a low dose of 2.5 three times daily, a subjective and objective efficacy can be achieved with fewer side effects than reported in the literature.

Evaluation of a new once-daily formulation of oxybutynin for the treatment of urinary urge incontinence

Objectives. To evaluate in a 16-center, single-treatment study once-daily controlled-release oxybutynin (Ditropan XL) for urinary urge incontinence. Methods. Two hundred fifty-six participants with urge incontinence or mixed incontinence with a significant urge component were treated. After baseline measurements, participants converting from conventional oxybutynin started Ditropan XL at their previous oxybutynin dose; others started at 5 mg/day. Doses were adjusted until participants reached a maintenance dose that produced continence or the best balance between continence and side effects. This dose was continued for 12 weeks. Effectiveness was assessed by urinary diaries. Results. Effectiveness was achieved across all doses studied (5 to 30 mg/day), with 70.8% of participants using maintenance doses of 5 to 15 mg/day. Mean urge incontinence episodes per week decreased from 18.8 at baseline to 3.9 in maintenance week 1, 2.7 in week 4, and 2.8 at the end of the study. For those participants who reported urge incontinence episodes at baseline but were free of urge incontinence at maintenance week 1, 31% remained free of urge incontinence at every subsequent assessment. Participants who converted from other medications showed symptomatic improvement after conversion. At some time during the study, 58.6% of participants reported dry mouth, with 23.0% of participants rating it moderate or severe. Only 1.6% of participants discontinued the medication because of dry mouth. Conclusions. Ditropan XL treatment reduced the number of incontinence episodes. Maximum benefit was demonstrated by maintenance week 4 and was sustained through 12 weeks of maintenance therapy.