Immediate-release Oxybutynin Research Articles

Antimuscarinic use and discontinuation in an older adult population

IntroductionAlthough antimuscarinics are typically the first-line pharmacological treatment option for overactive bladder, patients often discontinue therapy. The aim of this research project is to identify the rate of antimuscarinic discontinuation, switching, and continuation and differences in discontinuation among different antimuscarinics. MethodsUsing the 5% random sample of Medicare Claims Data, we identified a cohort of patients aged ≥ 66 years old who newly initiated antimuscarinics between January 1, 2007 and December 31, 2012. Treatment discontinuation was defined as no subsequent fills of the initial antimuscarinic in the days’ supply plus a 30 day grace period. We ascertained percentages of patients who discontinued antimuscarinics, switched antimuscarinics, or died within 12 months of antimuscarinic initiation. Cox proportional hazards models were used to determine time to discontinuation of individual antimuscarinics relative to oxybutynin immediate-release (IR). ResultsAmong the 42,886 new-users of antimuscarinics, 71.8% discontinued, 10.8% switched, and 3.2% died prior to antimuscarinic discontinuation or switching while only 14.2% continually filled an antimuscarinic for one year. In the multivariable analysis, patients who were initiated on oxybutynin extended-released (ER), tolterodine, trospium, darifenacin, solifenacin, and fesoterodine were significantly less likely to be discontinued therapy compared to oxybutynin IR (p < 0.001). ConclusionAfter one year of antimuscarinic initiation, only 14% of older adult patients continuously utilized their initial antimuscarinic therapy suggesting a need for clinical interventions to improve continual use of antimuscarinics.

Comparative efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents in overactive bladder: A systematic literature review and network meta-analysis.

To compare efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents for the treatment of overactive bladder (OAB). Literature searches of MEDLINE, Embase, and the Cochrane Library were undertaken to identify randomized controlled trials in OAB (2000-2015) for antimuscarinic agents. A network meta-analysis (NMA) was performed to estimate efficacy and tolerability outcomes for solifenacin 5 mg/day relative to other antimuscarinics. The NMA included 53 eligible trials (published, n = 48; unpublished on search date, n = 5). Solifenacin 5 mg/day was significantly more effective than tolterodine 4 mg/day for reducing incontinence and urgency urinary incontinence (UUI) episodes, but significantly less effective than solifenacin 10 mg/day for micturition; no other statistically significant differences were noted for efficacy. Solifenacin 5 mg/day had a statistically significant lower risk of dry mouth compared with darifenacin 15 mg/day, fesoterodine 8 mg/day, oxybutynin extended-release 10 mg/day, oxybutynin immediate-release (IR) 9-15 mg/day, tolterodine IR 4 mg/day, propiverine 20 mg/day, and solifenacin 10 mg/day. There were no significant differences between solifenacin 5 mg/day and other antimuscarinics for risk of blurred vision, or for 11 of 17 active comparators for risk of constipation. This NMA suggests that the efficacy of solifenacin 5 mg/day is at least similar to other common antimuscarinics across the spectrum of OAB symptoms analyzed, and is more effective than tolterodine 4 mg/day in reducing incontinence and UUI episodes. Solifenacin 5 mg/day has a lower risk of dry mouth compared with several agents.

Cost-Effectiveness of Mirabegron Compared with Antimuscarinic Agents for the Treatment of Adults with Overactive Bladder in the United Kingdom

BackgroundMirabegron, a first-in-class selective oral β3-adrenoceptor agonist, has similar efficacy to most antimuscarinic agents and a lower incidence of dry mouth in patients with overactive bladder (OAB). ObjectivesTo evaluate the cost-effectiveness of mirabegron 50 mg compared with oral antimuscarinic agents in adults with OAB from a UK National Health Service perspective. MethodsA Markov model including health states for symptom severity, treatment status, and adverse events was developed. Cycle length was 1 month, and the time horizon was 5 years. Antimuscarinic comparators were tolterodine extended release, solifenacin, fesoterodine, oxybutynin extended release and immediate release (IR), darifenacin, and trospium chloride modified release. Transition probabilities for symptom severity levels and adverse events were estimated from a mirabegron trial and a mixed treatment comparison. Estimates for other inputs were obtained from published literature or expert opinion. Quality-adjusted life-years (QALYs) and total health care costs, including costs of drug acquisition, physician visits, incontinence pad use, and botox injections, were modeled. Deterministic and probabilistic sensitivity analyses were performed. ResultsBase-case incremental cost-effectiveness ratios ranged from £367 (vs. solifenacin 10 mg) to £15,593 (vs. oxybutynin IR 10 mg) per QALY gained. Probabilistic sensitivity analyses showed that at a willingness-to-pay threshold of £20,000/QALY gained, the probability of mirabegron 50 mg being cost-effective ranged from 70.2% versus oxybutynin IR 10 mg to 97.8% versus darifenacin 15 mg. A limitation of our analysis is the uncertainty due to the lack of direct comparisons of mirabegron with other agents; a mixed treatment comparison using rigorous methodology provided the data for the analysis, but the studies involved showed heterogeneity. ConclusionsMirabegron 50 mg appears to be cost-effective compared with standard oral antimuscarinic agents for the treatment of adults with OAB from a UK National Health Service perspective.

Vaginal estrogen use in postmenopausal women with pelvic floor disorders: systematic review and practice guidelines.

Risk of pelvic floor disorders increases after menopause and may be linked to estrogen deficiency. We aimed to systematically and critically assess the literature on vaginal estrogen in the management of pelvic floor disorders in postmenopausal women and provide evidence-based clinical practice guidelines. MEDLINE and Cochrane databases were searched from inception to July 2014 for randomized controlled trials of commercially available vaginal estrogen products compared with placebo, no treatment, or any medication for overactive bladder or urinary incontinence. We double-screened 1,805 abstracts and identified 12 eligible papers. Studies were extracted for participant information, intervention, comparator, efficacy outcomes, and adverse events, and they were individually and collectively assessed for methodological quality and strength of evidence. Evidence was generally of poor to moderate quality. Vaginal estrogen application before pelvic organ prolapse surgery improved the vaginal maturation index and increased vaginal epithelial thickness. Postoperative vaginal estrogen use after a midurethral sling resulted in decreased urinary frequency and urgency. Vaginal estrogen and immediate-release oxybutynin were similar in improvement of urinary urgency, frequency, and urgency urinary incontinence in women with overactive bladder, but oxybutynin had higher rates of side effects and discontinuation. Conversely, the addition of vaginal estrogen to immediate or extended-release tolterodine did not improve urinary symptoms more than tolterodine alone. One study reported an improvement in stress urinary incontinence with use of vaginal estrogen. Vaginal estrogen application may play a useful role as an adjunct in the management of common pelvic floor disorders in postmenopausal women.

Overactive Bladder - Current Treatment Modalities

Overactive bladder is a common disorder that affects over 100 million adults worldwide though its prevalence has been grossly underestimated. The magnitude of this problem is increasing steadily with the growing elderly population, increased incidence of obesity, polypharmacy and increased awareness, making its treatment a challenging task for the physician. The treatment strategies may be nonpharmacologic or pharmacologic or both. Physical therapy techniques, such as bladder training, pelvic-floor exercises and electrical stimulation of the pelvic floor - are the nonpharmacological therapies that mitigate the sufferings of such patients. Anticholinergic agents remain the mainstay of the pharmacological therapy and act by decreasing or inhibiting the intensity of involuntary detrusor contractions. Immediate-release oxybutynin was the first dedicated antimuscarinic agent used for the treatment of overactive bladder symptoms. With geographic differences, other currently approved antimuscarinics are propiverine, tolterodine (immediate and extended release), trospium chloride (immediate and extended release), solifenacin (extended release), darifenacin (extended release) and fesoterodine(extended release). Still in the research phase and for use in refractory OAB are gabapentine and intradetrusor injection of botulinum toxin A. Symptom relief has been observed by more direct neuromodulatory techniques, such as acupuncture, posterior tibial nerve stimulation and sacral nerve stimulation, that address the underlying neurologic condition, although urodynamic data have not corroborated the same. Surgical intervention such as bladder augmentation, may rarely be resorted to in those with refractory urge incontinence and failure of conservative treatments. Eventually, the aim of all the treatment modalities is to improve the patients’ quality of life.

Cost-effectiveness analysis of solifenacin versus oxybutynin immediate-release in the treatment of patients with overactive bladder in the United Kingdom

Objective:To carry out a cost-utility analysis comparing initial treatment with solifenacin 5 mg/day vs oxybutynin immediate-release (IR) 15 mg/day for the treatment of patients with overactive bladder (OAB) from the perspective of the UK National Health Service (NHS).Methods:A Markov model with six health states was developed to follow a cohort of OAB patients treated with either solifenacin or oxybutynin during a 1-year period. Costs and utilities were accumulated as patients transited through the health states in the model and a drop-out state. Some of the solifenacin patients were titrated from 5 mg to 10 mg/day at 8 weeks. A proportion of drop-out patients were assumed to continue treatment with tolterodine ER. Utility values were obtained from a Swedish study and pad use was based on a multinational clinical trial. Adherence rates for individual treatments were derived from a UK database study. For pad use and utility values, the drop-out state was split between those patients who were no longer receiving treatment and those on second-line therapy. Patients on second-line therapy who drop-out were referred for a specialist visit. Results were expressed in terms of incremental cost-utility ratios.Results:Total annual costs for solifenacin and oxybutynin were £504.30 and £364.19, respectively. First-line drug use represents 49% and 4% of costs and pad use represent 23% and 40% of costs for solifenacin and oxybutynin, respectively. Differences between cumulative utilities were small but were greater for solifenacin (0.7020 vs 0.6907). The baseline incremental cost-effectiveness ratio was £12,309/QALY.Conclusion:Under the baseline assumptions, solifenacin would appear to be cost-effective with an incremental cost-utility of less than £20,000/QALY. However, small differences in utility between the alternatives and the large number of drop-outs means that the results are sensitive to small adjustments in the values of utilities assigned to the drop-out state.

Pharmacokinetics of Intravesical Versus Oral Oxybutynin in Healthy Adults: Results of an Open Label, Randomized, Prospective Clinical Study

We investigated the pharmacokinetics of intravesical oxybutynin and discuss the clinical implications of the results. We performed an open label, randomized, 3-period crossover clinical study in 20 healthy adults. In periods 1 and 2 subjects received a single dose of 10 mg oxybutynin HCl solution intravesically or a 5 mg tablet orally. Period 3 comprised repeat intravesical applications (7 doses) of 10mg oxybutynin HCl. Enantioselective concentrations of oxybutynin and N-desethyloxybutynin were quantified by liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental methods, analyzed by descriptive statistics and compared using the average bioequivalence approach. Systemic exposure to racemic oxybutynin after intravesical administration was significantly greater, yielding 294% (90% CI 211-408) of that after oral intake of immediate release preparations, as measured by the dose normalized area under the plasma concentration time curve. In contrast, systemic exposure to racemic N-desethyloxybutynin reached only 21% (90% CI 15-29). The area under the plasma concentration time curve ratio of N-desethyloxybutynin to oxybutynin was 14-fold decreased for intravesical administration. After intravesical multidose administration, the cumulation of oxybutynin (1.3-fold) and N-desethyloxybutynin (1.6-fold) was weak, absorption was prolonged and apparent elimination half-lives were longer. The study medication was well tolerated with a third of participants reporting anticholinergic adverse effects. Our study provides evidence of significantly higher bioavailability of intravesical vs oral administration of oxybutynin due to circumvention of the intestinal first pass metabolism. Given the high efficacy and decreased rate of adverse effects, intravesical oxybutynin should be considered in patients with neurogenic lower urinary tract dysfunction who do not tolerate oral administration or in whom oral preparations fail to improve detrusor overactivity.

Risks and Benefits of Bladder Antimuscarinics Among Elderly Residents of Veterans Affairs Community Living Centers

To evaluate risks and benefits of bladder antimuscarinics (BAMs) among elderly long term care nursing home residents. Retrospective cohort study using a new user design and propensity score matching. Veterans Affairs (VA) Community Living Centers (Nursing Homes). Older adults (65 and older) admitted for long term care between October 1, 2002, and September 30,2009. The study used multiple VA data sources (Minimum Data Set [MDS], inpatient, outpatient, and pharmacy prescriptions administrative files). The following outcomes were evaluated: (1) fractures (hip fracture and "any" fracture) identified from inpatient and/or outpatient data (ICD-9-CM codes) and from MDS; (2) cognitive performance measured using the validated MDS Cognitive Performance Scale; (3) improvement in urinary incontinence measured from MDS; (4) quality of life measured from MDS using 2 validated instruments: Index of Social Engagement and Health Status Index. Covariates included demographic characteristics, baseline continence status (bladder and bowel) and continence management, preexistent urinary tract infections, body mass index, comorbidities, other medication use, cognitive status, and mobility at baseline. These variables were used to calculate the predicted probability (propensity score) of being initiated on a BAM; the resulting propensity scores were used to match new users and nonusers. Outcomes were compared with Cox proportional hazards regression and generalized estimating equations methodology. BAMs were used by 9.8% of the residents 65 years and older admitted for long term care; 44% (1195) were new users. Of these, all but 53 received nonselective immediate release preparations, predominantly oxybutynin chloride (75%). BAM initiation resulted in improved urinary continence status (odds ratio= 1.27, 95% confidence interval [CI] 1.07-1.5) and better social engagement (difference in mean index of social engagement score= 0.2074, 95% CI 0.055-0.3598). The risk of fractures was significantly increased in new users as compared to nonusers (hip fracture: hazard ratio [HR]= 3.67, 95% CI 1.46-9.34; "any" fracture: HR= 2.64, 95% CI 1.37-5.10). The number needed to treat (NNT) to obtain improvement in urinary incontinence after 90 days of treatment (NNT= 32, 95% CI 17-125) was similar to the number needed to harm (NNH) at 90 days in the hip fracture analysis (NNH= 36, 95% CI 12-209). There were no differences in cognitive performance or overall quality of life scores associated with BAMuse. These results question the continued use of BAMs, particularly immediate-release oxybutynin chloride in elderly nursing home residents.

Percutaneous Tibial Nerve Stimulation for the Long-Term Treatment of Overactive Bladder: 3-Year Results of the STEP Study

We report the long-term efficacy and safety of percutaneous tibial nerve stimulation with the Urgent® PC Neuromodulation System for overactive bladder after 3 years of therapy. Fifty participants in the randomized, double-blind SUmiT (Sham Effectiveness in Treatment of Overactive Bladder Symptoms) Trial who met the primary effectiveness end point after 12 weekly percutaneous tibial nerve stimulation treatments were enrolled in this prospective study to assess long-term outcomes with percutaneous tibial nerve stimulation. STEP (Sustained Therapeutic Effects of Percutaneous Tibial Nerve Stimulation) Study patients were prescribed a fixed schedule 14-week tapering protocol followed by a personal treatment plan aimed at sustaining overactive bladder symptom improvement. Overactive bladder and quality of life questionnaires were completed every 3 months and 3-day voiding diaries were completed every 6 months. A total of 29 patients completed the 36-month protocol and received a median of 1.1 treatments per month after a 14-week treatment tapering protocol. A Bayesian model estimated that 77% (95% CI 64-90) of patients maintained moderate or marked improvement in overactive bladder symptoms at 3 years. Compared to baseline, median voids per day decreased from 12.0 (IQR 10.3-13.7) to 8.7 (IQR 7.3-11.3), nighttime voids per night decreased from 2.7 (IQR 1.7-3.3) to 1.7 (IQR 1.0-2.7) and urge incontinence episodes per day decreased from 3.3 (IQR 0.7-6.0) to 0.3 (IQR 0.0-1.0) (all p <0.0001). All quality of life parameters remained markedly improved from baseline through 3 years (all p <0.0001). One patient experienced 2 mild treatment related adverse events of bleeding at the needle site during followup. Most STEP participants with an initial positive response to 12 weekly percutaneous tibial nerve stimulation treatments safely sustained overactive bladder symptom improvement to 3 years with an average of 1 treatment per month.

Cost-effectiveness analysis of anti-muscarinic agents for the treatment of overactive bladder

Objective:To determine the cost-effectiveness of pharmacologic treatments for overactive bladder (OAB) in the US.Methods:A decision model was constructed based on studies of effectiveness, adverse consequences, co-morbid conditions, and medical costs for the treatment of OAB. Treatment success was defined as no incontinence episodes for 3–7 days or 3–7 consecutive dry days. Estimates of treatment success were obtained from clinical trials and included darifenacin, fesoterodine, oxybutynin immediate release (IR), oxybutynin extended release (ER), oxybutynin topical gel, oxybutynin transdermal patch, solifenacin, tolterodine IR, tolterodine ER, trospium IR, and trospium ER. Probabilistic sensitivity analysis was conducted using Monte Carlo simulation.Results:A total of 51 OAB studies were identified and 11 reported treatment success. Mean continence rates varied in the literature from 21.0% with trospium IR to 51.0% with solifenacin. The 95% CI for solifenacin's success rate was statistically higher than other regimens due to the higher continence rates from the clinical trials. Oxybutynin IR and oxybutynin ER were significantly less costly than other products. The product with the lowest incremental cost-effectiveness ratio (ICER) relative to oxybutynin IR was solifenacin at $1338 (±168) per additional continent patient. The cost-effectiveness acceptability curve indicated that oxybutynin IR was the most cost-effective regimen when willingness-to-pay values were less than $10,000 per additional continent patient. Solifenacin was most cost-effective at higher willingness-to-pay values.Conclusion:There was broad overlap in effectiveness among the anti-muscarinic products, except solifenacin had a significantly higher continence rate. Oxybutynin IR and oxybutynin ER were significantly less costly than other anti-muscarinic regimens, and these two products have a useful role to play in the management of OAB. However, for patients unable to tolerate the lower cost products, formularies benefit from solifenacin among branded products since the cost-effectiveness acceptability curve demonstrated it was the product most likely to be cost-effective after oxybutynin IR.

Oxybutynin and tolterodine for treatment of neurogenic detrusor overactivity: a pharmacoeconomic evaluation in the Brazilian context

Antimuscarinic agents are the first-line choice for the treatment of neurogenic detrusor overactivity (NDO). The currently available antimuscarinic drugs have been widely studied in patients presenting idiopathic detrusor overactivity; however, investigations evaluating the effects of these drugs on NDO are scant, particularly with regard to cost-effectiveness analyses. A pharmacoeconomic evaluation was performed to compare the costs and effectiveness of oxybutynin and tolterodine in two different formulations, extended (ER) and immediate-release (IR), for the treatment of NDO (based on Brazilian maximal consumer price index). A systematic review of literature was conducted in order to obtain significant clinical and urodynamic data (based on expert opinion), concerning the effects of these drugs in the neurogenic population. Furthermore, a pharmacoeconomic evaluation was performed and costs involved were calculated based on percentage effectiveness obtained for the timeframes of one month and of one year. The best cost-effectiveness ratio (CER) was observed with oxybutynin IR for the urodynamic parameters. In terms of clinical parameters, oxybutynin IR and ER showed the best CER. Based on the key urological parameters analyzed, oxybutynin IR was considered the most cost-effective antimuscarinic agent.

Comparative adherence to oxybutynin or tolterodine among older patients

Dear Editor,In their short communication, Gomes et al. [1] provide inter-esting data on the real-life use of two antimuscarinic agentsused in urinary incontinence. Nonetheless, in many countriesaround the world, these two agents are available in a range offormulations, as oxybutynin immediate-release (IR) tablets,extendedrelease(ER)tablets,andtransdermalpatches;andastolterodine IR tablets and ER capsules. Numerous studiessuggest that the incidence of dry mouth, cited by patients asa common reason for treatment discontinuation, varies signif-icantly between these formulations [2–4]. Consequently, theclinical value of the report by Gomes et al. would be greatlyincreased if the profile of oxybutynin and tolterodine formu-lations that comprise their data was described.Yours sincerely,Angus ThompsonReferences

Cost‐effectiveness analysis of newer anticholinergic drugs for urinary incontinence vs oxybutynin and no treatment using data on persistence from the Swedish prescribed drug registry

Study Type - Therapy (cost effectiveness). Level of Evidence 2a. What's known on the subject? and What does the study add? Anticholinergic drugs are a common treatment alternative in urinary incontinence, which results in large costs for caregivers. So far, most cost-effectiveness analyses of anticholinergic drugs have focused on small putative differences between the newer anticholinergics. This study takes a novel approach by treating the clinical effects of the newer alternatives as similar and evaluating them as a group in relation to no treatment and oxybutynin (immediate release). It also uses registry data to account for persistence. • To analyse the cost-effectiveness of newer anticholinergic drugs in relation to oxybutynin immediate release (IR) and no treatment for patients with urgency urinary incontinence. • A decision analytic model was constructed. • Results were collected from randomized trials and combined with registry data on persistence of medicine use and estimated number of severe adverse events. • The setting corresponds to Swedish clinical practice. • The costs and effects of the treatment options were analysed over a period of 1 year. Costs included drug costs, treatment costs and costs for pad use. Patients' utilities were based on treatment effect and the lack or presence of adverse events. • No treatment was the least costly treatment but also resulted in the fewest number of quality adjusted life years (QALYs). • Treatment with newer anticholinergic drug medications is the most costly option but also the most efficient treatment. Sensitivity analyses showed that the results were robust. • Treatment with newer anticholinergics resulted in a cost per QALY gained of €21 045 compared with no treatment and no effect and €65 435 compared with no treatment and placebo effect. Compared with oxybutynin IR, the cost per QALY gained was €37 119. These calculations are based on relatively low pad costs, resulting in higher costs per QALY for the original drugs. • The newer anticholinergic medications are likely to be cost effective in relation to oxybutynin IR. • The cost-effectiveness of the newer anticholinergics compared with no treatment depends on assumptions of the effect of no treatment, the severity of the treated condition and the treated individual's risk of adverse events. • Treatment is less likely to be cost effective for elderly persons or for persons otherwise at higher risk for adverse events.

Table of Contents

AbstractAtypical Antipsychotic Lurasidone Newly Approved for SchizophreniaMeta‐Analysis Finds Antipsychotics Superior to Mood Stabilizers in Acute ManiaAERS Detects Interaction between Paroxetine and PravastatinSwitching to an Antipsychotic with Lower Metabolic RiskRaloxifene Adjunctive to Antipsychotics in Postmenopausal SchizophreniaRisk of Psychotic Relapse with Haloperidol Discontinuation in AD PatientsVilazodone Long‐Term Safety and TolerabilitySertraline Response in Patients with and without DementiaImmediate‐Release Oxybutynin for Clozapine‐Induced SialorrheaMilnacipran Postmarketing Adverse EventsSafety Labeling Changes

PUK10 Cost-Effectiveness Analysis of Solifenacin Versus Oxybutynin Immediate-Release in the Treatment of Patients with Overactive Bladder in the United Kingdom

PUK10 Cost-Effectiveness Analysis of Solifenacin Versus Oxybutynin Immediate-Release in the Treatment of Patients with Overactive Bladder in the United Kingdom

Immediate-Release Oxybutynin for the Treatment of Clozapine-Induced Sialorrhea

To describe a case of clozapine-induced sialorrhea alleviated by immediate-release oxybutynin. A 53-year-old female with schizoaffective disorder-bipolar type was admitted to a psychiatric unit and initiated on clozapine. During titration to a dose of 300 mg daily and despite taking concomitant oral benztropine 1 mg twice daily, the patient began to experience mild sialorrhea. The sialorrhea became profuse when the clozapine dose reached 400 mg daily, and the patient was routinely seen with a saliva-soaked shirt. Additionally, she had become self-conscious and wanted to stop clozapine therapy. Immediate-release oxybutynin 5 mg daily was started, resulting in significant reduction of the sialorrhea within 24 hours. The patient was discharged on clozapine 300 mg daily, risperidone 6 mg at bedtime, immediate-release oxybutynin 5 mg twice daily, and oral benztropine 1.5 mg daily, with only mild sialorrhea. It is unknown why clozapine induces sialorrhea. One speculation is that clozapine interrupts muscarinic receptor homeostasis. Immediate-release oxybutynin is an anticholinergic agent with high affinity for salivary gland M₃ receptors that may have restored muscarinic receptor imbalance in our patient. N-Desethyl-oxybutynin, an active metabolite of oxybutynin, is largely responsible for oxybutynin's anticholinergic activity. The activity of oxybutynin and its metabolite may result in dry mouth in over 80% of patients taking the immediate-release formulation, while producing dry mouth in only 40% and 7.5% of patients taking the extended-release and topical formulations, respectively. To our knowledge, this is the first report of immediate-release oxybutynin successfully reducing clozapine-induced sialorrhea. If oxybutynin is considered for this indication, use of the immediate-release formulation seems prudent. Additional data, including randomized controlled trials, are needed to confirm whether immediate-release oxybutynin has a significant role in the management of this stigmatizing adverse effect.

Tolerability of solifenacin and oxybutynin immediate release in older (>65 years) and younger (≤65 years) patients with overactive bladder: sub-analysis from a Canadian, randomized, double-blind study

Objective:Overactive bladder (OAB) is a common condition whose prevalence increases with age. Antimuscarinic agents are the pharmacologic treatment of choice, but adverse events such as dry mouth may lead to early discontinuation. The purpose of this analysis was to compare the incidence and severity of dry mouth and other adverse events with solifenacin 5 mg/day and oxybutynin immediate release (IR) 15 mg/day in patients ≤65 years and >65 years in the Canadian VECTOR study (VEsicare in Comparison To Oxybutynin for oveRactive bladder patients).Research design and methods:VECTOR was a randomized, multicentre, prospective, double-blind, double-dummy study in 132 subjects with ≥1 urgency episode per 24 h, with or without urgency incontinence, and ≥8 micturitions per 24 h for ≥3 months. After a 2-week washout, patients received solifenacin 5 mg once daily or oxybutynin IR 5 mg tid for 8 weeks. For the current post-hoc analysis, adverse events were evaluated in subgroups of patients ≤65 years and >65 years, using a full logistic regression model, multinomial logit regression model and reduced model.Clinical trial registration:NCT00431041.Results:The incidence and severity of dry mouth and other adverse events with solifenacin were similar between younger and older patients. In both age subgroups, solifenacin 5 mg/day was associated with fewer episodes and lower severity of dry mouth, and a lower discontinuation rate, compared with oxybutynin IR 15 mg/day.Conclusions:Solifenacin 5 mg/day was better tolerated than oxybutynin IR 15 mg/day in younger (≤65 years) and older (>65 years) subgroups. Solifenacin was equally well tolerated in both age subgroups. Limitations of the analysis were that the study was not preplanned to perform post-hoc subgroup analysis, patients knew that dry mouth was a primary outcome, and the study used fixed doses of each drug.

Canadian cost-effectiveness analysis of solifenacin compared to oxybutynin immediate-release in patients with overactive bladder

Objective:To estimate the cost effectiveness of solifenacin 5 mg/day compared to oxybutynin immediate-release (IR) 15 mg/day in patients with overactive bladder, from the perspective of the Canadian healthcare (payer) system.Research design and methods:A Markov model was adapted to estimate the incremental cost per quality-adjusted life-year (QALY) of solifenacin and oxybutynin IR over a 1-year time horizon, based on efficacy and discontinuation data from the Canadian VECTOR (VEsicare in Comparison To Oxybutynin for oveRactive bladder patients) study. In the model, patients who discontinued treatment were offered tolterodine extended release 4 mg/day as second-line. Model robustness was tested using various sensitivity analyses. Utility values were derived from published literature; incontinence pads were included in a secondary analysis.Results:In the base-case analysis, total costs over 1 year were CAN$695 and CAN$550 in the solifenacin and oxybutynin IR groups, respectively. When including incontinence pad costs, there was an incremental saving of CAN$1,831 per patient with solifenacin. Solifenacin was associated with an incremental QALY gain of 0.01 over 1 year. In the base-case analysis without incontinence pads, the incremental cost-utility ratio for solifenacin was CAN$14,092. Probabilistic analyses showed no overlap in the 95% confidence intervals for total costs or QALYs with or without incontinence pads. Solifenacin was cost effective in >90% of cases, based on a willingness-to-pay threshold of CAN$50,000 per additional QALY, irrespective of whether pad costs were included in the model. The most influential variables were the discontinuation rates and the cost of incontinence pads. Limitations of the analysis relate mainly to the fact that data in the VECTOR study were collected using a direct questioning approach, which might have increased the reporting of dry mouth.Conclusions:Solifenacin 5 mg/day was a cost-effective treatment compared with oxybutynin IR 15 mg/day.Conclusions:NCT00431041 (of the VECTOR study, upon which the analysis in this paper was based).

The cost‐effectiveness of solifenacin vs fesoterodine, oxybutynin immediate‐release, propiverine, tolterodine extended‐release and tolterodine immediate‐release in the treatment of patients with overactive bladder in the UK National Health Service

To assess the cost-effectiveness of solifenacin vs other antimuscarinic strategies commonly used in UK clinical practice, based on the results of a recent published review. Overactive bladder (OAB) syndrome is characterized by symptoms of urgency, frequency, incontinence and nocturia. Pharmacological treatment comprises oral antimuscarinic agents, which are divided into older-generation treatments, including oxybutynin, and new-generation treatments, comprising solifenacin, tolterodine, darifenacin and fesoterodine. The latter have reduced central nervous system penetration and have better selectivity for the M3 subclass of acetylcholine receptors, resulting in improved tolerability. A recent systematic review and meta-analysis of the efficacy and safety of antimuscarinics provided an opportunity for an economic evaluation of these agents using a rigorous assessment of efficacy. A cost-utility analysis was undertaken using a 1-year decision-tree model. Treatment success was defined separately for urgency, frequency and incontinence, with efficacy data taken from the recent review. Treatment persistence rates were taken from the Information Management System database. Utility values for the calculation of quality-adjusted life-years (QALYs) were taken from published sources. The analysis included costs directly associated with treatment for OAB, i.e. antimuscarinic therapy, consultations with general practitioners, and outpatient contacts. Resource use was based on expert opinion. Costs were reported at 2007/2008 prices. Extensive deterministic and probabilistic analyses were conducted to test the robustness of the base-case results. Solifenacin was associated with the highest QALY gains (per 1000 patients) for all three outcomes of interest, i.e. urgency (712.3), frequency (723.1) and incontinence (695.0). Solifenacin was dominant relative to fesoterodine, tolterodine extended-release (ER) and tolterodine immediate-release (IR), and cost-effective relative to propiverine ER for urgency, frequency and incontinence. Solifenacin was not found to be cost-effective relative to oxybutynin IR for the frequency and incontinence outcomes, with an incremental cost-effectiveness ratio of > pound30,000/QALY threshold. Solifenacin provided the greatest clinical benefit and associated QALYs for all three outcomes of interest across all therapies considered, and to be either dominant or cost-effective relative to all other new-generation agents, but not cost-effective relative to oxybutynin for frequency and incontinence.

THE COST-EFFECTIVENESS OF SOLIFENACIN VS FESOTERODINE, OXYBUTYNIN IMMEDIATE-RELEASE, PROPIVERINE, TOLTERODINE EXTENDED-RELEASE AND TOLTERODINE IMMEDIATE-RELEASE IN THE TREATMENT OF PATIENTS WITH OVERACTIVE BLADDER IN THE UK NATIONAL HEALTH SERVICE

OBJECTIVE Please also see BJUI letters on page 586 To assess the cost-effectiveness of solifenacin vs other antimuscarinic strategies commonly used in UK clinical practice, based on the results of a recent published review. METHODS Overactive bladder (OAB) syndrome is characterized by symptoms of urgency, frequency, incontinence and nocturia. Pharmacological treatment comprises oral antimuscarinic agents, which are divided into older-generation treatments, including oxybutynin, and new-generation treatments, comprising solifenacin, tolterodine, darifenacin and fesoterodine. The latter have reduced central nervous system penetration and have better selectivity for the M3 subclass of acetylcholine receptors, resulting in improved tolerability. A recent systematic review and meta-analysis of the efficacy and safety of antimuscarinics provided an opportunity for an economic evaluation of these agents using a rigorous assessment of efficacy. A cost-utility analysis was undertaken using a 1-year decision-tree model. Treatment success was defined separately for urgency, frequency and incontinence, with efficacy data taken from the recent review. Treatment persistence rates were taken from the Information Management System database. Utility values for the calculation of quality-adjusted life-years (QALYs) were taken from published sources. The analysis included costs directly associated with treatment for OAB, i.e. antimuscarinic therapy, consultations with general practitioners, and outpatient contacts. Resource use was based on expert opinion. Costs were reported at 2007/2008 prices. Extensive deterministic and probabilistic analyses were conducted to test the robustness of the base-case results. RESULTS Solifenacin was associated with the highest QALY gains (per 1000 patients) for all three outcomes of interest, i.e. urgency (712.3), frequency (723.1) and incontinence (695.0). Solifenacin was dominant relative to fesoterodine, tolterodine extended-release (ER) and tolterodine immediate-release (IR), and cost-effective relative to propiverine ER for urgency, frequency and incontinence. Solifenacin was not found to be cost-effective relative to oxybutynin IR for the frequency and incontinence outcomes, with an incremental cost-effectiveness ratio of >£30 000/QALY threshold. CONCLUSIONS Solifenacin provided the greatest clinical benefit and associated QALYs for all three outcomes of interest across all therapies considered, and to be either dominant or cost-effective relative to all other new-generation agents, but not cost-effective relative to oxybutynin for frequency and incontinence.