Clinical Efficacy and Safety of Tolterodine Compared to Oxybutynin and Placebo in Patients with Overactive Bladder

Drutz, Harold P.; Appell, Rodney A.; Gleason, Donald M.; Klimberg, Ira; Radomski, Sidney B.

doi:10.1007/s001929970003

Cited by 216 publications

(116 citation statements)

References 11 publications

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“…For the proportion of OAB patients with urge incontinence (37%), 5 we assume they use an average of 4 pads per day at baseline. After treatment, low resource consumers require an average of 2 pads per day, the medium group will use 3 pads per day, and high resource consumers continue to use 4 pads per day.…”

Section: Incontinence Pad Usagementioning

confidence: 99%

A Pharmacoeconomic Model Comparing Two Long-Acting Treatments for Overactive Bladder

Noe

Becker²,

Williamson³

et al. 2002

JMCP

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Authorshe cost of overactive bladder (OAB) is a significant financial burden on patients, families, and the health care system. In 2000, the total economic cost of OAB in the United States was estimated at $18.2 billion, which is more than either osteoporosis or Parkinson' s disease. OAB costs at the community level were approximately $13.8 billion, while costs at institutions were $4.4 billion.1 A study examining insurance claims showed that total annual claims among OAB patients was $5,018 versus $1,767 among non-OAB controls (1995 dollars). 2Drug Treatment for OAB Head-to-head studies comparing 2 immediate-release forms of antimuscarinic drug therapy, oxybutynin, and tolterodine, have shown that they have similar efficacy; however, tolterodine has an improved side-effect profile, most notably less dry mouth, and is associated with fewer treatment withdrawals as a result of drug-related adverse events. 3-7The side effects from OAB drug therapy have resulted in poor compliance and, subsequently, low persistence with therapy over time. 4,8,9 Persistence with drug therapy is important for achieving long-term treatment benefits. In a number of retrospective claims studies, patients receiving tolterodine have been shown to remain on therapy longer than those receiving oxybutynin. 6,[9][10][11][12][13][14][15] There is also evidence that suggests that OAB patients who are able to continue with medication have greater symptom improvement and use fewer resources. 16Phase III clinical trials of controlled-release oxybutynin have indicated better patient compliance, reduced side effects, and equivalent efficacy as compared to oxybutynin IR. [17][18][19] Both extended-release tolterodine and controlled-release oxybutynin have been shown to be more effective and better tolerated than immediate-release tolterodine. 20,21 These data further suggest that extended-release tolterodine has better tolerability and fewer side effects than controlled-release oxybutynin. Although there are no head-to-head studies to suggest that one of the extended-release drugs is more efficacious than the other, one recent study compared extended-release tolterodine to controlled-release oxybutynin using a 4-way crossover design in a small number of patients. 22 Using change in bladder capacity as a surrogate for efficacy, a 6 mg dose of extended-release tolterodine was found to be equivalent to a 20 mg dose of oxybutynin. However, the 6 mg dose of extended-release tolterodine produced a side-effect profile with respect to dry mouth similar to the 10 mg dose of controlled-release oxybutynin. This implies that extended-release tolterodine might be as efficacious as oxybutynin but has an improved tolerability profile. T A B S T R A C TOBJECTIVE: To compare the estimated first-line treatment costs of extended-release tolterodine versus controlled-release oxybutynin in patients with overactive bladder (OAB).METHODS: We developed a decision-analysis model to estimate the patterns of treatment, resource consumption, and cost impact of treating OAB with...

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Section: Incontinence Pad Usagementioning

confidence: 99%

A Pharmacoeconomic Model Comparing Two Long-Acting Treatments for Overactive Bladder

Noe

Becker²,

Williamson³

et al. 2002

JMCP

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“…With the recent release of several M 3 -selective muscarinic antagonists has come the realization that there are only slight di¡erences in the clinical e⁄cacy between the M 3 -selective antagonists (darifenacin and solifenacin) and the more M 2 /M 3 balanced antagonists (tolterodine and trospium). Clinically, distinctions between these new agents may appear to be in their side e¡ects [Drutz et al, 1999;Appell et al, 2001;Chancellor et al, 2001;Diokno et al, 2002;Rovner and Wein, 2002;Siami et al, 2002;Sussman and Garely, 2002;Halaska et al, 2003;Haab et al, 2004;Chapple et al, 2005;MacDiarmid et al, 2005]. No studies have been reported on M 2 -selective anticholinergic medications in humans.…”

Section: Introductionmentioning

confidence: 99%

M₂ mediated contractions of human bladder from organ donors is associated with an increase in urothelial muscarinic receptors

Braverman¹,

Лебед²,

Linder³

et al. 2006

Neurourology and Urodynamics

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Aims: Previous studies have shown increased density of M 2 receptors in hypertrophied rat bladders that possess an M 2 contractile phenotype. The aim of the current study is to determine whether human bladders with an M 2 contractile phenotype also have a greater density of bladder M 2 receptors. Materials and Methods: Human bladders were obtained from 24 di¡erent organ transplant donors. Darifenacin and methoctramine a⁄nity was determined by the rightward shift of cumulative carbachol concentration contractile response curves for each bladder. Radioligand binding and immunoprecipitation was used to quantify M 2 and M 3 subtypes in isolated detrusor muscle and urothelium. In addition, pig bladder muscle and urothelial receptors were quanti¢ed for comparison. Results: In the human urothelium total, M 2 and M 3 muscarinic receptor density is signi¢cantly negatively correlated with the a⁄nity of darifenacin for inhibition of contraction of the detrusor muscle. In the detrusor muscle there is no correlation between receptor density and darifenacin a⁄nity for inhibition of contraction. Muscarinic receptor density is greater in the muscle than in the urothelium in human bladders whereas in the pig bladder the density is greater in the urothelium than in the muscle. Conclusions: The greater density of urothelial muscarinic receptors in human bladders with lower darifenacin a⁄nity, indicative of a greater contribution of M 2 receptors to the contractile response, points towards a possible role of the urothelium in controlling M 2 mediated contractile phenotype. In comparison between human and pig bladders, the distribution of muscarinic receptor subtypes in the muscle and urothelium are quite di¡erent.

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“…However, radioligand-binding data show that tolterodine is eight times less potent than oxybutynin at the muscarinic receptors in the parotid gland [10]. Tolterodine and its active 5-hydroxymethyl metabolite (5-HM) are 30 and >350 times less lipophilic than oxybutynin, respectively [11]; tolterodine also has a longer biological half-life than oxybutynin.In controlled clinical studies in adults with an overactive bladder, tolterodine at the normal clinical dosage of 2 mg twice daily is as effective as oxybutynin 5 mg three times daily in reducing the patients' symptoms, but causes significantly fewer side-effects [7,12]. Tolterodine has been shown to cause significantly less dry mouth (about half) and the severity of the dry mouth that does occur is significantly milder than with oxybutynin.…”

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confidence: 99%

The overactive bladder in children: a potential future indication for tolterodine

et al. 2001

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Objective To determine the safety, efficacy and pharmacokinetics of tolterodine in children with an overactive bladder. Patients and methods Thirty-three children (20 boys and 13 girls, aged 5-10 years) with an overactive bladder and symptoms of urgency, frequency and/or urge incontinence were enrolled in an open, dose-escalation study. Patients were treated with oral tolterodine 0.5 mg (n=11), 1 mg (n=10) or 2 mg (n=12) twice daily for 14 days. The primary safety endpoint was the change in residual urinary volume, as determined by ultrasonography. In addition, voiding diary variables (frequency and incontinence episodes) and pharmacokinetics were evaluated. Other safety endpoints included laboratory variables, electrocardiogram recordings and reported adverse events. Results There were no safety concerns in terms of the change in residual urinary volume for any of the three dosage groups; values were comparable with baseline after 2 weeks of treatment for all three dosages. Adverse events were reported by 20 patients (six on 0.5 mg, five on 1 mg, and nine on 2 mg). Most adverse events were not considered to be drug-related; of the 13 possibly related events, 10 occurred in those taking 2 mg. Headache was the most commonly reported adverse event. No serious adverse events were reported and there were no general safety concerns.There was an improvement in voiding diary variables in all treatment groups after 2 weeks of treatment, although the efficacy was greatest in those taking 1 mg and 2 mg. Pharmacokinetic findings were consistent with dose linearity over the range 0.5-2 mg. Conclusion The results support the use of 1 mg twice daily as the optimal dose of tolterodine for treating children aged 5-10 years with an overactive bladder. Keywords tolterodine, antimuscarinic agents, children, overactive bladder, dose-finding study IntroductionThe symptoms of an overactive bladder are urgency and frequency, with or without urge incontinence, caused by uncontrolled contractions of the detrusor muscle. As uncontrolled detrusor contractions are mediated by muscarinic receptor stimulation, antimuscarinic agents are the most frequently used medications for treating this condition [1]. Historically, antimuscarinic agents like oxybutynin have been effective for treating the overactive bladder but they are poorly tolerated because they are not selective for the bladder [2]. Side-effects on the parotid gland, CNS, gastrointestinal tract and on the eye limit their clinical usefulness [3]. Particularly frequent and troublesome is dry mouth, which has been shown to cause poor compliance and frequent discontinuation of treatment [1,[4][5][6].Tolterodine is a muscarinic receptor antagonist that has been shown to be effective for treating the overactive bladder [7][8][9]. The advantages of tolterodine are numerous and are ascribed to its selectivity for the bladder over other tissues and to its low lipophilicity. Differences between tolterodine and oxybutynin have been reported in several preclinical studies, including pharmacologi...

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Clinical Efficacy and Safety of Tolterodine Compared to Oxybutynin and Placebo in Patients with Overactive Bladder

Cited by 216 publications

References 11 publications

A Pharmacoeconomic Model Comparing Two Long-Acting Treatments for Overactive Bladder

A Pharmacoeconomic Model Comparing Two Long-Acting Treatments for Overactive Bladder

M₂ mediated contractions of human bladder from organ donors is associated with an increase in urothelial muscarinic receptors

The overactive bladder in children: a potential future indication for tolterodine

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Clinical Efficacy and Safety of Tolterodine Compared to Oxybutynin and Placebo in Patients with Overactive Bladder

Cited by 216 publications

References 11 publications

A Pharmacoeconomic Model Comparing Two Long-Acting Treatments for Overactive Bladder

A Pharmacoeconomic Model Comparing Two Long-Acting Treatments for Overactive Bladder

M2 mediated contractions of human bladder from organ donors is associated with an increase in urothelial muscarinic receptors

The overactive bladder in children: a potential future indication for tolterodine

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M₂ mediated contractions of human bladder from organ donors is associated with an increase in urothelial muscarinic receptors