Intravesical oxybutynin chloride: Experience with 42 patients

doi:10.1016/0090-4295(93)90098-U

Urology

Volume 41, Issue 6, June 1993, Pages 527-530

https://doi.org/10.1016/0090-4295(93)90098-U Get rights and content

Abstract

To evaluate the efficacy of intravesical oxybutynin chloride, 42 patients who were incontinent secondary to uninhibited detrusor contractions and had failed oral anticholinergic therapy were begun on intravesical oxybutynin chloride. Indications for intravesical therapy were detrusor hyperreflexia (N = 20), detrusor instability (N = 19), and bowel/bladder overactivity after augmentation cystoplasty (N = 3). A 5-mg tablet dissolved in 30 cc of sterile water was instilled into the bladder two to three times daily via clean self Intermittent catheterization. With a mean follow-up of 18.4 months, no patient reported side effects as a result of the intravesical therapy. Nine patients (21 %) dropped out of the study due to inability to tolerate the catheterization or difficulty retaining the solution in the bladder. Eighteen of the 33 patients (55 % ) who followed the protocol experienced elimination or significant improvement of their incontinence. The results of the current study confirm the safety and usefulness of intravesical oxybutynin in treating uninhibited detrusor contractions in a difficult patient population.

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Cited by (86)

Investigating Detrusor Muscle Concentrations of Oxybutynin after Intravesical Delivery in an Ex Vivo Porcine Model
2015, Journal of Pharmaceutical Sciences
Citation Excerpt :
For such patients, conservative management with intravesically delivered oxybutynin is an option.5 Intravesical oxybutynin is highly effective in increasing mean bladder capacity and decreasing mean maximum filling pressure.6,7 It is also well tolerated and associated with fewer adverse effects than its oral counterpart.8
Intravesical oxybutynin is highly effective in the treatment of overactive bladder. Traditionally the mechanism of action was explained by antagonism of muscarinic receptors located in the detrusor, however evidence now suggests antimuscarinics may elicit their effect by modifying afferent pathways in the mucosal region. This study aimed to investigate the bladder wall distribution of oxybutynin in an ex vivo setting providing tissue - layer specific concentrations of drug achieved after intravesical delivery. Whole ex vivo porcine bladders were intravesically instilled with 0.167 mg mL^− 1 oxybutynin solution. After 60 min, tissue samples were excised, serially sectioned parallel to the urothelial surface and extracted drug quantified. Drug distribution into the urothelium, lamina propria and detrusor was determined. Oxybutynin permeated into the bladder wall at a higher rate than other drugs previously investigated (apparent transurothelial K_p = 1.36 × 10^− 5 cm s^− 1). After 60 min intravesical instillation, concentrations achieved in the urothelium (298.69 μg g^− 1) and lamina propria (43.65 μg g^− 1) but not the detrusor (0.93 μg g^− 1) were greater than reported IC50 values for oxybutynin. This work adds to the increasing body of evidence suggesting antimuscarinics elicit their effects via mechanisms other than direct inhibition of detrusor contraction.
Pharmacokinetics of intravesical versus oral oxybutynin in healthy adults: Results of an open label, randomized, prospective clinical study
2013, Journal of Urology
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 10 mg 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.
Efficacy and Safety of Oxybutynin Transdermal System in Spinal Cord Injury Patients With Neurogenic Detrusor Overactivity and Incontinence: An Open-label, Dose-titration Study
2009, Urology
To evaluate the efficacy and safety of oxybutynin transdermal system (oxybutynin-TDS) in spinal cord injury patients with neurogenic detrusor overactivity and incontinence despite use of clean intermittent catheterization (CIC).
This multicenter, open-label, dose-titration study included patients ≥ 18 years old. During an 8-week dose-titration period, oxybutynin-TDS doses were adjusted every 2 weeks, depending on symptoms. The primary efficacy end point was a change in daily number of CIC periods without leakage, from baseline to 8 weeks or last observation. Outcome parameters included 3-day voiding diary, CIC volume, and urodynamic parameters. Changes from baseline were analyzed with paired t tests.
Of 24 study participants (mean age, 41.9 years), 18 (75.0%) completed the study. Final oxybutynin-TDS doses were 7.8, 9.1, and 11.7 mg/d for 4, 9, and 11 patients, respectively. Daily number of CIC periods without leakage increased significantly (mean change, 1.5 ± 2.2; P = .0036) from baseline (2.4 ± 1.8) to 8 weeks (3.9 ± 1.9). CIC volume (P = .0029), reflex volume (P = .0466), maximal cystometric bladder capacity (P = .0009), and residual urine volume (P = .0023) all increased significantly, whereas detrusor pressure at maximal bladder capacity decreased significantly (P = .0457). The most common adverse events were application site reaction (12.5% of patients), dry mouth (8.3%), and abnormal vision (8.3%). No patient discontinued treatment because of an adverse event.
Oxybutynin-TDS was efficacious in spinal cord injury patients with neurogenic detrusor overactivity and was well tolerated at up to 3 times the standard dose.
Intravesical Oxybutynin for Children With Poorly Compliant Neurogenic Bladder: A Systematic Review
2008, Journal of Urology
Citation Excerpt :
The incidence of side effects with the intravesical route was lower than the published incidence with oral administration, in keeping with the rationale for its use. Weese et al reported that the published incidence of significant side effects with oral therapy ranges from 57% to 94%.25 N-desethyl oxybutynin is the first pass hepatic metabolite of oxybutynin, and it is associated with anticholinergic effects.
Children with neurogenic bladder and poor bladder compliance are usually treated with bladder catheterization and oral anticholinergic medication. They may become nonresponders to the drug or present with severe side effects. We evaluated the effectiveness and tolerability of intravesical oxybutynin in children with poorly compliant neurogenic bladder.
We conducted a search of MEDLINE®, EMBASE®, CINAHL®, SciELO, dissertations/theses in ProQuest®, LILACS, the Cochrane Library, protocol registries and the gray literature. Two reviewers independently assessed study quality and extracted data.
Eight studies (2 prospective, 6 retrospective) assessed the effectiveness and side effects of intravesical oxybutynin in children with neurogenic bladder. A total of 297 children started treatment, of whom 22% (66 patients) discontinued therapy, with 9% (28) quitting due to systemic side effects. Mean change in bladder compliance (primary outcome) was reported in only 2 studies (+7.4 and +7.5 ml/cm H₂O). The pooled mean change in pressure at maximum bladder capacity was −16.4 cm H₂O (95% CI −22.8 to −10.0). Incontinence improved significantly in most studies, with “dry and improved” rates ranging from 61% to 83%. The funnel plot of pressure at maximum bladder capacity suggested no publication bias.
Adjunctive intravesical oxybutynin therapy increased mean maximum bladder capacity and decreased bladder pressure in children with neurogenic bladder. However, identified studies offered a low level of evidence, with most being poorly reported retrospective case series with potential biases. Although the incidence of side effects was lower with the intravesical route, side effects are still possible and should be discussed with patients and families. The evidence available is insufficient to recommend this therapy. Research of more sound study design such as a randomized controlled trial should be conducted to assess the efficacy and side effects of intravesical oxybutynin in children.
Drug treatment of urinary incontinence in women
2008, Female Urology: Text with DVD
Drug Treatment of Urinary Incontinence in Women
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Scientific articleIntravesical oxybutynin chloride: Experience with 42 patients

Abstract

J Urol

J Urol

J Urol

J Urol

Effects of intravesical instillation of verapamil in patients with detrusor hyperactivity

Neurourol Urodyn

Intravesical lidocaine and detrusor instability

Br J Urol

Relaxation of intestinal bladders by intravesical oxybutynin chloride

Neurourol Urodyn

Scientific article
Intravesical oxybutynin chloride: Experience with 42 patients