Transdermal Oxybutynin Research Articles

Efficacy and safety of transdermal oxybutynin in patients with urge and mixed urinary incontinence.

Efficacy and safety of transdermal oxybutynin in patients with urge and mixed urinary incontinence.

Comparative efficacy and safety of transdermal oxybutynin and oral tolterodine versus placebo in previously treated patients with urge and mixed urinary incontinence

Objectives To compare the efficacy and safety of an oxybutynin transdermal delivery system (OXY-TDS) and oral, long-acting tolterodine (TOL-LA) with placebo in previously treated patients with urge or mixed urinary incontinence. Methods After withdrawal of their current antimuscarinic therapy, 361 adult patients were randomized to 12 weeks of double-blind, double-dummy treatment with twice weekly OXY-TDS 3.9 mg/day, daily TOL-LA 4 mg, or placebo. Evaluations included change from baseline in patient urinary diary symptoms, incontinence-specific quality of life, and safety. Results OXY-TDS 3.9 mg/day and TOL-LA 4 mg/day significantly reduced the number of daily incontinence episodes (median change −3 OXY-TDS and −3 TOL-LA versus −2 placebo; P <0.05), increased the average void volume (median change 24 and 29 mL versus 5.5 mL, P <0.01), and improved quality of life (incontinence impact questionnaire [IIQ] total score, P <0.05; Urogenital Distress Inventory Irritative Symptom subscale, P <0.05) compared with placebo. The most common adverse event for OXY-TDS was localized application site pruritus (14% versus 4% placebo) accompanied by a low incidence of systemic side effects (eg, dry mouth 4.1%). Anticholinergic adverse events occurred with greatest frequency during TOL-LA treatment (dry mouth 7.3% versus 1.7% placebo, P <0.05). Conclusions OXY-TDS and TOL-LA are effective and comparable treatments for patients with urge and mixed incontinence. OXY-TDS improves systemic safety with regard to anticholinergic side effects. Local skin irritation occurs in some OXY-TDS patients.

Pharmacokinetics, Metabolism, and Saliva Output During Transdermal and Extended-Release Oral Oxybutynin Administration in Healthy Subjects

To compare the pharmacokinetics and adverse effect dynamics of 2 modified-release oxybutynin treatments. Between October 15 and November 6, 2001, 13 healthy subjects (7 men and 6 women) participated in a randomized, 2-way crossover study of transdermal (Oxytrol, 3.9 mg/d) and extended-release oral (Ditropan XL, 10 mg) oxybutynin. Multiple blood and saliva samples were collected. Pharmacokinetic parameters and total salivary output were assessed. Statistical analyses included 95% confidence intervals, paired t test, analysis of variance, and linear regression. Steady-state plasma concentrations were achieved after the first transdermal application and after the second extended-release oral dose. Mean +/- SD 24-hour oxybutynin areas under the concentration-time curve were comparable during transdermal and oral extended-release treatments, 10.8 +/- 24 vs 9.2 +/- 33 ng x h(-1) x mL(-1), respectively. However, the ratio of area under the curve (N-desethyloxybutynin/oxybutynin) after transdermal administration (1.2 +/- 03) was significantly lower (P < .001) than after extended-release oral administration (4.1 +/- 0.9). Mean plasma concentrations were less variable during transdermal compared with extended-release oral administration. Mean +/- SD saliva output was greater during transdermal than extended-release oral treatment (15.7 +/- 93 vs 12.2 +/- 6.8 g, respectively; P = .02). Lower N-desethyloxybutynin during transdermal application was associated with greater saliva output (r = -059, P = .04). No clinically important treatment-related adverse effects were observed. Transdermal oxybutynin administration results in greater systemic availability and minimizes metabolism to N-desethyloxybutynin compared with extended-release oral administration. Lower N-desethyloxybutynin plasma concentration and greater saliva output during transdermal treatment correspond to the reported low incidence of dry mouth in patients with overactive bladder.

Transdermal oxybutynin: a new treatment for overactive bladder

Transdermal oxybutynin: a new treatment for overactive bladder

Efficacy and Safety of Transdermal Oxybutynin in Patients With Urge and Mixed Urinary Incontinence

We evaluated the efficacy and safety of an oxybutynin transdermal delivery system (TDS) in a general population of patients with overactive bladder and urge or mixed urinary incontinence. Following symptom stabilization or treatment withdrawal 520 adult patients were randomized to 12 weeks of double-blind daily treatment with 1.3, 2.6 or 3.9 mg. oxybutynin TDS or placebo administered twice weekly, followed by a 12-week open-label, dose titration period to assess efficacy and safety further. Evaluations included patient urinary diaries, incontinence specific quality of life and safety. A dose of 3.9 mg. daily oxybutynin TDS significantly reduced the number of weekly incontinence episodes (median change -19.0 versus -14.5, p = 0.0165), reduced average daily urinary frequency (mean change -2.3 versus -1.7, p = 0.0457), increased average voided volume (median change 24 versus 6 ml., p = 0.0063) and significantly improved quality of life (Incontinence Impact Questionnaire total score, p = 0.0327) compared with placebo. Average voided volume increased in the daily 2.6 mg. group (19 ml., p = 0.0157) but there were no other significant differences between 1.3 and 2.6 mg. oxybutynin TDS and placebo. The most common adverse event was application site pruritus (oxybutynin TDS 10.8% to 16.8%, placebo 6.1%). Dry mouth incidence was similar in both groups (7.0% versus 8.3%, p not significant). In the open-label period a sustained reduction of nearly 3 incontinence episodes per day was reported for all groups. Doses of 2.6 and 3.9 mg. oxybutynin TDS daily improve overactive bladder symptoms and quality of life, and are well tolerated. Transdermal oxybutynin is an innovative new treatment for overactive bladder.

Efficacy and Safety of Transdermal Oxybutynin in Patients With Urge and Mixed Urinary Incontinence

Efficacy and Safety of Transdermal Oxybutynin in Patients With Urge and Mixed Urinary Incontinence

Influence of Age on Improvement in Overactive Bladder Symptoms and Adverse Events during Transdermal Oxybutynin Treatment*

Influence of Age on Improvement in Overactive Bladder Symptoms and Adverse Events during Transdermal Oxybutynin Treatment*

Anticholinergic Side Effects with Long-Term Transdermal Oxybutynin for Overactive Bladder Symptoms*

Davila, G. W. MD; Dmochowski, Roger R. MD; Sanders, Steven W. PharmD Author Information

Does Hormone Replacement Affect Overactive Bladder Symptoms and Quality of Life during Transdermal Oxybutynin Therapy?*

Cleveland Clinic Florida, Weston, FL *This document includes a discussion of use of a product that is unapproved by the U.S. Food and Drug Administration.

Does hormone replacement affect overactive bladder symptoms and quality of life during transdermal oxybutynin therapy?

Does hormone replacement affect overactive bladder symptoms and quality of life during transdermal oxybutynin therapy?

Influence of age on improvement in overactive bladder symptoms and adverse events during transdermal oxybutynin treatment

Influence of age on improvement in overactive bladder symptoms and adverse events during transdermal oxybutynin treatment

Anticholinergic side effects with long-term transdermal oxybutynin for overactive bladder symptoms

Anticholinergic side effects with long-term transdermal oxybutynin for overactive bladder symptoms

A SHORT-TERM, MULTICENTER, RANDOMIZED DOUBLE-BLIND DOSE TITRATION STUDY OF THE EFFICACY AND ANTICHOLINERGIC SIDE EFFECTS OF TRANSDERMAL COMPARED TO IMMEDIATE RELEASE ORAL OXYBUTYNIN TREATMENT OF PATIENTS WITH URGE URINARY INCONTINENCE

We compared the short-term efficacy, safety and tolerability of transdermal versus oral oxybutynin in adults with urge urinary incontinence. Volunteers with detrusor instability currently responding to oral immediate release oxybutynin were enrolled in our study. Those patients presenting with recurrence of incontinent symptoms after a 2-week washout underwent confirmatory cystometrogram with subsequent randomization to transdermal or oral treatment. Matching active and placebo medications included matrix patches applied twice weekly and capsules taken 2 or 3 times daily. Dose titration was based on anticholinergic symptoms. Outcome measures included comparison of baseline to 6 week changes in incontinence episodes on a 3 day urinary diary, a visual analog scale for efficacy and anticholinergic symptoms reported on a questionnaire. Safety monitoring included adverse events and skin tolerability of the transdermal system. A total of 76 patients were enrolled and 74 completed at least 4 weeks of treatment. Mean age in the transdermal and oral groups was 64 and 63 years, and 87% and 97% were female, respectively. Daily incontinent episodes decreased in the transdermal and oral groups (7.3 to 2.4 [66%] and 7.4 to 2.6 [72%], respectively, p = 0.39). The visual analog scale reduction in urinary leakage improved from washout in both groups (p <0.0001) with no difference between them (p = 0.9). Dry mouth occurred in significantly fewer patients in the transdermal (38%) compared with those in the oral group (94%, p <0.001). Of the patients in the transdermal group 67% noticed a reduction in dry mouth severity compared with previous oral treatment, and 90% had none or mild skin erythema. Transdermal delivery of oxybutynin resulted in comparable efficacy and a significantly improved anticholinergic side effect profile compared with oral administration in adults with urge urinary incontinence.

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.

Comparison of Oxybutynin and its Active Metabolite, N-Desethyl-Oxybutynin, in the Human Detrusor and Parotid Gland

To compare in vitro the antimuscarinic effect of oxybutynin and its active metabolite, N-desethyl-oxybutynin, on human detrusor, and their binding characteristics in detrusor and parotid gland. Antimuscarinic effect in the detrusor was assessed as the ability of the drugs to inhibit carbachol-induced contractions and contractions induced by electrical nerve stimulation. In addition, the drugs' ability to displace 3H-QNB from muscarinic receptors was investigated. Both oxybutynin and N-desethyl-oxybutynin caused a rightward shift of the concentration-response curve for carbachol without depression of the maximum, indicating a competitive antagonism. The pA2 values were 7.8 for oxybutynin and 7.6 for N-desethyl-oxybutynin. Contractions induced by electrical nerve stimulation were depressed by 87% by oxybutynin (10 microM) and by 91% by N-desethyl-oxybutynin (10 microM). In radioligand receptor binding studies on the detrusor, oxybutynin and N-desethyl-oxybutynin had uniform displacement curves and the same pKi value, 8.2. The affinity for N-desethyl-oxybutynin in the parotid gland was significantly higher, the pKi value being 8.7. The corresponding figure for oxybutynin was 8.5. We conclude that oxybutynin and N-desethyl-oxybutynin have a similar antimuscarinic effect in the human detrusor, and the same binding characteristics in detrusor and parotid gland, respectively.