Oxibutynin

Additional information

Anticholinergic drugs reduce the bladder detrusor muscle contractions and are used to treat urgency incontinence and symptoms of overactive bladder. Due to sex differences in etiology of these symptoms, drug therapy differs as urinary retention must be ruled out before starting treatment with anticholinergic drugs. In women,anticholinergic drugs are commonly used when non-pharmacological treatments such as bladder training are insufficient. In men, benign prostate hyperplasia is a common cause of urgency symptoms. Non-anticholinergic drugs, primarily alpha-1 blockers, are therefore often used as first-line treatment in men even though anticholinergic drugs are used in addition or as monotherapy [1-3].

The baseline symptoms described in studies differ between men and women regarding prevalence of incontinence episodes and frequency of urgency episodes [4, 5]. Treatment effects on these parameters are common outcomes in clinical studies and differences in treatment effect between men and women need to be interpreted in relation to differences at baseline. The placebo effect seen in clinical studies of overactive bladder treatment is relatively high. According to a meta-analysis, 41% of the patients in placebo groups report cure or symptom improvement [6]. Two other meta-analysis report that changes from baseline with placebo treatment are significant for mean micturitions, mean incontinence episodes and mean voided volume [7, 8].

It should be noted that most studies include more women than men, and the low number of men included can affect the ability to make statistically significant analysis.

Pharmacokinetics and dosing

According to a single-dose pharmacokinetic study (25 men, 24 women), Cmax and AUC for oxybutynin and the active metabolite n-desethyloxybutynin were similar in men and women. However, there was a big inter-individual variation. Tmax was slightly but significantly longer for n-desethyloxybutynin in men [11].In the manufacturer’s documentation to FDA for transdermal oxybutynin a discrepancy between studies is noted. In the first study Cmax of oxybutynin was 21% and AUC 14% higher in men. For the active metabolite n-desethyloxybutynin however, Cmax was 18% and AUC 22% higher in women. In the other study Cmax for both oxybutynin and the metabolite was higher in women. According to the report this variation is not clinically significant [12].In the FDA documentation for oxybutynin extended release tablets no significant effects of patients’ sex on pharmacokinetic parameters are reported based on pooled data from different studies [13].

No sex differentiation in dosing has been recommended by the manufacturer [12, 13].

Effects

In a randomized double-blind placebo-controlled study of oxybutynin gel for treatment of overactive bladder (85 men, 704 women) treatment efficacy was similar in men and women [14].

In a double-blind active controlled clinical study comparing oxybutynin and trospium chloride for treatment of patients with urinary urgency incontinence (112 men, 1114 women) no difference in efficacy measured as reduction of episodes of urgency incontinence  between treatment groups was found for male and female patients [15].

A subgroup analysis of 369 men included in an open-label randomized cohort study of the effect of transdermal oxybutynin showed effect in men with overactive bladder symptoms regardless of prostate condition [16]. The original study, in patients treated with transdermal oxybutynin for at least 6 months, involved mostly women (2508) and in the whole population the treatment showed clinically significant improvement in health related quality of life [17].

Adverse effects

In the subgroup analysis [16] the rate of application site reactions and common adverse effect were similar in men compared to the whole study population [17].In a retrospective register study of patient reported but not evaluated adverse reactions on anticholinergic medication (11 296 men, 21 839 women, of which 1565 patients used oxybutynin) men were more likely to report of cardiovascular or cerebrovascular side effects of varying severity [18].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

Patient satisfaction with anticholinergic treatment was evaluated in a survey study in Japanese patients with overactive bladder syndrome (in total 514 men, 455 women). In the entire study one third of all patients were satisfied and one third dissatisfied with their treatment, men were overall less satisfied than women. Dissatisfaction was commonly influenced by poor efficacy or adverse effects, mainly constipation [9].In a Swedish register study of the prescription of potentially inappropriate drugs in elderly patients, women were more likely to be prescribed anticholinergic drugs then men [10].A German registry study (26,834 patients, 3813 treated with oxybutynin) evaluated discontinuation rate of anticholinergic drugs in patients with urinary incontinence. Discontinuation rate for all drugs was 75% in women and 78% in men in the first year and 86% in women and 88% in men within three years. After adjusting for demographic and clinical variables, the risk of discontinuation was higher in men [19]. In a database study of medication adherence for tolterodine and oxybutynin for treatment of overactive bladder (2357 men, 5501 women in all, 2149 treated with oxybutynin) no difference was seen between men and women for non-persistence or switch rate. Men had higher median medication possession ratio, defined as total days of medication dispensed except for last refill divided by number of days between first dispense and last refill, for all medications [20].