Oxybutynin

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 [1]. 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 [2-5].The baseline symptoms described in studies differ between men and women regarding prevalence of incontinence episodes and frequency of urgency episodes [6, 7]. 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 [8]. Two other meta-analyses report that changes from baseline with placebo treatment are significant for mean micturitions, mean incontinence episodes and mean voided volume [9, 10].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 analyses.

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 were 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 transdermal oxybutynin for treatment of overactive bladder (85 men, 704 women), the change from baseline in the number of urge incontinence episodes  was similar in men and women [14].No sex difference in reduction of episodes of urgency incontinence between treatment groups was found in a double-blind active controlled clinical study comparing oxybutynin and trospium chloride in patients with urinary urgency incontinence (112 men, 1114 women) [15].

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].Men were more likely to report cardiovascular or cerebrovascular adverse events (data obtained from the FDA) from anticholinergic medication in a retrospective register study (11,296 men, 21,839 women, of which 1565 patients used oxybutynin) [18].The risk of dementia among anticholinergic (overactive bladder medication) users (21,058 men, 26,266 women) compared to beta-3 agonist users (10529 men, 13133 women) was increased in men (HR 1.41; 95%CI 1.23-1.62) but not in women (HR 1.08; 95%CI 0.95-1.23) [19].

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 [20].Patterns of adherence and persistence of anticholinergic drugs varies depending on the population studied and type of study [21-27].