Drug products: Emselex®
ATC code: G04BD10
Substances: darifenacin, darifenacin hydrobromide
Results from clinical studies show conflicting results regarding differences between men and women. Pathogenesis and symptoms of urinary incontinence and over active bladder differ between men and women. Most studies have included few men and thus it is difficult to evaluate potential sex differences.
Low long term persistence to anticholinergic treatment has been shown for both men and women.
Based on the present evidence, there is no reason to differentiate the treatment between men and women with urinary urgency incontinence.
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 . 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.
According to studies conducted by the manufacturer, clearance was 39% higher and AUC 28% lower in men . In a population pharmacology study with pooled data from 18 studies (44 men, 293 women), clearance was 31% lower in women . Despite the pharmacokinetic differences of darifenacin, the clinical studies have shown effect with similar doses in men and women, and no sex differentiation in dosing has been suggested .
A post hoc analysis of an open label study of 3766 patients (77% women) treated with darifenacin for overactive bladder symptoms reported a correlation between men and women and efficacy of darifenacin treatment, measured as improvement in urgency, micturition and nocturia episodes. However the differences were small and probably not clinically relevant according to the authors .
Both men and women were reported to have long-term effect of darifenacin regarding health related quality of life in a long term open-label study, designed as a two year extension to two placebo-controlled double blind studies (41 men and 262 women on darifenacin) .
According to the manufacturer’s documentation to FDA  the magnitude of treatment effect of darifenacin was higher in women. The effect is shown as reduction in incontinence episodes.
No studies with a clinically relevant sex analysis regarding adverse effects of darifenacin have been found.
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
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 .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 .A German database study (26,834 patients, 1995 treated with darifenacin) 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 .
Date of litterature search: 2015-03-12
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson