Solifenacin

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 studies conducted by the manufacturer, no relevant difference in pharmacokinetic parameters in single or multi-dose studies was seen between men and women [11]. In a multiple-dose crossover study (24 men, 23 women) Cmax and AUC were comparable in men and women within the same age group [12]. A small study (6 men, 6 women) found a 30-60% higher exposure in women after a single dose of 10 mg [11]. No sex differentiation in dosing has been recommended by the manufacturer [11]. 

Effects

In a prospective open label study in patients with overactive bladder syndrome treated with 5 mg solifenacin for 12 weeks (332 men, 316 women), women had better therapeutic efficacy measured as change in urgency severity scale (USS) and voided volume compared to baseline. Lack of placebo control limits the relevance of these findings [13]. However pooled data from four randomized double blind placebo controlled studies (582 men, 2266 women) showed the effect of 5 mg and 10 mg solifenacin to be the same in men and women [14].

Adverse effects

The sex of the patient was not associated with rate of adverse effects in a 12-week open label study (734 men, 3716 women) [15]. In two other similar studies (in total 447 men, 2219 women), the rates of adverse effects in men were mostly comparable to the entire study population [16].In a retrospective register study of patient reported (but not evaluated) adverse reactions on anticholinergic medication (11 296 men, 21 839 women, of which 2827 patients used solifenacin) men were more likely to report of cardiovascular or cerebrovascular side effects of varying severity [17].

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, 4844 treated with solifenacin) 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 [18].In contrast to this, another retrospective study of persistence with first line anticholinergic treatment in treatment naïve patients (52 men, 325 women, 48 patients were treated with solifenacin) the persistence was 27% after 12 months without any difference between men and women [19].