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Solifenacin

Classification: B

Drug products: Solifenacin Accord, Solifenacin Glenmark, Solifenacin Krka, Solifenacin Medical Valley, Solifenacin Orion, Solifenacin Sandoz, Solifenacin STADA, Solifenacin Teva, Vesicare, Vesikur

ATC code: G04BD08

Substances: solifenacin, solifenacin succinate

Summary

Results from clinical studies of solifenacin show conflicting results regarding differences between men and women in efficacy. Pathogenesis and symptoms of urinary incontinence and overactive 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 of overactive bladder has been shown for both men and women.

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 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

Studies on sex differences in efficacy of solifenacin treatment show incongruent results which probably partly reflects the differences in pathology and symptoms in men and women.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 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]. A meta-analysis of 11 RCTs (934 men, 4224 women) showed that solifenacin was more efficacious than placebo for all overactive bladder symptoms in both men and women [15].

Adverse effects

The overall frequency of adverse reactions was slightly higher in women than men, in both the solifenacin and placebo groups [15].The sex of the patient was not associated with rate of adverse reactions in a 12-week open-label study (734 men, 3716 women) [16]. In two other similar studies (in total 447 men, 2219 women), the rates of adverse reactions in men were mostly comparable to the entire study population [17].In a retrospective register study of patient reported but not evaluated adverse events on anticholinergic medication (11296 men, 21839 women, of which 2827 patients used solifenacin) men were more likely to report of cardiovascular or cerebrovascular adverse events 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). One third of all patients were satisfied and one third dissatisfied with their treatment, and men were overall less satisfied than women. Dissatisfaction was commonly influenced by poor efficacy or adverse effects, mainly constipation [19].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].

Updated: 2022-09-23

Date of litterature search: 2022-04-14

References

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  2. Kaplan SA, Roehrborn CG, Abrams P, Chapple CR, Bavendam T, Guan Z. Antimuscarinics for treatment of storage lower urinary tract symptoms in men: a systematic review. Int J Clin Pract. 2011;65:487-507. PubMed
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Authors: Diana Rydberg

Reviewed by: Carl-Olav Stiller, Pauline Raaschou

Approved by: Karin Schenck-Gustafsson