Drug products: Detrusitol, Detrusitol SR, Detrusitol®, Detrusitol® SR, Tolterodin 2care4, Tolterodin Ebb, Tolterodin Mylan, Tolterodin Orifarm, Tolterodin Rivopharm, Tolterodin Sandoz, Tolterodin STADA, Tolterodin Upjohn, Tolterodine Accord, Tolterodine Sandoz, Tolterodine Teva
ATC code: G04BD07
Substances: tolterodine, tolterodine tartrate
Results from clinical studies 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 s0 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.
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 [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 . 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
Three studies (37 men, 30 women) conducted by the manufacturer show no significant differences in pharmacokinetic parameters for tolterodine or the active metabolite DD 01 between men and women after a single 2 mg dose. No sex differentiation in dosing has been recommended by the manufacturer [11, 12].
Studies on sex differences in efficacy of tolterodine treatment show incongruent results which probably partly reflects the differences in pathology and symptoms in men and women.In a double-blind study, urgency perception in patients with overactive bladder was analyzed in a placebo-controlled double-blind study (123 men, 649 women). Notably, men in both tolterodine and placebo groups experienced similar improvements in urgency perception, whereas in women the effect was better in the tolterodine group. For perceived effect on bladder symptoms, the difference in effect between tolterodine and placebo was only significant in women . An observational post-marketing surveillance study in Germany (520 men, 1730 women) found no difference between men and women regarding voiding frequency or urgency. However, men had a higher likelihood of successful treatment of incontinence but less favorable rating of global efficacy .Data from two randomized placebo-controlled studies of extended release tolterodine for treatment of overactive bladder (745 men, 953 women) were evaluated for efficacy and tolerability. At baseline, 73% of the men and 57% of the women were continent, and tolterodine compared to placebo reduced symptoms in both men and women .The speed of onset of treatment effect of tolterodine did not differ between men and women with overactive bladder, when comparing patients with or without previous treatment (302 men, 836 women) .Pooled data from two randomized double-blind studies compared the effect of fesoterodine, tolterodine extended release, or placebo for 12 weeks in patients with urinary incontinence or urgency (673 men, 3435 women). In women, tolterodine treatment significantly improved the diary-dry-rates and all bladder diary variables except nocturnal micturations compared to placebo. In men, tolterodine treatment significantly improved micturitions, nocturnal micturitions, frequency–urgency sum, PPBC scores and scores on the OAB-q HRQL scale and Coping, Sleep and Social Interaction domains at week 12, compared with placebo .In one open label study on patient reported treatment effect on their most bothersome symptom (155 men, 708 women), no difference between men and women was found after 12 weeks of treatment .
An analysis of two studies of extended release tolterodine reported equal levels of total adverse reactions, dry mouth (10.8% in men, 11.7% in women) and constipation (2.2% in men 3.4% in women) . The incidence of headache was higher in women (1.1% in men 3.6% in women), however it was not different from the level in the placebo group (1.3% in men 4.0% in women) .Reported adverse events in a post-marketing surveillance study in Germany (520 men, 1730 women) were low and no analysis of influence of sex differences was done on specific symptoms. Instead an analysis of global tolerability was performed that revealed no association with patient sex .In a retrospective register study of patient reported but not evaluated adverse events on anticholinergic medication (11296 men, 21839 women, of which 11670 patients used tolterodine) men were more likely to report cardiovascular or cerebrovascular side effects of varying severity .
Reproductive health issues
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (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 .
Patterns of adherence and persistence of anticholinergic drugs varies depending on the population studied and type of study [21-27].
Date of litterature search: 2022-04-07
- EAU Guidelines. Non-neurogenic Female LUTS. Uroweb [www]. [cited 2022-04-14]. länk
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- Nabi G, Cody JD, Ellis G, Herbison P, Hay-Smith J. Anticholinergic drugs versus placebo for overactive bladder syndrome in adults. Cochrane Database Syst Rev. 2006;18:CD003781. PubMed
- Lee S, Malhotra B, Creanga D, Carlsson M, Glue P. A meta-analysis of the placebo response in antimuscarinic drug trials for overactive bladder. BMC Med Res Methodol. 2009;9:55. PubMed
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- Food and Drug Administration (FDA). Clinical Pharmacology and Biopharmaceutics Review - DETROL (tolterodine)
- Food and Drug Administration (FDA). Clinical Pharmacology and Biopharmaceutics Review - DETROL LA (tolterodine)
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- Ginsberg D, Schneider T, Kelleher C, Van Kerrebroeck P, Swift S, Creanga D et al. Efficacy of fesoterodine compared with extended-release tolterodine in men and women with overactive bladder. BJU Int. 2013;112:373-85. PubMed
- Elinoff V, Bavendam T, Glasser DB, Carlsson M, Eyland N, Roberts R. Symptom-specific efficacy of tolterodine extended release in patients with overactive bladder: the IMPACT trial. Int J Clin Pract. 2006;60:745-51. PubMed
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Reviewed by: Carl-Olav Stiller, Pauline Raaschou
Approved by: Karin Schenck-Gustafsson