Drug products: Ditropan, GELNIQUE, Kentera®, Oxibutynin AB Unimedic, Oxibutynin APL, Oxybutynin 2care4, Oxybutynin Accord, Oxybutynin Chloride Syrup USP, Oxybutynin Ebb, Oxybutynin Mylan, Oxybutynin Unimedic
ATC code: G04BD04
Substances: oxybutynin, oxybutynin chloride
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.
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
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 .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 . 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 .No sex differentiation in dosing has been recommended by the manufacturer [12, 13].
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 .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) .
In the subgroup analysis , the rate of application site reactions and common adverse effect were similar in men compared to the whole study population .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) .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) .
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: 2022-07-05
- EAU Guidelines. Non-neurogenic Female LUTS. Uroweb [www]. [cited 2022-04-14]. länk
- 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
- Giannitsas K, Athanasopoulos A. Male overactive bladder: pharmacotherapy for the male. Curr Opin Urol. 2013;23:515-9. PubMed
- Andersson KE. The use of pharmacotherapy for male patients with urgency and stress incontinence. Curr Opin Urol. 2014;24:571-7. PubMed
- EAU Guidelines. Management of Non-neurogenic Male LUTS. Uroweb [www]. [cited 2022-04-14]. länk
- Coyne KS, Sexton CC, Thompson CL, Milsom I, Irwin D, Kopp ZS et al. The prevalence of lower urinary tract symptoms (LUTS) in the USA, the UK and Sweden: results from the Epidemiology of LUTS (EpiLUTS) study. BJU Int. 2009;104:352-60. PubMed
- Irwin DE, Milsom I, Hunskaar S, Reilly K, Kopp Z, Herschorn S et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol. 2006;50:1306-14; discussion 1314-5. PubMed
- 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
- Mangera A, Chapple CR, Kopp ZS, Plested M. The placebo effect in overactive bladder syndrome. Nat Rev Urol. 2011;8:495-503. PubMed
- Lukkari E, Hakonen T, Neuvonen PJ. The pharmacokinetics of oxybutynin is unaffected by gender and contraceptive steroids. Eur J Clin Pharmacol. 1998;53:351-4. PubMed
- Food and Drug Administration (FDA). Clinical Pharmacology and Biopharmaceutics Review - OXYTROL (oxybutynin)
- Food and Drug Administration (FDA). Clinical Pharmacology and Biopharmaceutics Review - DITROPAN XL (oxybutynin)
- Staskin DR, Dmochowski RR, Sand PK, Macdiarmid SA, Caramelli KE, Thomas H et al. Efficacy and safety of oxybutynin chloride topical gel for overactive bladder: a randomized, double-blind, placebo controlled, multicenter study. J Urol. 2009;181:1764-72. PubMed
- Zellner M, Madersbacher H, Palmtag H, Stöhrer M, Bödeker RH, P195 Study Group. Trospium chloride and oxybutynin hydrochloride in a german study of adults with urinary urge incontinence: results of a 12-week, multicenter, randomized, double-blind, parallel-group, flexible-dose noninferiority trial. Clin Ther. 2009;31:2519-39. PubMed
- Staskin DR, Rosenberg MT, Dahl NV, Polishuk PV, Zinner NR. Effects of oxybutynin transdermal system on health-related quality of life and safety in men with overactive bladder and prostate conditions. Int J Clin Pract. 2008;62:27-38. PubMed
- Sand P, Zinner N, Newman D, Lucente V, Dmochowski R, Kelleher C et al. Oxybutynin transdermal system improves the quality of life in adults with overactive bladder: a multicentre, community-based, randomized study. BJU Int. 2007;99:836-44. PubMed
- Alzayer R, Hughes J, Parsons R, Lee YP. Comparison of risk of neurovascular and cardiovascular side effects between tiotropium and other anticholinergic agents. Qual Prim Care. 2010;18:189-99. PubMed
- Welk B, McArthur E. Increased risk of dementia among patients with overactive bladder treated with an anticholinergic medication compared to a beta-3 agonist: a population-based cohort study. BJU Int. 2020;126(1):183-190. PubMed
- Akino H, Namiki M, Suzuki K, Fuse H, Kitagawa Y, Miyazawa K et al. Factors influencing patient satisfaction with antimuscarinic treatment of overactive bladder syndrome: results of a real-life clinical study. Int J Urol. 2014;21:389-94. PubMed
- Johnell K, Weitoft GR, Fastbom J. Sex differences in inappropriate drug use: a register-based study of over 600,000 older people. Ann Pharmacother. 2009;43:1233-8. PubMed
- Kalder M, Pantazis K, Dinas K, Albert US, Heilmaier C, Kostev K. Discontinuation of treatment using anticholinergic medications in patients with urinary incontinence. Obstet Gynecol. 2014;124:794-800. PubMed
- Krhut J, Gärtner M, Petzel M, Sykora R, Nemec D, Tvrdik J et al. Persistence with first line anticholinergic medication in treatment-naïve overactive bladder patients. Scand J Urol. 2014;48:79-83. PubMed
- Cardozo L, Hall T, Ryan J, Ebel Bitoun C, Kausar I, Darekar A et al. Safety and efficacy of flexible-dose fesoterodine in British subjects with overactive bladder: insights into factors associated with dose escalation. Int Urogynecol J. 2012;23:1581-90. PubMed
- Wagg A, Darekar A, Arumi D, Khullar V, Oelke M. Factors associated with dose escalation of fesoterodine for treatment of overactive bladder in people >65 years of age: A post hoc analysis of data from the SOFIA study. Neurourol Urodyn. 2015;34:438-43. PubMed
- Lua LL, Pathak P, Dandolu V. Comparing anticholinergic persistence and adherence profiles in overactive bladder patients based on gender, obesity, and major anticholinergic agents. Neurourol Urodyn. 2017;36(8):2123-2131. PubMed
- Goodson AB, Cantrell MA, Shaw RF, Lund BC. Comparative Effectiveness of Anticholinergic Agents for Lower Urinary Tract Symptoms. J Manag Care Spec Pharm. 2018;24(1):65-72. PubMed
- Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2021 [cited 2022-03-15.] länk
Reviewed by: Carl-Olav Stiller, Pauline Raaschou
Approved by: Karin Schenck-Gustafsson