Drugs used to control detrusor instability (overactive bladder)

Drugs with antimuscarinic activity e.g. oxybutinin, are used in the pharmacologic management of detrusor stability because they inhibit the cholinergically innervated unstable detrusor muscle contractions.

• oxybutynin - this drug also has a direct smooth-muscle relaxant action on the bladder in addition to its antimuscuranic action, is widely used in the management of detrusor instability. Oxybutin is however associated with a high incidence of side effects which limits its use. Modified release oxybutinin, propiverine and tolderodine may be considered as an alternative for patients unable to tolerate conventional-release oxybutinin (1)

Other possible treatment options include:

• a modified-release preparation of oxybutynin is effective and has fewer side-effects; a transdermal patch is also available
• tolterodine -side effects and efficacy are comparable to those of modified-release oxybutynin
• flavoxate - less marked side-effects but it is also less effective
• propiverine, solifenacin and trospium are newer antimuscarinic drugs licensed for urinary frequency, urgency, and incontinence

Notes:

• the need for continuing antimuscarinic drug therapy should be reviewed after 3-6 month (2)
• propantheline and tricyclic antidepressants were used for urge incontinence but they are little used now because of their side-effects
• use of imipramine is limited by its potential to cause cardiac side-effects
• NICE guidance for drug therapy for overactive bladder syndrome (OAB) in women suggests (3)
  • Choosing OAB drugs
    • Do not use flavoxate, propantheline and imipramine for the treatment of UI or OAB in women
    • Do not offer oxybutynin (immediate release) to frail older women
      • one of the following choices should be offered first to women with OAB or mixed UI:
        • oxybutynin (immediate release), or
        • tolterodine (immediate release), or
        • darifenacin (once daily preparation)
        • if the first treatment for OAB or mixed UI is not effective or well-tolerated, offer another drug with the lowest acquisition cost
      • ofer a transdermal OAB drug to women unable to tolerate oral medication
    • Reviewing OAB drug treatment
      • offer a face-to-face or telephone review 4 weeks after the start of each new OAB drug treatment. Ask the woman if she is satisfied with the therapy:
        • If improvement is optimal, continue treatment
        • If there is no or suboptimal improvement or intolerable adverse effects change the dose, or try an alternative OAB drug, and review again 4 weeks later
      • offer review before 4 weeks if the adverse events of OAB drug treatment are intolerable
      • offer referral to secondary care if the woman does not want to try another drug, but would like to consider further treatment
      • offer a further face-to-face or telephone review if a woman's condition stops responding optimally to treatment after an initial successful 4-week review
      • review women who remain on long-term drug treatment for UI or OAB annually in primary care (or every 6 months for women over 75)
      • offer referral to secondary care if OAB drug treatment is not successful
• NICE guidance related to lower urinary tract symptoms in men states (4):
  • offer an anticholinergic to men to manage the symptoms of OAB
  • consider offering an anticholinergic as well as an alpha blocker to men who still have storage symptoms after treatment with an alpha blocker alone
  • review men taking anticholinergics every 4-6 weeks until symptoms are stable, and then every 6-12 months
• NICE guidance has suggested Mirabegron an option for treating the symptoms of overactive bladder only for people in whom antimuscarinic drugs are contraindicated or clinically ineffective, or have unacceptable side effects (5):
  • mirabegron is a beta-3-adrenoceptor agonist, which activates beta-3-adrenoceptors causing the bladder to relax, which helps it to fill and also to store urine
  • administered orally
  • available as 25 mg and 50 mg tablets, with the recommended dose being 50 mg daily, and 25 mg if there is renal or hepatic impairment

Reference:

1. MeReC Bulletin (2000); 11 (3): 9-12.
2. BNF 7.1 (Volume 52, September 2006)
3. NICE (September 2013). Urinary incontinence - The management of urinary incontinence in women
4. NICE (May 2010). Lower urinary tract symptoms The management of lower urinary tract symptoms in men
5. NICE (June 2013). Mirabegron for treating symptoms of overactive bladder.