What medication can be prescribed for a patient with urinary frequency and a normal urinalysis (UA)?

Pharmacologic Management of Urinary Frequency with Normal Urinalysis

For a patient with urinary frequency and normal UA, prescribe either an antimuscarinic medication (tolterodine, solifenacin, darifenacin, fesoterodine, oxybutynin, or trospium) or the beta-3 agonist mirabegron as second-line therapy after behavioral interventions. 1

First-Line Treatment Requirement

• Behavioral therapies should be offered first as they are equally effective as antimuscarinic medications for reducing symptom levels and carry no risk of adverse effects 1
• Behavioral interventions include bladder training, bladder control strategies, pelvic floor muscle training, and fluid management 1
• However, behavioral therapies may be combined with pharmacologic management simultaneously if the patient has moderate to severe symptoms 1

Second-Line Pharmacologic Options

Antimuscarinic Medications (Listed Alphabetically, No Hierarchy Implied)

The AUA/SUFU guidelines recommend offering oral antimuscarinics as second-line therapy, with no compelling evidence for differential efficacy across medications: 1

• Darifenacin
• Fesoterodine
• Oxybutynin
• Solifenacin
• Tolterodine
• Trospium

Beta-3 Agonist Alternative

• Mirabegron is an effective alternative with a different mechanism of action and lower anticholinergic side effect profile 1
• Mirabegron achieved continence more than placebo (NNTB 12) and improved urinary incontinence (NNTB 9) with moderate-quality evidence 1
• Mirabegron demonstrated statistically significant reductions in micturition frequency per 24 hours compared to placebo (p<0.001 to p=0.015 across three trials) 2

Medication Selection Based on Side Effect Profile

Most Tolerable Options

For patients concerned about side effects, particularly elderly patients, tolterodine or darifenacin should be preferred: 3

• Tolterodine has discontinuation rates due to adverse effects similar to placebo with high-quality evidence 1, 3
• Tolterodine achieved continence (NNTB 12) and improved urinary incontinence (NNTB 10) more than placebo 1
• Darifenacin offers comparable tolerability with discontinuation rates not significantly different from placebo 3

Solifenacin as Alternative

• Solifenacin is associated with the lowest risk for discontinuation due to adverse effects among antimuscarinics (NNTB 9 for achieving continence) 1, 3
• High-quality evidence shows solifenacin achieved continence more than placebo (NNTB 9) and resolved urinary incontinence (NNTB 6) 1
• Solifenacin 5 mg once daily is the recommended starting dose; higher doses (10 mg) did not decrease frequency of episodes and were associated with increased adverse effects 1

Medications to Use with Caution

Oxybutynin should be avoided as first-line therapy due to highest discontinuation rate (NNTH 16) and highest risk of dry mouth, constipation, and cognitive impairment: 1, 3

• Fesoterodine has poor tolerability with NNTH for adverse effects of only 7, the worst among antimuscarinics 1, 3
• Fesoterodine has higher risk of withdrawal due to adverse events (RR 1.45) and dry mouth (RR 1.80) compared to extended-release tolterodine 4

Dosing Recommendations

Starting Doses

• Tolterodine: 2 mg twice daily (or 1 mg twice daily for reduced dry mouth risk) 3, 4
• Solifenacin: 5 mg once daily 1, 3
• Mirabegron: 25 mg once daily, may increase to 50 mg 2
• Darifenacin, fesoterodine, oxybutynin, trospium: per standard dosing 1

Critical Safety Considerations

Absolute Contraindications and Cautions

Antimuscarinics should not be used in patients with narrow-angle glaucoma unless approved by ophthalmologist, and should be used with extreme caution in patients with: 1

• Impaired gastric emptying
• History of urinary retention
• Patients taking 7 or more concomitant medications (increased risk of adverse effects) 1

Cognitive Risk Warning

The 2024 AUA/SUFU guideline requires discussing the potential risk for developing dementia and cognitive impairment with all patients prescribed antimuscarinic medications: 1

• Evidence suggests an association between antimuscarinic medications and incident dementia, which may be cumulative and dose-dependent 1
• A trial of beta-3 agonists (mirabegron) is typically preferred before antimuscarinic medications due to this cognitive risk 1

Treatment Algorithm

1. Confirm diagnosis: Urinary frequency with normal UA suggests overactive bladder symptoms 1

2. Initiate behavioral therapies first (bladder training, fluid management, pelvic floor exercises) 1

3. If behavioral therapy inadequate or patient has moderate-to-severe symptoms, add pharmacologic therapy: 1

   • First choice: Mirabegron 25-50 mg once daily (lower cognitive risk) 1, 2
   • Alternative first choices: Tolterodine 2 mg twice daily or darifenacin (best tolerability among antimuscarinics) 3
   • Second alternative: Solifenacin 5 mg once daily (lowest discontinuation risk) 1, 3

4. If inadequate response or unacceptable adverse effects: 1

   • Try dose modification
   • Switch to different antimuscarinic
   • Switch between antimuscarinic and beta-3 agonist

5. Avoid as first-line: Oxybutynin and fesoterodine due to poor tolerability 1, 3

Common Pitfalls to Avoid

• Do not prescribe antimuscarinics without discussing dementia risk, especially for chronic use 1
• Do not use higher doses of solifenacin (10 mg) initially as they increase adverse effects without improving efficacy 1
• Do not abandon antimuscarinic therapy after one medication fails - patients may respond better to a different agent or dose modification 1
• Do not prescribe antimuscarinics in narrow-angle glaucoma without ophthalmology clearance 1
• Consider post-void residual measurement in patients at risk for urinary retention before initiating therapy 1