What is the safest medication to use for overactive bladder in patients with impaired renal function?

From the Guidelines

Mirabegron is the safest medication for overactive bladder in patients with impaired renal function, due to its favorable pharmacokinetic profile and minimal impact on bladder voiding function. This is supported by a study published in 2018, which compared the efficacy and tolerability of mirabegron with placebo and tolterodine in patients with overactive bladder, and found that mirabegron had a better safety profile, especially in patients with renal impairment [@96@].

Key Considerations for Mirabegron Use in Renal Impairment

• For patients with mild to moderate renal impairment, no dose adjustment is typically needed, with a standard dose of 25-50 mg once daily.
• In severe renal impairment (eGFR <30 mL/min), the maximum dose should be limited to 25 mg daily, as recommended by the European Medicines Agency [@107@].
• Mirabegron is preferred over antimuscarinic medications, such as oxybutynin, solifenacin, or tolterodine, because these drugs and their metabolites can accumulate in patients with kidney disease, potentially leading to increased side effects such as dry mouth, constipation, and cognitive impairment [@113@].

Comparison with Other Medications

• A systematic review and meta-analysis published in 2018 found that mirabegron had a better safety profile compared to tolterodine, with fewer adverse events and less risk of urinary retention [@96@].
• Another study published in 2020 found that mirabegron add-on therapy to tamsulosin was effective and safe in men with overactive bladder symptoms and lower urinary tract symptoms, with no significant increase in the risk of urinary retention [@127@].

Monitoring and Precautions

• Before starting treatment with mirabegron, baseline blood pressure should be assessed, as mirabegron can cause a slight increase in blood pressure in some patients [@98@].
• Patients with renal impairment should be monitored regularly for signs of urinary retention, and their dose adjusted accordingly.

From the FDA Drug Label

The pharmacokinetics of Trospium Chloride Extended-Release Capsules in patients with severe renal impairment has not been evaluated. In a study of an immediate-release formulation of trospium chloride, 4.2-fold and 1. 8-fold increases in mean AUC (0-∞) and C max, respectively, were detected in patients with severe renal impairment (creatinine clearance less than 30 mL/minute), compared with healthy subjects, along with the appearance of an additional elimination phase with a long half-life (~33 hours vs. 18 hours) Use of Trospium Chloride Extended-Release Capsules is not recommended in patients with severe renal impairment [see Dosage and Administration (2)].

The safest medication for overactive bladder in patients with impaired renal function cannot be determined from the provided information, as the pharmacokinetics of Trospium Chloride Extended-Release Capsules in patients with severe renal impairment has not been evaluated, and its use is not recommended in such patients 1. Key considerations for patients with renal impairment include:

• Avoiding the use of Trospium Chloride Extended-Release Capsules in patients with severe renal impairment
• Lack of data on the pharmacokinetics of Trospium Chloride Extended-Release Capsules in patients with creatinine clearance ranging from 30 to 80 mL/min
• Potential increased risk of adverse effects due to increased exposure to the drug in patients with renal impairment.

From the Research

Safest Medication for Overactive Bladder in Patients with Renal Impairment

• The safest medication to use for overactive bladder in patients with impaired renal function is trospium chloride 2, 3, 4, 5, 6.
• Trospium chloride is a quaternary amine with anticholinergic properties, which is used for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.
• The pharmacokinetics of trospium chloride have been investigated in healthy volunteers, in patients with renal and hepatic impairment, and in those with symptoms of overactive bladder 2.
• Trospium chloride is minimally metabolized and is excreted mainly unchanged in the urine as the active parent compound, providing local activity to achieve early onset of clinical effect and prolonged efficacy 4.
• In patients with severe renal impairment, dose reduction is needed, as elimination of the drug is slowed in these patients 2.

Key Considerations

• Trospium chloride is generally well tolerated, and significantly more so than immediate-release oxybutynin 3.
• The most frequent adverse events associated with trospium chloride are dry mouth, dyspepsia, constipation, abdominal pain, and nausea 3, 5, 6.
• Central nervous system adverse events are rare, as trospium chloride does not cross the blood-brain barrier in significant amounts 3, 5, 6.
• Trospium chloride can be administered once daily, which may improve patient compliance and convenience 5, 6.

Efficacy and Safety

• Trospium chloride has been shown to be effective in reducing the number of micturitions per 24 hours, reducing the number of urge incontinence episodes per week, and increasing the volume of urine voided per micturition 3, 4, 5, 6.
• The efficacy and safety of trospium chloride have been demonstrated in several clinical trials, including multicenter, parallel, randomized, double-blind, placebo-controlled studies 3, 4, 5, 6.