What medications for overactive bladder (OAB) have a lower risk of anticholinergic side effects?

From the Guidelines

Medications for overactive bladder with lower anticholinergic side effect risks include mirabegron (Myrbetriq), vibegron (Gemtesa), and beta-3 adrenergic agonists. These medications work differently than traditional anticholinergic drugs by targeting beta-3 receptors in the bladder to relax the detrusor muscle and increase bladder capacity. Mirabegron is typically started at 25mg once daily and can be increased to 50mg if needed, while vibegron is dosed at 75mg once daily 1.

Key Considerations

• These medications avoid common anticholinergic side effects like dry mouth, constipation, blurred vision, and cognitive issues, making them particularly suitable for elderly patients or those with cognitive concerns.
• They may cause different side effects including hypertension, headache, and nasopharyngitis.
• Patients with uncontrolled hypertension should use these medications cautiously.
• For patients who need anticholinergic medications but want fewer side effects, newer generation options like solifenacin (VESIcare), darifenacin (Enablex), and trospium chloride (Sanctura) have better selectivity for bladder receptors and reduced ability to cross the blood-brain barrier, resulting in fewer cognitive side effects 1.

Additional Guidance

• Clinicians should offer antimuscarinic medications or beta-3 agonists to patients with OAB to improve urinary urgency, frequency, and/or urgency urinary incontinence 1.
• Combination therapy with an alpha blocker and an antimuscarinic medication or beta-3 agonist may be considered for patients with BPH and OAB 1.

From the FDA Drug Label

Mirabegron was also evaluated for safety in 1,632 patients who received mirabegron 50 mg once daily (n=812 patients) or mirabegron 100 mg (n=820 patients) in a 1-year, randomized, fixed- dose, double-blind, active-controlled, safety study in patients with OAB (Study 4). The most frequent adverse events (0. 2%) leading to discontinuation in Studies 1,2 and 3 for the 25 mg or 50 mg dose were nausea, headache, hypertension, diarrhea, constipation, dizziness, and tachycardia. Table 3 the lists adverse reactions, derived from all adverse events that were reported in Studies 1,2 and 3 at an incidence greater than placebo and in 1% or more of patients treated with mirabegron 25 mg or 50 mg once daily for up to 12 weeks The most commonly reported adverse reactions (greater than 2% of mirabegron patients and greater than placebo) were hypertension, nasopharyngitis, urinary tract infection, and headache

Medications for Overactive Bladder with Lower Risk of Anticholinergic Side Effects:

• Mirabegron is a beta-3 adrenergic agonist that has been shown to have a lower risk of anticholinergic side effects compared to traditional anticholinergic medications for OAB.
• The adverse reaction profile of mirabegron does not typically include anticholinergic side effects such as dry mouth, constipation, and blurred vision, which are commonly seen with anticholinergic medications.
• Key points about mirabegron include:
  • It is a moderate CYP2D6 inhibitor, which may increase the systemic exposure to CYP2D6 substrates.
  • It has been evaluated for safety in several clinical trials, including a 1-year study with over 1,600 patients.
  • The most commonly reported adverse reactions include hypertension, urinary tract infection, headache, and nasopharyngitis.
  • Mirabegron should be administered with caution to patients with clinically significant bladder outlet obstruction or those taking muscarinic antagonist medications for OAB 2.

From the Research

Overactive Bladder Medications with Lower Risk of Anticholinergic Side Effects

• Mirabegron is a beta-3 adrenoceptor agonist that does not add to the anticholinergic load or exert central nervous system side effects, making it a suitable option for patients with overactive bladder (OAB) who are at risk of anticholinergic side effects 3.
• Trospium chloride is a quaternary amine anticholinergic that is less likely to cross the blood-brain barrier and exert central side effects, potentially reducing the risk of anticholinergic side effects 3.
• Combination therapy of mirabegron and solifenacin has been shown to be effective in treating OAB, with an acceptable safety profile, although it may increase the risk of anticholinergic side effects compared to mirabegron monotherapy 4, 5.

Comparison of Medications

• Mirabegron has been compared to solifenacin in several studies, with results showing that mirabegron has a lower incidence of dry mouth, a common anticholinergic side effect 4, 6.
• Vibegron is another beta-3 adrenoceptor agonist that, like mirabegron, does not have anticholinergic properties and is typically well tolerated 7.

Treatment Considerations

• Patients who are dissatisfied with previous antimuscarinic treatment due to lack of efficacy may benefit from mirabegron or combination therapy with solifenacin 6.
• Step therapy and prior authorization policies may limit patient access to newer OAB medications like mirabegron and vibegron, potentially delaying treatment and increasing the risk of adverse events 7.