There are a number of medications that can be used for urge urinary incontinence, also known as “overactive bladder syndrome”. However, it can be somewhat difficult to parse out the differences between the medications and decide which might be the right choice for a patient. Today, we’ll be taking a closer look at the urinary anticholinergics used to treat urinary incontinence. We’ve provided a Urinary Anticholinergics Comparison Table at the end of this post in case you are studying for a board exam!

Overactive bladder syndrome is caused by overactivity of the detrusor muscle leading to increased urinary urgency, increased daytime frequency, and nocturia. This can have a significant impact on a patient’s quality of life, which is why it is so important to find a medication that will work well for them. Anticholinergics are the main class of medications used for this type of bladder incontinence, with beta-3 agonists (mirabegron) often being used as second line.

Anticholinergics are all limited primarily by their tolerability as none are fully specific to the bladder. However, some are more specific than others. Oxybutynin is the least specific of the urinary anticholinergics, with the most propensity for side effects. If you are looking for more information on those side effects, check out this podcast episode. This can be improved with the extended-release formulation, however, side effects are still fairly common. Despite these drawbacks, oxybutynin does tend to be the most affordable option and can therefore be a good place to start. It is also available in the most formulations for patients who might not be able to tolerate swallowing easily or who need a liquid formulation.

On the other end of things, solifenacin and darifenacin are the most specific for muscarinic receptors in the bladder, with cognitive side effects being much less likely compared to other agents. We’ve noted this selectivity in the urinary anticholinergics comparison table below. Of the two, solifenacin has been found to be more tolerable compared to both darifenacin and other agents. Other agents, including tolterodine, fesoterodine (a prodrug for tolterodine), and trospium land somewhere in the middle with tolerability. Trospium and darifenacin would likely be on the lower end of contributing to CNS adverse effects like confusion because of their lower ability to penetrate the CNS. 

Another important consideration is drug interactions. Oxybutynin concentrations can be significantly increased when used concurrently with CYP3A4 inhibitors. Fesoterodine has similar issues with CYP3A4 inhibitors (though no dosing adjustments are recommended for CYP3A4 inducers). Tolterodine can be affected by both CYP3A4 inhibitors and CYP2D6 inhibitors. Darifenacin and solifenacin are also affected by potent CYP3A4 inhibitors. Trospium is the best option for patients taking CYP inhibitors concurrently, as there are no clinically relevant metabolic drug interactions, making it an optimal choice when drug interactions are a concern. If you are looking for more on drug interactions, my book on Drug Interactions in Primary Care will be very helpful for you.

At the end of the day, it’s reasonable to start with any of the urinary anticholinergics. However, it should be mentioned that it is important to encourage lifestyle modifications first and in conjunction with medications. Fluid restrictions (as clinically appropriate), scheduled voiding, and pelvic floor exercises can all play a role in managing symptoms.

Urinary Anticholinergics Comparison Table

Drug Name	Formulations	Dosing	Side Effects	Benefits
Oxybutynin	Oral Tablet (IR and ER), Oral Syrup, Transdermal Gel, Transdermal Patch	IR: 5 mg BID to TIDER: 5-10 mg dailyPatch: One patch applied twice weekly.	Constipation, diarrhea, dry mouth and eyes, dizziness, headache, confusion, agitation	Available in multiple formulations. Immediate-release tablets are the least expensive option.
Fesoterodine (Toviaz)	Oral ER Tablet	4-8 mg once daily	Constipation, diarrhea, dry mouth and eyes, headache	Less cognitive effects are expected due to lower lipophilicity. Relatively selective for M2 and M3 receptors.
Tolterodine	Oral IR Tablet, Oral ER Capsule	IR: 1-2 mg BIDER: 2-4 mg once daily	Constipation, dry mouth, headache	Relatively selective for M2 and M3 receptors.
Darifenacin	Oral ER Tablet	7.5-15 mg once daily	Constipation, dry mouth, headache	More selective for M3 receptor compared to other agents.
Solifenacin	Oral IR Tablet, Oral Suspension	5-10 mg once daily	Constipation, dry mouth, QT prolongation, confusion	More selective for M3 receptor compared to other agents.
Trospium	Oral IR Tablet, Oral ER Capsule	IR: 20 mg BIDER: 60 mg once daily	Constipation, dry mouth, headache; Syncope, SJS, delirium	Less CNS penetration leads to fewer CNS side effects. Fairly selective for M2 and M3 receptors. Fewer drug interactions due to renal clearance.

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This article was written by Jordyn Erkel, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP.

References

Darifenacin Hydrobromide. IBM Micromedex ® Drug Summary [online]. Updated periodically. IBM Watson Health, Greenwood Village, Colorado, USA. Accessed at: https://www-micromedexsolutions-com.ezp1.lib.umn.edu/micromedex2/librarian/PFDefaultActionId/evidencexpert.DoIntegratedSearch?navitem=headerLogout#. Accessed: 12/1/22.

Fesoterodine Fumarate. IBM Micromedex ® Drug Summary [online]. Updated periodically. IBM Watson Health, Greenwood Village, Colorado, USA. Accessed at: https://www-micromedexsolutions-com.ezp1.lib.umn.edu/micromedex2/librarian/PFDefaultActionId/evidencexpert.DoIntegratedSearch?navitem=headerLogout#. Accessed: 12/1/22.

Oxybutynin Chloride. IBM Micromedex ® Drug Summary [online]. Updated periodically. IBM Watson Health, Greenwood Village, Colorado, USA. Accessed at: https://www-micromedexsolutions-com.ezp1.lib.umn.edu/micromedex2/librarian/CS/D5887B/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSYNC/EB359A/ND_PG/evidencexpert/ND_B/evidencexpert/ND_AppProduct/evidencexpert/ND_T/evidencexpert/PFActionId/evidencexpert.DoIntegratedSearch?SearchTerm=Oxybutynin+Chloride&fromInterSaltBase=true&UserMdxSearchTerm=%24userMdxSearchTerm&false=null&=null#. Accessed: 12/1/22.

Peyronnet, B., Mironska, E., Chapple, C., Cardozo, L., Oelke, M., Dmochowski, R., … & Cornu, J. N. (2019). A comprehensive review of overactive bladder pathophysiology: on the way to tailored treatment. European urology, 75(6), 988-1000.

Solifenacin Succinate. IBM Micromedex ® Drug Summary [online]. Updated periodically. IBM Watson Health, Greenwood Village, Colorado, USA. Accessed at: https://www-micromedexsolutions-com.ezp2.lib.umn.edu/micromedex2/librarian/PFDefaultActionId/evidencexpert.DoIntegratedSearch?navitem=topHome&isToolPage=true#. Accessed: 12/1/22

Tolterodine Tartrate. IBM Micromedex ® Drug Summary [online]. Updated periodically. IBM Watson Health, Greenwood Village, Colorado, USA. Accessed at: https://www-micromedexsolutions-com.ezp1.lib.umn.edu/micromedex2/librarian/PFDefaultActionId/evidencexpert.DoIntegratedSearch?navitem=headerLogout#. Accessed: 12/1/22

Trospium Chloride. IBM Micromedex ® Drug Summary [online]. Updated periodically. IBM Watson Health, Greenwood Village, Colorado, USA. Accessed at: https://www-micromedexsolutions-com.ezp2.lib.umn.edu/micromedex2/librarian/PFDefaultActionId/evidencexpert.DoIntegratedSearch?navitem=headerLogout#. Accessed: 12/1/22.