Alternative Choices to Oxybutynin: When, Why, and How Much?

Overactive bladder is one of the most common disease states managed in the outpatient setting, typically affecting the elderly.

Oxybutynin is the typical drug of choice for providers and for good reason, because it is fairly inexpensive and effective.

Oxybutynin is the 108th most prescribed medication in the world, and 1 of just 2 medications used for overactive bladder to be included in the top 300 most prescribed ones.¹

In some cases, however, the patient may not adequately respond to the treatment, or the anticholinergic adverse effects may be unacceptable to the patient. A study, for example, found an alarmingly high discontinuation rate for oxybutynin within the first 30 days.²

As pharmacists, what recommendations can we make to this patient?

For many patients, medication adherence is an issue. A wide array of variables may contribute to the problem, including adverse effects, cost, and general pill burden. Common adverse effects of the medication class include confusion, constipation, dizziness, drowsiness, and dry eye and mouth.

A study found that patients discontinued their overactive bladder medications at a rate of 43% to 83% within the first 30 days.² Another study found that adherence improved when patients used extended-release (ER) tolterodine instead of immediate-release oxybutynin. In addition to a 16.5% increase in continuation over the first month, tolterodine was the more economical choice overall, with commercially insured patients spending less on tolterodine ER than oxybutynin.³ Because tolterodine ER demonstrates improved efficacy in terms of continuation compared with oxybutynin while costing less overall, pharmacists should consider tolterodine ER when making recommendations for overactive bladder.

Other medications prescribed for overactive bladder include darifenacin (Enablex), fesoterodine (Toviaz), mirabegron (Myrbetriq), solifenacin (Vesicare), tolterodine (Detrol), and trospium (Sanctura).

Any of these medications can be used as first-line pharmacological therapy, following behavioral modification and bladder control exercises, according to the American Urological Association Clinical Guideline for Overactive Bladder published in 2012 and amended in 2014,

The exception is mirabegron, which was only approved in 2012.⁴

At cash price, many of these medications exceed $10 per tablet. Insurance plans will often cover the majority of these medication costs, but patients without insurance coverage, in the coverage gap, or who have not yet met their deductible, must spend heavily in order to treat overactive bladders.

Because of the availability of generics, tolterodine and trospium are significantly less expensive, at about $2 per pill, before any type of coverage is applied. Based on their absences in the top 300,¹ trospium and tolterodine are infrequently prescribed, but pharmacists must recognize their place in therapy.

As an anticholinergic, trospium has the adverse effects of dry mouth, constipation, or blurred vision. However, it does not readily cross the blood brain barrier due to its polar quaternary amine structure.⁵

The aforementioned anticholinergic medications, on the other hand, possess a tertiary amine structure, which is highly lipophilic. When anticholinergic medications cross the blood brain barrier, CNS effects such as drowsiness or dizziness may occur, which is especially of concern in the elderly population.

In terms of efficacy, a trial comparing trospium and oxybutynin in patients with detrusor hyperreflexia found that both medications were substantially equal in regards to urinary incontinence, with trospium having certain advantages in terms of side effect profile.⁶ Due to its similar efficacy, side effect profile, and comparable cost, trospium should be considered in recommendations for urinary incontinence.

As health care professionals, pharmacists should always make recommendations with the patients’ best interests in mind. Often, that means recommending the most economical, yet effective, medication to the patient and prescriber. Though trospium and tolterodine may be infrequently prescribed and some pharmacists and providers may not be familiar with them, studies suggest that these medications are just as effective as the first choice often used—with similar or even less cost.

This article was co-written with Justin Luu, PharmD Candidate 2019, and Andrew Yabusaki, PharmD.

References

• Kane SP. The Top 300 of 2018, ClinCalc DrugStats Database, Version 18.0. ClinCalc: http://clincalc.com/DrugStats/Top300Drugs.aspx. Updated February 3, 2018. Accessed January 31, 2019.
• Dhaliwal P, Wagg A. Current neurology and neuroscience reports. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902140/. Published June 3, 2016. Accessed January 31, 2019.
• Varadharajan S, Jumadilova Z, Girase P, Ollendorf DA. Economic impact of extended-release tolterodine versus immediate- and extended-release oxybutynin among commercially insured persons with overactive bladder. Am J Manag Care. https://www.ncbi.nlm.nih.gov/pubmed/16161387. Published July 2005. Accessed January 31, 2019.
• Armstrong C. AUA Releases Guideline on Diagnosis and Treatment of Overactive Bladder. American Family Physician. https://www.aafp.org/afp/2013/0601/p800.html. Published June 1, 2013. Accessed January 31, 2019.
• Chancellor MB, Staskin DR, Kay GG, Sandage BW, Oefelein MG, Tsao JW. Blood-Brain Barrier Permeation and Efflux Exclusion of Anticholinergics Used in the Treatment of Overactive Bladder. SpringerLink. https://link.springer.com/article/10.2165/11597530-000000000-00000. Published August 31, 2012. Accessed January 31, 2019.
• Madersbacher H, Stöhrer M, Richter R, Burgdörfer H, Hachen HJ, Mürtz G. Trospium chloride versus oxybutynin: a randomized, double-blind, multicentre trial in the treatment of detrusor hyper-reflexia. Current neurology and neuroscience reports. https://www.ncbi.nlm.nih.gov/pubmed/7788255. Published April 1995. Accessed January 31, 2019.