Neurourology and Urodynamics 36 : 822 – 823 ( 2017 ) LETTER TO THE EDITOR We Should Not Use Oxybutynin Chloride in OAB

Oxybutynin chloride is a first-generation anticholinergic drug. At the bladder level, it acts on both urothelium and detrusor muscle providing a combination of mixed anticholinergic, spasmolytic, and local anesthetic effects. Since its first urological use in 1972, it has been extensively prescribed worldwide to treat overactive bladder syndrome (OAB). Its efficacy in relieving lower urinary tract symptoms and improving urodynamic parameters associated with neurogenic and non-neurogenic bladder disorders has however been counterbalanced by a low tolerability profile. Indeed, a number of adverse events, inherent to all anticholinergic drugs, including dry mouth, dry eyes, dizziness, constipation as well as confusion have been repeatedly reported and responsible of frequent treatment withdrawals. In an attempt to improve tolerability, a number of oxybutynin formulation have been successively developed, including oral extended-release (ER) tablet, transdermal gel, transdermal patch, vaginal ring, and rectal suppository. In parallel, several novel oral anticholinergic drugs targeting more specifically the lower urinary tract muscarinic receptors (M2-M3) have been developed during the last two decades. Among them, tolterodine tartrate, solifenacin succinate, fesoterodine fumarate, and trospium chroride have been repeatedly compared head-to-head with oral oxybutynin chloride in randomized controlled trials. Logically, a number of systematic reviewsandmeta-analyses focusingon the efficacyand the safety of these different anticholinergic drugs have been recently published, providing a high level of evidence regarding these important issues. They all reported a higher or equal efficacy of these novel drugs, when compared with oxybutynin chloride, in terms of perception of improvement, bladder diary parameters andurodynamicoutcomes, inbothneurologicandnon-neurologic populations. In addition, regarding safety, they all concluded that patients taking oxybutynin were more likely to withdraw from the studies because of related adverse effects, mainly dry mouth. In particular, Veenboer and Rudd Bosch demonstrated in a 14-studies systematic review with 190,279 uniquepatients focusing on the long-term adherence to antimuscarinic therapy, that the use of oxybutynin was an important risk factor for discontinuation. Furthermore, the use of oxybutynin chloride in both immediate release (IR) and ER formulation resulted in negative effects on cognitive function, electroencephalogram findings, and memory loss, especially within the elderly population, while most of other anticholinergic agents did not. Despite these poor results, the low cost associated with oral oxybutynin chloride is one of the frequent arguments provided by physicians and healthcare systems to continue its prescription in a daily practice. However, some recent cost-effectiveness analyses clearly contradict this statement. In 2010, Herschorn et al. estimated, using a Markov model, the incremental cost per quality-adjusted life-year (QALY) of solifenacin and oxybutynin IR over a 1-year time horizon, based on efficacy and discontinuation data from the CanadianVECTOR study. The authors concludedthat solifenacin5mg/daywasacost-effective treatment compared with oxybutynin IR 15mg/day. Similarly, in 2012, Nilsson et al. analyzed the cost-effectiveness of newer anticholinergic treatments compared to oral oxybutynin IR for patientswith urgency urinary incontinence, using data from the Swedish Program Drug Register. Focusing on the incremental cost per QALY, they concluded that the newer anticholinergic medications were more likely to be cost-effective in comparison withoxybutynin IR.Although,weagree that these results should be extended with cautions to other countries – because health care systemsanddrugprices vary greatly over the globe –wecan reasonably point out that the newer anticholinergic drugs are not associated with higher costs, in at least some systems. In addition, it is important to note that, since these publications, a number of generic versions have been successively introduced on the market (tolterodine fumarate, solifenacin succinate, and trospium chloride) making the cost-effectiveness of oral oxybutynin argument no longer valid to explain its advantage in OAB treatment. Because several newer anticholinergic medications have been repeatedly reported to provide similar efficacy and better tolerability than oral oxybutynin chloride, we recommend that these newer drugs be considered as first-line options for overactive bladder treatment.