Oxybutynin immediate-release

Oxybutynin immediate-release (IR) has been the drug of first choice for UUI and the gold standard against which other drugs are compared. Financial considerations favor generic oxybutynin IR. 

Anderson, R.U., et al. 1999. Once daily controlled versus immediate release oxybutynin chloride for urge urinary incontinence. J Urol 161 1809. 

Gupta, S.K., and G. Sathyan. 1999. Phamacokinetics of an oral once-a-day controlled-release oxybutynin formulation compared with immediate-release oxybutynin. J Clin Pharmacol 39 289. 

There have been several comparisons of tolterodine and oxybutynin. All agree that oxybutynin, in its standard formulation at a dose of 5 mg bd, while of similar efficacy, produces significantly more adverse effects (5). The incidence of dry mouth reached 60%, and over 75% in patients taking the highest dose of 5 mg tds. Direct measurements of saliva production confirmed that oxybutynin 5 mg/day reduces saliva output significantly more than tolterodine 2 mg or a modified-release formulation of oxybutynin 10 mg, all given as single doses (6). In over 300 patients modified-release oxybutynin once-daily produced less dry mouth (28 versus 33%) than immediate-release tolterodine 2 mg bd (7). 

An extended-release formulation of oxybutynin has been compared with an immediate-release formulation it had similar efficacy but fewer adverse effects (8). The overall conclusion of an unsystematic review was that, as expected, dry mouth is very common it occurred in about two-thirds of those taking the extended-release formulation (up to a dose of 30 mg/day) and in nearly 90% of those who took the immediate-release formulation. In about 25% of those who took the extended-release formulation the dry mouth was classified as severe, compared with nearly 50% of those who took the immediate-release formulation. Other adverse effects were very uncommon and significant toxicity was not reported. In total the two comparative trials involved 331 patients, and an open study of 256 patients was also discussed. 

Davila GW, Daugherty CA, Sanders SW. A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence. J Urol 2001 166 140-145. 

Overactive urinary bkuMer disease can be successfully treated with muscarinic antagonists, primarily tolterodine and trospium chloride, which lower intravesicular pressure, increase capacity, and reduce the frequency of contractions by antagonizing parasympathetic control of the bladder. Oxybu-tynin is used as a transdermal system (oxytrol) that delivers 3.9 mg/day and is associated with a lower incidence of side effects than the oral immediate- or extended-release formulations. Tolterodine is metabolized by CYP2D6 to a 5-hydroxymethyl metabolite since this metabolite possesses similar activity to the parent drug, variations in CYP2D6 levels do not affect the duration of drug action. Trospium is as effective as oxybutynin, with better tolerability. Solifenacin is newly approved for overactive bladder with a favorable efficacy side effect ratio. Stress urinary incontinence has been treated with some success with duloxetine (YENTREVE), which acts centrally to influence 5-HT and NE levels. 

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