Oxybutynin extended-release

Oxybutynin extended-release is better tolerated than oxybutynin IR and is as effective in reducing the number of UI episodes, restoring continence, decreasing the number of micturitions per day, and increasing urine volume voided per micturition. 

The maximum benefit of oxybutynin extended-release is not realized for up to 4 weeks after starting therapy or dose escalation. 

Emerging evidence suggests that the high incidence of adverse effects, especially dry mouth, of oxybutynin IR, and to a lesser extent oxybutynin extended-release (XL) and oxybutynin transder-mal system (TDS), may be largely due to the active metabolite, A-desethyloxybutynin (DEO). This metabofite is generated by extensive first-pass metabolism in the liver and upper gastrointestinal tract. ° Since many of the adverse effects seen with oxybutynin are felt to be related to the primary hepatic metabolite DEO, the lower DEO plasma concentrations seen with oxybutynin TDS and oxybutynin XL (which are due to reduced first-pass metabolism) compared to those of oxybutynin IR may explain their lesser propensity to cause dry mouth and other anticholinergic adverse effects. 

Because of problems noted with oxybutynin IR, oxybutynin extended-release (XL) was developed. It can be considered an alternative for the first-line therapy of UUI (see Table 83-5). 

Muscle relaxants and antispasmodics methocarbamol (Robaxin), carisoprodol (Soma), chlorzoxazone (Paraflex), metaxalone (Skelaxin), cyclobenzaprine (Flexeril), and oxybutynin (Ditropan) Do not consider the extended-release Ditropan XL Most muscle relaxants and antispasmodic drugs are poorly tolerated by elderly patients, because these cause anticholinergic adverse effects, sedation, and weakness. Additionally, their effectiveness at doses tolerated by elderly patients is questionable. High... 

Appel, R.A., Sand, P., Dmochowski, R., et al., (2000). Prospective randomized controlled trial of extended-release oxybutynin chloride and tolterodine tartrate in the tteatment of overactive bladder results of the Object Study. Mayo Clin Proc 78 358-363. 

Goldenberg, M.M. 1999. An extended-release formulation of oxybutynin chloride for the treatment of overactive urinary bladder. Clin Ther 21 634. 

In neurodegenerative disorders, patients often experience urinary urgency, which is thought to be caused by spasm of the urinary sphincter or detrusor muscle. Oxybutynin (Ditropan) and tolterodine (Detrol) are effective for urinary urgency. For ALS patients and some PD patients, swallowing tablets may be difficult due to dysphagia. Extended release oxybutynin allows for infrequent daily dosing and oxytrol patches avoids the oral route of administration. 

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. 

Michel MC. A benefit-risk assessment of extended-release oxybutynin. Drug Saf 2002 25(12) 867-76. 

Ditropan XL (oxybutynin chloride) once-a-day extended-release tablet for the treatment of overactive bladder characterized by symptoms of urinary incontinence, urgency, and frequency. 

ALZA Corporation. Ditropan XL (oxybutynin chloride) extended-release tablets. Data on file. Palo Alto, CA, 1999. 

Appell RA, Chancellor MB, Zobrist RH, et al. Pharmacokinetics, metabolism, and saliva output during transdermal and extended-release oxybutynin administration in healthy subjects. Mayo Clin Proc 2003 78 696-702. 

Diokno AC, Appell RA, Sand PK, et al. Prospective, randomized, doubleblind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder Results of the OPERA trial. Mayo Clin Proc 2003 78 687-695. 

Sussman D, Garely A. Treatment of overactive bladder with once-daily extended-release tolterodine or oxybutynin The Antimuscarinic Clinical Effectiveness Trial (ACET). Curr Med Res Opin 2002 18 177-184. 

Dmochowski R, Sathyan G, Ye C, et al. The pH effect of drug release from extended-release formulations of oxybutynin and tolterodine. Proceedings of the Second International Consultation on Incontinence. Paris, France, July 2001. 

Ditropan tablets 5 mg, syrup 5 mg/5 mL, Ditropan XL tablets, extended-release 5 mg, tablets, extended-release 10 mg, tablets, extended-release 15 mg, Oxytrol transdermal system 36 mg of oxybutynin delivering 3.9 mg or oxybutynin/day)... 

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. 

A placebo-controlled, crossover study in 21 healthy subjeets, found that when extended-release oxybutynin 10 mg DitropanXL) was given at the same time as Maalox 20 mL (aluminium/magnesium hydroxide and simethicone) there was no change in the pharmaeokineties of oxybutynin... 

In a placebo-controlled, crossover study in 39 healthy subjects, pre-treatment with omeprazole 20 mg daily for 4 days did not alter the pharmacokinetics of extended-release oxybutynin 10 mg [Ditropan XL], The metabolites of oxybutynin were similarly unaffected. Pretreatment with omeprazole increased the maximum plasma level a single 4-mg dose of extended release tolterodine [Detrol LA by 38%, but did not change any other pharmacokinetic parameter (time to maximum level, elimination half-life, AUC). ... 

Sathyan G, Dmochowski RR, Appell RA, Guo C, Gupta SK. Effect of antacid on the pharmacokinetics of extended-release formulations of tolterodine and oxybutynin. Clin Pharmacoki-net 200A) 43, 1059-68. 

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