Enablex is used to treat symptoms of overactive bladder, such as frequent or urgent urination, and incontinence urine leakage. You should not take Enablex if you are have untreated or uncontrolled narrow-angle glaucoma, a stomach disorder causing delayed emptying, or if you have trouble emptying your bladder. Avoid becoming overheated or dehydrated during exercise and in hot weather. Enablex can decrease perspiration and you may be more prone to heat stroke. Stop using this medication and call your doctor if you have serious side effects such as hot and dry skin, extreme thirst, severe stomach pain or constipation, pain or burning when you urinate, or if you stop urinating.
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Free to read. Overactive bladder OAB is a medical syndrome defined by symptoms of urgency, with or without urge urinary incontinence any involuntary loss of urine , usually with frequency and nocturia. Although anticholinergic agents have been the first-line treatment for OAB for many years, the efficacious pharmacologic management of this condition has been compromised by concerns regarding tolerability. Flavoxate was the first anticholinergic and antispasmodic agent approved by the Food and Drug Administration FDA to treat symptoms of OAB but is not routinely used today since newer agents are more effective.
The more recent drugs, oxybutynin and tolterodine, have appeared to be equally efficacious in treating the symptoms of OAB in clinical trials; however, tolterodine has proven to be better tolerated with fewer adverse effects. In , the FDA approved the three newest agents for the class: darifenacin, solifenacin, and trospium.
Compared with oxybutynin and tolterodine, these agents have a more favorable side effect profile, which can enhance tolerability and patient compliance. Side effects are reduced in part because of the drugs' greater tissue selectivity for inhibiting the bladder muscle contraction over other anticholinergic receptors in the body. In recent clinical trials, darifenacin, solifenacin, and trospium have shown superiority to placebo and efficacy comparable to that of oxybutynin and tolterodine.
Symptoms of overactive bladder OAB , also termed urge urinary incontinence, occur because the detrusor muscle is overactive and contracts inappropriately during the filling phase.
The symptoms of OAB include urinary frequency, urgency, and urge incontinence. Anticholinergic and antispasmodic agents act by antagonizing cholinergic muscarinic receptors, through which different parasympathetic nerve impulses evoke detrusor contraction.
Then, in , oxybutynin became the mainstay of treatment for OAB, as it was shown to be more efficacious than flavoxate. The next agent introduced in the class was tolterodine in Lastly, in , three newer agents—darifenacin, solifenacin, and trospium—challenged older compounds by having a less frequent dosing schedule and a more favorable side effect profile.
Darifenacin, oxybutynin, solifenacin, tolterodine, and trospium are indicated for the treatment of OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency 3 — Additionally, oxybutynin is indicated in the treatment of pediatric patients aged 6 years and older with symptoms of detrusor overactivity associated with neurological conditions i. These agents have also been used to treat voiding disorders in patients with spinal trauma or other neurological diseases, although they are not approved by the FDA for that indication.
Of the five known muscarinic subtypes M 1 through M 5 , M 3 appears to be the most clinically relevant in the human bladder. M 3 receptors are also involved in contraction of the gastrointestinal smooth muscle, saliva production, and iris sphincter function. Inhibition of the muscarinic receptors in the urinary bladder results in decreased urinary bladder contraction, increased residual urine volume, and decreased detrusor muscle pressure. Oxybutynin, tolterodine, darifenacin, solifenacin, and trospium antagonize the effects of acetylcholine at muscarinic receptors on the detrusor muscle and are known as antimuscarinic agents.
These agents potently and selectively bind to the M 3 receptor subtype more than other muscarinic receptor subtypes, with the exception of tolterodine, which has demonstrated no specificity for any subtype.
Oxybutynin is a racemic mixture of R - and S -isomers, and its antimuscarinic actions are predominantly a result of the R -isomer.
All of the antimuscarinic agents exhibit functional selectivity for urinary bladder over secretory glands e. The newer agents i. Oxybutynin also exerts a direct spasmolytic papaverine-like action on smooth muscles to allow an increased urinary bladder capacity. Flavoxate is a spasmolytic agent with no antimuscarinic activity. Flavoxate and oxybutynin have little or no effect on the smooth muscle of blood vessels, unlike papaverine. In animals in vitro, flavoxate's and oxybutynin's spasmolytic effects have been demonstrated in the small intestine, gallbladder, uterus, seminal vesicle, and colon in addition to the detrusor muscle.
Flavoxate and oxybutynin have also shown moderate antihistaminic, some local anesthetic, some mild analgesic, and low mydriatic and antisialagogue activity in animals. Trospium, a quaternary ammonium antimuscarinic, is hydrophilic and theoretically should not cross the blood-brain barrier like lipophilic anticholinergic agents e. Pharmacokinetics of agents for overactive bladder. From references 3 and 4. The efficacy and safety of flavoxate in the treatment of OAB have not been evaluated in recent clinical trials.
Two randomized, double-blind clinical studies have been conducted to compare the efficacy and safety of oxybutynin extended release ER and oxybutynin immediate release IR 5. When decreases in the number of episodes of urge incontinence were compared, one study indicated that the formulations were comparable; although comparable efficacy was not demonstrated according to predetermined criteria in the second study, there was no substantial difference between the formulations.
The efficacy of oxybutynin ER tablets was maintained after 12 weeks of therapy in one study The safety and efficacy of once-daily controlled and IR oxybutynin was evaluated in a multicenter, randomized, double-blind study by Anderson et al One hundred five patients with urge incontinence or mixed incontinence with a clinically significant urge component received dose titration of oxybutynin ER 5, 10, 15, 20, 25, or 30 mg daily or oxybutynin IR 5 mg one to four times daily.
The number of weekly urge incontinence episodes decreased from Total weekly incontinence episodes decreased from Single daily doses of tolterodine ER appear to be slightly more effective in relieving certain urinary symptoms e. In a week comparative, randomized, double-blind, placebo-controlled study in patients with OAB by Van Kerrebroeck et al 15 , patients were randomized to treatment with tolterodine ER 4 mg once daily, tolterodine IR 2 mg twice daily, or placebo.
Median decreases in the number of micturitions per 24 hours were 1. In one multicenter, randomized, double-blind, placebo-controlled study of 12 weeks' duration by Abrams et al, the efficacy of oxybutynin 5 mg three times daily and tolterodine 2 mg twice daily appeared to be similar in reducing the symptoms of OAB Tolterodine and oxybutynin were equivalent in decreasing urinary frequency: the number of micturitions per 24 hours decreased by Compared with placebo, however, only tolterodine produced a significantly greater decrease in urinary frequency, and only oxybutynin produced a significantly greater decrease in incontinence episodes.
Dry mouth was the most commonly reported adverse event but occurred with significantly greater frequency and severity in the oxybutynin group than in the tolterodine group. Treatment withdrawals and dose reductions also occurred significantly more often in the oxybutynin group than in the tolterodine group. The authors acknowledged that the 5-mg dose of oxybutynin used in this study was higher than the typical starting dose used in clinical practice. Three additional reports noted similar findings for tolterodine and oxybutynin 17 — In these studies, darifenacin 7.
One multicenter, double-blind, placebo-controlled study enrolled patients with symptoms of OAB Patients were randomized to once-daily darifenacin 3. Reduction in the number of urge incontinence episodes was observed within the first 2 weeks of therapy, and this effect was sustained throughout the week treatment period. At 12 weeks the number of incontinence episodes per week was reduced from baseline by The 3.
The most common adverse events were mild to moderate dry mouth However, no patients withdrew from the study as a result of dry mouth, and discontinuation related to constipation was rare 0. In addition, there was a low need for laxative use, with no difference between the darifenacin groups and the placebo group. There were no reports of blurred vision, and the CNS and cardiac safety profile was comparable to that of placebo In a flexible-dose study by Steers et al, patients were randomized to receive darifenacin 7.
In this study, urge incontinence episodes were decreased from baseline by 8. Among patients who required dosage escalation to 15 mg daily, the clinical outcome achieved at 12 weeks was comparable to that achieved in patients who initially responded to the 7.
The number of CNS and cardiovascular adverse events was comparable to that with placebo A 2-week multicenter, randomized, double-blind, placebo-controlled crossover study evaluated the efficacy of darifenacin 15 mg once daily compared with oxybutynin IR 5 mg three times daily in reducing the frequency of urinary incontinence and the frequency and severity of urgency in 76 patients with OAB Darifenacin and oxybutynin were associated with significantly fewer incontinence episodes per week Blurred vision and dizziness were reported only during oxybutynin therapy In these studies, solifenacin 5 to 10 mg daily was more effective than placebo in reducing the number of micturitions and urge incontinence episodes per 24 hours and increasing the volume of urine voided per micturition The study by Cardozo et al found that solifenacin 10 mg daily may also be effective in decreasing the frequency of nocturia This multicenter, multinational, randomized, double-blind, placebo-controlled trial enrolled patients for 12 weeks.
Compared with changes obtained with placebo —1. A significant decrease was observed in the number of incontinence episodes and episodes of urge incontinence. Mean volume voided per micturition was significantly increased with both solifenacin doses.
Episodes of nocturia were significantly decreased in patients treated with solifenacin 10 mg — Treatment with solifenacin was well tolerated; dry mouth, mostly mild, was reported in 7. In a multicenter, placebo- and tolterodine-controlled double-blind dose-finding trial, solifenacin 5 mg and 10 mg doses were found to be the most clinically effective and best tolerated in the treatment of OAB Two hundred twenty-five patients were randomized to receive either solifenacin 2.
However, the change caused by solifenacin 2. Tolterodine 2 mg twice a day caused a change that was between that caused by solifenacin 2. Furthermore, the mean volume voided with solifenacin 5, 10, or 20 mg was significantly larger than with either tolterodine or placebo. Efficacy for all parameters with solifenacin was dose-related. There were also fewer episodes of urgency or incontinence with solifenacin than with either tolterodine or placebo.
All adverse effects were mild to moderate and led to a low rate of discontinuation of therapy Solifenacin 5 and 10 mg once daily improved symptoms of OAB and was well tolerated in an international multicenter, randomized, double-blind, tolterodine- and placebo-controlled phase 3 clinical trial There was also an increase from baseline in mean volume per void for the placebo group 7.
The percentage of patients discontinuing therapy because of an adverse effect was 3. The most common adverse reactions were dry mouth, constipation, and blurred vision. Solifenacin treatment resulted in withdrawal rates similar to those for placebo In two week randomized, placebo-controlled clinical studies in adults with OAB, trospium 20 mg twice daily was more effective than placebo in reducing the number of micturitions per 24 hours, reducing the number of urge incontinence episodes per week, and increasing the volume of urine voided per micturition In the first clinical study by Zinner et al, adult patients with OAB received trospium 20 mg twice daily or placebo The results of this study found decreases from baseline in urinary frequency by a mean of 2.
Dry mouth occurred in Adverse events leading to discontinuation occurred in 8. In the second, nearly identical study of patients with OAB, urinary frequency decreased from baseline by a mean of 2.
Agents for treatment of overactive bladder: a therapeutic class review.