On October 31, 2008, the FDA approved fesoterodine fumarate (Toviaz) for the treatment of overactive bladder (OAB) syndrome, which affects about 16% of the adult population, especially the elderly.1,2 Manufactured by Schwarz Pharma of Zwickau, Germany, and distributed by Pfizer, this agent gives patients an option that may help improve their symptoms, as well as their quality of life.3

According to the International Continence Society, OAB is a collection of symptoms, especially urinary urgency with or without urgency incontinence, and usually accompanied by increased frequency and nocturia.4 OAB is treated mainly by nonsurgical interventions, including bladder training, biofeedback, medication, or any combination of these.5

The mainstay in pharmacologic treatment of OAB has been the muscarinic receptor antagonists.1,2,5-7 The antimuscarinic agents, also referred to as anticholinergic agents, include darifenacin, oxybutynin, solifenacin, tolterodine, and trospium chloride.2 All of these agents have shown benefits in the treatment of OAB, but they carry an increased risk of adverse reactions. These adverse reactions are usually dose-dependent and can include dry mouth, constipation, and typical anticholinergic effects.2,6

Due to the adverse reactions experienced with the antimuscarinic agents, research is underway to find a medication that either minimizes these adverse reactions or eliminates them altogether. This research has led to the development of the medication fesoterodine fumerate.

Mechanism of action

Fesoterodine is a nonselective antimuscarinic medication that shows its benefit as a competitive antagonist at the muscarinic receptor.8,9 Fesoterodine is approved for the treatment of OAB with symptoms of urgency, frequency, and urge urinary incontinence.10 After fesoterodine is taken orally, it is hydrolyzed by nonspecific esterases to 5-hydroxymethyl tolterodine (5-HMT), its active metabolite.1,7 This metabolite is responsible for antimuscarinic activity. 5-HMT is a competitive antagonist of the muscarinic receptors that are found in the urinary bladder.1 Muscarinic receptors are cholinergic receptors that are stimulated by the alkaloid muscarine and blocked by atropine. Contraction of the urinary bladder smooth muscle and stimulation of salivary secretion is mediated by the muscarinic receptors. Fesoterodine causes inhibition of these receptors in the bladder, which is how the medication works.10

Contraindications and precautions

Fesoterodine is contraindicated in those with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma, as well as patients with a known hypersensitivity to fesoterodine or any of its ingredients.10 The drug is not recommended for use in patients with severe hepatic dysfunction.10

Caution must be used when administering fesoterodine to patients who may have bladder outlet obstruction, controlled narrow-angle glaucoma, reduced renal or hepatic function, decreased gastrointestinal motility, myasthenia gravis, or patients taking a CYP3A4 inhibitor such as clarithromycin, ketoconazole, or itraconazole.10

Adverse reactions

Fesoterodine at doses of 4 mg and 8 mg is generally well tolerated. It is safe and effective, with a low overall incidence of adverse reactions. The most frequently observed adverse reaction is dry mouth, which occurs more commonly in patients taking the 8 mg dose.6 Most of these occurrences are mild to moderate, and therapy discontinuations are less likely.2 Other adverse reactions include constipation, dyspepsia, dry eyes, and urinary retention.10

Dosing and administration

Fesoterodine is manufactured in an extended-release formulation in 4 mg and 8 mg tablets. Fesoterodine is started at 4 mg daily and may be increased to 8 mg once daily based on response and tolerability.10 In patients who have renal impairment with a creatinine clearance less than 30 mL/minute or those who are taking concomitant CYP3A4 inhibitors, the dose of fesoterodine is 4 mg once daily.10 Since fesoterodine is an extended-release product, it should be swallowed whole and not chewed, crushed, or divided.

Special instructions

NPs must consider the following when prescribing this drug:

* Fesoterodine can cause antimuscarinic adverse reactions including constipation, dry mouth, and urinary retention.1

* The patient may experience blurred vision, so advise caution when starting this medication.1

* Fesoterodine interacts with the concomitant use of alcohol and can cause excessive drowsiness.

* The combination of fesoterodine with another anticholinergic agent will increase the risk and incidence of the adverse reactions that these agents produce.1

* Fesoterodine is a category C drug, so its use during pregnancy is warranted only if the benefit outweighs the risk.10

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