Fesoterodine

• Overactive Bladder
• Urinary Incontinence
• Urinary Urgency and Frequency
• Bladder Control Problems

Fesoterodine is a muscarinic receptor antagonist (anticholinergic) used for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. This prodrug is rapidly converted to its active metabolite, 5-hydroxymethyl tolterodine, which provides effective bladder relaxation.

Mechanism of Action

Fesoterodine fumarate is a prodrug that is rapidly and extensively hydrolyzed by ubiquitous nonspecific esterases to 5-hydroxymethyl tolterodine (5-HMT), the active metabolite. 5-HMT is a competitive antagonist of muscarinic receptors, particularly the M2 and M3 subtypes that predominate in the bladder. M3 receptors mediate detrusor muscle contraction, while M2 receptors may modulate M3-mediated contractions. By blocking these receptors, fesoterodine reduces involuntary detrusor contractions, decreasing urinary urgency, frequency, and incontinence episodes. The prodrug design allows for more consistent plasma levels of the active metabolite compared to direct tolterodine administration.

Available Formulations

Fesoterodine fumarate is available as extended-release tablets in 4 mg and 8 mg strengths. The tablets should be swallowed whole with liquid and should not be crushed, divided, or chewed. The medication can be taken with or without food.

Medical Uses

Fesoterodine is FDA-approved for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults. Clinical trials demonstrated significant reductions in urinary frequency, urgency episodes, and urge incontinence episodes compared to placebo. The medication provides symptom relief while improving quality of life measures.

Dosing Guidelines

The recommended starting dose is 4 mg once daily. Based on individual response and tolerability, the dose may be increased to 8 mg once daily. The maximum dose is 4 mg once daily for patients with severe renal impairment (CrCl less than 30 mL/min), those taking potent CYP3A4 inhibitors, or those with moderate hepatic impairment. The medication should not be used in patients with severe hepatic impairment.

Important Safety Information

Fesoterodine is contraindicated in patients with urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, and known hypersensitivity. As with all antimuscarinics, it should be used with caution in patients with clinically significant bladder outflow obstruction (risk of urinary retention), gastrointestinal obstructive disorders, decreased GI motility, controlled narrow-angle glaucoma, myasthenia gravis, and reduced hepatic or renal function. Angioedema of the face, lips, tongue, and/or larynx has been reported.

Drug Interactions

Potent CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin) increase fesoterodine exposure significantly; the dose should not exceed 4 mg when used concurrently. CYP3A4 inducers may decrease fesoterodine effectiveness. Concurrent use with other anticholinergic medications may increase the risk and severity of anticholinergic adverse effects (dry mouth, constipation, urinary retention, cognitive impairment). Fesoterodine does not significantly inhibit CYP enzymes at therapeutic concentrations.

Special Populations

There are no adequate studies in pregnant women; animal studies showed no developmental toxicity. Use during pregnancy only if clearly needed. It is unknown whether fesoterodine is excreted in human breast milk; caution is advised during breastfeeding. Safety and efficacy have not been established in pediatric patients. Elderly patients may be more sensitive to anticholinergic effects, including cognitive impairment; use with caution. Maximum dose is 4 mg for severe renal impairment. Use with caution in mild to moderate hepatic impairment (maximum 4 mg); contraindicated in severe hepatic impairment.