New drug to treat overactive bladder
Pharmacologic class: Muscarinic receptor antagonist
Active ingredient: Fesoterodine fumarate 4 mg, 8 mg; extended-release tablets.
Indication: Overactive bladder (OAB) with urge urinary incontinence, urgency, and frequency.
Pharmacology: Fesoterodine is a pro-drug that is metabolized to an active metabolite, 5-hydroxymethyl tolterodine, following oral administration. It relaxes the smooth muscle of the bladder by competitive inhibition at muscarinic receptor sites.
Clinical trials: Two 12-week studies were conducted to evaluate fesoterodine in the treatment of OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency. Patients had symptoms for six months or more, with eight or more micturitions per day and six or more urinary urgency episodes or three urge incontinence episodes per three-day diary period. They were randomized to fesoterodine 4 mg/day, fesoterodine 8 mg/day, or placebo. One of the studies included an active control arm. The primary efficacy end points were the mean change in the number of urge urinary incontinence episodes in 24 hours and the mean change in the number of micturitions in 24 hours. A secondary end point was the mean change in voided volume per micturition.
In Study 1, the change from baseline in the number of urge incontinence episodes for patients given fesoterodine 4 mg/day was -2.06, compared with -1.20 for placebo and -2.27 for patients given fesoterodine 8 mg/day. For the number of micturitions in 24 hours, the change from baseline for fesoterodine 4 mg/day was -1.74 and -1.94 for patients given 8 mg/day of fesoterodine, compared with -1.02 for placebo. For volume voided per micturition, patients given fesoterodine 4 mg/day reported 27 mL and 33 mL for those taking fesoterodine 8 mg/day, compared with 10 mL for those given placebo.
In Study 2, the change from baseline in the number of urge incontinence episodes for patients taking fesoterodine 4 mg/day was -1.77 and -2.42 for those taking fesoterodine 8 mg/day, compared with -1.00 for placebo. For the number of micturitions in 24 hours, the change from baseline for fesoterodine 4 mg/day was -1.86 and -1.94 for those taking 8 mg/day of fesoterodine, compared with -1.02 for placebo. For the volume voided per micturition, patients given fesoterodine 4 mg/day reported 17 mL and 33 mL for those taking fesoterodine 8 mg/day, compared with 8 mL for those given placebo.
These findings indicate that fesoterodine is an effective agent in the treatment of OAB.
Adults: Swallow whole. 4 mg once daily; maximum 8 mg once daily. Severe renal insufficiency (creatinine clearance <30 mL/min) or concomitant potent CYP3A4 inhibitors: maximum 4 mg/day.
Children: Not recommended.
Contraindications: Urinary or gastric retention. Uncontrolled narrow angle glaucoma.
Precautions: Severe hepatic impairment: not recommended. Bladder outlet obstruction. Controlled narrow angle glaucoma. Hepatic or renal dysfunction. Myasthenia gravis. Decreased gastric motility. Exposure to high environmental temperatures. Pregnancy (Cat. C). Nursing mothers.
Interactions: Increased levels with CYP3A4 inhibitors (e.g., erythromycin). Central nervous system (CNS) depression with alcohol, other CNS depressants.
Adverse reactions: Dry mouth, constipation, urinary retention/urinary tract infection, blurred vision, dry eyes, back pain, insomnia, dyspepsia.
How supplied: Tabs—30, 90
For more information, call 800.438.1985 or visit www.Toviaz.com.