Fesoterodine Fumarate

Pronunciation: FES-oh-TER-oh-deen FUE-ma-rate
Class: Anticholinergic

Trade Names

Toviaz
- Tablets, ER 4 mg
- Tablets, ER 8 mg

Pharmacology

Contracts urinary bladder smooth muscles.

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Pharmacokinetics

Absorption

Well absorbed following oral administration. Rapidly and extensively metabolized to its active metabolite, which is 52% bioavailable. T _max reached in approximately 5 h. C _max ranges from 1.89 to 3.98 ng/mL in extensive metabolizers and 3.45 to 6.9 ng/mL in poor metabolizers.

Distribution

Protein binding of the active metabolite is approximately 50%, primarily bound to albumin and alpha-1 acid glycoprotein. Mean steady-state Vd of the active metabolite is 169 L.

Metabolism

Rapidly and extensively metabolized to its active metabolite. The active metabolite is metabolized in the liver by CYP2D6 and CYP3A4 isozymes to metabolites that do not have muscarinic activity.

Elimination

Approximately 70% of the administered dose is recovered in the urine as the active metabolite and smaller amounts are recovered in the feces. The terminal half-life of the active metabolite is approximately 4 h following IV administration and 7 h following oral administration.

Special Populations

Plasma concentrations of the active metabolite are increased in patients with renal impairment. No dosage adjustment is recommended in patients with mild or moderate renal insufficiency. Doses greater than 4 mg are not recommended in patients with severe renal insufficiency (CrCl less than 30 mL/min).

Plasma concentrations of the active metabolite are increased in patients with hepatic impairment. No dosage adjustment is recommended in patients with mild or moderate hepatic impairment. There are no data for patients with severe hepatic impairment; therefore, administration is not recommended.

Indications and Usage

Treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.

Contraindications

Urinary retention; gastric retention; uncontrolled narrow-angle glaucoma; hypersensitivity to any component of the product.

Dosage and Administration

PO Start with 4 mg once daily. Based upon response and tolerability, the dose may be increased to 8 mg once daily.

PO Patients with severe renal insufficiency (CrCl less than 30 mL/min) or those taking potent CYP3A4 inhibitors (eg, clarithromycin, itraconazole, ketoconazole) should not receive more than 4 mg daily. Administration is not recommended in patients with severe hepatic impairment.

General Advice

• May be administered without regard to meals.
• The ER tablets should be swallowed whole and not broken, crushed, or chewed.

Storage/Stability

Store at 59° to 86°F. Protect from moisture.

Drug Interactions

Frequency and severity of adverse reactions may be increased.

Plasma concentrations of the active metabolite of fesoterodine may be increased in poor metabolizers for CYP2D6.

Plasma concentrations of the active metabolite of fesoterodine may be reduced, decreasing the clinical effect.

Plasma concentrations of the active metabolite of fesoterodine may be elevated, increasing the pharmacologic effects and adverse reactions.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

QTc prolongation.

CNS

Insomnia (1%).

Dermatologic

Rash (1%).

EENT

Dry eyes (4%); dry throat (2%).

GI

Dry mouth (35%); constipation (6%); dyspepsia, nausea (2%); upper abdominal pain (1%); diverticulitis, irritable bowel syndrome.

Genitourinary

UTI (4%); dysuria (2%); urinary retention (1%).

Lab Tests

Increased ALT, increased gamma-glutamyltransferase (1%).

Musculoskeletal

Back pain (2%).

Respiratory

Upper respiratory tract infection (3%); cough (2%).

Miscellaneous

Peripheral edema (1%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

No overall differences is safety and efficacy were found in patients 65 yr of age and older compared with younger patients.

Renal Function

Dosages greater than 4 mg once daily are not recommended in patients with severe renal insufficiency.

Hepatic Function

Administration is not recommended in patients with severe hepatic impairment.

Bladder outlet obstruction

Administer with caution in patients with clinically important bladder outlet obstruction because of risk of urinary retention.

Special risk patients

Use with caution in patients with decreased GI motility (eg, severe constipation), controlled narrow-angle glaucoma, or myasthenia gravis.

Overdosage

Symptoms

Severe anticholinergic effects.

Patient Information

• Instruct patients that product may be administered without regard to meals.
• Instruct patients to swallow the medication whole and not divide, crush, or chew the tablets.
• Inform patients that blurred vision may occur and to exercise caution until the effects of the drug on the patient have been determined.
• Inform patients that heat prostration due to decreased sweating can occur when patients are exposed to a hot environment.
• Instruct patients to avoid alcohol because the risk of drowsiness may be increased.

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