tolterodine (Rx)

>10%

Dry mouth (40%)

1-10%

Blurred vision

Constipation

Dizziness

Drowsiness

Dyspepsia

Headache

Xerophthalmia

Contraindications

Urinary or gastric retention

Uncontrolled narrow-angle glaucoma

Hypersensitivity to drug or ingredients or to fesoterodine fumarate, which is metabolized to 5-hydroxymethyl tolterodine

Cautions

Controlled narrow-angle glaucoma, hepatic, or renal impairment

Anaphylaxis and angioedema necessitating hospitalization and emergency treatment reported with first or subsequent doses; discontinue immediately if angioedema and hypotension, difficulty breathing, or airway obstruction develop

Anticholinergic central nervous system effects (eg, dizziness, somnolence) reported; patients should not drive or operate heavy machinery until they adjust to therapy

Use with caution in patients with myasthenia gravis, which is characterized by decreased cholinergic activity at neuromuscular junction

When coadministered with strong CYP3A4 inhibitors, tolterodine should be given at reduced dosage

QTc prolongation reported with high doses; use caution in patients with congenital prolonged QT or in patients receiving concurrent therapy with QTc-prolonging drugs (class Ia or III antiarrhythmics)

Anticholinergics may potentially adversely affect the clinical course of alzheimer disease in patients receiving cholinesterase inhibitors; monitor for decreases in congnition, functional abilities and increased problematic behaviors in patients with dementia receiving dual therapy with an anticholinesterase inhibitor and a bladder anticholinercgic agent like tolterodine

May increase risk of urinary retention in patients with bladder flow obstruction (eg, benign prostatic hypertrophy)

May increase risk of gastric retention in patients with decreased GI motility or gastrointestinal obstructive disorders

Pregnancy

There are no available data with use in pregnant women to inform drug-associated risks; in animal reproduction studies, oral administration of tolterodine and its 5-HMT metabolite to pregnant mice during organogenesis did not produce adverse developmental outcomes at doses approximately 9 to 12 times the clinical exposure at a dose of 20 mg/kg/day; however, higher doses produced adverse developmental outcomes

Lactation

There is no information on presence in human milk, effects on breastfed infant, or on milk production; based on limited data, tolterodine is excreted into milk in mice in low amounts; the development and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Competitive muscarinic receptor antagonist; decreases bladder contractions; is more specific for bladder than oxybutynin

Absorption

Bioavailability: 77%

Onset: Overactive bladder, 1 wk; urge incontinence, 1 hr

Time to peak effect: 2-4 wk

Peak plasma time: Immediate release, 1-2 hr; extended release, 2-6 hr

Distribution

Vd: 113 L

Metabolism

Metabolized in liver by CYP2D6 and (to minor extent) CYP3A4

Metabolites: 5-Hydroxymethyl, dealkylated tolterodine

Elimination

Half-life: Parent drug, 1.9-3.7 hr; active metabolite (5-hydroxymethyl), 3 hr (8.7 hr in cirrhosis)

Total body clearance: 5.7 L/kg/hr

Excretion: Urine (77%), feces (17%)