Tolterodine

• Overactive Bladder
• Urge Incontinence
• Urinary Frequency

Tolterodine is a competitive muscarinic receptor antagonist used to treat overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. It was one of the first antimuscarinic agents specifically developed for bladder disorders.

Mechanism of Action

Tolterodine works through muscarinic receptor blockade:

• Muscarinic receptor antagonism: Blocks M2 and M3 receptors
• Bladder selectivity: Shows some functional selectivity for bladder over salivary glands
• Reduces detrusor contractions: Blocks involuntary bladder muscle contractions
• Increases bladder capacity: Allows greater urine storage before urgency

The M3 receptor mediates bladder contraction; M2 may play a modulatory role.

Available Formulations

• Immediate-release tablets: 1 mg, 2 mg
• Extended-release capsules (Detrol LA): 2 mg, 4 mg

Medical Uses

FDA-Approved Indication:

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

Dosing Guidelines

Immediate-Release:

• 2 mg twice daily
• May reduce to 1 mg twice daily based on tolerability

Extended-Release:

• 4 mg once daily
• May reduce to 2 mg once daily based on tolerability

With CYP3A4 or CYP2D6 Inhibitors:

• Limit to 1 mg twice daily (IR) or 2 mg once daily (ER)

Hepatic or Renal Impairment:

• Reduce to 1 mg twice daily (IR) or 2 mg once daily (ER)

Important Safety Information

Contraindications:

• Urinary retention
• Gastric retention
• Uncontrolled narrow-angle glaucoma
• Known hypersensitivity to tolterodine or fesoterodine

Warnings and Precautions:

• Central nervous system effects: Somnolence, confusion, hallucinations; monitor especially in elderly
• Angioedema: Discontinue if occurs
• QT prolongation: Use with caution in patients with known QT prolongation
• Decreased gastrointestinal motility: Use with caution in patients with GI obstruction
• Myasthenia gravis: May worsen condition
• Controlled narrow-angle glaucoma: Use with caution

Drug Interactions

Strong CYP3A4 Inhibitors (ketoconazole, clarithromycin, ritonavir):

• Limit tolterodine to 1 mg twice daily (IR) or 2 mg once daily (ER)

CYP2D6 Inhibitors (fluoxetine, paroxetine):

• May increase tolterodine levels in extensive metabolizers; adjust dose if needed

Other Anticholinergics:

• Additive anticholinergic effects

QT-Prolonging Drugs:

• Use with caution; may have additive effects

Warfarin:

• No significant interaction, but monitor INR

Special Populations

• Hepatic Impairment: Reduce dose (1 mg IR twice daily or 2 mg ER once daily)
• Renal Impairment (CrCl 10-30): Reduce dose
• Elderly: May be more sensitive to anticholinergic effects; start at lower dose
• Pregnancy: Limited data; use only if benefit outweighs risk
• Lactation: Unknown if excreted in milk
• Pediatric: Safety and efficacy not established