Tolterodine: A Muscarinic Receptor Antagonist for Overactive Bladder
Tolterodine is a competitive muscarinic receptor antagonist specifically developed for treating overactive bladder syndrome, which works by blocking muscarinic receptors in the bladder to reduce involuntary detrusor muscle contractions. 1
Mechanism of Action
Tolterodine acts as a competitive antagonist at muscarinic receptors with high specificity, showing:
- Selective inhibition of bladder muscarinic receptors
- Inhibition of involuntary bladder contractions
- Increased bladder capacity
- Decreased detrusor pressure
- Increased residual urine volume 1
The 5-hydroxymethyl metabolite, formed through liver metabolism, exhibits similar antimuscarinic activity to tolterodine and contributes significantly to the therapeutic effect. 1
Clinical Uses
Tolterodine is primarily indicated for:
- Urge urinary incontinence (involuntary leakage with strong urge)
- Urinary urgency (sudden compelling desire to urinate)
- Urinary frequency (voiding often)
These symptoms collectively represent overactive bladder syndrome. 1
Efficacy
Clinical studies demonstrate that tolterodine effectively:
- Reduces micturition frequency by approximately 20-25%
- Decreases urge incontinence episodes by 70-75%
- Increases bladder capacity (volume voided per micturition) by about 20-25% 2
- Provides similar efficacy to oxybutynin but with better tolerability 3
Formulations and Dosing
Tolterodine is available in two formulations:
- Immediate-release (IR) tablets: 1-2 mg twice daily
- Extended-release (ER) capsules: 4 mg once daily 1, 3
The extended-release formulation offers the advantage of once-daily dosing with a 23% lower incidence of dry mouth compared to the immediate-release formulation. 3
Side Effects
Common side effects include:
- Dry mouth (most common, but generally milder than with oxybutynin)
- Constipation
- Headache
- Dizziness
- Blurred vision
- Drowsiness 1
Serious allergic reactions can occur rarely, with symptoms including swelling of the face, lips, throat, or tongue, requiring immediate medical attention. 1
Special Considerations
Drug Interactions
Dosage adjustment is needed when co-administered with:
Contraindications
Tolterodine should not be used in patients with:
- Urinary retention
- Gastric retention
- Uncontrolled narrow-angle glaucoma
- Known hypersensitivity to the drug 1
Use in Special Populations
- Elderly patients: Similar efficacy and safety profile to younger adults 4
- Hepatic impairment: Dosage adjustment recommended 1
- Pregnancy: Limited data available; use only if benefits outweigh risks 1
Advantages Over Other Antimuscarinic Agents
Tolterodine offers several advantages:
- Bladder selectivity resulting in fewer systemic anticholinergic effects
- Lower incidence and severity of dry mouth compared to oxybutynin
- Maintained efficacy during long-term treatment (up to 24 months)
- Good tolerability in elderly patients 3, 4
Long-term Treatment
Studies show that tolterodine maintains its clinical efficacy during long-term treatment (9+ months) with:
- Sustained reduction in urinary frequency and urgency
- Continued improvement in urge incontinence episodes
- Stable side effect profile over time 2
Approximately 70% of patients remain on treatment after 9 months, indicating good long-term tolerability and sustained efficacy. 2
In conclusion, tolterodine represents an effective first-line pharmacological treatment for overactive bladder with a favorable benefit-risk profile, particularly for patients who require long-term therapy or who are sensitive to anticholinergic side effects.