What are the adverse side effects of tolterodine?

Adverse Side Effects of Tolterodine

Tolterodine causes anticholinergic adverse effects, most commonly dry mouth (35% vs 10% placebo), but has a favorable safety profile with no significant increase in treatment discontinuation due to adverse effects compared to placebo. 1

Most Common Adverse Effects

The primary adverse effects of tolterodine are anticholinergic in nature and include:

• Dry mouth occurs in 34.8% of patients (vs 9.8% placebo), making it the most frequently reported adverse event, though only 1% discontinue treatment specifically due to this symptom 2
• Headache is commonly reported (7% vs 5% placebo) 2
• Constipation affects 7% of patients (vs 4% placebo) 2
• Vertigo/dizziness occurs in 5% of patients (vs 3% placebo) 2
• Abdominal pain is reported in 5% of patients (vs 3% placebo) 2

Additional Anticholinergic Effects

Expected antimuscarinic class effects include:

• Abnormal vision/accommodation abnormalities occur in 2% of patients (vs 1% placebo) 2
• Xerophthalmia (dry eyes) affects 3% of patients (vs 2% placebo) 2
• Urinary retention is a potential adverse effect, though specific incidence rates are not quantified 2
• Dyspepsia occurs in 4% of patients (vs 1% placebo) 2

Serious and Uncommon Adverse Effects

Post-marketing surveillance has identified rare but notable events:

• Hallucinations have been reported, with tolterodine showing a 4.85-fold increased risk compared to other drug classes (though only 1.25-fold compared to terodiline) 3
• Tachycardia and palpitations are infrequently associated with tolterodine 3
• Confusion, disorientation, and memory impairment have been reported, particularly concerning in patients taking cholinesterase inhibitors for dementia 2
• Anaphylaxis and angioedema are rare but serious allergic reactions 2
• Peripheral edema has been reported in post-marketing experience 2

Treatment Discontinuation Profile

Tolterodine demonstrates a favorable discontinuation profile compared to other antimuscarinics:

• High-quality evidence shows no statistically significant difference in discontinuation rates due to adverse effects between tolterodine and placebo (relative risk 1.0,95% CI 0.6-1.7) 1
• Only 7% of patients discontinued tolterodine treatment due to adverse events (vs 6% placebo), with dizziness and headache being the most common reasons 2
• The frequency of discontinuation is highest during the first 4 weeks of treatment 2

Comparative Tolerability

Tolterodine is better tolerated than oxybutynin but may have slightly more adverse effects than some other antimuscarinics:

• Dry mouth occurs significantly less frequently with tolterodine (40%) than oxybutynin (78%, p<0.001) 4
• Moderate to severe dry mouth occurs more than three times less frequently with tolterodine compared to oxybutynin 5
• Discontinuation due to adverse effects is significantly higher with oxybutynin than tolterodine (NNTH 14, CI 7-145) 1
• Fesoterodine causes more dry mouth, headache, and UTIs than tolterodine (NNTH 18, CI 11-52) 1
• Blurred vision is more common with tolterodine than solifenacin, though dry mouth and constipation are more common with solifenacin 1

Cardiovascular Safety

• No significant ECG changes in QT or QTc intervals have been demonstrated in clinical studies 2
• Despite post-marketing reports of cardiac events, there is insufficient evidence to indicate tolterodine causes ventricular arrhythmia or specific cardiac rhythm abnormalities 5

Special Populations

• The safety profile is similar in elderly patients (≥65 years) and younger adults, with no dosage adjustment needed based on age alone 5
• Dosage reduction to 1 mg twice daily is recommended in patients with hepatic impairment or those taking strong CYP3A4 inhibitors (e.g., ketoconazole) 2

Clinical Pitfalls to Avoid

• Do not prescribe tolterodine to patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma 2
• Exercise caution in patients with myasthenia gravis or QT prolongation syndrome 2
• Be vigilant for cognitive effects in elderly patients, particularly those on cholinesterase inhibitors for dementia 2
• Monitor for anticholinergic effects in patients on polypharmacy (≥7 medications), as they experience more adverse effects 6