DETROL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DETROL (DETROL).
Competitive muscarinic receptor antagonist, primarily targeting M3 receptors in the bladder, reducing detrusor muscle contractions and increasing bladder capacity.
| Metabolism | Primarily hepatic via cytochrome P450 2D6 (CYP2D6) to active metabolite 5-hydroxymethyl tolterodine; also minor pathways via CYP3A4. |
| Excretion | Renal: 77% (as metabolites, <1% unchanged); Fecal: 17%; Biliary: minor. |
| Half-life | Terminal half-life 6.9 hours (range 4-10 hours) for tolterodine; 7.7 hours (range 5-13 hours) for active 5-hydroxymethyl metabolite; prolonged in hepatic impairment (up to 3-fold). |
| Protein binding | Tolterodine: 96.3% bound to proteins; active metabolite: 64% bound (primarily alpha-1-acid glycoprotein). |
| Volume of Distribution | Tolterodine: 1.83 L/kg (extensive tissue distribution); active metabolite: 2.65 L/kg. |
| Bioavailability | Immediate-release: 77% (first-pass metabolism to active metabolite); extended-release: approximately 65% (due to slower absorption and presystemic metabolism). |
| Onset of Action | Oral immediate-release: 30-60 minutes; oral extended-release: 2-4 hours. |
| Duration of Action | Immediate-release: 5-6 hours; extended-release: 24 hours (sustained effect over 24 hours due to prolonged release). |
| Molecular Weight | 475.6 |
2 mg orally twice daily; may increase to 4 mg daily in divided doses based on response.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-89 mL/min: no adjustment; GFR <30 mL/min: maximum dose 2 mg daily. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: maximum dose 2 mg daily; Class C: not recommended. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | Initiate at 2 mg daily; increase to 2 mg twice daily based on tolerability and response; monitor for anticholinergic effects. |
| 1st trimester | Teratogenic effects have been observed in animal studies. Use only if potential benefit justifies potential risk. |
| 2nd trimester | Limited human data. May cause fetal tachycardia or other anticholinergic effects. Use cautiously. |
| 3rd trimester | May cause neonatal anticholinergic effects if used near term. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for DETROL (DETROL).
| Placental transfer | Tolterodine crosses the placenta in animal studies; human data are limited but likely similar. Molecular weight (475.6 Da) suggests potential for some transfer. |
| Breastfeeding | Tolterodine is excreted into breast milk in small amounts. Due to potential anticholinergic effects in the infant, caution is advised. Monitor infant for constipation, sedation, or feeding difficulties. |
■ FDA Black Box Warning
None
| Serious Effects |
Urinary retentionGastric retentionUncontrolled narrow-angle glaucomaHypersensitivity to tolterodine or any component
| Precautions | Urinary retention: Use with caution in patients with bladder outflow obstruction., Gastric retention: Use with caution in patients with gastrointestinal obstructive disorders., Angle-closure glaucoma: May exacerbate condition; use with caution., QT prolongation: Tolterodine may prolong QT interval, especially in patients with risk factors (e.g., electrolyte imbalances, bradycardia, concurrent QT-prolonging drugs)., Decreased hepatic function: Dosage adjustment recommended in significant hepatic impairment., Decreased renal function: Caution in severe renal impairment., CNS effects: May cause dizziness, somnolence; advise caution in activities requiring alertness. |
| Food/Dietary | Grapefruit and grapefruit juice may increase tolterodine levels; avoid concurrent use. No other significant food interactions. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category B. No evidence of fetal harm in animal studies. No adequate studies in pregnant women. First trimester: low risk, but caution advised. Second/third trimesters: unknown effects; use only if clearly needed. |
| Fetal Monitoring | Monitor for anticholinergic effects (dry mouth, constipation, blurred vision) in mother; fetal heart rate monitoring if prolonged use near term. |
| Fertility Effects | No effect on fertility in animal studies; human data lacking. |
| Clinical Pearls | DETROL (tolterodine) is an antimuscarinic for overactive bladder. Start with 2 mg twice daily; reduce to 1 mg twice daily in patients with hepatic impairment or significant renal dysfunction. Monitor for anticholinergic side effects like dry mouth, constipation, blurred vision, and cognitive impairment, especially in elderly. Avoid use in patients with uncontrolled narrow-angle glaucoma, myasthenia gravis, or gastroparesis. QT prolongation risk at high doses; caution with other QT-prolonging drugs. |
| Patient Advice | Take exactly as prescribed; do not increase dose without consulting doctor. · May cause dry mouth, constipation, or blurred vision; drink plenty of water and use sugar-free gum or candy for dry mouth. · Avoid activities requiring mental alertness until you know how this medication affects you. · Contact your doctor if you experience difficulty urinating, severe abdominal pain, or vision changes. · Store at room temperature away from moisture and heat. · Do not stop abruptly; consult doctor before discontinuing. |