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). |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DETROL (DETROL).
| Breastfeeding | Excreted into breast milk in animal studies; unknown in humans. M/P ratio not determined. Use caution; consider infant risk of anticholinergic effects. |
| 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 |
■ FDA Black Box Warning
None
| Serious Effects |
["Urinary retention","Gastric retention","Uncontrolled narrow-angle glaucoma","Hypersensitivity to tolterodine or any component","TAK-003 interaction: Avoid use in patients with known hypersensitivity to the active substance."]
| 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."] |
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| 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. |