DETROL LA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DETROL LA (DETROL LA).
Tolterodine is a competitive muscarinic receptor antagonist. It blocks acetylcholine binding at muscarinic receptors (M1–M5), reducing detrusor muscle contraction and bladder pressure, thereby increasing bladder capacity and decreasing urinary frequency.
| Metabolism | Primarily hepatic via CYP2D6 and 3A4. Major metabolite: 5-hydroxymethyl tolterodine (desfesoterodine), which is active and contributes to clinical effect. Metabolites are further conjugated and eliminated renally. |
| Excretion | Approximately 77% eliminated in urine (primarily as metabolites, <1% unchanged) and 17% in feces. |
| Half-life | Terminal elimination half-life is approximately 7 hours (range 5-10 hours) for the extended-release formulation, allowing once-daily dosing. |
| Protein binding | Approximately 96% bound to plasma proteins, primarily alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is about 2.7 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Absolute bioavailability of the extended-release capsule is approximately 4.1% due to extensive first-pass metabolism; relative bioavailability vs immediate-release is 75%. |
| Onset of Action | Oral extended-release: Therapeutic effect on urinary frequency and urgency is observed within 2-4 weeks of starting therapy. |
| Duration of Action | 24 hours due to extended-release formulation; clinical effects on urodynamic parameters persist for at least 24 hours post-dose. |
| Molecular Weight | 475.6 |
4 mg orally once daily; may be reduced to 2 mg once daily based on tolerability.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | For CrCl 30-89 mL/min: no adjustment recommended. For CrCl <30 mL/min: not recommended (no data). |
| Liver impairment | Child-Pugh Class A or B: maximum dose 2 mg once daily. Child-Pugh Class C: not recommended. |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established. |
| Geriatric use | No specific dose adjustment; monitor anticholinergic effects (e.g., constipation, confusion) more frequently. Initial dose may be 2 mg once daily if frail or at risk of adverse effects. |
| 1st trimester | Avoid use; animal studies show fetal harm and there are no adequate human studies. |
| 2nd trimester | Avoid use; potential for fetal harm outweighs benefits. |
| 3rd trimester | Avoid use; may cause premature labor or fetal effects. |
Clinical note
Comprehensive clinical and safety monograph for DETROL LA (DETROL LA).
| Placental transfer | Predicted to cross placenta based on molecular weight and lipophilicity; no human data. |
| Breastfeeding | Excretion into breast milk unknown; not recommended due to potential anticholinergic effects on infant. |
| Lactation Rating | L4 |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Urinary retentionGastric retentionUncontrolled narrow-angle glaucomaHypersensitivity to tolterodine or any component
| Precautions | QT prolongation (caution in patients with risk factors, electrolyte abnormalities, or concurrent QT-prolonging drugs)., Urinary retention and gastric retention (use with caution in patients with bladder outflow obstruction or decreased GI motility)., Angioedema (discontinue if occurs)., Hepatic impairment (contraindicated in severe impairment; dose reduction in moderate impairment)., Myasthenia gravis (may exacerbate symptoms). |
| Food/Dietary | No specific food restrictions. However, grapefruit and grapefruit juice may increase tolterodine concentrations via CYP3A4 inhibition, though clinical significance is uncertain. Avoid excessive alcohol consumption due to additive effects on drowsiness and dry mouth. |
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| Teratogenic Risk | Pregnancy Category C. First trimester: no adequate studies; potential risk based on animal data showing fetal toxicity at high doses. Second and third trimesters: no well-controlled human studies; risk cannot be ruled out. Drug should be used only if potential benefit justifies potential risk to fetus. |
| Fetal Monitoring | Monitor for anticholinergic effects (e.g., constipation, blurred vision, urinary retention). If used near term, monitor neonate for anticholinergic effects. No specific fetal monitoring required. |
| Fertility Effects | No human studies on fertility. Animal studies showed no impairment of fertility in rats. Theoretical anticholinergic effects may impact reproductive function. |
| Clinical Pearls | Detrol LA (tolterodine ER) is a competitive muscarinic receptor antagonist used for overactive bladder. Key pearls: (1) Extended-release formulation allows once-daily dosing; (2) Metabolized primarily by CYP2D6; poor metabolizers have higher exposure; (3) Contraindicated in uncontrolled narrow-angle glaucoma and urinary retention; (4) May cause dry mouth and constipation; consider dose reduction in hepatic impairment or significant renal impairment. |
| Patient Advice | Take once daily with liquid, swallow whole; do not crush, chew, or break capsule. · Avoid driving or operating heavy machinery until you know how the medication affects you due to potential dizziness or blurred vision. · Report symptoms of urinary retention (difficulty urinating) or severe constipation. · Limit alcohol intake as it can increase drowsiness and dry mouth. · Inform your doctor if you have glaucoma, liver or kidney disease, or are taking other medications that affect CYP2D6. |