Brands, Medical Use, Clinical Data
Drug Category
- Antispasmodics
- Anti-Incontinence Agents
- Genitourinary Smooth Muscle Relaxants
Dosage Forms
- Capsule (sustained-release)
Brands / Synonyms
Detrol; Detrol LA; Tolterodina [Inn-Spanish]; Tolterodine Extended Release; Tolterodine L-Tartrate; Tolterodine Tartrate; Tolterodine [Inn]; Tolterodinum [Inn-Latin]; Tolterondine Tartrate
Indications
For the treatment of overactive bladder (with symptoms of urinary frequency, urgency, or urge incontinence).
Pharmacology
Tolterodine is a competitive muscarinic receptor antagonist. Both urinary bladder contraction and salivation are mediated via cholinergic muscarinic receptors. After oral administration, tolterodine is metabolized in the liver, resulting in the formation of the 5-hydroxymethyl derivative, a major pharmacologically active metabolite. The 5-hydroxymethyl metabolite, which exhibits an antimuscarinic activity similar to that of tolterodine, contributes significantly to the therapeutic effect. Both tolterodine and the 5-hydroxymethyl metabolite exhibit a high specificity for muscarinic receptors, since both show negligible activity or affinity for other neurotransmitter receptors and other potential cellular targets, such as calcium channels. Tolterodine has a pronounced effect on bladder function. The main effects of tolterodine are an increase in residual urine, reflecting an incomplete emptying of the bladder, and a decrease in detrusor pressure, consistent with an antimuscarinic action on the lower urinary tract.
Mechanism of Action
Both tolterodine and its active metabolite, 5-hydroxymethyltolterodine, act as competitive antagonists at muscarinic receptors. This results in inhibition of bladder contraction, decrease in detrusor pressure, and an incomplete emptying of the bladder.
Absorption
Not Available
Toxicity
Not Available
Biotrnasformation / Drug Metabolism
Not Available
Contraindications
DETROL LA Capsules are contraindicated in patients with urinary retention, gastric retention, or
uncontrolled narrow-angle glaucoma. DETROL LA is also contraindicated in patients who have demonstrated
hypersensitivity to the drug or its ingredients.
Drug Interactions
CYP3A4 Inhibitors: Ketoconazole, an inhibitor of the drug metabolizing enzyme CYP3A4,
significantly increased plasma concentrations of tolterodine when coadministered to subjects who were poor
metabolizers (see CLINICAL PHARMACOLOGY, Variability in Metabolism and
Drug-Drug Interactions). For patients receiving ketoconazole or other potent CYP3A4 inhibitors such as other
azole antifungals (eg, itraconazole, miconazole) or macrolide antibiotics (eg, erythromycin, clarithromycin) or
cyclosporine or vinblastine, the recommended dose of DETROL LA is 2 mg daily.
Drug-Laboratory-Test Interactions
Interactions between tolterodine and laboratory tests have not been studied.
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