Clinical Results

Three placebo-controlled, 12 week studies were held involving a total of 339 patients who received Detrol 2 mg twice daily and 177 patients who received the placebo. The majority of patients were Caucasian (95%) and female (75%), with the mean age being 60 years of age (range 19-91). At their entrance into the study almost all patients perceived symptoms of urgency (98%) and increased frequency of micturitions (89%) and urge incontinence (83%). These characteristics were balanced across treatment groups for all three studies.

Side Effects

The most common side effects include, but are not limited to:

dry mouth

dyspepsia

headache

constipation

xerophthalmia (eye disorder that results from a deficiency of vitamin A)

abnormal vision

Many of these side effects are expected of antimuscarinic agents. Detrol is present in the breast milk of nursing mice. It is not known if it is present in the milk of nursing mothers. This drug also causes increased fetal abnormalities in mice. No studies have been done with pregnant mothers. Therefore the drug should only used by pregnant mothers if the benefit to the mother outweighs the potential risk to the fetus.

Detrol is contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. Detrol is also contraindicated in patients who have showed hypersensitivity to the drug or its ingredients.

Drug Interactions:

Pharmokinetic studies with patients concomitantly receiving cytochrome P450 3A4 inhibitors, such as macrolide antibiotics (erythromycin and clarithromycin) or antifungal agents (ketoconazole, itraconazole, and miconazole) have not been performed. Patients receiving cytochrome P450 3A4 inhibitors should not receive doses of Detrol greater than 1 mg twice daily. (From FDA Label)

Mechanism of Action

Tolterodine is a competitive muscarinic receptor antagonist. Both urinary bladder contraction and salivation are mediated via cholinergic muscarinic receptors. In the anesthetized cat, tolterodine shows a selectivity for the urinary bladder over salivary glands; however, the clinical relevance of this finding has not been established.

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 the 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 in healthy volunteers. The main effects following a 6.4-mg single dose of tolterodine were an increase in residual urine, reflecting an incomplete emptying of the bladder, and a decrease in detrusor pressure. These findings are consistent with a potent antimuscarinic action on the lower urninary tract. (From FDA Label)