General Information

Detrol/Detrol LA (tolterodine tartrate) is an antimuscarinic. Both urinary bladder contraction and salivation are mediated via cholinergic muscarinic receptors.

Detrol/Detrol LA is specifically indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.

Detrol is supplied as a 1 mg tablet. The initial recommended dose of Detrol tablets is 2 mg twice daily. The dose may be lowered to 1 mg twice daily based on individual response and tolerability.

Detrol LA is supplied as a 4 mg tablet. The recommended dose of Detrol LA Capsules is 4 mg once daily with water and swallowed whole. The dose may be lowered to 2 mg daily based on individual response and tolerability; however, limited efficacy data are available for Detrol LA 2 mg.

Mechanism of Action

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 the muscarinic receptors, since both show negligible activity or affinity for other neurotransmitter receptors and other potential cellular targets, such as calcium channels.

Side Effects

Adverse effects associated with the use of Detrol/Detrol LA may include, but are not limited to, the following:

• dry mouth
• dyspepsia
• headache
• constipation
• xerophthalmia (eye disorder that results from a deficiency of vitamin A)
• abnormal vision

Clinical Trial Results

The FDA approval of Detrol was based on four randomized, double-blind, placebo-controlled, 12-week studies. A total of 853 patients received Detrol 2 mg twice daily and 685 patients received placebo. The efficacy endpoints for study 007 included the change from baseline for:

• Number of incontinence episodes per week
• Number of micturitions per 24 hours (averaged over 7 days)
• Volume of urine voided per micturition (averaged over 2 days)

The efficacy endpoints for studies 008, 009, and 010 were identical to the above endpoints with the exception that the number of incontinence episodes was per 24 hours (averaged over 7 days). 

The difference between Detrol (2 mg bid) and placebo for the Mean Change at Week 12 from Baseline was significant for each measured endpoint.

The FDA approval of Detrol LA was based on a study of Detrol LA Capsules 2 mg, evaluated in 29 patients in a Phase 2 dose-effect study. Detrol 4 mg was evaluated for the treatment of overactive bladder with symptoms of urge urinary incontinence and frequency in a randomized, placebo-controlled, multicenter, double-blind, Phase 3, 12-week study. A total of 507 patients received Detrol LA 4 mg once daily in the morning and 508 received placebo. 

The primary efficacy assessment was change in mean number of incontinence episodes per week at week 12 from baseline. Secondary efficacy measures included change in mean number of micturitions per day and mean volume voided per micturition at week 12 from baseline. Patients treated with Detrol LA experienced a statistically significant decrease in number of urinary incontinence per week from baseline to last assessment (week 12) compared with placebo as well as a decrease in the average daily urinary frequency and an increase in the average urine volume per void.