Detrol LA (tolterodine tartrate)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
General Information
Detrol LA (tolterodine tartrate) is indicated for the treatment
of overactive bladder with symptoms of urge urinary incontinence,
urgency and frequency. It is available by prescription only in a 2
and 4 mg extended release capsule formulation.
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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)
