Detrusin LA Capsule (Extended Release)

Detrusin LA is indicated for the treatment of an overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.

Tolterodine is a competitive, specific muscarinic receptor antagonist which exhibits a selectivity for the urinary bladder over salivary glands, which have been demonstrated in non clinical pharmacological in vivo studies. Tolterodine has a high specificity for muscarinic receptors. A major active metabolite (5-hydroxymethyl derivative) of tolterodine exhibits a pharmacological profile which is similar to that of the parent compound. In extensive metabolisers this metabolite contributes significantly to the therapeutic effect of tolterodine. The effect of treatment can be expected within 4 weeks.

Extended-release capsule: The recommended dose is Tolterodine Tartrate 4 mg once daily. The dose may be lowered to 2 mg once daily based on individual response and tolerability. For patients with significantly reduced hepatic or renal function or who are currently taking drugs that are potent inhibitors of CYP3A4, the recommended dose is Tolterodine Tartrate 2 mg daily.

Film-coated tablet: The recommended dose is Tolterodine Tartrate 2 mg twice daily except in patients with impaired liver function or severely impaired renal function (GFR<30 ml/min) for whom the recommended dose is one Tolterodine Tartrate 1 mg tablet twice daily. In case of troublesome side effects, the dose may be reduced from 2 mg to 1 mg twice daily. The effect of treatment should be re-evaluated after 2-3 months.

Pediatric use: The safety and effectiveness of tolterodine in children have not been established.

Geriatric use: No overall differences in safety were observed between the older and younger patients treated with Tolterodine.

Ketoconazole, an inhibitor of the drug metabolizing enzyme CYP3A4, significantly increased plasma concentrations of Detrusin LA when co-administered to subjects who were poor metabolizers. 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 Detrusin LA is 2 mg daily.

Tolterodine Tartrate is contra-indicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma, or in patients who have demonstrated hypersensitivity to Tolterodine Tartrate.

The most common side effects reported by patients receiving Detrusin LA were dry mouth, headache, constipation, and abdominal pain. Dry mouth was the most frequently reported adverse event for patients treated with Detrusin LA tablets occurring in 23.4% of patients treated with Detrusin LA tablets and 7.7% of placebo-treated patients. Dry mouth, constipation, abnormal vision (accommodation abnormalities), urinary retention, and dry eyes are expected side effects of antimuscarinic agents. The adverse events were reported regardless of causality.

There are no studies of Tolterodine in pregnant women. Therefore, Tolterodine Tartrate tablets should be used during pregnancy only if the potential benefit for the mother justifies the potential risk to the fetus. It is not known whether Tolterodine is excreted in human milk. Therefore, Tolterodine Tartrate tablets should not be administered during nursing. A decision should be made whether to discontinue nursing or to discontinue Tolterodine Tartrate tablets in nursing mothers.

Detrusin LA should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention and to patients with gastrointestinal obstructive disorders, such as pyloric stenosis, because of the risk of gastric retention and in patients being treated for narrow-angle glaucoma. For patients with significantly reduced hepatic function or renal function, the recommended dose for Detrusin LA is 2 mg daily. In a study of the effect of Detrusin LA immediate release tablets on the QT interval, the effect on the QT interval appeared greater for 8 mg/day (two times the therapeutic dose) compared to 4 mg/day and was more pronounced in CYP2D6 poor metabolizers than extensive metabolizers. The effect of Detrusin LA 8 mg/day was not as large as that observed after four days of therapeutic dosing with the active control moxifloxacin. However, the confidence intervals overlapped. These observations should be considered in clinical decisions to prescribe Detrusin LA tablets for patients with a known history of QT prolongation or patients who are taking Class I A (e.g., quinidine, procainamide) or Class III (e.g.,amiodarone, sotalol) antiarrhythmic medications. Patients should be informed that antimuscarinic agents such as Detrusin LA tablets may produce the following effects: blurred vision, dizziness, or drowsiness.

Overdosage with Detrusin LA capsules can potentially result in severe central anticholinergic effects and should be treated accordingly. ECG monitoring is recommended in the event of overdosage.

BPH/ Urinary retention/ Urinary incontinence

Store in a cool and dry place. Protect from light. Keep out of the reach of children.