Tolterodine
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Tolterodine: From Overactive Bladder to Low Compliance Bladder
One-Sentence Summary
Tolterodine is an antimuscarinic drug originally used to treat overactive bladder. The TxGNN model predicts it may be effective for low compliance bladder. No clinical trials are registered for this use, but 9 publications were found, of which 1 is a randomised study in neurogenic bladder, so the evidence is limited.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Overactive bladder (the Singapore licence records contain no approved indication text; this comes from the knowledge graph) |
| Predicted New Indication | Low compliance bladder |
| TxGNN Prediction Score | 96.31% |
| Evidence Level | L3 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 10 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, tolterodine is a competitive antimuscarinic (M2/M3) agent. It relaxes the detrusor muscle, reduces overactivity and can increase bladder capacity.
Low bladder compliance, especially in neurogenic bladder, means the bladder wall stores urine at high pressure. Antimuscarinics are commonly used to lower this storage pressure, so the mechanism is plausible and clinically coherent with the original indication.
There are caveats. Most evidence comes from neurogenic detrusor overactivity populations, not from studies using compliance as the primary endpoint. The spina bifida data come from a small pilot crossover study. Patients who do not respond to anticholinergics may need add-on therapy such as mirabegron.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 20969642 | 2010 | RCT | Int J Urol | Evaluated extended-release tolterodine 4 mg/day for neurogenic detrusor overactivity and/or low-compliance bladder using urodynamic parameters |
| 26676394 | 2011 | Crossover pilot study | Lower Urin Tract Symptoms | Compared oxybutynin and tolterodine in neurogenic bladder patients with spina bifida |
| 25656013 | 2015 | Clinical study (retrospective, 7 patients) | Hinyokika Kiyo | Adding mirabegron in anticholinergic-resistant neurogenic bladder with detrusor overactivity or low compliance, assessed by videourodynamics |
| 26149965 | 2015 | Review | Curr Urol Rep | Tolterodine for storage lower urinary tract symptoms in men; antimuscarinics are the pharmacological gold standard |
| 16465186 | 2006 | Review | Br J Pharmacol | Role of M2/M3 muscarinic receptors in the bladder and antimuscarinic therapy |
| 17594185 | 2007 | Review | Expert Opin Investig Drugs | Overactive bladder treatments in early phase trials |
| 15978301 | 2005 | Review (trospium, related drug) | Clin Ther | Trospium for overactive bladder with urge incontinence |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN09911P | Detrusitol Tablet 1 mg | Film-coated tablet | Not stated in the licence record |
| SIN09912P | Detrusitol Tablet 2 mg | Film-coated tablet | Not stated in the licence record |
| SIN11857P | Detrusitol SR Capsule 4 mg | Extended-release capsule | Not stated in the licence record |
| SIN11859P | Detrusitol SR Capsule 2 mg | Extended-release capsule | Not stated in the licence record |
| SIN16313P | Tolterodine Mevon IR Film-Coated Tablet 2 mg | Film-coated tablet | Not stated in the licence record |
Ten single-ingredient licences are valid in total; the five above are the main ones. The others include Tolcord 1 mg and 2 mg, Tolterodine Mevon IR 1 mg and Tolterodine Mevon SR 2 mg and 4 mg.
Safety Considerations
Package insert warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert for safety information.
- Conditions linked to contraindication in the knowledge graph (not label text): long QT syndrome (including familial), torsades de pointes, liver failure, dementia, angle-closure glaucoma, myasthenia gravis and other neuromuscular junction disease, pyloric stenosis, and bladder neck obstruction.
- Drug Interactions: 100 interactions were recorded. The most notable:
- Major: potassium citrate.
- Moderate: other anticholinergics and antimuscarinics (hyoscyamine, atropine, glycopyrronium, clidinium, dicyclomine, trospium, mepenzolate, methscopolamine), loperamide, morphine, aprepitant, cimetidine, clarithromycin, eluxadoline, metoclopramide and miconazole.
- Minor: bupropion, lorcaserin and eliglustat.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The mechanism is coherent, and one randomised study and some small clinical studies in neurogenic bladder support it. However, there are no registered trials, and the evidence rests on neurogenic detrusor overactivity populations rather than compliance as the primary endpoint. The other nine predicted indications (for example polycystic kidney disease and thoracic malformation) have only model scores, with no mechanistic link or evidence, and should remain on Hold.
To proceed, the following is needed:
- Package insert warnings and contraindications from the Singapore regulator, which are currently missing
- Mechanism of action data
- Studies using bladder compliance or detrusor storage pressure as the primary endpoint
- Confirmation of the approved indication wording on the Singapore licences
- A safety plan for patients with the contraindicated conditions listed above and for those taking other anticholinergics
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.