Tolterodine


Concise Prescribing Info
Indications/Uses
Overactive bladder.
Dosage/Direction for Use
Adult : PO As immediate-release tab: 2 mg bid, may be decreased to 1 mg bid according to patient response and tolerability. As extended-release cap: 4 mg once daily, may be decreased to 2 mg once daily according to patient response and tolerability. Re-evaluate effects after 2-3 months of treatment.
Dosage Details
Oral
Overactive bladder
Adult: As immediate-release tab: 2 mg bid, may be decreased to 1 mg bid according to patient response and tolerability. As extended-release cap: 4 mg once daily, may be decreased to 2 mg once daily according to patient response and tolerability. Re-evaluate effects after 2-3 months of treatment.
Special Patient Group
Patient taking strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, ritonavir): 1 mg bid (immediate-release tab); 2 mg once daily (extended-release cap).

Pharmacogenomics:

Tolterodine is mainly metabolised via oxidation by CYP2D6 to form active 5-hydroxymethyl metabolite (5-HMT). Some studies determined that individuals with reduced CYP2D6 activity, known as CYP2D6 poor metabolisers, may have significantly higher tolterodine plasma concentrations and may be at increased risk of QTc interval prolongation. Although tolterodine in normal metabolisers or poor metabolisers is not expected to cause significant QT prolongation, the degree of QT prolongation between poor metabolisers is higher than normal metabolisers. The prevalence of CYP2D6 poor metabolisers is estimated at approx 7% in Caucasians and approx 2% in African American populations.
Renal Impairment
CrCl (mL/min) Dosage
10-30
1 mg bid (immediate-release tab); 2 mg once daily (extended-release cap).
Hepatic Impairment
As immediate-release tab: 1 mg bid. As extended-release cap: Mild to moderate (Child-Pugh Class A or B): 2 mg once daily. Severe (Child-Pugh Class C): Not recommended.
Contraindications
Urinary or gastric retention, severe ulcerative colitis, toxic megacolon, myasthenia gravis, uncontrolled narrow-angle glaucoma.
Special Precautions
Patient at risk of QT prolongation (e.g. congenital prolonged QT, concurrent class Ia or III antiarrhythmics therapy, electrolyte imbalance, bradycardia, pre-existing cardiac disease), bladder flow obstruction (e.g. benign prostatic hypertrophy); decreased gastrointestinal motility (e.g. intestinal atony) or obstructive disorder (e.g. pyloric stenosis); controlled or treated narrow-angle glaucoma, Alzheimer's disease, autonomic neuropathy, hiatus hernia. Hepatic and renal impairment. Elderly. Pregnancy and lactation. Patient taking potent CYP3A4 inhibitors. CYP2D6 poor metabolisers.
Adverse Reactions
Significant: Angioedema, QT prolongation (high doses, CYP2D6 poor metabolisers), urinary or gastric retention, decreased gastrointestinal motility, CNS effects (e.g. dizziness, drowsiness, blurred vision), anaphylaxis.
Cardiac disorders: Palpitations, tachycardia.
Eye disorders: Dry eyes, abnormal vision and accommodation.
Gastrointestinal disorders: Dry mouth, dyspepsia, constipation, abdominal pain, diarrhoea, flatulence.
General disorders and administration site conditions: Fatigue, flu-like symptoms.
Investigations: Increased weight.
Metabolism and nutrition disorders: Peripheral oedema.
Nervous system disorders: Headache, somnolence.
Renal and urinary disorders: Dysuria.
Respiratory, thoracic and mediastinal disorders: Sinusitis, chest pain.
Patient Counseling Information
This drug may cause dizziness, drowsiness, or blurred vision, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor LFTs and renal function (e.g. BUN, creatinine); postvoid residual urine volume prior to treatment initiation. Assess for signs of anticholinergic effects (e.g. dry mouth, dizziness, constipation).
Overdosage
Symptoms: Accommodation disturbances, micturition difficulties, severe central anticholinergic effects (e.g. hallucinations, severe excitation), convulsions or pronounced excitation, respiratory insufficiency, tachycardia, urinary retention, mydriasis, QT prolongation. Management: Symptomatic and supportive treatment. May consider gastric lavage and administration of activated charcoal within 1 hour of ingestion. May give physostigmine for severe central anticholinergic effects; β-blockers for tachycardia; diazepam for convulsions or pronounced excitation. Place the patient in a dark room and/or administer pilocarpine eye drops for mydriasis. Consider catheterisation for urinary retention. Monitor ECG for QT prolongation and provide artificial respiration for respiratory insufficiency.
Drug Interactions
Increased risk of QT prolongation with class IA (e.g. quinidine, procainamide) and Class III (e.g. amiodarone, sotalol) antiarrhythmics. Increased serum concentrations thereby greater risk of overdosage with potent CYP3A4 inhibitors (e.g. erythromycin, clarithromycin, ketoconazole, itraconazole, protease inhibitors), especially in CYP2D6 poor metabolisers. May decrease prokinetic effects of metoclopramide and cisapride. Additive therapeutic and adverse effects with other antimuscarinic drugs. Reduced therapeutic effects with muscarinic/cholinergic receptor agonists. May increase exposure of tolterodine (immediate-release) with potent CYP2D6 inhibitor (e.g. fluoxetine), especially in CYP2D6 extensive metabolisers.
Food Interaction
Increased bioavailability with food (immediate-release tab). May increase plasma concentration and risk of toxicity with grapefruit or grapefruit juice.
Action
Description: Tolterodine is a competitive muscarinic receptor antagonist with selectivity for urinary bladder receptors over salivary receptors. It increases residual urine volume and decreases detrusor muscle pressure.
Pharmacokinetics:
Absorption: Rapidly absorbed (immediate-release tab). Bioavailability: Increased by approx 53% with food (immediate-release tab); 17% (extensive metabolisers); 65% (poor metabolisers). Time to peak plasma concentration: 1-2 hours (immediate-release tab); 2-6 hours (modified-release cap).
Distribution: Volume of distribution: 113±27 L. Plasma protein binding: >96%, (mainly to α1-acid glycoprotein).
Metabolism: Extensively metabolised in the liver mainly via oxidation by CYP2D6 to 5-hydroxymethyltolterodine (active metabolite), further metabolism to form 5-carboxylic acid and N-dealkylated 5-carboxylic acid metabolites. Poor CYP2D6 metabolisers: Via dealkylation by CYP3A4 into inactive N-dealkylated tolterodine metabolite. Predominantly metabolised by CYP3A4 isoenzyme in CYP2D6 poor metabolisers.
Excretion: Via urine (77%) and faeces (17%); mainly as metabolites, <1% as unchanged drug. Elimination half-life: Immediate-release tab: Approx 2 hours (extensive metabolisers); approx 10 hours (poor metabolisers). Modified-release cap: Approx 7 hours (extensive metabolisers); approx 18 hours (poor metabolisers).
Chemical Structure

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Storage
Store at 25°C. Protect from light.
ATC Classification
G04BD07 - tolterodine ; Belongs to the class of urinary antispasmodics.
Disclaimer: This information is independently developed by MIMS based on Tolterodine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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