Pronunciation: tol-TER-oh-deen TAR-trate
- Tablets, oral 1 mg
- Tablets, oral 2 mg
- Capsule, ER, oral 2 mg
- Capsule, ER, oral 4 mg
Antagonizes muscarinic receptor, which mediates urinary bladder contraction.
Tolterodine is rapidly absorbed; bioavailability is at least 77%. T max is within 1 to 2 h (immediate release) and 2 to 6 h (ER). Food increases bioavailability (approximately 53%) of immediate-release tolterodine, but has no effect on ER tolterodine.
Tolterodine is highly protein bound, primarily to alpha-1 acid glycoprotein. Vd is approximately 113 L.
Tolterodine is extensively metabolized by the liver. The primary metabolic route involves oxidation of the 5-methyl group and is mediated by the CYP2D6 isoenzyme and leads to a pharmacologically active 5-hydroxymethyl tolterodine (5-HMT) metabolite.
77% is recovered in urine and 17% is recovered in feces within 7 days. Half-life is approximately 2 h (immediate release) and 7 h (ER).
Special PopulationsRenal Function Impairment
In patients with CrCl 10 to 30 mL/min, immediate-release tolterodine and metabolite levels were 2- to 3-fold higher compared with healthy patients. ER tolterodine has not been studied in patients with CrCl less than 10 mL/min.Hepatic Function Impairment
The elimination half-life of immediate-release tolterodine was longer and Cl was substantially lower in cirrhotic patients compared with healthy patients.Elderly
Serum concentrations of immediate-release tolterodine and 5-HMT were 20% to 50% higher in elderly patients.Children
Pharmacokinetics of immediate-release tolterodine have not been established in pediatric patients. Dose-plasma concentration relationship was linear over the range of tolterodine ER doses assessed.Gender
Pharmacokinetics of immediate-release tolterodine are not influenced by gender.Race
Pharmacokinetic differences because of race have not been established.
Indications and Usage
For the treatment of overactive bladder with symptoms of urinary frequency, urgency, and urge urinary incontinence.
Gastric retention; hypersensitivity to any component of the product or to fesoterodine; uncontrolled narrow-angle glaucoma; urinary retention.
Dosage and AdministrationImmediate Release
PO 2 mg twice daily; lower dosage to 1 mg twice daily based on individual response and tolerability.ER
PO 4 mg once daily; lower dosage to 2 mg once daily based on individual response and tolerability.Renal function impairment
Immediate release Significantly reduced renal function
PO 1 mg twice daily.ER Severe renal impairment (CrCl 10 to 30 mL/min)
PO 2 mg once daily.CrCl less than 10 mL/min
PO Use is not recommended.Hepatic function impairment
Immediate release Significantly reduced hepatic function
PO 1 mg twice daily.ER Mild to moderate hepatic impairment (Child-Pugh class A or B)
PO 2 mg once daily.Severe hepatic impairment (Child-Pugh class C)
PO Use is not recommended.Concomitant therapy
PO For patients currently taking potent inhibitors of CYP3A4 (eg, ketoconazole, clarithromycin, ritonavir), the recommended dosage is 2 mg once daily (ER) or 1 mg twice daily (immediate release).
- ER capsules should be swallowed whole.
Store between 59° and 86°F. Protect ER capsules from light.
Coadministration may increase the frequency and/or severity of anticholinergic adverse effects (eg, blurred vision, constipation, dry mouth, somnolence).Class IA (eg, procainamide, quinidine) or class III (eg, amiodarone, sotalol) antiarrhythmic agents
The effect of tolterodine on QT interval prolongation has been found to correlate with tolterodine plasma concentrations. The QTc interval increase appears to be greater in CYP2D6 poor metabolizers than extensive metabolizers. These observations should be considered in clinical decisions to prescribe tolterodine for patients who are taking class IA or class III antiarrhythmic agents.Cyclosporine
Tolterodine plasma concentration may be increased. The recommended dosage of immediate-release tolterodine is 1 mg twice daily during coadministration.CYP3A4 potent inhibitors (eg, clarithromycin, erythromycin, itraconazole, ketoconazole, miconazole, nefazodone, protease inhibitors [eg, ritonavir])
May increase tolterodine plasma levels, which may increase activity and adverse effects. During coadministration with potent CYP3A4 inhibitors, the recommended dosage of immediate-release tolterodine is 1 mg twice daily and the recommended dosage of ER tolterodine is 2 mg once daily.Fluoxetine
Plasma levels of tolterodine may be increased; no dosage adjustment is required.Potassium chloride
All solid dosage forms of potassium chloride are contraindicated for use in any patient receiving anticholinergic agents. Arrest or delay in tablet passage through the GI tract may occur. Administration of potassium chloride as a liquid preparation is a suitable alternative.Proton pump inhibitors (eg, omeprazole)
Plasma concentrations of tolterodine and its active metabolites may be increased, with the potential for excessive pharmacologic effects and adverse reactions. Monitor for potential adverse effects and adjust the tolterodine dose as needed.Vinblastine
Tolterodine plasma concentrations may be increased. The recommended dosage of immediate-release tolterodine is 1 mg twice daily during coadministration.Warfarin
The anticoagulant effect of warfarin may be increased. Monitor anticoagulant activity and adjust the warfarin dose as needed.
Palpitations, tachycardia (postmarketing).
Headache (7%); vertigo/dizziness (5%); fatigue (4%); somnolence (3%); anxiety (1%); confusion, disorientation, hallucinations, memory impairment (postmarketing).
Dry skin (1%).
Xerophthalmia (3%); abnormal accommodation (2%); abnormal vision (1%).
Dry mouth (35%); constipation (7%); abdominal pain (5%); diarrhea, dyspepsia (4%).
Weight gain (1%); peripheral edema (postmarketing).
Influenza-like symptoms (3%); chest pain (2%); infection (1%); anaphylaxis, angioedema (postmarketing).
Category C .
Undetermined. Breast-feeding is not recommended.
Safety and efficacy not established.
Use with caution and at reduced doses. ER tolterodine is not recommended in patients with CrCl less than 10 mL/min.
Use with caution and at reduced doses. ER tolterodine is not recommended in patients with severe hepatic impairment (Child-Pugh class C).
Special Risk Patients
Use with caution in patients with clinically significant bladder outflow obstruction, GI obstructive disorders (eg, pyloric stenosis), decreased GI motility (eg, intestinal atony), controlled narrow-angle glaucoma, or myasthenia gravis.
Has occurred and required hospitalization and emergency medical treatment.
Has occurred when tolterodine was used at higher than recommended doses and was more pronounced in CYP2D6 poor metabolizers. Consider this when prescribing to patients with a known history of QT prolongation or in patients taking class IA (eg, quinidine, procainamide) or class III antiarrhythmics (eg, amiodarone, sotalol).
Abdominal distension, ataxia, blurred vision, cardiac slowing followed by acceleration, CNS stimulation, coma, decreased intestinal peristalsis, delirium, dilated pupils, drowsiness, dry mouth, flushing, hallucinations, headache, hot skin, hypertension, hypotension, inhibition of sweating, palpitations, photophobia, restlessness, seizures, speech disturbances, stupor, thirst.
- Advise patients to swallow ER capsule whole.
- Advise patients that antimuscarinic agents, such as tolterodine, may produce side effects, including blurred vision, dizziness, and drowsiness. Advise patients to exercise caution while doing potentially dangerous activities, such as driving, until the drug's effects have been determined.
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