Tolterodine Tartrate
(Tolterodine)Tolterodine Tartrate Prescribing Information
Tolterodine tartrate extended-release capsules are an antimuscarinic indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. (
1 INDICATIONS AND USAGETolterodine tartrate extended-release capsules are an antimuscarinic indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.
Tolterodine tartrate extended-release capsules are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency [
- 4 mg capsules taken orally once daily with water and swallowed whole. ()2.1 Dosing Information
The recommended dose of tolterodine tartrate extended-release capsules is 4 mg once daily with water and swallowed whole. The dose may be lowered to 2 mg daily based on individual response and tolerability; however, limited efficacy data are available for tolterodine tartrate extended-release capsules 2 mg [
see].CLINICAL STUDIES - 2 mg capsules taken orally once daily with water and swallowed whole in the presence of:
° mild to moderate hepatic impairment (Child-Pugh class A or B) ()2.2 Dosage Adjustment in Specific PopulationsFor patients with mild to moderate hepatic impairment (Child-Pugh Class A or B) or severe renal impairment (CCr 10 to 30 mL/min), the recommended dose of tolterodine tartrate extended-release capsules is 2 mg once daily. Tolterodine tartrate extended-release capsules are not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C). Patients with CCr<10 mL/min have not been studied and use of tolterodine tartrate extended-release capsules in this population is not recommended [
see]WARNINGS AND PRECAUTIONSandUSE IN SPECIFIC POPULATIONS.
° severe renal impairment [Creatinine Clearance (CCr) 10 to 30 mL/min] ()2.2 Dosage Adjustment in Specific PopulationsFor patients with mild to moderate hepatic impairment (Child-Pugh Class A or B) or severe renal impairment (CCr 10 to 30 mL/min), the recommended dose of tolterodine tartrate extended-release capsules is 2 mg once daily. Tolterodine tartrate extended-release capsules are not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C). Patients with CCr<10 mL/min have not been studied and use of tolterodine tartrate extended-release capsules in this population is not recommended [
see]WARNINGS AND PRECAUTIONSandUSE IN SPECIFIC POPULATIONS.
° drugs that are potent CYP3A4 inhibitors. ()2.2 Dosage Adjustment in Specific PopulationsFor patients with mild to moderate hepatic impairment (Child-Pugh Class A or B) or severe renal impairment (CCr 10 to 30 mL/min), the recommended dose of tolterodine tartrate extended-release capsules is 2 mg once daily. Tolterodine tartrate extended-release capsules are not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C). Patients with CCr<10 mL/min have not been studied and use of tolterodine tartrate extended-release capsules in this population is not recommended [
see]WARNINGS AND PRECAUTIONSandUSE IN SPECIFIC POPULATIONS. - Tolterodine tartrate extended-release capsules are not recommended for use in patients with CCr <10 mL/min. ()2.2 Dosage Adjustment in Specific Populations
For patients with mild to moderate hepatic impairment (Child-Pugh Class A or B) or severe renal impairment (CCr 10 to 30 mL/min), the recommended dose of tolterodine tartrate extended-release capsules is 2 mg once daily. Tolterodine tartrate extended-release capsules are not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C). Patients with CCr<10 mL/min have not been studied and use of tolterodine tartrate extended-release capsules in this population is not recommended [
see]WARNINGS AND PRECAUTIONSandUSE IN SPECIFIC POPULATIONS. - Tolterodine tartrate extended-release capsules are not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C). ()2.2 Dosage Adjustment in Specific Populations
For patients with mild to moderate hepatic impairment (Child-Pugh Class A or B) or severe renal impairment (CCr 10 to 30 mL/min), the recommended dose of tolterodine tartrate extended-release capsules is 2 mg once daily. Tolterodine tartrate extended-release capsules are not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C). Patients with CCr<10 mL/min have not been studied and use of tolterodine tartrate extended-release capsules in this population is not recommended [
see]WARNINGS AND PRECAUTIONSandUSE IN SPECIFIC POPULATIONS.
Capsules: 2 mg and 4 mg (
3 DOSAGE FORMS AND STRENGTHSCapsules: 2 mg and 4 mg
The 2 mg capsules are size "4", hard gelatin capsules having a green cap and green body, imprinted "1189" on the cap with white ink, containing off-white to brownish colored pellets.
The 4 mg capsules are size "3", hard gelatin capsules having a blue cap and blue body, imprinted "1190" on the cap with white ink, containing off-white to brownish colored pellets.
- Renal Impairment:Tolterodine tartrate extended-release capsules are not recommended for use in patients with CCr <10 mL/min. Dose adjustment in severe renal impairment (CCr: 10 to 30 mL/min). ()8.6 Renal Impairment
Renal impairment can significantly alter the disposition of tolterodine immediate release and its metabolites. In a study conducted in patients with creatinine clearance between 10 and 30 mL/min, tolterodine and 5-HMT levels were approximately 2 to 3 fold higher in patients with renal impairment than in healthy volunteers. Exposure levels of other metabolites of tolterodine (e.g., tolterodine acid,
N-dealkylated tolterodine acid,N-dealkylated tolterodine, andN-dealkylated hydroxy tolterodine) were significantly higher (10 to 30 fold) in renally impaired patients as compared to the healthy volunteers. The recommended dose for patients with severe renal impairment (CCr: 10 to 30 mL/min) is tolterodine tartrate extended-release capsules 2 mg daily. Patients with CCr<10 mL/min have not been studied and use of tolterodine tartrate extended-release capsules in this population is not recommended [seeandDOSAGE AND ADMINISTRATION]WARNINGS AND PRECAUTIONS.Tolterodine tartrate extended-release capsules have not been studied in patients with mild to moderate renal impairment [CCr 30 to 80 mL/min]. - Hepatic Impairment:Not recommended for use in severe hepatic impairment (Child Pugh Class C). Dose adjustment in mild to moderate hepatic impairment (Child Pugh Class A, B). ()8.7 Hepatic Impairment
Liver impairment can significantly alter the disposition of tolterodine immediate release. In a study of tolterodine immediate release conducted in cirrhotic patients (Child-Pugh Class A and B), the elimination half-life of tolterodine immediate release was longer in cirrhotic patients (mean, 7.8 hours) than in healthy, young, and elderly volunteers (mean, 2 to 4 hours). The clearance of orally administered tolterodine immediate release was substantially lower in cirrhotic patients (1.0 ± 1.7 L/h/kg) than in the healthy volunteers (5.7 ± 3.8 L/h/kg). The recommended dose for patients with mild to moderate hepatic impairment (Child-Pugh Class A or B) is tolterodine tartrate extended-release capsules 2 mg once daily. Tolterodine tartrate extended-release capsules are not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C) [see
andDOSAGE AND ADMINISTRATION] .WARNINGS AND PRECAUTIONS
Tolterodine tartrate extended-release capsules are contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. Tolterodine tartrate extended-release capsules are also contraindicated in patients with known hypersensitivity to the drug or its ingredients, or to fesoterodine fumarate extended-release tablets which, like tolterodine tartrate extended-release capsules, are metabolized to 5-hydroxymethyl tolterodine. (
4 CONTRAINDICATIONSTolterodine tartrate extended-release capsules are contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. Tolterodine tartrate extended-release capsules are also contraindicated in patients with known hypersensitivity to the drug or its ingredients, or to fesoterodine fumarate extended-release tablets which, like tolterodine tartrate extended-release capsules, are metabolized to 5-hydroxymethyl tolterodine.
Tolterodine tartrate extended-release capsules are contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. Tolterodine tartrate extended-release capsules are also contraindicated in patients with known hypersensitivity to the drug or its ingredients, or to fesoterodine fumarate extended-release tablets which, like tolterodine tartrate extended-release capsules, are metabolized to 5-hydroxymethyl tolterodine [
- Anaphylaxis and angioedema requiring hospitalization and emergency medical treatment have occurred with the first or subsequent doses of tolterodine tartrate extended-release capsules. ()5.1 Angioedema
Anaphylaxis and angioedema requiring hospitalization and emergency medical treatment have occurred with the first or subsequent doses of tolterodine tartrate extended-release capsules. In the event of difficulty in breathing, upper airway obstruction, or fall in blood pressure, tolterodine tartrate extended-release capsules should be discontinued and appropriate therapy promptly provided.
- Urinary Retention: use caution in patients with clinically significant bladder outflow obstruction because of the risk of urinary retention. ()5.2 Urinary Retention
Administer tolterodine tartrate extended-release capsules with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention [
see].CONTRAINDICATIONS - Gastrointestinal Disorders: use caution in patients with gastrointestinal obstructive disorders or decreased gastrointestinal motility because of the risk of gastric retention. ()5.3 Gastrointestinal Disorders
Administer tolterodine tartrate extended-release capsules with caution in patients with gastrointestinal obstructive disorders because of the risk of gastric retention.
Tolterodine tartrate extended-release capsules, like other antimuscarinic drugs, may decrease gastrointestinal motility and should be used with caution in patients with conditions associated with decreased gastrointestinal motility (e.g., intestinal atony) [
see].CONTRAINDICATIONS - Controlled Narrow-Angle Glaucoma: use caution in patients being treated for narrow-angle glaucoma. ()5.4 Controlled Narrow-Angle Glaucoma
Administer tolterodine tartrate extended-release capsules with caution in patients being treated for narrow-angle glaucoma [
see].CONTRAINDICATIONS - Central Nervous System Effects: Somnolence has been reported with tolterodine tartrate extended-release capsules. Advise patients not to drive or operate heavy machinery until they know how tolterodine tartrate extended-release capsules affect them. ()5.5 Central Nervous System Effects
Tolterodine tartrate extended-release capsules are associated with anticholinergic central nervous system (CNS) effects
[see Adverse Reactions ]including dizziness and somnolence[see Adverse Reactions ]. Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing the dose. Advise patients not to drive or operate heavy machinery until the drug's effects have been determined. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered. - Myasthenia Gravis: use caution in patients with myasthenia gravis. ()5.8 Myasthenia Gravis
Administer tolterodine tartrate extended-release capsules with caution in patients with myasthenia gravis, a disease characterized by decreased cholinergic activity at the neuromuscular junction.
- QT Prolongation : consider observations from the thorough QT study in clinical decisions to prescribe tolterodine tartrate extended-release capsules to patients with a known history of QT prolongation or to patients who are taking Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications. ()5.9 Use in Patients with Congenital or Acquired QT Prolongation
In a study of the effect of tolterodine immediate release tablets on the QT interval [
see], 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 (PM) than extensive metabolizers (EMs). The effect of tolterodine 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.CLINICAL PHARMACOLOGYThese observations should be considered in clinical decisions to prescribe tolterodine tartrate extended-release capsules to patients with a known history of QT prolongation or to patients who are taking Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications. There has been no association of Torsade de Pointes in the international post-marketing experience with tolterodine tartrate immediate release tablets or tolterodine tartrate extended-release capsules.