Tolterodine L-Tartarate

Pharmacologic Category

Anticholinergic Agent

Dosing: Adult

Treatment of overactive bladder: Oral:

Immediate release tablet: 2 mg twice daily; the dose may be lowered to 1 mg twice daily based on individual response and tolerability

Dosing adjustment in patients concurrently taking strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, ritonavir): 1 mg twice daily

Extended release capsule: 4 mg once daily; dose may be lowered to 2 mg once daily based on individual response and tolerability

Dosing adjustment in patients concurrently taking strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, ritonavir): 2 mg once daily

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Renal Impairment: Adult

Immediate release tablet: Significantly reduced renal function (studies conducted in patients with CrCl 10 to 30 mL/minute): 1 mg twice daily; use with caution

Extended release capsule:

CrCl 10 to 30 mL/minute: 2 mg once daily

CrCl <10 mL/minute: Use is not recommended; has not been studied.

Dosing: Hepatic Impairment: Adult

Immediate release tablet: Significantly reduced hepatic function: 1 mg twice daily; use with caution

Extended release capsule:

Mild to moderate impairment (Child-Pugh class A or B): 2 mg once daily

Severe impairment (Child-Pugh class C): Use is not recommended; has not been studied.

Calculations

• Creatinine Clearance by Cockcroft-Gault
• Creatinine Clearance by Cockcroft-Gault (SI units)
• Creatinine Clearance by Cockcroft-Gault with IBW
• Creatinine Clearance by Cockcroft-Gault with IBW (SI units)
• Creatinine Clearance by Jelliffe
• Creatinine Clearance by Sanaka
• Glomerular Filtration Rate by Abbreviated MDRD
• Glomerular Filtration Rate by Abbreviated MDRD (SI units)
• Glomerular Filtration Rate by MDRD
• Glomerular Filtration Rate by MDRD (IDMS-Traceable SCr)
• Glomerular Filtration Rate by MDRD (SI units)
• Glomerular Filtration Rate Estimate in African Americans by AASK Equation

Use: Labeled Indications

Treatment of patients with an overactive bladder with symptoms of urge urinary incontinence, urgency, or frequency

* See Uses in AHFS Essentials for additional information.

Clinical Practice Guidelines

Benign Prostatic Hyperplasia:

CUA, “Guideline on Male Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia (MLUTS/BPH),” 2018

Overactive Bladder:

AUA/SUFU, "Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline Amendment 2019," April 2019

Administration: Oral

ER capsule: Swallow whole; do not crush, chew, or open.

Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. IR tablet formulation is available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery.

Administration: Pediatric

Oral: Administer without regard to food; do not break, crush, or chew extended-release capsules.

Storage/Stability

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat an overactive bladder.

Frequently reported side effects of this drug

• Dizziness

• Fatigue

• Headache

• Abdominal pain

• Constipation

• Dry mouth

• Dry eyes

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Unable to pass urine

• Vision changes

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Geriatric Patients: High-Risk Medication:

Contraindications

Hypersensitivity to tolterodine or fesoterodine (both are metabolized to 5-hydroxymethyl tolterodine) or any component of the formulation; urinary retention; gastric retention; uncontrolled narrow-angle glaucoma

Warnings/Precautions

Concerns related to adverse effects:

• Angioedema: Cases of angioedema have been reported; some cases have occurred after a single dose. Discontinue immediately if angioedema and associated difficulty breathing, airway obstruction, or hypotension develop.

• CNS effects: May cause drowsiness, dizziness, and/or blurred vision, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Dose reduction or discontinuation should be considered if CNS effects occur.

• QT prolongation: Has been associated with QTc prolongation at high (supratherapeutic) doses. The manufacturer recommends caution in patients with congenital prolonged QT or in patients receiving concurrent therapy with QTc-prolonging drugs (class Ia or III antiarrhythmics). However, the extent of QTc prolongation even at supratherapeutic dosages was less than 15 msec. Individuals who are CYP2D6 poor metabolizers or in the presence of inhibitors of CYP2D6 and CYP3A4 may be more likely to exhibit prolongation.

Disease-related concerns:

• Alzheimer disease: Preliminary data suggests that long-term use of anticholinergics may potentially adversely affect the clinical course of Alzheimer disease in patients receiving cholinesterase inhibitors (Lu 2003; Sink 2008). Additional monitoring for decreases in cognition, functional abilities and increased problematic behaviors should be considered in patients with dementia receiving dual therapy with an acetylcholinesterase inhibitor and a bladder anticholinergic, such as tolterodine.

• Bladder flow obstruction: Use with caution in patients with bladder flow obstruction (eg, benign prostatic hypertrophy); may increase the risk of urinary retention.

• GI obstructive disorders: Use with caution in patients with decreased GI motility or gastrointestinal obstructive disorders (ie, pyloric stenosis); may increase the risk of gastric retention.

• Glaucoma: Use with caution in patients with controlled (treated) narrow-angle glaucoma.

• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment is required.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment is required.

Concurrent drug therapy issues:

• CYP3A4 inhibitors: Dosage adjustment is recommended in patients receiving CYP3A4 inhibitors; a lower dose of tolterodine is recommended.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Given the ability of tolterodine to antagonize central and peripheral muscarinic receptors, it has the potential to cause constipation, dry eyes, dry mouth, confusion, and urinary retention. For these reasons, it should be used with caution in the elderly. Efficacy with tolterodine is limited, with resolution of urge urinary incontinence occurring in only 85 for every 1,000 women treated. In those same 1,000 women, it would be expected 83 would have adverse effects (Shamliyan 2012).

There is a theoretical pharmacodynamic drug-drug interaction between medications with antimuscarinic/anticholinergic effects and cholinesterase inhibitors, therefore, cognitive, functional, and behavioral worsening should be monitored upon the addition of a bladder antimuscarinic, such as tolterodine. (Lu 2003; Sink 2008)

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies.

Breast-Feeding Considerations

It is not known if tolterodine is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Briggs' Drugs in Pregnancy & Lactation

• Tolterodine

Adverse Reactions

As reported with immediate release tablet, unless otherwise specified.

>10%: Gastrointestinal: Xerostomia (35%; extended release capsules: 23%)

1% to 10%:

Cardiovascular: Chest pain (2%)

Central nervous system: Headache (7%; extended release capsules: 6%), dizziness (5%; extended release capsules: 2%), fatigue (4%; extended release capsules: 2%), drowsiness (immediate and extended release: 3%), anxiety (extended release capsules: 1%)

Dermatologic: Xeroderma (1%)

Endocrine & metabolic: Weight gain (1%)

Gastrointestinal: Constipation (7%; extended release capsules: 6%), abdominal pain (5%; extended release capsules: 4%), diarrhea (4%), dyspepsia (4%; extended release capsules: 3%)

Genitourinary: Dysuria (2%; extended-release capsules: 1%)

Infection: Infection (1%)

Neuromuscular & skeletal: Arthralgia (2%)

Ophthalmic: Xerophthalmia (immediate and extended release: 3%), visual disturbance (2%; extended release capsules: 1%)

Respiratory: Flu-like symptoms (3%), bronchitis (2%), sinusitis (extended release capsules: 2%)

<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, confusion, dementia (aggravated), disorientation, hallucination, memory impairment, palpitations, peripheral edema, prolonged QT interval on ECG, tachycardia

* See Cautions in AHFS Essentials for additional information.

Toxicology

• Anticholinergic Agents

Metabolism/Transport Effects

Substrate of CYP2C19 (minor), CYP2C9 (minor), CYP2D6 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Asunaprevir is contraindicated in combination with drugs metabolized by CYP2D6 for which increased levels are associated with ventricular arrhythmias and sudden death (eg, thioridazine, flecanide, propafenone); use caution with any CYP2D6 substrate. Risk D: Consider therapy modification

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol. Risk C: Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination

CloBAZam: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination. Some combinations are specifically contraindicated by manufacturers; others may have recommended dose adjustments. If combined, monitor for increased substrate effects. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Tolterodine. Management: The maximum recommended adult dose of tolterodine is 2 mg/day when used together with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Dacomitinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. Risk D: Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Imatinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination

Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy

Opioid Agonists: Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapy

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Panobinostat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Perhexiline: CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Risk X: Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination

QuiNINE: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy

Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

VinBLAStine: May increase the serum concentration of Tolterodine. Management: Reduce tolterodine dose to 1 mg twice daily (regular release formulation) or 2 mg daily (extended release formulation) (adult doses) and monitor for increased levels/effects of tolterodine with initiation of vinblastine therapy. Risk D: Consider therapy modification

Warfarin: Tolterodine may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy

Food Interactions

Food increases bioavailability (~53% increase) of tolterodine tablets (dose adjustment not necessary); does not affect the pharmacokinetics of tolterodine extended release capsules. As a CYP3A4 inhibitor, grapefruit juice may increase the serum level and/or toxicity of tolterodine, but unlikely secondary to high oral bioavailability. Management: Monitor patients closely with concurrent grapefruit juice use.

Genes of Interest

• CYP2D6 - Tolterodine
• Cytochrome P450 3A4

Monitoring Parameters

Anticholinergic effects (ie, dry mouth, constipation, dizziness); renal function (BUN, creatinine); hepatic function; postvoid residual (PVR) urine volume prior to initiation of therapy (ACOG 2015)

Advanced Practitioners Physical Assessment/Monitoring

Obtain renal function tests and liver function tests; dosage adjustment may be needed. Obtain postvoid residual urine volume prior to initiation. Assess other medicines patient may be taking; alternate therapy or dosage adjustments may be needed. Assess for anticholinergic adverse effects.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor for and educate patient to report anticholinergic adverse effects (dry mouth, constipation, or dizziness).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Extended Release 24 Hour, Oral, as tartrate:

Detrol LA: 2 mg, 4 mg

Generic: 2 mg, 4 mg

Tablet, Oral, as tartrate:

Detrol: 1 mg, 2 mg

Generic: 1 mg, 2 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Extended Release 24 Hour, Oral, as tartrate:

Detrol LA: 2 mg, 4 mg [contains fd&c blue #2 (indigotine)]

Generic: 2 mg, 4 mg

Tablet, Oral, as tartrate:

Detrol: 1 mg, 2 mg

Generic: 1 mg, 2 mg

Anatomic Therapeutic Chemical (ATC) Classification

• G04BD07

Generic Available (US)

Yes

Pricing: US

Capsule ER 24 Hour Therapy Pack (Detrol LA Oral)

2 mg (per each): $14.60

4 mg (per each): $14.60

Capsule ER 24 Hour Therapy Pack (Tolterodine Tartrate ER Oral)

2 mg (per each): $8.03 - $13.55

4 mg (per each): $8.03 - $14.18

Tablets (Detrol Oral)

1 mg (per each): $8.59

2 mg (per each): $8.82

Tablets (Tolterodine Tartrate Oral)

1 mg (per each): $3.31

2 mg (per each): $3.40

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Tolterodine is a competitive antagonist of muscarinic receptors. In animal models, tolterodine demonstrates selectivity for urinary bladder receptors over salivary receptors. Urinary bladder contraction is mediated by muscarinic receptors. Tolterodine increases residual urine volume and decreases detrusor muscle pressure.

Pharmacodynamics/Kinetics

Absorption: Immediate release tablet: Rapid; ≥77%

Distribution: IV: Vd: 113 ± 27 L

Protein binding: >96% (primarily to alpha1-acid glycoprotein)

Metabolism: Extensively hepatic, primarily via CYP2D6 to 5-hydroxymethyltolterodine (active) and 3A4 usually (minor pathway). In patients with a genetic deficiency of CYP2D6, metabolism via 3A4 predominates.

Bioavailability: Immediate release tablet: Increased 53% with food

Half-life elimination:

Immediate release tablet: Extensive metabolizers: ~2 hours; Poor metabolizers: ~10 hours

Extended release capsule: Extensive metabolizers: ~7 hours; Poor metabolizers: ~18 hours

Time to peak: Immediate release tablet: 1-2 hours; Extended release capsule: 2-6 hours

Excretion: Urine (77%); feces (17%); primarily as metabolites (<1% unchanged drug) of which the active 5-hydroxymethyl metabolite accounts for 5% to 14% (<1% in poor metabolizers); as unchanged drug (<1%; <2.5% in poor metabolizers)

Pharmacodynamics/Kinetics: Additional Considerations

Renal 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.

Geriatric: Serum concentrations of immediate-release tolterodine and 5-HMT were 20% to 50% higher in elderly patients.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

The anticholinergic effects of tolterodine are selective for the urinary bladder rather than salivary glands; xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation).

Effects on Bleeding

No information available to require special precautions

Related Information

• Beers Criteria 2019: Potentially Inappropriate Medication Use in Older Adults ≥65 Years of Age
• Oral Medications That Should Not Be Crushed or Altered

Index Terms

Tolterodine Tartrate

FDA Approval Date

March 25, 1998

References

American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 155: Urinary Incontinence in Women. Obstet Gynecol. 2015;126(5):e66-81.[PubMed 26488524]

2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694.[PubMed 30693946]10.1111/jgs.15767

Detrol (tolterodine) [prescribing information]. New York, NY: Pfizer; November 2016.

Detrol LA (tolterodine) [prescribing information]. New York, NY: Pfizer; July 2018.

Lu CJ, Tune LE. Chronic exposure to anticholinergic medications adversely affects the course of Alzheimer disease. Am J Geriatr Psychiatry. 2003;11(4):458-461.[PubMed 12837675]

Shamliyan T, Wyman J, Kane RL. Nonsurgical Treatments for Urinary Incontinence in Adult Women: Diagnosis and Comparative Effectiveness. Comparative Effectiveness Review No. 36. (Prepared by the University of Minnesota Evidence-based Practice Center under Contract No. HHSA 290-2007-10064-I.) AHRQ Publication No. 11(12)-EHC074-EF. Rockville, MD. Agency for Healthcare Research and Quality. April 2012. http://www.effectivehealthcare.ahrq.gov/reports/final.cfm.

Sink KM, Thomas J 3rd, Xu H, Craig B, Kritchevsky S, Sands LP. Dual use of bladder anticholinergics and cholinesterase inhibitors: long-term functional and cognitive outcomes. J Am Geriatr Soc. 2008;56(5):847-853. doi: 10.1111/j.1532-5415.2008.01681.x.[PubMed 18384584]

Brand Names: International

Bapter (IN); BeiKe (CN); Breminal (AR); Caristenol (IE); Conturine (EG); Defur (PL); Detrodin SR (KR); Detrusitol (AE, AR, AT, AU, BE, BG, BH, BR, BZ, CL, CN, CO, CR, CY, CZ, DE, DO, EC, EE, ES, FI, FR, GB, GR, GT, HN, HU, IE, IL, IN, IQ, IR, IS, IT, JO, JP, KW, LB, LT, LU, LV, LY, MT, MX, MY, NI, NL, NZ, OM, PA, PE, PH, PK, PL, QA, RU, SA, SE, SG, SI, SK, SV, SY, TR, TW, UA, VE, YE); Detrusitol Retard (BE, BH, BR, DK, EG, KW, PT, SA); Detrusitol SR (BG, CH, CL, CO, CZ, HR, IL, KR, LT, MY, NO, PE, RO, SE, SG, SK, TH, VE); Detrusitol XL (GB, IE); Effosomyl XL (GB); Eltoven (CL, PY); Fluserin (UY); Le Zai (CN); Mariosea XL (GB); Neditol XL (GB); Roliten (LK); Sedoter (EG); Tendrotil (IE); Toladine (LK); Toldin (BD); Tolevo (EG); Toltem (AR); Tolter (BD, LK); Tolterox (UY); Toltin (UY); Toltrex (BD); Tolusitol (IE); Torq (IN); Torq SR (IN); Trusitev (IE); Uretol SR (KR); Urginol (AR); Uridin (TW); Uridyne (PK); Uritol (BD); Uro-Q (KR); Uroflow (CZ, EE); Urolina (BE); Urositol (KR); Urotin S SR (KR); Urotol (UA); Urotrol (CR, DO, ES, GT, HN, NI, PA, SV)

Last Updated 5/1/20