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
Extended release capsule: 4 mg once daily; dose may be lowered to 2 mg once daily based on individual response and tolerability
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
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.
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
Yes
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
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.
Oral: Administer without regard to food; do not break, crush, or chew extended-release capsules.
Treatment of patients with an overactive bladder with symptoms of urge urinary incontinence, urgency, or frequency
Tolterodine may be confused with fesoterodine, tolcapone
Detrol may be confused with Ditropan
Beers Criteria: Tolterodine is identified in the Beers Criteria as a potentially inappropriate medication in patients 65 years and older due to its strong anticholinergic properties (Beers Criteria [AGS 2019]).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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
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
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.
Substrate of CYP2C19 (minor), CYP2C9 (minor), CYP2D6 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
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
Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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. 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
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
CYP2D6 Inhibitors (Strong): May increase the serum concentration of Tolterodine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Tolterodine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Tolterodine. Management: The maximum recommended dose of tolterodine is 2 mg per day (1 mg twice daily for immediate-release tablets or 2 mg daily for extended-release capsules) when used together with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
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
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
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. 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
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
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
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
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
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
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
Warfarin: Tolterodine may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy
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.
Adverse events were observed in some animal reproduction studies.
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.
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)
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.
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)
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.
Capsule ER 24 Hour Therapy Pack (Detrol LA Oral)
2 mg (per each): $14.67
4 mg (per each): $14.67
Capsule ER 24 Hour Therapy Pack (Tolterodine Tartrate ER Oral)
2 mg (per each): $0.80 - $13.55
4 mg (per each): $0.80 - $14.18
Tablets (Detrol Oral)
1 mg (per each): $9.01
2 mg (per each): $9.25
Tablets (Tolterodine Tartrate Oral)
1 mg (per each): $1.00 - $3.31
2 mg (per each): $1.00 - $3.40
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