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Pronunciation
(tole TER oh deen)
Generic Available (U.S.)
No
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of patients with an overactive bladder with symptoms of urinary frequency, urgency, or urge incontinence
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects were observed in some animal studies. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit to the mother outweighs the possible risk to the fetus.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to tolterodine or any component of the formulation; urinary retention; gastric retention; uncontrolled narrow-angle glaucoma
Warnings/Precautions
Concerns related to adverse effects:
• CNS effects: May cause drowsiness 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).
• 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:
• Bladder flow obstruction: Use with caution in patients with bladder flow obstruction; may increase the risk of urinary retention.
• Gastrointestinal 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. Also see QT prolongation in “Concerns related to adverse effects” above.
Adverse Reactions
As reported with immediate release tablet, unless otherwise specified
>10%: Gastrointestinal: Dry mouth (35%; extended release capsules 23%)
1% to 10%:
Cardiovascular: Chest pain (2%)
Central nervous system: Headache (7%; extended release capsules 6%), somnolence (3%; extended release capsules 3%), fatigue (4%; extended release capsules 2%), dizziness (5%; extended release capsules 2%), anxiety (extended release capsules 1%)
Dermatologic: Dry skin (1%)
Gastrointestinal: Abdominal pain (5%; extended release capsules 4%), constipation (7%; extended release capsules 6%), dyspepsia (4%; extended release capsules 3%), diarrhea (4%), weight gain (1%)
Genitourinary: Dysuria (2%; extended release capsules 1%)
Neuromuscular & skeletal: Arthralgia (2%)
Ocular: Abnormal vision (2%; extended release capsules 1%), dry eyes (3%; extended release capsules 3%)
Respiratory: Bronchitis (2%), sinusitis (extended release capsules 2%)
Miscellaneous: Flu-like syndrome (3%), infection (1%)
Postmarketing and/or case reports: Anaphylactoid reactions, angioedema, confusion, dementia aggravated, disorientation, hallucinations, memory impairment, palpitation, peripheral edema, QTc prolongation, tachycardia
Metabolism/Transport Effects
Substrate of CYP2C9 (minor), 2C19 (minor), 2D6 (major), 3A4 (major)
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. 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
AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Risk C: Monitor therapy
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Levocabastine (Nasal); Paliperidone. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Tolterodine. This is likely only of concern in CYP2D6-deficient patients (ie, "poor metabolizers") Risk D: Consider therapy modification
Cannabinoids: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoids. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Management: Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Risk D: Consider therapy modification
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Fluconazole: May decrease the metabolism of Tolterodine. This is likely only of concern in CYP2D6-deficient patients (ie, "poor metabolizers") Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Risk D: Consider therapy modification
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Risk C: Monitor therapy
Secretin: Anticholinergic Agents may diminish the stimulatory effect of Secretin. Risk D: Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
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
Ethanol/Nutrition/Herb 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.
Herb/Nutraceutical: St John's wort (Hypericum) appears to induce CYP3A enzymes.
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.
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: I.V.: 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 tablet: 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)
Dosage
Oral: Adults: Treatment of overactive bladder:
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 CYP3A4 inhibitors: 1 mg twice daily
Extended release capsule: 4 mg once a day; dose may be lowered to 2 mg daily based on individual response and tolerability
Dosing adjustment in patients concurrently taking CYP3A4 inhibitors: 2 mg daily
Elderly: Safety and efficacy in patients >64 years was found to be similar to that in younger patients; no dosage adjustment is needed based on age
Dosing adjustment in renal impairment: Use with caution (studies conducted in patients with Clcr 10-30 mL/minute):
Immediate release tablet: 1 mg twice daily
Extended release capsule: 2 mg daily
Dosing adjustment in hepatic impairment:
Immediate release tablet: 1 mg twice daily
Extended release capsule: 2 mg daily
Administration: Oral
Extended release capsule: Swallow whole; do not crush, chew, or open
Monitoring Parameters
Renal function (BUN, creatinine); hepatic function
Patient Education
Take as directed. Do not break, crush, or chew extended release medication. May cause headache, dry mouth, dizziness, nervousness, sleepiness, abdominal discomfort, diarrhea, constipation, nausea, or vomiting. Report back pain, muscle spasms, alteration in gait, or numbness of extremities; unresolved or persistent constipation, diarrhea, or vomiting; or symptoms of upper respiratory infection or flu. Report immediately any chest pain or palpitations, difficulty urinating, or pain on urination.
Geriatric Considerations
No difference in safety has been noted between elderly and younger patients, therefore, no dosage adjustment is recommended.
Dental Health: 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).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause drowsiness, dizziness, hallucinations, or nervousness
Mental Health: Effects on Psychiatric Treatment
Fluoxetine and likely paroxetine increase the serum concentration of tolterodine; however, the magnitude of this increase is small (~25%, as reported for fluoxetine) and thus no dosage adjustment is required.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release, oral, as tartrate:
Detrol® LA: 2 mg, 4 mg
Tablet, oral, as tartrate:
Detrol®: 1 mg, 2 mg
Pricing: U.S. (www.drugstore.com)
Capsule, 24-hour (Detrol LA)
2 mg (30): $156.99
4 mg (30): $163.00
Tablets (Detrol)
1 mg (60): $179.00
2 mg (60): $178.99
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
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