Brand name: Detrol
Drug class: Antimuscarinics
VA class: AU350
Chemical name: (R)-2-[3-[Bis(1-methylethyl)amino]-1-phenylpropyl]-4-methylphenol [R-(R*,R*)]-2,3-dihydroxybutanedioate (1:1) salt
Molecular formula: C₂₂H₃₁NO•C₄H₆O₆
CAS number: 124937-52-6

Medically reviewed by Drugs.com on Apr 21, 2023. Written by ASHP.

Introduction

Genitourinary antispasmodic agent; a synthetic tertiary amine antimuscarinic agent.

Uses for Tolterodine

Overactive Bladder

Treatment of overactive bladder for the relief of symptoms associated with voiding such as urge urinary incontinence, urgency, and frequency. Efficacy not established in pediatric patients.

Tolterodine (conventional tablets) appears to be as effective as conventional oxybutynin in reducing urinary symptoms in patients with overactive bladder and is associated with a lower incidence of dry mouth.

Tolterodine (2 mg twice daily as conventional tablets) appears to be less effective than extended-release oxybutynin (10 mg once daily as extended-release tablets) in reducing urinary symptoms in patients with overactive bladder. The incidence of adverse effects (e.g., dry mouth) is similar between conventional tolterodine tartrate and extended-release oxybutynin.

Single daily doses of extended-release capsules of tolterodine tartrate appear to be slightly more effective in relieving certain urinary symptoms (i.e., urge incontinence) than 2 daily doses of conventional tablets of the drug.

Related/similar drugs

Botox, estradiol, oxybutynin, Myrbetriq, Gemtesa, solifenacin, Detrol

Tolterodine Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals. (See Food under Pharmacokinetics.) Some clinicians recommend administering tolterodine tartrate in a consistent manner relative to food intake.

Extended-release capsules should be administered with adequate amounts of fluid and swallowed whole.

Dosage

Available as tolterodine tartrate; dosage expressed in terms of the salt.

Adults

Overactive Bladder

Oral

Conventional tablets: Initially, 2 mg twice daily. May reduce dosage to 1 mg twice daily according to individual response and tolerance.

Extended-release capsules: Initially, 4 mg once daily. May reduce dosage to 2 mg once daily according to individual response and tolerance; however, efficacy data for this lower dosage are limited.

Special Populations

Renal Impairment

1 mg twice daily (as conventional tablets) or 2 mg once daily (as extended-release capsules) in patients with substantially reduced renal function.

Hepatic Impairment

1 mg twice daily (as conventional tablets) or 2 mg once daily (as extended-release capsules) in patients with substantially reduced hepatic function.

Geriatric Patients

No dosage adjustments required for otherwise healthy geriatric patients. (See Geriatric Use under Cautions.)

Cautions for Tolterodine

Contraindications

• Urinary retention.

• Gastric retention.

• Uncontrolled angle-closure glaucoma.

• Known hypersensitivity to tolterodine or any ingredient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Anaphylactoid reactions (e.g., angioedema) reported during postmarketing surveillance; however, a causal relationship not established.

General Precautions

Urinary or Gastric Retention

Risk of urinary or gastric retention; use with caution in patients with clinically important bladder outflow obstruction or GI obstructive disorders (e.g., pyloric stenosis).

Decreased GI Motility

Use with caution in patients with decreased GI motility.

Angle-closure Glaucoma

Use with caution in patients receiving therapy for angle-closure glaucoma.

Myasthenia Gravis

Use with caution in patients with myasthenia gravis.

Cardiovascular Effects

Prolongation of QT_c interval observed following administration of therapeutic (2 mg twice daily) and supratherapeutic (4 mg twice daily) dosages in healthy adults. Effect is more pronounced with 8-mg daily dosage and in individuals with poor-oxidizer phenotype. The 8-mg daily dosage also associated with more pronounced increase in heart rate than 4-mg daily dosage. Associated torsades de pointes not reported during postmarketing experience.

Consider effect on QT_c interval when deciding to use tolterodine in patients with history of QT interval prolongation or in those receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk in mice; not known whether distributed into human milk. Discontinue nursing or the drug.

Pediatric Use

Efficacy not established in children <18 years of age.

In patients 5–10 years of age with urinary frequency and urge incontinence, incidence of urinary tract infections was higher following therapy with tolterodine extended-release capsules than with placebo (6.6 versus 4.5%). Aggressive, abnormal, and hyperactive behavior and attention disorders reported in 2.9% of patients receiving extended-release capsules compared with 0.9% of those receiving placebo.

Geriatric Use

No substantial differences in safety relative to younger adults. (See Absorption: Special Populations, under Pharmacokinetics.) Aggravation of symptoms of dementia (e.g., confusion, disorientation, delusion) reported during postmarketing experience after initiation of tolterodine in patients taking acetylcholinesterase inhibitors for the treatment of dementia.

Renal or Hepatic Impairment

Renal or hepatic impairment may substantially affect the disposition of tolterodine; dosage reduction necessary in patients with substantially reduced renal or hepatic function. (See Renal and Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

Dry mouth, headache, constipation, abdominal pain, vertigo/dizziness.

Drug Interactions

Appears to be metabolized principally by CYP2D6 in individuals with the extensive-oxidizer phenotype (i.e. those with CYP2D6); metabolized by CYP3A4 in individuals with the poor-oxidizer phenotype (i.e. those devoid of CYP2D6).

Does not inhibit CYP1A2, 2D6, 2C9, 2C19, or 3A4; however, may inhibit CYP2D6 at high concentrations.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP2D6: Potential pharmacokinetic interaction (increased tolterodine concentrations).

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased tolterodine concentrations). (See Specific Drugs under Interactions.)

Specific Drugs

Tolterodine Pharmacokinetics

Absorption

Bioavailability

≥77% of a dose is absorbed rapidly from the GI tract.

Absolute oral bioavailability is variable (10–74%) and may depend on a patient’s genetically determined ability to metabolize the drug. The absolute bioavailability is higher in individuals with the poor-oxidizer phenotype (i.e. those devoid of CYP2D6) than that in patients with the extensive-oxidizer phenotype (i.e. those with CYP2D6).

Peak and trough serum tolterodine concentrations achieved with extended-release capsules are approximately 75 and 150%, respectively, of those achieved with conventional tablets.

Peak serum concentrations usually occur within 1–2 hours following administration of conventional tablets or 2–6 hours following administration of extended-release capsules.

Onset

Following oral administration in healthy men, inhibitory effects on urinary bladder function were observed within 1 hour.

Duration

Following oral administration in healthy men, inhibitory effects on urinary bladder function persisted for at least 5 hours.

Food

Food may increase oral bioavailability of conventional tablets; however, such changes are not expected to be clinically important. Food does not appear to alter the pharmacokinetics of extended-release capsules. (See Administration under Dosage and Administration.)

Special Populations

In geriatric adults receiving conventional tablets, serum concentrations of tolterodine and 5-hydroxymethyl metabolite (5-hydroxymethyl tolterodine) may be similar or possibly higher than those observed in younger adults. (See Geriatric Use under Cautions.)

Following administration of extended-release capsules, pediatric patients (11–15 years of age) with the extensive-oxidizer phenotype have low serum concentrations of tolterodine and high concentrations of 5-hydroxymethyl metabolite, while patients with the poor-oxidizer phenotype had high concentrations of tolterodine and negligible concentrations of 5-hydroxymethyl metabolite.

In patients with renal impairment, serum concentrations of tolterodine tartrate and 5-hydroxymethyl metabolite following administration of conventional tablets are twofold to threefold or higher than in healthy individuals. (See Renal Impairment under Dosage and Administration.)

Distribution

Extent

Distribution of tolterodine not fully characterized. Tolterodine and its 5-hydroxymethyl metabolite do not appear to distribute extensively into erythrocytes.

Distributed into milk in mice; not known whether tolterodine crosses the placenta or is distributed into human milk.

Plasma Protein Binding

Tolterodine: approximately 96.3% (mainly α₁-acid glycoprotein. )

5-hydroxymethyl metabolite: approximately 64%.

Elimination

Metabolism

Undergoes extensive first-pass metabolism in the liver by CYP2D6 to 5-hydroxymethyl tolterodine (active metabolite) in individuals with the extensive-oxidizer phenotype. (Fesoterodine, another antimuscarinic agent used in the treatment of overactive bladder, also is metabolized to 5-hydroxymethyl tolterodine; however, fesoterodine metabolism to 5-hydroxymethyl tolterodine is via nonspecific esterases.)

Metabolized by CYP3A4 to N-dealkylated tolterodine (inactive metabolite) in individuals with the poor-oxidizer phenotype (i.e. those devoid of CYP2D6); undergoes only limited first-pass metabolism in these individuals.

Approximately 93% of Caucasians exhibit the extensive-oxidizer phenotype and about 7% exhibit the poor-oxidizer phenotype.

Elimination Route

Following oral administration, approximately 77 and 17% of administered dose was recovered within 7 days in urine and feces, respectively, principally within the first 24 hours.

Half-life

Special Populations

Elimination half-life of tolterodine prolonged in patients with hepatic impairment. (See Hepatic Impairment under Dosage and Administration.)

Stability

Storage

Oral

Extended-Release Capsules and Conventional Tablets

25°C (may be exposed to 15–30°C).

Actions

• Nonselective competitive antagonist at muscarinic receptors present in the bladder, salivary glands, and other organs.

• Generally exhibits pharmacologic actions similar to those of other antimuscarinics.

• Decreases contraction of the detrusor muscle of normal and overactive urinary bladder and increases volumes of residual urine.

• May cause inhibition of salivation. (See Common Adverse Effects under Cautions.)

• Little or no activity at α-adrenergic receptors, histaminergic receptors, calcium-channel receptors, and the neuromuscular junction.

Advice to Patients

• Risk of blurred vision, dizziness, or drowsiness. Use caution when engaging in potentially hazardous activities until effects on individual are known.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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