Tolterodine Tartrate

DETROL Tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.

Dosage Forms And Strengths

The 2 mg capsules are blue-green with symbol and 2 printed in white ink. Sections or subsections omitted from the full prescribing information are not listed. The 4 mg capsules are blue with symbol and 4 printed in white ink.

Storage And Handling

DETROL LA Capsules are supplied as follows:

Store at 20°–25°C (68°–77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Protect from light.

Distributed by: Pharmacia & Upjohn Co, Division of Pfizer Inc, NY, NY 10017. Revised: Aug 2012

Overdosage with DETROL LA Capsules can potentially result in severe central anticholinergic effects and should be treated accordingly.

ECG monitoring is recommended in the event of overdosage. In dogs, changes in the QT interval (slight prolongation of 10% to 20%) were observed at a suprapharmacologic dose of 4.5 mg/kg, which is about 68 times higher than the recommended human dose. In clinical trials of normal volunteers and patients, QT interval prolongation was observed with tolterodine immediate release at doses up to 8 mg (4 mg bid) and higher doses were not evaluated [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

A 27-month-old child who ingested 5 to 7 tolterodine immediate release 2 mg tablets was treated with a suspension of activated charcoal and was hospitalized overnight with symptoms of dry mouth. The child fully recovered.

Tolterodine reduces spasms of the bladder muscles.

Tolterodine is used to treat overactive bladder with symptoms of urinary frequency, urgency, and incontinence.

Tolterodine may also be used for purposes not listed in this medication guide.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials Experience

The efficacy and safety of DETROL LA Capsules was evaluated in 1073 patients (537 assigned to DETROL LA; 536 assigned to placebo) who were treated with 2, 4, 6, or 8 mg/day for up to 15 months. These included a total of 1012 patients (505 randomized to DETROL LA 4 mg once daily and 507 randomized to placebo) enrolled in a randomized, placebo-controlled, double-blind, 12-week clinical efficacy and safety study.

Adverse events were reported in 52% (n=263) of patients receiving DETROL LA and in 49% (n=247) of patients receiving placebo. The most common adverse events reported by patients receiving DETROL LA were dry mouth, headache, constipation, and abdominal pain. Dry mouth was the most frequently reported adverse event for patients treated with DETROL LA, occurring in 23.4% of patients treated with DETROL LA and 7.7% of placebo-treated patients. Dry mouth, constipation, abnormal vision (accommodation abnormalities), urinary retention, and dry eyes are expected side effects of antimuscarinic agents. A serious adverse event was reported by 1.4% (n=7) of patients receiving DETROL LA and by 3.6% (n=18) of patients receiving placebo.

Table 1 lists the adverse events, regardless of causality, that were reported in the randomized, doubleblind, placebo-controlled 12-week study at an incidence greater than placebo and in greater than or equal to 1% of patients treated with DETROL LA 4 mg once daily.

Table 1. Incidence* (%) of Adverse Events Exceeding Placebo Rate and Reported in ≥1% of Patients Treated with DETROL LA (4 mg daily) in a 12- week, Phase 3 Clinical Trial

The frequency of discontinuation due to adverse events was highest during the first 4 weeks of treatment. Similar percentages of patients treated with DETROL LA or placebo discontinued treatment due to adverse events. Dry mouth was the most common adverse event leading to treatment discontinuation among patients receiving DETROL LA [n=12 (2.4%) vs. placebo n=6 (1.2%)].

Post-Marketing Experience

The following events have been reported in association with tolterodine use in worldwide postmarketing experience:

General: anaphylaxis and angioedema; Cardiovascular: tachycardia, palpitations, peripheral edema; Gastrointestinal: diarrhea; Central/Peripheral Nervous: confusion, disorientation, memory impairment, hallucinations.

Reports of aggravation of symptoms of dementia (e.g., confusion, disorientation, delusion) have been reported after tolterodine therapy was initiated in patients taking cholinesterase inhibitors for the treatment of dementia.

Because these spontaneously reported events are from the worldwide post-marketing experience, the frequency of events and the role of tolterodine in their causation cannot be reliably determined.

Read the entire FDA prescribing information for Detrol LA (Tolterodine Tartrate)

Genitourinary antispasmodic agent; a synthetic tertiary amine antimuscarinic agent.17 19

Overactive Bladder

Treatment of overactive bladder for the relief of symptoms associated with voiding such as urge urinary incontinence, urgency, and frequency.1 3 9 10 19 23 Efficacy not established in pediatric patients.1 23

Tolterodine (conventional tablets) appears to be as effective as conventional oxybutynin in reducing urinary symptoms in patients with overactive bladder3 12 and is associated with a lower incidence of dry mouth.2 3 9 12 21

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.26 The incidence of adverse effects (e.g., dry mouth) is similar between conventional tolterodine tartrate and extended-release oxybutynin.26

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.24 25

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).1 23

Does not inhibit CYP1A2, 2D6, 2C9, 2C19, or 3A4; however, may inhibit CYP2D6 at high concentrations.1 23

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP2D6: Potential pharmacokinetic interaction (increased tolterodine concentrations).1 2 10

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased tolterodine concentrations).1 23 (See Specific Drugs under Interactions.)

Specific Drugs

• Nonselective competitive antagonist at muscarinic receptors present in the bladder, salivary glands, and other organs.1 2 3 4 5 6 7 8 9 10 22 23

• Generally exhibits pharmacologic actions similar to those of other antimuscarinics.17 18

• Decreases contraction of the detrusor muscle of normal and overactive urinary bladder17 18 and increases volumes of residual urine.1 23

• May cause inhibition of salivation.2 3 4 6 9 10 19 (See Common Adverse Effects under Cautions.)

• Little or no activity at α-adrenergic receptors, histaminergic receptors, calcium-channel receptors, and the neuromuscular junction.1 2 19 23