E-lactancia.org

PRODUCT MONOGRAPH PRDETROL LA*
(tolterodine L-tartrate extended release capsules)
2 mg and 4 mg Capsules
Anticholinergic - Antispasmodic Agent
Date of Revision:
17,300 Trans-Canada Highway
2 February 2015
Kirkland, Quebec H9J 2M5
* TM Pfizer Enterprises SARL
Pfizer Canada Inc., Licensee
Pfizer Canada Inc. 2011


Submission Control No: 180260
Table of Contents

DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 2 of 32 PRDETROL LA*
(tolterodine L-tartrate extended release capsules)
PART I: HEALTH PROFESSIONAL INFORMATION

SUMMARY PRODUCT INFORMATION
Dosage Form / Clinically Relevant Nonmedicinal Ingredients
Administration Strength
Blue-green (2mg)
Blue (4mg)
Starch, sucrose, hypromellose, ethylcellulose, ammonium hydroxide, medium chain triglycerides, oleic acid, gelatin and FD & C Blue 2. The 2 mg capsules also contain yellow iron oxide. Both capsule strengths are imprinted with a pharmaceutical grade ink, Opacode White S-1-7085 that contains shellac glaze, titanium dioxide, ammonium hydroxide, propylene glycol and simethicone.
INDICATIONS AND CLINICAL USE
DETROL LA* (tolterodine L-tartrate extended release capsules) is indicated for:
 the symptomatic management of patients with an overactive bladder with symptoms of urinary
frequency, urgency, or urge incontinence, or any combination of these symptoms.(see
WARNINGS AND PRECAUTIONS and DETAILED PHARMACOLOGY,
Electrophysiology).

Geriatrics (≥ 65 years of age): No overall differences were observed in safety between older
(patients ≥ 65 years) and younger patients (patients < 65 years) on tolterodine extended release
capsules; and therefore, no dosage adjustment for elderly patients is recommended (see
WARNINGS AND PRECAUTIONS, Special Populations, DETAILED PHARMACOLOGY
and CLINICAL TRIALS).



DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 3 of 32 CONTRAINDICATIONS

DETROL LA (tolterodine L-tartrate extended release capsules) is contraindicated in patients with:
 urinary
gastric retention, uncontrolled narrow angle glaucoma, a known hypersensitivity to this drug or to any ingredient in the formulation or component
of the container (see PHARMACEUTICAL INFORMATION).


WARNINGS AND PRECAUTIONS
Gastrointestinal and Genitourinary

Patients at Risk of Urinary Retention and Gastric Retention
DETROL LA (tolterodine L-tartrate extended release capsules) should be administered with
caution to patients with clinically significant bladder outflow obstruction because of the risk of
urinary retention, to patients at risk of decreased gastrointestinal motility, and to patients with
gastrointestinal obstructive disorders, such as pyloric stenosis, because of the risk of gastric
retention (see CONTRAINDICATIONS).
Cardiovascular
Patients with Congenital or Acquired QT Prolongation:
In a clinical QT study, the QT prolonging effect of two times the highest labeled dose of tolterodine
(8 mg/per day in divided doses, given as DETROL immediate release tablets) was 50% to 60%
less than that of the active control moxifloxacin (400 mg) at its labeled dose. At the recommended
therapeutic dose (4 mg daily) of DETROL (tolterodine L-tartrate tablets), the effect was lower.
Since the QT prolongation effect is in linear relationship with exposure, any QT effect of DETROL
LA (tolterodine L-tartrate extended release capsules) would also be expected to be similarly lower.
This study, however, was not designed to make direct statistical comparisons between drugs,
tolterodine formulations, or dose levels.

The clinical relevance of these findings will depend on individual patient risk factors and
susceptibilities present. Particular care should be exercised in patients who are at an increased risk
of experiencing torsade de pointes during treatment with QT/QTc-prolonging drugs. This
especially holds true in patients with abnormally long baseline QT/QTc intervals or when taking
potent CYP3A4 inhibitors (see DRUG INTERACTIONS, Drug-Drug Interactions, DOSAGE
AND ADMINISTRATION, DETAILED PHARMACOLOGY, Electrophysiology).
In the general population, the risk factors for torsade de pointes include, but are not limited to, the following:  elderly (65 years);
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 4 of 32  genetic variants affecting cardiac ion channels or regulatory proteins, especially congenital long QT syndrome;  family history of sudden cardiac death at <50 years;  cardiac disease (e.g., myocardial ischemia or infarction, congestive heart failure, left ventricular hypertrophy, cardiomyopathy);  demonstrated history of arrhythmias (especially ventricular arrhythmias, atrial fibrillation, or recent conversion from atrial fibrillation);  bradycardia (<50 beats per minute);  acute neurological events (e.g., intracranial or subarachnoid haemorrhage, stroke, intracranial  electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypocalcemia);  nutritional deficits (e.g., eating disorders, extreme diets);  diabetes mellitus;  autonomic neuropathy;  hepatic or renal dysfunction if relevant to the elimination of the drug.
Approximately 7% of Caucasians are poor metabolizers of CYP2D6 substrates. A
pharmacokinetic/pharmacodynamic model estimated that QTc interval increases in poor
metabolizers treated with tolterodine 2 mg BID are comparable to those observed in extensive
metabolizers receiving 4 mg BID.
Discontinuation of the drug should be considered if symptoms suggestive of arrhythmia occur.

Aggravation with Pre-existing Cardiac Conditions
Although there are no clinical trial or post-marketing data to confirm the potential for DETROL
LA to aggravate certain pre-existing cardiac conditions, this product is in the class anticholinergic
medications which are known to have cardiac effects. Prescribers should therefore use caution when
prescribing DETROL LA to patients with ischemic heart disease, congestive heart failure, cardiac
arrhythmias, or tachycardia.

Neurologic
DETROL LA should be used with caution in patients with myasthenia gravis.

Ophthalmologic

Controlled Narrow Angle Glaucoma
DETROL LA should be used with caution in patients being treated for narrow angle glaucoma.
Hepatic/Biliary/Pancreatic/Renal

Patients with impaired hepatic function and patients with renal impairment should not receive doses
of DETROL LA greater than 2 mg daily (see DETAILED PHARMACOLOGY,
Pharmacokinetics in Special Populations).

DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 5 of 32
Special Populations
Pregnant Women: Studies in mice have shown that at doses of 30 to 40 mg/kg/day, tolterodine
caused embryolethality, reduced fetal weight, and increased incidence of fetal abnormalities (cleft
palate, digital abnormalities, intra-abdominal hemorrhage, various skeletal abnormalities, primarily
reduced ossification in mice). At these doses, AUC values were about 20- to 25-fold higher than in
humans. At doses of 20 mg/kg/day (AUC value was about 15-fold higher than in humans), no
anomalies or malformations were seen in mice. There are no studies of tolterodine in pregnant
women. Therefore, DETROL LA should be used during pregnancy only if the potential benefit for
the mother justifies the potential risk for the fetus. Women of childbearing potential should be
considered for treatment only if using adequate contraception (see TOXICOLOGY).
Nursing Women: Tolterodine is excreted into the milk in mice. It is not known whether
tolterodine is excreted in human milk. Because many drugs are excreted into human milk,
administration of DETROL LA should be avoided during nursing.
Pediatrics: The safety and effectiveness of DETROL LA in pediatric patients have not been
established.
Geriatrics (65 – 93 years of age): Of the 1120 patients who were treated in the four, phase III, 12-
week clinical studies of DETROL, 474 (42%) were 65 to 91 years of age. No overall differences in
safety were observed between the older and younger patients.
Of the 1526 patients who were treated in the 12-week clinical study comparing DETROL LA and
tolterodine immediate release tablets versus placebo, 642 (42%) were 65 to 93 years of age. No
overall differences in safety were observed between the older and younger patients (see
DETAILED PHARMACOLOGY, Pharmacokinetics in Special Populations).
Monitoring and Laboratory Tests

Monitoring of the QT/QTc interval and/or serum electrolyte levels may be appropriate in high risk
patients who are being treated with DETROL LA, such as:
 patients with known congenital or acquired QT/QTc prolongation or electrolyte  patients with impaired hepatic or renal function or other comorbid conditions that may increase tolterodine exposure or cause QT/QTc prolongation;  patients who are taking drugs that have been associated with QT/QTc prolongation and/or torsade de pointes such as Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications, or those taking potent CYP3A4 inhibitors.
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 6 of 32 (see WARNINGS AND PRECAUTIONS, Cardiovascular, DRUG INTERACTIONS, Drug-
Drug Interactions, DOSAGE AND ADMINISTRATION, DETAILED PHARMACOLOGY,
Electrophysiology).
Discontinuation of the drug should be considered if symptoms suggestive of arrhythmia occur or if
the QT/QTc interval becomes markedly prolonged.

Information For Patients
The ability to drive and use machinery may be negatively affected. Patients should be advised to
exercise caution.
ADVERSE REACTIONS
Adverse Drug Reaction Overview
In a large randomized, multicenter, double-blind, 12-week study, patients treated with DETROL
LA (tolterodine L-tartrate extended release capsules), 4 mg once daily (N=505), tolterodine
immediate release tablets, 2 mg twice daily (N=512), or placebo (N=507), were evaluated for
safety.
DETROL LA, 4 mg once daily, was generally well tolerated, with an overall incidence of adverse
events comparable to tolterodine immediate release tablets, 2 mg twice daily, and placebo. 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, 30.5% in patients treated with
tolterodine immediate release tablets and 7.7% of placebo-treated patients. The overall dry mouth
rate for patients taking DETROL LA, in this single pivotal trial, was 23% lower than for
tolterodine immediate release tablets (P<0.02).
Adverse events considered to be related to treatment with DETROL LA,
tolterodine immediate release tablets, versus placebo
DETROL LA
Tolterodine
immediate
extended release
release tablets
Dizziness/Vertigo 2.2%
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 7 of 32 Dry mouth, constipation, abnormal vision (accommodation abnormalities), urinary retention, and
dry eyes are expected side effects of antimuscarinic agents.
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, tolterodine immediate
release tablets or placebo, discontinued treatment due to adverse events; the most common adverse
events associated with discontinuation were dry mouth (1.6%), headache (1.0%), and constipation
(0.7%).
Clinical Trial Adverse Drug Reactions
Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.
The following table lists the adverse events reported in ≥ 5% or more of patients treated with
DETROL LA, 4 mg once daily, in the 12-week study. The adverse events were reported regardless
of causality.
Incidence (%) of Adverse Events that Occurred in ≥ 5% of Patients
Treated with DETROL LA and tolterodine immediate release tablets in a 12-week Controlled Clinical
DETROL LA
Tolterodine
immediate release
extended release
capsules)
2 mg twice daily
4 mg Once Daily
% Patients Reporting Serious Events % Patients Discontinuing due to Adverse
Less Common Clinical Trial Adverse Drug Reactions (1% to < 5%)
Other events reported by 1% to < 5% of patients treated with DETROL LA and numerically
greater than those reported for patients receiving placebo are listed in order of descending
frequency: abdominal pain, dry eyes, urinary tract infection, dyspepsia, upper respiratory tract
infection, somnolence, dizziness, fatigue, flatulence, sinusitis, edema, pain, abnormal vision, and
dysuria.

DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 8 of 32 Over 400 patients treated for up to 6 months with DETROL LA, 4 mg once daily, had an overall
incidence and adverse event profile similar to those patients treated with DETROL LA for
12 weeks.

Post-Market Adverse Drug Reactions
The following events have been reported in association with tolterodine use in clinical practice:
anaphylactoid reactions (including angioedema), tachycardia, palpitations, peripheral edema,
hallucinations, disorientation, memory impairment, and diarrhea.
Cholinesterase Inhibitors: Worsening 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.
DRUG INTERACTIONS

Overview

Concomitant medication with other drugs that possess antimuscarinic properties may result in more
pronounced therapeutic and/or adverse effects. Conversely, the therapeutic effect of tolterodine
may be reduced by concomitant administration of muscarinic receptor agonists.
Drug-Drug Interactions
Effects of Other Drugs on DETROL LA

Drugs Which Prolong the QT/QTc Interval: Drugs that have been associated with QT/QTc interval
prolongation and/or torsade de pointes include, but are not limited to, the examples in the following
list. Chemical/pharmacological classes are listed if some, although not necessarily all, class
members have been implicated in QT/QTc prolongation and/or torsade de pointes:
 Antiarrhythmics (Class IA, e.g., quinidine, procainamide, disopyramide; Class III, e.g., amiodarone, sotalol, ibutilide; Class IC, e.g., flecainide, propafenone);  Antipsychotics (e.g., thioridazine, chlorpromazine, pimozide, haloperidol, droperidol);  Antidepressants (e.g., amitriptyline, imipramine, maprotiline, fluoxetine, venlafexine);  Opioids (e.g., methadone);  Antibacterials (e.g., erythromycin, clarithromycin, telithromycin, moxifloxacin,  Antimalarials (e.g., quinine);  Pentamidine;  Azole antifungals (e.g., ketoconazole, fluconazole, voriconazole);  Gastrointestinal drugs (e.g., domperidone, dolasetron, ondasetron);  B2-adrenoreceptor agonist (salmeterol, formoterol);
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 9 of 32
This list of potentially interacting drugs is not comprehensive. Prior to initiating drug treatment in
the presence of concomitant medications, physicians should consult current scientific literature for
information on the ability of newly approved drugs to prolong the QT/QTc interval, inhibit the
metabolizing enzyme or transporter, or cause electrolyte disturbances, as well for older drugs for
which these effects have recently been established (see WARNINGS AND PRECAUTIONS).
Cytochrome P450 3A4 inhibitors: Patients treated with ketoconazole or other potent CYP3A4
inhibitors such as other azole antifungals (e.g., itraconazole, miconazole) or macrolide antibiotics
(e.g., erythromycin, clarithromycin) or cyclosporine or vinblastine, should not receive doses of
DETROL LA(tolterodine L-tartrate extended release capsules) greater than 2 mg daily (see
DETAILED PHARMACOLOGY, Drug Interactions).
Fluoxetine: Fluoxetine, a potent inhibitor of P450 2D6, inhibits significantly the metabolism of
tolterodine in extensive metabolizers. The sum of unbound serum concentrations of tolterodine and
the 5-hydroxymethyl derivative (DD 01) is 25% higher when the two drugs are administered
concomitantly. No dose adjustment is required (see DETAILED PHARMACOLOGY, Drug
Interactions).
Effects of DETROL LA on Other Drugs

Other Drugs Metabolized by P450 2D6: The potential effect of tolterodine on the pharmacokinetics
of drugs that are metabolized by P450 2D6 (such as flecainide, vinblastine, carbamazepine, tricyclic
antidepressants) has not been formally evaluated (see DETAILED PHARMACOLOGY, Drug
Interactions).
Diuretics: Coadministration of diuretics (such as indapamide, hydrochlorothiazide, triamterene,
bendroflumethiazide, chlorothiazide, methylchlorothiazide, or furosemide) with DETROL (2 mg,
twice daily) did not cause any adverse ECG effects, however, in the presence of diuretics causing
hypokalemia, and, concomitant medications known or suspected to cause adverse ECG effects
(such as QT/QTC prolongation), the physician is advised to exercise caution and advise the patient
about the signs and symptoms of cardiac arrhythmia (see DETAILED PHARMACOLOGY, Drug
Interactions).
Oral Contraceptives: Clinical drug interaction studies have shown that there are no known
interactions between tolterodine immediate release tablets and oral contraceptives (ethinyl
estradiol/levonorgestrel).
Warfarin: Clinical drug interaction studies have shown that there are no known interactions
between tolterodine immediate release tablets and warfarin.

Concomitant use of DETROL LA with alpha-blockers in men

DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 10 of 32 DETROL LA efficacy has not been established in studies of men on an alpha-blocker therapy. The
two trials conducted in men with overactive bladder symptoms (OAB) with and without benign
prostatic hyperplasia or in men with persistent OAB symptoms on alpha-blocker therapy
demonstrated that DETROL LA, in addition to an alpha-blocker therapy, showed no excess
incidence of acute urinary retention. However, in these studies, the incidence of adverse events such
as dry mouth, constipation, nasal congestion, ejaculation failure, headache, and dysuria was
increased in patients treated with an alpha-blocker in combination with DETROL LA (n=554)
compared to those patients treated with an alpha-blocker alone (n=538). An increase in
discontinuation due to adverse events was also observed in patients treated with an alpha-blocker in
combination with DETROL LA (7%) compared to those treated with an alpha-blocker alone (3%).
DETROL LA should be administered with caution in men who are suspicious of having bladder
outlet obstruction (see WARNINGS AND PRECAUTIONS, Gastrointestinal and Genitourinary).
Drug-Food Interactions

Food intake does not result in clinically relevant changes in the pharmacokinetic profile of either the
tolterodine immediate release tablets or extended release capsules.

Drug-Herb Interactions
Interaction with herbal products has not been established.

Drug-Laboratory Interactions
Interactions between tolterodine and laboratory tests have not been studied.
Patient Counselling
Patients should be informed that antimuscarinic agents such as DETROL LA (tolterodine L-
tartrate extended release capsules) may produce blurred vision or dizziness.
DOSAGE AND ADMINISTRATION
Dosing Considerations
Dosing of DETROL LA (tolterodine L- tartrate extended release capsules) may be affected by the
following:

individual response and tolerability impaired hepatic function and renal impairment potent CYP3A4 inhibitors
(see WARNINGS AND PRECAUTIONS and DOSAGE AND ADMINISTRATION,
Recommended Dose and Dosage Adjustment)
Recommended Dose and Dosage Adjustment

DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 11 of 32 The initial recommended maximum dose of DETROL LA (tolterodine L- tartrate extended release
capsules) is 4 mg once daily. The dose may be reduced to 2 mg once daily based on individual
response and tolerability. However, limited efficacy data are available for DETROL LA 2 mg
once daily. For patients with impaired hepatic function and patients with renal impairment, the
recommended dose is 2 mg once daily (see WARNINGS AND PRECAUTIONS). No dosage
adjustment for elderly patients (≥ 65 years of age) is recommended (see WARNINGS AND
PRECAUTIONS, Special Populations and DETAILED PHARMACOLOGY).
Patients treated with potent CYP3A4 inhibitors should not receive doses of DETROL LA greater
than 2 mg once daily (see WARNINGS AND PRECAUTIONS).
The maximum recommended daily dose of 4 mg should not be exceeded.
Administration
DETROL LA can be taken with food. It should be swallowed whole.
OVERDOSAGE
The highest dose of tolterodine tartrate given to human volunteers was 12.8 mg as single dose. The
most severe adverse events observed were accommodation disturbances and micturition difficulties.
One case of overdose has been reported prior to the marketing of the tolterodine immediate release
tablets that involved a 27-month-old child who ingested 5 to 7 tablets of tolterodine immediate
release 2 mg. He was hospitalized overnight with symptoms of dry mouth and was treated with a
suspension of activated charcoal. The child recovered fully.
Management of Overdosage
Treatment of overdosage with DETROL LA (tolterodine L-tartrate extended release capsules)
should consist of gastric lavage and activated charcoal. Treatments for symptoms are recommended
as follows. For severe central anticholinergic effects (hallucinations, severe excitation), an
anticholinesterase agent, such as physostigmine, may be used. If excitation and convulsions occur,
administer an anticonvulsant, such as diazepam. Patients with respiratory insufficiency should be
given respiratory assistance. If respiratory arrest occurs, patients should be given artificial
respiration. Patients with tachycardia may be treated with a beta-blocker, and those with urinary
retention may be catheterized. Patients with troublesome mydriasis may be placed in a dark room
or treated with pilocarpine eye drops, or both. ECG should be monitored.
In clinical trials of normal volunteers, QT interval prolongation was observed with tolterodine
immediate release at doses of 8 mg (4 mg BID). The risk of torsade de pointes with a QT/QTc-
prolonging drug is usually dose-dependent. It is recommended that continuous ECG monitoring
may be appropriate in cases of overdose with Detrol (or Detrol LA). Concomitant therapy should be
immediately reviewed and stopped if potential for drug-drug interaction and exacerbation of the QT
prolongation effect is possible (see WARNINGS AND PRECAUTIONS, DRUG
INTERACTIONS, Drug-Drug Interactions, DETAILED PHARMACOLOGY,
Electrophysiology).


DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 12 of 32 ACTION AND CLINICAL PHARMACOLOGY
Mechanism of Action
Tolterodine L-tartrate, is a competitive muscarinic receptor antagonist, which has been shown to
inhibit carbachol-induced contraction of isolated bladder preparations from rats, guinea pigs, and
man. Tolterodine L-tartrate (henceforth referred to as tolterodine) inhibits contractions of the
detrusor muscle from the guinea pig, and electrically induced contractions of human detrusor
muscle from stable and overactive bladders ex vivo. Tolterodine is significantly more active in
inhibiting acetylcholine-induced urinary bladder contractions than electrically induced salivation in
the anesthetized cat.
Pharmacodynamics

Tolterodine has a pronounced effect on bladder function in healthy volunteers. The main effects
following a 6.4 mg single dose of tolterodine were an increase in residual urine, reflecting an
incomplete emptying of the bladder, and a decrease in detrusor pressure. These findings are
consistent with antimuscarinic action on the lower urinary tract.
In patients with an overactive bladder who received recommended therapeutic doses of the
tolterodine immediate release tablets, urodynamic measurements have shown that tolterodine
increased the volume at first contraction and maximum cystometric capacity.
Tolterodine is converted to a pharmacologically active 5-hydroxymethyl metabolite (DD 01) by the
isozyme cytochrome P450 2D6 (debrisoquine hydroxylase). This metabolite exhibits an
antimuscarinic profile similar to that of tolterodine, both in vitro and in vivo. In view of the
antimuscarinic activity of DD 01 and pharmacokinetic data from both humans and animals, it has
been concluded that this metabolite contributes significantly to the therapeutic effect in extensive
metabolizers (see Metabolism below, and DETAILED PHARMACOLOGY).
A dose-effect relationship was established in a Phase II study for the tolterodine extended release
capsule (002) for mean residual volume per micturition during 12 hours. The dose of the
tolterodine extended release capsule that has the same effect as the tolterodine immediate release
tablets, 2 mg twice daily, was estimated to be 4.7 mg (3.7 mg after correction for relative exposure
to the active moiety). A dose-effect relationship was also observed for the inhibition of salivation
(see DETAILED PHARMACOLOGY).
Pharmacokinetics

Absorption: In a study of 14C-tolterodine in healthy volunteers who received a 5 mg oral dose, at
least 77% of the radiolabeled dose was absorbed. Tolterodine immediate release tablets are rapidly
absorbed, and maximum serum concentrations (Cmax) occur within 1 to 2 hours after dose
administration. The pharmacokinetics of tolterodine immediate release tablets, based on Cmax and area under the concentration-time curve (AUC) determinations, are dose-proportional over the
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 13 of 32 range of 1 to 4 mg. Based on the sum of unbound serum concentrations of tolterodine and DD 01, the AUC of tolterodine extended release capsules, 4 mg once daily, is equivalent to tolterodine immediate release tablets, 2 mg twice daily. Cmax and Cmin levels of the extended release capsule are about 75% and 150% of the immediate release tablet, respectively, with maximum serum
concentrations observed 2 to 6 hours after dose administration. Food intake does not result in
clinically relevant changes in the pharmacokinetic profile of either the tolterodine immediate release
tablets or extended release capsules (see DETAILED PHARMACOLOGY).
Metabolism: Tolterodine is extensively metabolized by the liver following oral dosing, and is
converted to DD 01 by the isozyme cytochrome P450 2D6. Further metabolism leads to formation
of the 5-carboxylic acid and N-dealkylated 5-carboxylic acid metabolites which account for 51% +
14% and 29% + 6.3% of the metabolites recovered in the urine respectively. (see DETAILED
PHARMACOLOGY).
The potential effect of tolterodine on the pharmacokinetics of other drugs also metabolized by P450
2D6, such as tricyclic antidepressants, some antiarrhythmics and selective serotonin reuptake
inhibitors, and neuroleptics has not been formally evaluated.
Variability in Metabolism: A subset (about 7%) of the population is devoid of the
drug-metabolizing isoenzyme cytochrome P450 2D6, the enzyme responsible for the formation of
DD 01. The identified pathway of metabolism for these individuals, referred to as "poor
metabolizers" (PMs), is dealkylation via cytochrome P450 3A4 to N-dealkylated tolterodine. The
remainder of the population is referred to as "extensive metabolizers" (EMs). Pharmacokinetic
studies revealed that tolterodine is metabolized at a slower rate in PMs than in EMs. Since
tolterodine and DD 01 have similar antimuscarinic effects, the net activity of DETROL LA is
expected to be similar in EMs and PMs (see DETAILED PHARMACOLOGY).
Distribution: Tolterodine is highly bound to plasma proteins, primarily  1-acid glycoprotein.
Unbound concentrations of tolterodine average 3.7% ± 0.13% over the concentration range
achieved in clinical studies. The 5-hydroxymethyl metabolite (DD 01) is not extensively protein
bound, with unbound fraction concentrations averaging 36% ± 4.0%. The blood to serum ratio of
tolterodine and DD 01 averages 0.6 and 0.8, respectively, indicating that these compounds do not
distribute extensively into erythrocytes. The volume of distribution of tolterodine following
administration of a 1.28 mg intravenous dose is 113 ± 26.7 L.
Excretion: Following administration of a 5 mg oral dose of 14C-tolterodine solution to healthy
volunteers, 77% of radioactivity was recovered in urine and 17% was recovered in feces in 7 days.
Less than 1% (<2.5% in poor metabolizers) of the dose was recovered in urine and feces as intact
tolterodine; 5% to 14% (<1% in poor metabolizers) was recovered as DD 01 within the first 24
hours. This is consistent with the apparent half-life of tolterodine: 1.9 to 3.7 hours.
The levels of the serum metabolites other than DD 01 determined in four poor metabolizers and
four extensive metabolizers, were comparable for the tolterodine extended release capsule and
immediate release tablet.

DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 14 of 32 Special Populations and Conditions
Age: No overall differences were observed in safety between older and younger patients on
tolterodine immediate release tablets in Phase III, 12 week, controlled clinical studies; and
therefore, no dosage adjustment for elderly patients is recommended (see DETAILED
PHARMACOLOGY).

Gender: There are no sex dependent differences in the pharmacokinetic profile of tolterodine or
DD 01.
Race: Pharmacokinetic differences due to race have not been identified.
Hepatic Insufficiency: Subjects with hepatic cirrhosis exhibit higher serum concentrations and
longer half-lives of tolterodine and DD 01 compared to young healthy subjects given the same dose
(see DETAILED PHARMACOLOGY).
Renal Insufficiency: Potential pharmacologic effects and also the toxicological significance of
metabolite levels should be taken into account if exposing subjects with renal impairment (GFR <
30 mL/min) to repeated doses of tolterodine (see DETAILED PHARMACOLOGY).

STORAGE AND STABILITY
Store at room temperature 15ºC to 30ºC. Protect from light.
SPECIAL HANDLING INSTRUCTIONS
Not applicable.

DOSAGE FORMS, COMPOSITION AND PACKAGING
DETROL LA (tolterodine L-tartrate extended release capsules) is available as 2 mg capsules
(blue-green with symbol and "2" printed in white ink), and 4 mg capsules (blue with symbol and
"4" printed in white ink) and are supplied as follows:
Bottles of 30 and 90: 2 mg and 4 mg

DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 15 of 32 PART II: SCIENTIFIC INFORMATION

PHARMACEUTICAL INFORMATION
Drug Substance
Proper name: tolterodine L-tartrate Chemical name: (1) (R)-2-[3[bis(1-methylethyl)amino]-1-phenylpropyl]-4-methylphenol [R-(R*,R*)]-2,3-dihydroxybutanedioate (1:1) (salt) (2) (+)-(R)-2-[-[2-(diisopropylamino)ethyl]benzyl]-p-cresol L-tartrate (1:1) (salt) Molecular formula and molecular mass: C26H37NO7; 475.6 Structural formula: Physicochemical properties: Crystalline, white powder Soluble at 12 mg/mL in water at room temperature, soluble in methanol, slightly soluble in ethanol and practically insoluble in toluene. 3.0 - 4.5 in water (1%, m/V) 206°C – 212°C
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 16 of 32 CLINICAL TRIALS
Study demographics and trial design
DETROL LA (tolterodine L-tartrate extended release capsules) was evaluated in patients with
symptoms of overactive bladder with urinary urge incontinence, frequency, and/or urgency in a
large randomized, placebo-controlled, multicenter, double-blind, 12-week study. A total of 507
patients were treated with DETROL LA, 4 mg once daily, 514 were treated with tolterodine
immediate release tablets, 2 mg twice daily, and 508 were treated with placebo. The majority of
patients were Caucasian (95%), with a mean age of 61 years (range, 20 to 93 years). Women (81%)
and men (19%) participated in the study; 53% of patients had prior pharmacotherapy for overactive
bladder (included responders and nonresponders). At study entry, 97% of patients had at least 5
urge incontinence episodes per week and 91% of patients had 8 or more micturitions per day. The
primary efficacy endpoint was change in mean number of incontinence episodes per week at week
12 from baseline. Secondary efficacy endpoints included change in mean number of micturitions
per day and mean volume voided per micturition at week 12 from baseline. As shown below, the
efficacy results for DETROL LA and tolterodine immediate release tablets were significantly
better than placebo for all efficacy parameters.
Study results
Difference between DETROL LA (4 mg once daily), tolterodine immediate release tablets
(2 mg twice daily) and Placebo for Mean Change at Week 12 from Baseline*
DETROL LA
Tolterodine
immediate
(N=508)†
extended release
capsules)
Number of incontinence episodes/week Mean Change from Baseline (%) Number of micturitions/day Mean Change from Baseline (%) Volume per micturition (mL) Mean Change from Baseline (%) *Intent-to-treat analysis †1 to 2 patients missing in placebo group for each efficacy parameter ‡Mean change versus placebo
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 17 of 32
DETAILED PHARMACOLOGY

Preclinical Pharmacology
Tolterodine is a competitive muscarinic receptor antagonist, which has been shown to inhibit
carbachol-induced contraction of isolated bladder preparations from rats, guinea pigs, and man.
Tolterodine is significantly more active in inhibiting acetylcholine-induced urinary bladder
contractions (ID50 = 101 nmol/kg) than electrically induced salivation (ID50 = 257 nmol/kg) in the
anesthetized cat; whereas oxybutynin exhibits the opposite selectivity profile (urinary bladder contraction ID50 = 200 nmol/kg; salivation ID50 = 104 nmol/kg). At unbound serum concentrations relevant to those observed clinically, tolterodine has no effects on central nervous system (CNS) or intestinal motility in mice. Tolterodine has high affinity for muscarinic receptors and has a very weak affinity for  - adrenoreceptors, histamine receptors, the neuromuscular junction, and calcium channels. Preclinical studies have shown that tolterodine is as active as oxybutynin in inhibiting contractions of the detrusor muscle from the guinea pig. Tolterodine also has similar activity to oxybutynin in inhibiting electrically induced contractions of human detrusor muscle from stable and overactive bladders ex vivo. These electrically induced contractions are completely blocked by tolterodine. Effects on the cardiovascular system in conscious dogs, treated orally with tolterodine for 10 days, have been investigated using telemetry technique. Heart rate and diastolic blood pressure were increased at 1 mg/kg (tolterodine 103 µg/L, 5-hydroxymethyl metabolite (DD 01) 25 µg/L). Except for a prolongation of the QT-interval (10-20 %) observed at 4.5 mg/kg (tolterodine >600 µg/L, DD 01 100 µg/L), there were no abnormalities of the ECG pattern and no signs of arrhythmias were observed. In anaesthetised dogs, tolterodine had little or no effect on the cardiovascular and respiratory systems when administered as a continuous i.v. infusion. Marked effects (20-40% prolongation of the QT-interval and T-wave duration) occurred only at tolterodine concentrations 500 µg/L. Heart rate, blood pressure and respiration remained virtually unaffected (1000 µg/L). Effects of tolterodine (p.o.) on the central nervous system, gastrointestinal tract and renal function have been evaluated in the mouse. The strict no observed effect level for these effects is 1.5 mg/kg (tolterodine 2.1 µg/L, DD 01 2.4 µg/L). However, the dose at which effects were observed (15 mg/kg) was in some other studies a no effect dose. The true no observed effect level may therefore be closer to 15 mg/kg than to 1.5 mg/kg. A dose of 15 mg/kg can be expected to result in high serum levels of both tolterodine (83 µg/L) and DD 01 (63 µg/L). Most of the effects observed at high doses in the mouse (≥15 mg/kg) and dog (≥1 mg/kg) were antimuscarinic in nature. Increased locomotor activity, mydriasis, decreased intestinal motility, increased residual urine and increased heart rate can all be attributed to the primary action of
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 18 of 32 tolterodine and DD 01 on muscarinic receptors. Preclinical studies have shown that DD 01 exhibits
a similar antimuscarinic profile to that of tolterodine, and a greater antimuscarinic activity on the
bladder relative to the salivary gland in vivo.
The degree of serum protein binding differs between species and this must be taken into account
when comparisons to humans are made. Thus, the unbound concentrations of tolterodine (2.2 µg/L)
and DD 01 (8 µg/L) at which an increased heart rate was observed in the dog, are 17 and 8 times
higher than the unbound serum concentrations achieved in most patients treated with tolterodine 2
mg bid (tolterodine: 0.13 µg/L; DD 01: 1.04 µg/L). The unbound concentrations at which effects
on the central nervous system, intestinal motility and renal function were observed in the mouse
(tolterodine: 13 µg/L; DD 01: 45 µg/L) are approximately 100 and 40 times, respectively, higher
than those expected to be achieved in patients. Almost the same factors (100 and 30 times) were
calculated for the unbound concentrations at which a slight QT-prolongation was recorded in the
conscious dog (tolterodine: 13 µg/L; DD 01: 32 µg/L).
Clinical Pharmacology

Pharmacodynamics

After oral administration, tolterodine is metabolized in the liver, resulting in the formation of the 5-
hydroxymethyl derivative, a major pharmacologically active metabolite. The 5-hydroxymethyl
metabolite (DD 01), which exhibits an antimuscarinic activity similar to that of tolterodine,
contributes significantly to the therapeutic effect. Both tolterodine and DD 01 exhibit a high
affinity for muscarinic receptors and have a very weak affinity for -adrenoreceptors, histamine
receptors, neuromuscular junction, and calcium channels.
Preclinical studies have shown that tolterodine is as active as oxybutynin in inhibiting contractions
of the detrusor muscle from the guinea pig; it has a potency similar to that of oxybutynin in
inhibiting electrically induced contractions of human detrusor muscle from stable and overactive
bladders ex vivo.
Bioavailability

The absolute bioavailability of the tolterodine immediate release tablet was determined using a 1.28
mg intravenous dose as reference. Reported values in the oral dose interval 3.2 - 12.8 mg were 29-
39%. In selected extensive metabolizers (EMs) and poor metabolizers (PMs) the bioavailability was
17±9% and 65±26%. This difference is explained by a higher degree of first-pass metabolism in
EMs. The bioavailability estimate as such is, however, not an informative parameter with respect to
clinical effect, since DD 01 is found in pharmacologically active concentrations in the majority of
the population (EMs).
In a phase II study (002), serum concentrations of tolterodine and DD 01 were assessed in 25 to
29 patients per dose group. At the end of the 7-day treatment using the prototype tolterodine
extended release capsule, blood samples were taken periodically during the 24 hours following the

DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 19 of 32 last dose of capsules (2, 4, 6 or 8 mg), and 12 hours following tolterodine immediate release tablets, 2 mg bid. The relative bioavailability (dose-normalized AUCt estimated over all doses) of the prototype extended release capsule used compared with the immediate release tablet averaged 71% for
tolterodine and 73% based on DD 01. The relative exposure to the active moiety from the prototype
capsule used compared with the tablet averaged 79% based on dose-normalized AUC12.

Pharmacokinetics

Absorption: In a study of 14C-tolterodine in healthy volunteers who received a 5 mg oral dose, at
least 77% of the radiolabeled dose was absorbed. Tolterodine is rapidly absorbed, and maximum
serum concentrations (Cmax) typically occur within 1 to 2 hours after dose administration. The
pharmacokinetics of tolterodine immediate release tablets, based on Cmax and area under the concentration-time curve (AUC) determinations, are dose-proportional over the range of 1 to 4 mg. After single-dose administration, dose-normalized AUC (corrected for differences in dose) of both tolterodine and DD 01 showed equivalence after administration of the final extended release capsule (2x4 mg) and the immediate release tablets (2x2mg). Cmax for the capsule was markedly lower than for the tablet. After multiple-dose administration, the final extended release capsule was equivalent to the immediate release tablet based on AUC for the active moiety. The extended release capsule showed the desired extended release properties with Cmax levels of the active moiety, which were approximately 75% of the tablet Cmax. Cmin levels (active moiety) were about 1.4 times higher for the capsule. The fluctuation index was consequently lower for the capsule than for the tablet.
Food intake does not result in clinically relevant changes in the pharmacokinetic profile of either the
tolterodine immediate release tablets or extended release capsules.
Metabolism: Tolterodine is extensively metabolized by the liver following oral dosing. The
primary metabolic route involves the oxidation of the 5-methyl group and is mediated by the
isoenzyme cytochrome P450 2D6 and leads to the formation of a major pharmacologically active
5-hydroxymethyl metabolite. Further metabolism leads to formation of the 5-carboxylic acid and
N-dealkylated 5-carboxylic acid metabolites, which account for 51% ± 14% and 29% ± 6.3%,
respectively, of the metabolites recovered in the urine.
Variability in Metabolism: A subset (about 7%) of the population is devoid of the
drug-metabolizing isoenzyme cytochrome P450 2D6, the enzyme responsible for the formation of
DD 01. The identified pathway of metabolism for these individuals, referred to as "poor
metabolizers" (PMs), is dealkylation via cytochrome P450 3A4 to N-dealkylated tolterodine. The
remainder of the population is referred to as "extensive metabolizers" (EMs). Pharmacokinetic
studies revealed that tolterodine is metabolized at a slower rate in PMs than in EMs. This results in
significantly higher serum concentrations of tolterodine and in negligible concentrations of DD 01.
Because of differences in the protein-binding characteristics of tolterodine and DD 01, the sum of

DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 20 of 32 unbound serum concentrations of tolterodine and DD 01 is similar in EMs and PMs at steady state.
Since tolterodine and DD 01 have similar antimuscarinic effects, the net activity of DETROL LA
(tolterodine L-tartrate extended release capsules) is expected to be similar in EMs and PMs.
The AUC24 data for serum metabolites measured in 4 PMs and 4 EMs after multiple-dose
administration indicated that the levels of the known serum metabolites are similar for the tolterodine extended release capsules and immediate release tablets. As for the tablet, the exposure to the active moiety is within the same range after administration to PMs and EMs. The PMs in this study had levels of the active moiety that are within the range observed in the EMs, both for the extended release capsules and immediate release tablets. For the PMs, the effect of the sustained release and slower absorption of tolterodine is less pronounced than for the EMs.
Excretion: Following administration of a 5 mg oral dose of 14C-tolterodine to healthy volunteers,
about 77% of radioactivity was recovered in urine and 17% was recovered in feces. Less than 1%
(<2.5% in PMs) of the dose was recovered as intact tolterodine, and 5% to 14% was recovered as
the active DD 01 metabolite. Most of the radioactivity was recovered within the first 24 hours,
which is consistent with the apparent half-life of tolterodine: 1.9 to 3.7 hours in pharmacokinetic
studies.
Pharmacokinetics in Special Populations

Age: In phase I multiple-dose studies in which tolterodine immediate release tablets 2 mg were
administered twice daily, serum concentrations of tolterodine and of DD 01 were similar in healthy
elderly volunteers (aged 64 through 80 years) and healthy young volunteers (aged less than
40 years). In another phase I study, elderly volunteers (aged 71 through 81 years) were given
tolterodine immediate release tablets, 1 or 2 mg twice daily. Mean serum concentrations of
tolterodine and DD 01 in these elderly volunteers were approximately 20% and 50% higher,
respectively, than reported in young healthy volunteers. However, no overall differences were
observed in safety between older and younger patients in phase III, 12- week, controlled clinical
studies; and therefore, no dosage adjustment is recommended (see WARNINGS AND
PRECAUTIONS, Special Populations).
Pediatric: The pharmacokinetics of the extended release capsules have not been established in
pediatric patients.
Gender: Pharmacokinetic data from three Phase I clinical studies (Studies 022, 024, and 028) in
which a tolterodine immediate release tablet dose of 2 mg was administered in the fasting state were
analyzed with respect to gender. The pharmacokinetics of tolterodine and DD 01 are not influenced
by gender. Mean Cmax of tolterodine (1.6 µg/L in males versus 2.2 µg/L in females) and DD 01 (2.2
µg/L in males versus 2.5 µg/L in females) are similar in males and females who were administered tolterodine immediate release tablets 2 mg. Mean AUC values of tolterodine (6.7 µg/h/L in males versus 7.8 µg/h/L in females) and DD 01 (10 µg/h/L in males versus 11 µg/h/L in females) are also similar. The elimination half-life of tolterodine immediate release tablets for both males and females is 2.4 hours, and the half-life of DD 01 is 3.3 hours in males and 3.0 hours in females.
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 21 of 32
Race: Differences among races regarding metabolic capacity can be assumed to be of quantitative
nature and are probably less than the thoroughly documented difference between extensive and poor
metabolizers. The few non-Caucasians included do not show a different pharmacokinetic profile of
tolterodine or DD 01.
Renal Impairment: A study was conducted to evaluate the pharmacokinetics of tolterodine
immediate release tablets in 12 subjects with renal impairment compared to 12 healthy volunteers.
The exposure to unbound tolterodine and DD 01 was on average 2-3 fold higher in patients with
renal impairment compared with healthy volunteers. AUC of N-dealkylated tolterodine was in an
extreme case, about 60-fold higher in a poor metabolizer (PM) in the renal impairment group than
in the only healthy extensive metabolizer (EM) with quantifiable AUC. However, the
corresponding ratio for what is generally observed in healthy PMs is about 10. Tolterodine acid
levels and N-dealkylated tolterodine acid were on average 5 times and 11 times higher, respectively,
in the renal impairment group with respect to AUC (extreme case 9-fold and 31-fold higher than
most exposed healthy subjects). Potential pharmacologic effects and also the toxicological
significance of metabolite levels should be taken into account if exposing subjects with renal
impairment (GFR < 30 mL/min) to repeated doses of tolterodine (see WARNINGS AND
PRECAUTIONS).
Hepatic Insufficiency: As might be predicted from a drug in which hepatic metabolism is the
primary route of elimination, liver impairment can significantly alter the disposition of tolterodine.
In a study of cirrhotic patients, elimination half-life of tolterodine immediate release tablets was
longer in cirrhotic patients (mean, 8.7 hours) than in healthy, young and elderly volunteers (mean, 2
to 4 hours). The clearance of orally administered tolterodine immediate release tablets was
substantially lower in cirrhotic patients (1.1 ± 1.7 L/h/kg) than in the healthy volunteers (5.7 ± 3.8
L/h/kg). Patients with significantly reduced hepatic function should not receive doses of DETROL
LA (tolterodine L-tartrate extended release capsules) greater than 2 mg daily (see WARNINGS
AND PRECAUTIONS).
Drug Interactions

Fluoxetine: Fluoxetine is a selective serotonin reuptake inhibitor and a potent inhibitor of
cytochrome P450 2D6 activity. In a study to assess the effect of fluoxetine on the pharmacokinetics
of tolterodine and its metabolites, it was observed that fluoxetine significantly inhibited the
metabolism of tolterodine immediate release tablets in extensive metabolizers, resulting in a
4.8-fold increase in tolterodine AUC. However, DD 01 showed a 52% decrease in Cmax and a 20%
decrease in AUC. Fluoxetine thus alters the pharmacokinetics in patients who would otherwise be
extensive metabolizers of tolterodine to resemble the pharmacokinetic profile in poor metabolizers.
The sums of unbound serum concentrations of tolterodine and DD 01 are 25% higher during the
interaction. However, no dose adjustment is required when DETROL LA and fluoxetine are
coadministered (see DRUG INTERACTIONS).
Other Drugs Metabolized by P450 2D6: The potential effect of DETROL LA on the
pharmacokinetics of drugs that are metabolized by P450 2D6 (such as flecainide, vinblastine,

DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 22 of 32 carbamazepine, tricyclic antidepressants) has not been formally evaluated (see DRUG
INTERACTIONS).
Warfarin: In healthy volunteers, coadministration of tolterodine immediate release tablets 2 mg
twice daily for 7 days and a single dose of warfarin 25 mg on day 4 had no effect on prothrombin
time, Factor VII suppression, or on the pharmacokinetics of warfarin.
Oral Contraceptives: Tolterodine immediate release tablets, 2 mg twice daily, has no effect on the
pharmacokinetics of an oral contraceptive (ethinyl estradiol 30 µg; levonorgestrel 150 µg) as
evidenced by the monitoring of ethinyl estradiol and levonorgestrel over a 2-month cycle in healthy
female volunteers.
Diuretics: Coadministration of tolterodine immediate release tablets up to 4 mg twice daily for up
to 12 weeks with diuretic agents, such as indapamide, hydrochlorothiazide, triamterene,
bendroflumethiazide, chlorothiazide, methylchlorothiazide, or furosemide, did not cause any
adverse electrocardiographic (ECG) effects in patients with overactive bladder.
Cytochrome P450 3A4 inhibitors: The use of tolterodine immediate release tablets in combination
with ketoconazole, a potent CYP3A4 inhibitor, was studied in 8 healthy subjects, all of whom were
poor metabolizers of CYP2D6. Concomitant treatment with ketoconazole resulted in a 2.2 fold
increase in tolterodine AUC at steady state. Based on these findings, potent CYP3A4 inhibitors
such as macrolide antibiotics (erythromycin and clarithromycin) or azole antifungal agents
(ketoconazole, itraconazole and miconazole), or cyclosporin or vinblastine may also lead to
increases of tolterodine plasma concentrations (see DRUG INTERACTIONS).
A clinical explorative study with marker drugs for the major P450 isoenzymes suggests that
metabolic activity of CYP2D6, 2C9, 2C19, 3A4 or 1A2 is unlikely to be inhibited by tolterodine
immediate release tablets.
Electrophysiology

The QT effect of 2 mg BID and 4 mg BID doses of DETROL (tolterodine L-tartrate tablets)
immediate release tablets was evaluated in a steady-state, 4-way crossover, double-blind, placebo-
and active-controlled (moxifloxacin 400 mg QD) study in 48 healthy volunteers (18-55 yrs age,
with approximately equal representations of males and females and of CYP2D6 poor and extensive
metabolizers). The QT interval was measured over a 12-hour period including peak times at steady
state. This evaluation was done at up to two times the highest dose of DETROL immediate release
tablets at peak exposures equivalent to three times the highest dose of DETROL LA (tolterodine L-
tartrate extended release capsules).
The following table summarizes the largest time-matched, placebo and baseline-adjusted mean effects on Fridericia-corrected QTc (QTcF) at steady-state. The mean increase of heart rate associated with a 4 mg/day dose of tolterodine in this study was 2.0 beats/minute and 6.3 beats/minute with 8 mg/day tolterodine. The change in heart rate with moxifloxacin was 0.5 beats/minute.
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 23 of 32
Largest Time-Matched, Placebo and Baseline-Adjusted Mean Effects on Fridericia-corrected
QTc (QTcF) at Steady-State

Treatment
Multiple of
Machine-Read QTcF(msec) **
Manually-Read QTcF(msec) **
Recommend
Estimate*
Confidence
Estimate*
Confidence
Increase
Interval
Increase
Interval
* The point estimate is the difference between arithmetic means for pair-wise comparisons of the drug versus placebo treatments.
QTc values are corrected for heart rate using Fridericia's formula (QTc=QT/RR 0.33)
** The machine-read methodology is based on earliest Q onset to latest T offset in 12 simultaneous recorded leads, while the manual
over-read method is based on lead II only.
The reason for the difference between machine and manual read of QT interval is unclear.
*** The effect on QTc interval with 4 days of moxifloxacin dosing in this QT trial may be greater than typically observed in QT
trials of other drugs.
The QT effect appeared greater for 8 mg/day compared with 4 mg/day tolterodine immediate
release tablets. The effect of the highest tolterodine dose (two times the therapeutic dose) was 50-
60% less than that of the active control moxifloxacin (400 mg) at its therapeutic dose. Tolterodine's
effect on QT interval was found to correlate with plasma concentration of tolterodine. The peak
exposures of tolterodine and its 5-hydroxymethyl metabolite following dosing with DETROL LA
(tolterodine L-tartrate extended release capsules) are about 61% and 67%, respectively, compared
with DETROL (tolterodine L-tartrate tablets). Since the QT prolongation effect is in linear
relationship with exposure, any QT effect of DETROL LA (tolterodine L-tartrate extended release
capsules) would also be expected to be similarly lower. The effect on QTc interval appeared to be
greater in CYP2D6 poor metabolizers than in CYP2D6 extensive metabolizers. In this study, the
point estimates of manual-read QTc interval increase were 2.1 msec in extensive metabolizers and
8.7 msec in poor metabolizers receiving tolterodine 2 mg BID treatment. However, this study was
not designed to make direct statistical comparisons by CYP2D6 metabolizer status nor between
drugs or dose levels. At both doses of tolterodine, no subject, irrespective of their metabolic profile
(ie. poor/extensive metabolizers), exceeded 500 msec for absolute QTcF or 60 msec for change
from baseline. The clinical relevance of these findings will depend on individual patient risk factors
and susceptibilities present (see WARNINGS AND PRECAUTIONS, Cardiovascular).
TOXICOLOGY

Acute toxicity
The single oral dose administration studies in mice, rats and dogs showed species differences. At
300 mg/kg in mice, a 10-60% mortality was recorded, whereas 375 mg/kg was non-lethal in rats. In
mice, a dose of 200 mg/kg caused no lethality. In the dog, at 40 mg/kg (the highest dose tested) no

DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 24 of 32 mortality occurred, but pronounced clinical signs were seen such as decreased locomotor activity,
clouding of consciousness and stupor. Following a single intravenous dose, 8 mg/kg was a no
observed effect level in both rats and mice. At 24 mg/kg, 30% mortality was recorded in rats, and
80% mortality in mice.
Long-term toxicity
The metabolic profiles in urine from the mouse, rat, dog and man given an oral dose of
radioactively labeled tolterodine show that the mouse, dog and man have a similar metabolic pattern
including the formation of the pharmacologically active 5-hydroxymethyl metabolite, DD 01. In
contrast, the metabolism of tolterodine in the rat is more extensive and occurs also via other
pathways involving mono- and dihydroxylation of the unsubstituted benzene ring. The mouse is
considered to be a more appropriate species than the rat for the safety evaluation of tolterodine in
man.
Mouse In the 2 week study, dose levels of 4, 12, 40 or 80 mg/kg/day were used, and in the 13 week
study, the dose levels were 4, 12 or 40 mg/kg/day. In the 26 week study dose levels of 3, 10 or
30 mg/kg/day were used. In the 2 week study, no toxicity was found after doses up to
80 mg/kg/day. During the 13 week study, 7 males and 8 females receiving 40 mg/kg/day died
shortly after dosing. Treatment related deaths also occurred in the 26 week study, where 12 males
and 15 females treated at 30 mg/kg/day died within one hour of dosing. In both studies, the deaths
were distributed throughout the treatment period starting from the second week of treatment.
Although the mechanism of the unexpected deaths is unknown, it is most likely related to
exaggerated pharmacological effects (circulatory and/or respiratory failure) occurring at serum peak
levels.
Rat In the 13 week repeated dose study in rats, doses of 4, 12 or 40 mg/kg/day were given. In
females given 40 mg/kg/day depressed body weight gain and reduced food consumption were
recorded. Also, ten female rats died approximately 20 hours after dosing. The deaths occurred
from week 3. Cause of death could not be established, but is most likely related to exaggerated
pharmacologic effects (circulatory and/or respiratory failure) following the accumulation of
tolterodine with time.
Dog The clinical signs that were associated with tolterodine treatment in the 13 week, 26 week and
52 week (0.5, 1.5 or 4.5 mg/kg/day) studies were characterized mainly by dose related peripheral
antimuscarinic effects, i.e. dry mouth, mydriasis and dryness of the eye. In some dogs receiving
1.5 or 4.5 mg/kg/day, diminished lacrimation caused conjunctivitis and/or corneal changes
especially at the high dose level.
Tolterodine, as well as its active human metabolites prolong action potential duration (90%
repolarization) in canine purkinje fibers (23 - 123 times therapeutic levels) and block the K+-current
in cloned human ether-a-go-go-related gene (hERG) channels (0.8 – 14.7 times therapeutic levels).
In dogs prolongation of the QT interval has been observed after application of tolterodine and its
human metabolites (5.1 - 62.7 times therapeutic levels).

DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 25 of 32 Central antimuscarinic effects, i.e. locomotor disturbances and drowsiness, were seen in all three studies on day 1, in a few dogs receiving 4.5 or 8 mg/kg/day. These symptoms occurred in dogs with high serum concentrations of tolterodine (Cmax 800-1250 µg/L), and DD 01. Ataxia and tremor were also observed occasionally in high dose animals during the 26 week study.
Carcinogenicity
Carcinogenicity studies with tolterodine were conducted in mice and rats. At the maximum-
tolerated dose in mice (30 mg/kg/day [123 mg/m2/day]), female rats (20 mg/kg/day), and male rats
(30 mg/kg/day), AUC values obtained for tolterodine were 355, 291, and 462 µgh/L, respectively.
In comparison, the human AUC value for a 2-mg dose administered twice daily is estimated at
34 µgh/L. Thus, tolterodine exposure in the carcinogenicity studies was 9- to 14-fold higher than
expected in humans. No increase in tumors was found in either mice or rats.
Mutagenicity
No mutagenic effects of tolterodine were detected in a battery of in vitro tests, including bacterial
mutation assays (Ames test) in four strains of Salmonella typhimurium and in two strains of
Escherichia coli, a gene mutation assay in L5178Y mouse lymphoma cells, and chromosomal
aberration tests in human lymphocytes. Tolterodine was also negative in vivo in the bone marrow
micronucleus test in the mouse.
Reproduction and Teratology
In female mice treated for 2 weeks before mating and during gestation with 20 mg/kg/day
(corresponding to AUC value of about 500 µgh/L), neither effects on reproductive performance or
fertility nor any anomalies or malformations were seen. Based on AUC values, the systemic
exposure was about 15-fold higher in animals than in humans. At doses of 30 to 40 mg/kg/day,
tolterodine caused a dose-related increase in embryolethality, reduced fetal weight, and increased
incidence of fetal abnormalities. At these doses, AUC values were about 20- to 25-fold higher than
in humans. In male mice, a dose of 30 mg/kg/day did not induce any adverse effects on fertility.

DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 26 of 32 REFERENCES
1. Abrams P, Jackson S, Mattiasson A, et. al. A randomised, double-blind, placebo controlled, dose-ranging study of the safety and efficacy of tolterodine in patients with hyperreflexia [abstract]. 26th Annual Meeting of International Continence Society; 27-30 August 1996; Athens, Greece: International Continence Society, 1996. Publication Citation. 2. Bertilsson L. Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19. Clin Pharmacokinet 1995;29:192-209. 3. Brøsen K, Gram LF, Haghfelt T, Bertilsson L. Extensive metabolizers of debrisoquine become poor metabolizers during quinidine treatment. Pharmacology & Toxicology 1987;60:312-4. 4. Brynne N, Olofsso S, Hallén B, Grälls M. Pharmacokinetics of tolterodine in subjects with renal failure compared to healthy volunteers. An open controlled non-randomized parallel group study. CTN 97-OATA-040. Document c–0013132 (1999) - Data on file. 5. Brynne N, Stahl M, Hallén B, Edlund PO, Palmér L. Clinical Pharmacokinetics of Tolterodine: A New Drug in the Treatment of Urge Incontinence [abstract]. Therapie 1995; 50 (Suppl): abstr 353. Publication Citation. 6. Chapple C, Herschorn S, Abrams P, Sun F, Brodsky M, Guan Z. Tolterodine Treatment Improves Storage Symptoms Suggestive of Overactive Bladder in Men Treated With alpha-Blockers. Eur Urol 2009;56(3):534-41. 7. Eichelbaum M, Gross AS. The genetic polymorphism of debrisoquine/sparteine metabolism-clinical aspects. Pharmacol Ther 1990;46:377-94. 8. Ekstrōm B, Stahl M, Mattiasson A, Andersson K-E. Effects of Tolterodine on Bladder Function in Healthy Volunteers [abstract]. AUA; J Urol 1995;153 (4 Suppl): 394A. Publication Citation. 9. Fantl JA, Newman DK, Co-Chair. Treatment of urinary incontinence. In: Urinary incontinence in adults: acute and chronic management, clinical practice guideline; Number 2, 1996 update. US Department of Health and Human Services, Agency for Health Care Policy and Research, 1996: 31-73. 10. Freeman R, Hill S, Millard R, Slack M, Sutherst J. Tolterodine study group. Reduced perception of urgency in treatment of overactive bladder with extended-release tolterodine. Obstet Gynecol 2003;102(3):605-11. 11. Frewen W. Role of bladder training in the treatment of the unstable bladder in the female. Urol Clin North Am 1979;6:273-7. 12. Griebling TL, Kraus SR, Richter HE, Glasser DB, Carlsson M. Tolterodine extended release is well tolerated in older subjects. Int J Clin Pract. 2009; 63(8):1198-204. 13. Gustafsson L. The influence of ketoconazole on the pharmacokinetics and safety of tolterodine. An open, single group study in healthy volunteers. CTN 97-OATA-036 Pharmacia & Upjohn Document 9810186 (1998) - Data on file. 14. Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA 2006;296(19):2319-28. 15. Keam SJ, Perry CM. Management of overactive bladder: Defining the role of extended- release tolterodine. Dis Manage Health Outcomes 2004;12 (2): 121-142.
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 27 of 32 16. Khullar V, Hill S, Laval KU, Schiøtz HA, Jonas U, Versi E. Treatment of urge-predominant mixed urinary incontinence with tolterodine extended release: A randomized, placebo-controlled trial. urology. 2004;64(2):269-75. 17. Landis JR, Kaplan S, Swift S, Versi E. Efficacy of antimuscarinic therapy for overactive bladder with varying degrees of incontinence severity. J Urol 2004;171(2 Pt 1):752-6. 18. Larsson G, Hallén B, Nilvebrant L. Tolterodine in the Treatment of Urge Incontinence. Analysis of the Pooled Phase II Efficacy and Safety Data [abstract]. 26th Annual Meeting of International Continence Society; 27-30 August 1996; Athens, Greece: International Continence Society, 1996. Publication Citation. 19. Layton D, Pearce GL, Shakir SAW. Safety profile of tolterodine as used in general practice in England – Results of prescription-event monitoring. Drug Saf 2001; 24(9):703-13. 20. Malone-Lee J, Lubel D, Szonyi G. Low dose oxybutynin for the unstable bladder [abstract]. BMJ 1992;304:1053. 21. Marinac JS, Foxworth JW, Willsie SK. Dextromethrophan polymorphic hepatic oxidation (CYP2D6) in healthy black American adult subjects. Therapeutic Drug Monitoring 1995:17,120-4. 22. Maurice M, Pichard L, Daujat M, Fabre I, Joyeux H, Domergue J, Maurel P. Effects of imidazole derivates of cytochromes P450 from human heapatocytes in primary culture. The FASEB Journal 1992; 6:752-8. 23. Messelink EJ, Soler JM, Madersbacher H, et al. Urodynamic Aspects of the Efficacy of Tolterodine, A New Antimuscarinic Drug in the Treatment of Detrusor Hyperreflexia [abstract]. 25th Annual Meeting of International Continence Society; 17-20 October 1995; Sydney, Australia: International Continence Society, 1995. Publication Citation. 24. Naerger H, Fry CH, Nilvebrant L. Effect of tolterodine on electrically induced contractions of isolated human detrusor muscle from stable and unstable bladders [abstract]. Neurology and Urodynamics 1995;14:524-6. 25. Olsson B, Szamosi J. Multiple dose pharmacokinetics and pharmacodynamics of tolterodine prolonged release capsules in comparison with tolterodine immediate release tablets. An open-randomized, cross-over trial in healthy volunteers. Final report of the trial CTN 98-TOCR-006 Pharmacia & Upjohn Document No. c0008272 (13 October 1999) – data on file. 26. Olsson B, Szamosi J. The effect of food on the bioavailability of tolterodine prolonged- release capsules. An open, randomized, cross-over trial in healthy volunteers. Final report of the trial CTN 98-TOCR-010. Pharmacia & Upjohn Document No. c0003212 (25 February 1999) – data on file. 27. Otton SV, Wu D, Joffe RT, Cheung SW and Sellers EM. Inhibition by fluoxetine of cytochrome P450 2D6 activity. Clin Pharmaco Ther 1992;53:401-9. 28. Ouslander JG, Blaustein J, Coonor A, Orzeck S, Yong CL. Pharmacokinetics and clinical effects of oxybutynin in geriatric patients. Journal of Urology 1988;140: 47-50. 29. Ouslander JG. Management of overactive bladder. N Engl J Med. 2004;350(8):786-99. 30. Rentzhog L, Abrams P, Cardozo L, et al. Tolterodine - A New Bladder Selective Drug for the Treatment of Detrusor Instability [abstract]. 25th Annual Meeting of International Continence Society; 17-20 October 1995; Sydney, Australia: International Continence Society, 1995. Publication Citation.
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 28 of 32 31. Riva D, Casolati E. Oxybutynin chloride in the treatment of female idiopathic bladder instability. Results from double blind treatment. Clin Exp Obstet Gynecol 1984;11:37-42. 32. Salvatore S, Khullar V, Cardozo L, Kelleher CJ, Abbott D, Hill S. Long term outcome of women with detrusor instability treated with oxybutynin [abstract]. Neurourol Urodyn 1995;14:460-1. 33. Söderström J, Szamosi J. Clinical efficacy and tolerability/safety of tolterodine prolonged release capsules and tolterodine immediate release tablets vs. placebo. A randomized, double-blind, placebo-controlled, multinational study in patients with symptoms of overactive bladder. Final report of the trial 98-TOCR-007. Pharmacia & Upjohn Document No. c0013194 (13 December 1999) – data on file. 34. Stahl M, Brynne N, Ekström, et al. Pharmacokinetics of Tolterodine in Relation to Effects on the Bladder in Healthy Volunteers [abstract]. Therapie 1995; 50 (Suppl): abstr 355. Publication Citation. 35. Stahl MMS, Ekström B, Sparf B, Mattiasson A, Andersson K-E. Urodynamic and Ohter Effects of Tolterodine: A Novel Antimuscarinic Drug for the Treament of Detrusor Overactivity [abstract]. Neurol Urodyn 1995; 14:647-55. Publication Citation. 36. Strömberg J, Vågerö M, Olsson B. Dose effect trial of tolterodine prolonged release capsules. A double-blind, double-dummy, cross-over trial in patients with overactive bladder. Final report of the study 97-TOCR-002. Pharmacia & Upjohn Document No. c0003471 (29 November 1999) – data on file. 37. Tapp AJS, Cardozo LD, Versi E, Cooper D. The treatment of detrusor instability in post- menopausal women with oxybutynin chloride: a double blind placebo controlled study. Br J Obstet Gynaecol 1990; 97: 521-6. 38. Thomas TM, Plymat KR, Blannin J, Meade TW. Prevalence of urinary incontinence. BMJ 1980;281:1243-5. 39. Thüroff JW, Bunke B, Ebner A, Faber P, de Geeter P, Hannappel J, Heidler H, Madersbacher H, Melchoir H, Schafer W, Schwenzer T, Stockle M. Randomized, double-blind, multicenter trial on treatment of frequency, urgency and incontinence related to detrusor hyperactivity: Oxybutynin versus propantheline versus placebo. J Urol 1991;145:813-7. 40. Urinary incontinence in adults - National Institute of Health consensus statement. JAMA 1989;261:2685-90. 41. Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A. Tolterodine Once-Daily: Superior Efficacy and Tolerability in the Treatment of the Overactive Bladder. Urology 2001;57(3):414-21. 42. Winter S. Tolterodine: a new drug for urinary incontinence. Inpharma 1996;1040. Publication Citation. 43. Yarker YE, Goa KL, Fitton A. Oxybutynin. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in detrusor instability. Drugs and Aging 1995;6:243-62. 44. Zinner NR, Mattiasson A, Stanton S.L. Efficacy, Safety, and Tolerability of Extended- Release Once-Daily Tolterodine Treatment for Overactive Bladder in Older versus Younger Patients. J Am Geriatr Soc 2002; 50: 799-807.
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 29 of 32 IMPORTANT: PLEASE READ
What dosage forms it comes in:
PART III: CONSUMER INFORMATION
DETROL LA 2 mg capsules have a blue-green symbol and "2"
DETROL LA*
printed in white ink. (tolterodine L-tartrate extended release capsules)
DETROL LA 4 mg capsules have blue symbol and "4" printed in
This leaflet is part III of a three-part "Product
Monograph" published when DETROL LA* (tolterodine
L-tartrate extended release capsules) was approved for
WARNINGS AND PRECAUTIONS
sale in Canada and is designed specifically for Consumers.
This leaflet is a summary and will not tell you everything
about DETROL LA*. Contact your doctor or pharmacist
DETROL LA may have an effect on the electrical activity of the
if you have any questions about the drug.
heart. This effect can be measured as a change in the electrocardiogram (ECG). It is important to follow the instructions of your doctor with regard to dosing or any special ABOUT THIS MEDICATION
tests. In very rare cases, drugs with an effect on the ECG can lead to disturbances in heart rhythm (arrhythmias/dysrhythmias). What the medication is used for:
These heart rhythm disturbances are more likely in patients with risk factors, such as heart disease, or in the presence of certain The name of this medication is DETROL LA. It is used for
interacting drugs. If you experience any symptoms of a possible the treatment of the symptoms of overactive bladder which heart rhythm disturbance, such as dizziness, palpitations include frequency, urgency, and urge incontinence. (sensation of rapid pounding, or irregular heart beat), fainting, or seizures, you should stop taking DETROL LA and seek
REMEMBER: This medication is for YOU. Never give it
immediate medical attention. to others. It may harm them even if their symptoms are
the same as yours.
BEFORE you use DETROL LA talk to your doctor or
pharmacist if:
What it does:
you are pregnant, or trying to become pregnant you are breastfeeding your child Tolterodine works to prevent bladder contractions or spasms. you have myasthenia gravis (a chronic autoimmune This results in more bladder capacity and less frequency, neuromuscular disease which cause muscle weakness) urgency and involuntary loss of urine. you have stomach problems affecting passage and digestion When it should not be used:
you have liver problems you have kidney problems You should not take DETROL LA if you have:
you are taking medication bought without a prescription.  urinary retention, They may affect your condition, or how DETROL LA
 gastric retention  uncontrolled narrow angle glaucoma, you are a female or are over 65 years in age; you have a  known hypersensitivity to tolterodine L-tartrate or disorder known as Long QT Syndrome; a heart disease; a any of the other ingredients in DETROL LA.
history of stroke or brain hemorrhage; a personal history of fainting spells; a family history of sudden cardiac death at What the medicinal ingredient is:
<50 years; electrolyte disturbances (e.g., low blood potassium levels); an eating disorder or are following an Each capsule contains film-coated beads of 2 mg or 4 mg of extreme diet; diabetes, especially with associated nerve the active ingredient, tolterodine L-tartrate. The film-coated beads dissolve over time, releasing the active ingredient over INTERACTIONS WITH THIS MEDICATION
What the important nonmedicinal ingredients are:
The following list includes some, but not all, of the drugs that The tablets also contain the following inactive ingredients: may increase the risk of side effects while receiving DETROL
Sucrose, starch, hypromellose, ethylcellulose, ammonium LA. You should check with your doctor or pharmacist before
hydroxide, medium chain triglycerides, oleic acid, gelatin and taking any other medication with DETROL LA.
FD & C Blue 2. The 2 mg capsules also contain yellow iron oxide. Both capsule strengths are imprinted with a Drugs that may interact with DETROL LA include:
pharmaceutical grade ink, Opacode White S-1-7085 that other drugs that possess antimuscarinic/anticholinergic contains shellac glaze, titanium dioxide, ammonium properties (drugs that cause blurred vision, constipation, dry hydroxide, propylene glycol and simethicone. antifungals (drugs to treat fungal infections, such as,
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 30 of 32 IMPORTANT: PLEASE READ
fluconazole, ketoconazole, or itraconazole) If you experience any symptoms of a possible heart rhythm antibiotics (ie. erythromycin, clarithromycin) disturbance, such as dizziness, palpitations (sensation of rapid, cyclosporine (a drug to prevent rejection of organ pounding, or irregular heart beat), fainting, or seizures, you should stop taking DETROL LA and seek mediate medical
vinblastine (a drug to treat some types of cancer) antiarrhythmics (drugs that stabilize the heart rhythm function, such as procainamide, quinidine, amiodarone, Check with your doctor or pharmacist right away if you have any
bothersome or unusual effects while taking DETROL LA.
antidepressants (mood disorder drugs) antipsychotics (drugs to stabilize thinking and behavior) Use caution while driving or using machinery until you know anti-asthmatic (salmeterol) how DETROL LA affects you.
SERIOUS SIDE EFFECTS, HOW OFTEN THEY
PROPER USE OF THIS MEDICATION
HAPPEN AND WHAT TO DO ABOUT THEM
Take DETROL LA as instructed by your doctor. Do not
increase, decrease or stop taking DETROL LA without first
Symptom / effect talking to your doctor. Usual dose:
The usual starting dose is 4 mg once daily, but may be Uncommon Allergic decreased to 2 mg once daily. The capsule should be swallowed whole. DETROL LA can be taken with food.
Overdose:
This is not a complete list of side effects. For any unexpected
effects while taking DETROL LA, stop taking the drug and
Do not take more capsules than your doctor has told you to. If contact your doctor or pharmacist.
you take too many tablets by accident, call your doctor or pharmacist or a poison control centre immediately. HOW TO STORE IT
Missed Dose:
Store at room temperature 15ºC to 30ºC. Protect from light. If you miss taking your capsule, take it as soon as you You should not use your medication after the expiration date remember. But if it is almost time for the next dose, skip the printed on the carton and label. missed dose and just take the next dose. Do not take more than one dose at a time. Keep all medications out of the reach of children. This medication could harm them. SIDE EFFECTS AND WHAT TO DO ABOUT THEM

As with most drugs, DETROL LA can cause some side
effects.

Tell your doctor or pharmacist right away if you suffer from
any of the following side effects while taking this medication:

decreased tear production (dry irritable eye) palpitations (sensation of rapid, pounding, or irregular heart beat) difficulty in urination (passing water) The most common side effect is dry mouth. Less commonly reported side effects are headache, constipation, dizziness, fatigue, abdominal pain and dry eyes.
DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 31 of 32 IMPORTANT: PLEASE READ
REPORTING SUSPECTED SIDE EFFECTS
You can report any suspected adverse reactions
associated with the use of health products to the Canada
Vigilance Program by one of the following 3 ways:
 Report online at www.healthcanada.gc.ca/medeffect
 Call toll-free at 1-866-234-2345
 Complete a Canada Vigilance Reporting Form and:
- Fax toll-free to 1-866-678-6789, or
- Mail to: Canada Vigilance Program
Health Canada
Postal Locator 0701C
Ottawa, ON K1A 0K9
Postage paid labels, Canada Vigilance Reporting Form
and the adverse reaction reporting guidelines are
available on the MedEffectTM Canada Web site at
www.healthcanada.gc.ca/medeffect.
NOTE: Should you require information related to the
management of side effects, contact your health
professional. The Canada Vigilance Program does not
provide medical advice.

MORE INFORMATION

This document plus the full Product Monograph, prepared for
Health Professionals can be found at:
http://www.pfizer.ca
http://www.detrol.ca
or by contacting the sponsor, Pfizer Canada Inc., at 1-800-
463-6001.
This leaflet was prepared by Pfizer Canada Inc.
Last revised: February 2, 2015



DETROL LA* (tolterodine L-tartrate) Product Monograph
Page 32 of 32

Source: http://e-lactancia.org/media/papers/Tolterodine-DS-Pfizer2015.pdf