Taboo DETROL LA (tolterodine L - tartrate extended-release capsules) is contraindicated in patients: urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, known allergy drugs or any ingredient or component in the development of container. Warnings and Precautions cardiovascular disease, congenital or acquired QT interval prolongation, QT interval in clinical studies, twice prolong the QT interval effects of tolterodine marked the highest dose (8 mg / day in divided taking, DETROL immediate-release tablets) 50% vs. active control moxifloxacin (400 mg), in its label dose reduced by 60%. In the recommended therapeutic dose DETROL (L - Tolterodine Tartrate tablets) (4 mg), the effect is low. Because the effect of QT interval prolongation is a linear relationship with exposure to any DETROL LA (tolterodine L - tartrate extended-release capsules) of the QT interval of the same will also be expected to be lower.

This study, however, there is no design of drug tolterodine formulations, direct statistical comparisons between doses. Will depend on individual patient risk factors and sensitivity of current clinical significance of these findings.

After ventricular tachycardia torsades and QT / QTc interval prolongation during drug therapy in patients with increased risk, should pay special attention to exercise. This is especially true with unusually long baseline QT / QTc intervals or taking strong CYP3A4 inhibitors (see drug interactions, drug interactions, dosage and administration) of the patients. In the general population, torsades de pointes ventricular tachycardia risk factors include, but are not limited to: women, the elderly (65 years); family history; affect cardiac ion channels or regulatory proteins, especially congenital long QT syndrome genetic variation in the <50-year-old sudden cardiac death, heart disease (eg, myocardial ischemia or infarction, congestive heart failure, left ventricular hypertrophy, cardiomyopathy); arrhythmias (especially ventricular arrhythmias, atrial fibrillation , the recent conversion of atrial fibrillation) history has proven, bradycardia (<50 times per minute); acute neurological events (eg, intracranial or subarachnoid hemorrhage, stroke, brain trauma; electrolyte disorders (such as low potassium blood disease, hypomagnesemia, hypocalcemia); nutritional deficiencies (eg, eating disorders, extreme diet), diabetic autonomic neuropathy; liver or kidney dysfunction, drug-related if the elimination of about 7% of Caucasians of CYP2D6 substrate metabolism in a poor pharmacokinetic / pharmacodynamic model to estimate, QTc interval increase in poor metabolizers of tolterodine 2 mg bid should be considered comparable to the treatment received 4 mg bid metabolism observed. stop the drug, if symptoms suggestive of arrhythmia.

Urinary retention, gastric retention DETROL LA (tolterodine L - tartrate extended-release capsules) of the risk of gastrointestinal and genitourinary system, patients should be careful to reduce the risk of gastrointestinal motility in patients with gastrointestinal obstructive disorders, such as pyloric stenosis , patients with clinically significant bladder outlet obstruction in patients, due to the risk of urinary retention, gastric retention because of the risk management (see Contraindications) liver / gallbladder / pancreas / liver function and with impaired renal insufficiency in patients with kidney disease should not be DETROL LA received per day is greater than 2 mg dose. Eye-controlled narrow-angle glaucoma DETROL LA patients being treated should be used with caution.

Narrow-angle glaucoma, pregnant women, studies in mice showed that tolterodine in 30 to 40 mg / kg / day dose, resulting in embryonic death, decreased fetal weight and increased fetal malformations (cleft palate, digital abnormalities, intra-abdominal incidence of special populations in these doses.

Bleeding, a variety of skeletal deformities, mainly to reduce the ossification in mice), AUC values ​​of about 20 - 25 times more than the human dose of 20 mg / kg / day (AUC value higher by about 15 times better than humans), in mice No abnormalities or deformities, pregnant women have not studied the tolterodine.

Therefore, DETROL LA should be used during pregnancy, only to prove the mother of the potential benefits of the potential risk to the fetus. Women of childbearing potential should be considered for treatment, only the use of appropriate contraception.

Lactating women, tolterodine is excreted in the milk of mice, it is not known whether tolterodine is excreted in human milk, Because many drugs are excreted in human milk, DETROL LA administration should be avoided in the care process , pediatric patient safety in children and effectiveness of DETROL LA has not been determined.

Geriatrics 1120 who treated four patients (65-93 years), the third stage, the 12-week clinical study of DETROL LA, 474 (42%) 65-91 years of age, no overall differences in safety were observed between elderly and younger patients.

1526 cases in the 12-week clinical study compared DETROL LA and tolterodine in patients with placebo, 642 (42%) immediate release tablets 65-93 years of age. No overall differences in safety were observed both older and younger patients (see Warnings and Precautions) between. QT / QTc interval monitoring, surveillance and laboratory tests and / or serum electrolyte levels are treated with DETROL LA high-risk patients, such as: the known congenital or acquired QT / QT interval prolongation or electrolyte disorders in patients with impaired liver or kidney function or other complications may be appropriate in patients with tolterodine may increase exposure or cause QT / QTc extension; those with QT / QTc prolongation and / or class IA (eg quinidine, procaine by amine) or class III (eg amiodarone, such as torsades de pointes ventricular tachycardia in patients related to drugs, sotalol) antiarrhythmic drugs, or taking strong CYP3A4 inhibitors (see WARNINGS and precautions, cardiovascular disease, drug interactions, drug interactions and dosage and administration.) drugs should be stopped to consider whether the symptoms suggesting arrhythmia or QT interval / QTc interval was prolonged as the ability to provide information to patients may adversely affect driving and use of machinery. Patients should be advised to exercise caution. Adverse reactions to adverse drug reactions in an overview of a large randomized, multicenter, double-blind 12-week study, 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 patients), was evaluated for safety.
DETROL LA 4 mg once daily was generally well tolerated, tolterodine immediate release tablets, 2 mg, twice daily, and placebo comparable to the overall incidence of adverse events, dry mouth is the most common occurrence of DETROL LA DETROL LA patients 23.4%, 30.5%, with tolterodine immediate release tablets in patients treated with placebo-treated patients and 7.7% of treated patients reported adverse events.

DETROL LA patients taking the overall rate of dry mouth, a single hub in this trial, 23%, compared with tolterodine immediate release tablets (P <0.02) (Table 1) Table 1: lower. DETROL LA DETROL LA is that, tolterodine immediate release tablets and treatment-related adverse events to placebo DETROL LA (tolterodine extended-release capsules) Tolterodine immediate-release tablets placebo dry mouth 23.4% 30.5% 3.8 % 2.5% 1.6% 7.7% 3.0% 3.1% abdominal pain, dyspepsia 1.4%, dizziness / vertigo of 2.2% 1.8% 2.2% 1.0% 1.2% fatigue, sinusitis 0.8% 1.8% 0.6% 0.6% 1.2%, visual abnormalities, 0.8%, 0.4%, dysuria, 1.0%, 1.6%, 0.2%, dry mouth, constipation, abnormal vision (accommodation abnormalities), urinary retention, dry eyes are expected side effects of anticholinergic drugs to stop because of adverse events most frequently in the first 4 weeks treatment similar to the percentage of DETROL LA, tolterodine immediate release tablets or placebo discontinued treatment due to adverse reactions in patients; and withdrawal-related dry mouth the most common adverse events (1.6%), headache (1.0%), constipation (0.7%) adverse drug reactions in clinical trials, because clinical trials are conducted under very specific conditions, in clinical trials the adverse reaction rates observed may not reflect the rates observed.

In practice should not be compared to another drug in clinical trials from the clinical trials the rate of adverse drug reaction information to identify drug-related adverse events and similar rates were very useful.

Table 2 lists the reports of adverse events ≥ 5% or more of DETROL LA 4 mg once-daily treatment of patients in the 12-week study, adverse events reported regardless of causality Table 2: DETROL LA in ≥ 5% of patients the incidence of adverse events (%) DETROL LA tolterodine and immediate-release tablets (tolterodine extended-release capsules) in 12-week controlled clinical trials DETROL LA 4 mg daily N = 505 after ñ = 507 placebo tolterodine immediate release tablets 2 mg, twice daily N = 512% of patients reported serious events 1.4 3.6 2.3% of patients discontinued due to headache 7.7 23.4 30.5 6.3 4.5 3.7 5.3 6.5 5.4 Dry mouth constipation 5.9 4.3 6.6 adverse events in clinical trials are not common adverse drug reactions (1% <5%) reported from 1% to other activities <DETROL LA and values ​​than those receiving the placebo patients reported greater treatment 5% of patients, listed in order of decreasing frequency: abdominal pain, dry eyes, urinary tract infection, dyspepsia, upper respiratory tract infection, drowsiness, dizziness, fatigue, flatulence, sinusitis, edema, pain, abnormal vision, and dysuria more than 400 cases. Up to 6 months of treatment with DETROL LA 4 mg once a day, an overall incidence of adverse events similar to the DETROL LA and in patients treated for 12 weeks post-marketing adverse drug reactions have been following events in association tolterodine use in clinical practice: allergic reactions (including angioedema), tachycardia, palpitations, peripheral edema, hallucinations, confusion, memory impairment, cholinesterase inhibitors and diarrhea symptoms of worsening dementia (such as confusion, disorientation, delusion) have been reported after tolterodine therapy of cholinesterase inhibitors for the treatment of Alzheimer's patients may begin treatment and lead to more significant drug interactions with other drugs while taking drugs with anticholinergic properties Overview / or adverse effects, on the contrary, the treatment effect of tolterodine may be reduced muscarinic receptor agonists in combination with other drugs drug interactions extend to the DETROL LA has been associated with the Qt / drugs QT / QTc interval of the drug QTc interval prolongation and / or torsades de pointes ventricular tachycardia, including, but not limited to, the following list of examples. If some, though not necessarily all, class members have been implicated in QT / QTc prolongation and / chemistry / drug listed or torsades de pointes ventricular tachycardia anti-arrhythmic drugs (IA level, for example, Kui Nitin, procainamide, disopyramide; III class, for example, amiodarone, sotalol, ibutilide; class IC, for example, flecainide, propafenone); antipsychotics ( such as thioridazine, chlorpromazine, haloperidol, pimozide droperidol); antidepressants (eg amitriptyline, imipramine, maprotiline, fluoxetine, venlafexine); opioids (eg methadone); antibiotics (such as erythromycin, clarithromycin, telithromycin, moxifloxacin, gatifloxacin); antimalarial drugs (such as quinine); amidine; azole antifungals ( such as ketoconazole, fluconazole, voriconazole), gastrointestinal drugs (such as domperidone, dolasetron, ondasetron); B2 - adrenergic receptor agonists (salmeterol, formoterol); tacrolimus Division of this potential drug interaction list is not complete before the start of medication. There combined drug treatment, the doctor should consult the current scientific literature information on the ability of new drugs approved by the QT / QTc interval prolongation, inhibition of metabolic enzymes or transport, or cause electrolyte imbalance, and the old drug these effects have recently been established (see Warnings and Precautions).

Cytochrome P450 3A4 inhibitors ketoconazole or other potent CYP3A4 inhibitors, such as other azole antifungals (eg, itraconazole, miconazole) or macrolide antibiotics (such as erythromycin, clarithromycin mold factors) or vinblastine in patients treated with cyclosporine, should not receive a dose of DETROL LA (tolterodine L - tartrate extended-release capsules) is greater than 2 mg daily of fluoxetine fluoxetine, cytochrome P450 2D6 potent inhibitor, significantly inhibited the metabolism of tolterodine extensive metabolism sum of unbound serum. The concentration of tolterodine and 5-hydroxymethyl derivative (DD - 01) is 25%, the management of the two drugs followed.

No dosage adjustment is necessary. DETROL LA by the cytochrome P450 2D6 metabolism of other drugs, the potential impact of tolterodine effects of other drugs by the cytochrome P450 2D6 (eg flecainide, vinblastine, carbamazepine, tricyclic antidepressants) drugs, drug metabolism pharmacokinetics has not been formally evaluated. Diuretics diuretics (such as: indapamide, hydrochlorothiazide, triamterene, bendroflumethiazide, chlorothiazide, methylchlorothiazide, or furosemide) DETROL (2 mg twice daily) did not cause any adverse ECG impact, but, in the presence of diuretics cause hypokalemia, and concomitant medications known or suspected adverse ECG effects (such as QT / QTc prolongation), doctors are advised to exercise caution and inform the patient's arrhythmia signs and symptoms.

Oral contraceptives clinical drug interaction studies showed that tolterodine immediate release tablets and oral contraceptives (ethinyl estradiol / levonorgestrel) without any known interaction between warfarin's clinical drug interaction studies have shown that there is no known tolterodine immediate release tablets and the interaction between warfarin drug interactions of food intake of food is not the result of tolterodine immediate release tablets or slow release capsules of the pharmacokinetics of clinically relevant changes. Herbal drug interactions with herbal products have not yet established the interaction. Drug Laboratory Test Interactions between tolterodine and laboratory study of the interaction has not been.

Counseling patients should inform patients, anticholinergic agents such as DETROL LA (tolterodine L - tartrate extended-release capsules) may cause blurred vision or dizziness, the measurement of dose and dosing dosing DETROL LA (care Castro set L - tartrate extended-release capsules) of the Notes may be affected by the following: the individual response and tolerability of liver dysfunction, renal insufficiency strong CYP3A4 inhibitors (see Warnings and Precautions and Dosage and management, the recommended dose and dose adjustments.) recommended initial dose and dose adjustment recommendations DETROL LA (tolterodine L - tartrate extended-release capsules) of the maximum dose is 4 mg once daily, the dose can be reduced to 2 mg once a day, based on individual response and tolerability. However, limited efficacy data DETROL LA 2 mg once a day.

For the impaired liver function and renal dysfunction in patients, the recommended dose is 2 mg daily (see Warnings and Precautions), patients once treatment with potent CYP3A4 inhibitors should not receive DETROL LA greater than 2 mg per day one (see Warnings and Precautions) dose should not exceed the maximum daily recommended dose of DETROL LA 4 mg of government can be taken with food, it should be swallowed whole.

Excessive amount of a suspected drug overdose management, CPHA is recommended that you contact your local poison control center a list of poison control centers, please refer to the CPS Directory section. The highest dose of tolterodine tartrate single dose to human volunteers was 12.8 mg.
The most serious adverse events accommodation disturbances and micturition difficulties. Excessive case has been reported before, the immediate release of the tolterodine tablets, to 27 months involving the child's intake of 5-7 marketing tolterodine immediate release 2 mg.

Overnight hospital stay dry mouth symptoms, and treatment with activated carbon suspension.

Child fully recovered

Overdose overdose treatment DETROL LA (tolterodine L - tartrate extended-release capsules) should be managed, including gastric lavage, activated charcoal, to treat the symptoms suggest the following: For severe central anticholinergic effects (hallucinations, severe excitation), anti- cholinesterase agents, such as lentils, can be used if the excitation and convulsions occur, management anticonvulsant such as diazepam in patients with respiratory insufficiency, respiratory assistance should be given, if respiratory arrest, the patient should be given artificial respiration, with heart Patients may be too fast with a β-blocker, and those with urinary retention may catheterization. Mydriasis trouble patients may be placed in a dark room, or with pilocarpine eye drops, or treatment should be monitored ECG.

Tolterodine 8 mg dose (4 mg bid) immediate release of clinical trial in normal volunteers, QT interval prolongation. Torsades de pointes ventricular tachycardia DE risks.

pointes is a QT / QTc interval prolongation drugs are usually dose-dependent. It is suggested that continuous ECG monitoring, may be with Detrol (or Detrol LA) over the combined treatment, where appropriate, should immediately review and cease, if the potential drug interactions and drug increased QT interval prolongation effect is likely to (see warnings and precautions, drug interactions, drug interactions).

Action and action of tolterodine L - Tartrate Clinical Pharmacology mechanism is a competitive muscarinic receptor antagonist, which has been shown from rats, guinea pigs, the human isolated bladder preparations inhibited carbamoyl choline-induced contraction of large Tolterodine tartrate (hereinafter referred to as tolterodine) inhibition of guinea pig detrusor contraction, and the electrically evoked contraction of human detrusor from stable.

Overactive bladder in vitro. Tolterodine is a cat drooling over electric induction of anesthesia significantly inhibited acetylcholine-induced contraction of the bladder more active. Pharmacodynamics of tolterodine in healthy volunteers on bladder function has a significant effect.

Following a single dose of 6.4 mg of the main effects of tolterodine, reflecting an incomplete emptying of the bladder, reducing detrusor pressure increased residual urine, these results with lower urinary tract anticholinergic and action. Who received the recommended dose of tolterodine for overactive bladder in patients with immediate-release tablets, urodynamic measurements indicate that tolterodine in the first contraction and maximum bladder capacity increased volume. Tolterodine convert a pharmacological activity of 5 - hydroxymethyl metabolite (DD - 01) cytochrome isoenzymes of cytochrome P450 2D6 (guanidine hydroxylase), this metabolite of tolterodine exhibits in in vitro and in vivo anticholinergic profile similar DD 01, from human and animal pharmacokinetic data anticholinergic activity, it has been concluded that this metabolite can help in a wide range of metabolic significant treatment effect ( see Metabolism).

A dose-response relationship is built on the second stage of the study of tolterodine extended-release capsules (002) per residue in the urine within 12 hours.
Dose of tolterodine extended-release capsules, have the same effect of tolterodine immediate release tablets, 2 mg, twice daily, estimated to be 4.7 mg (3.7 mg of active ingredient relative exposure correction).
A dose-response relationship for inhibition of salivation. A pharmacokinetic study of 14C absorbed in healthy volunteers, who received a 5 mg oral dose of tolterodine, at least 77% of the radiolabelled dose is absorbed, rapidly absorbed. Tolterodine immediate release tablets, and maximum plasma concentration (Cmax) for the administration of 1 or 2 hours after the occurrence. Of tolterodine immediate release tablets of the pharmacokinetics, area under the concentration time curve (AUC) of Cmax and area measured on the basis of the range of 1 to 4 mg dose proportional based on tolterodine and DD 01, unbound The sum of plasma concentrations.
Tolterodine extended-release capsules, 4 mg, once daily, AUC is equivalent to tolterodine immediate release tablets, 2 mg, twice daily. , Sustained-release capsules Cmax and trough concentration levels are about 75%, and immediate release tablets of 150%, respectively, with maximum plasma concentrations observed after administration of 2-6 hours of food intake does not lead to distribution of tolterodine tolterodine immediate release tablets or sustained-release capsules of the pharmacokinetics of clinically relevant change is highly bound to plasma proteins, mainly α1.
- Tolterodine average acid glycoprotein, Unbound concentrations above 3.7% ± 0.13% obtained in clinical studies within the concentration range. , 5 - hydroxymethyl metabolite (DD - 01) is not extensive protein binding, the unbound fraction of an average of 36% ± 4.0% concentration.
Blood serum of tolterodine and DD 01 on average were 0.6 and 0.8, which indicates that these compounds are not widely distributed to the proportion of red blood cells. 1.28 mg intravenous dose of tolterodine following administration of the allocations is 113 ± 26.7 L. on behalf of the Xietuoteluo extensive hepatic metabolism after oral administration and converted to the DD 01 of the isozyme cytochrome P450 2D6 and further metabolism, leading to the formation of 5 carboxylic acid and N-dealkylated 5-carboxylic acid metabolite accounted for 51% ± 14% and 29% ± were recovered in the urine metabolites of 6.3%.
Tolterodine is also, such as tricyclic antidepressants, anti-arrhythmic drugs, selective 5 - HT reuptake inhibitors and antipsychotics, cytochrome P450 2D6 metabolism of other drugs, the potential impact of pharmacokinetics has not been formal assessment of the variation.
In metabolism: a subset of the population (about 7%) is not drug-metabolizing isozyme cytochrome P450 2D6, the enzyme responsible for the formation of the DD 01 to determine the metabolic pathways for these people, known as "poor metabolizers." (PMS) by cytochrome P450 3A4 to N-dealkylated tolterodine of dealkylation rest of the population is called "metabolic" (EMS) of the pharmacokinetic studies, metabolic rate than in the tolterodine EMS slower than in the PMS.
Because tolterodine and DD 01 have similar anticholinergic effects, net DETROL LA activity is expected to be similar to the EMS and PMS.
Excretion following 5 mg oral dose of 14C - tolterodine solution to healthy volunteers, administration, 77% of the radioactive material was recovered 5-14% (<1% of poor metabolizers) was recovered in urine and 17% 7-day stool, urine and feces as a full dose of tolterodine is less than 1% (<2.5%), poor metabolic recovery;. DD 01 is the first 24 hours of recovery, which is consistent with the apparent half-life of tolterodine: a. 1.9 to 3.7 hours, four more than DD 01 poor metabolizers and four metabolites in serum metabolites to determine the level of comparability of tolterodine extended-release capsules and immediate release tablet of special populations and conditions of age, no overall difference Tolterodine given immediate release tablets in patients older and younger in the third stage, 12 weeks, controlled clinical studies of safety between the observations, therefore, no dosage adjustment is recommended in elderly patients there is no gender-dependent differences in the pharmacokinetics of tolterodine or DD 01. Racial-ethnic differences in pharmacokinetics has not been determined.
Cirrhosis of liver dysfunction subjects showed higher plasma concentrations and long half-life of tolterodine. And the DD 01 to give the same dose compared to young healthy subjects, renal insufficiency potential pharmacological effects, metabolism should also be considered toxicological significance, if exposed subjects with renal insufficiency (glomerular filtration rate <30 ml / min), repeated doses of tolterodine storage and storage stability at room temperature 15 ~ 30 ° C. Dark special handling instructions for the patient Detrol LA information does not apply. Formulations, ingredients and packaging of each 2 mg of sustained-release capsules blue-green, with symbol and "2" white ink, contains: Tolterodine L - tartrate 2 mg Nonmedicinal ingredients:. Ammonium hydroxide, ethyl cellulose, FD & C Blue 2, gelatin, hydroxypropyl methylcellulose, medium chain triglycerides, oleic acid, Opacode white trumpet --1--7085 (shellac glaze, titanium dioxide, ammonium hydroxide , propylene glycol and simethicone), starch, sugar and yellow iron oxide 4 mg sustained-release capsules of each blue, and white ink printed with the symbol "4", includes: Tolterodine L - tartrate 4 mg Nonmedicinal . Ingredients: ammonium hydroxide, ethyl cellulose, FD & Comets Blue 2, gelatin, hydroxypropyl methylcellulose, medium chain triglycerides, oleic acid, Opacode white trumpet --1--7085 (shellac glaze, titanium dioxide, hydrogen ammonium oxide, propylene glycol and simethicone), starch and sugar.