Detrol Information
Detrol (Tolterodine) Description
Detrol (Tolterodine) Tablets contain tolterodine tartrate. The active moiety, tolterodine, is a muscarinic receptor antagonist. The chemical name of tolterodine tartrate is (R)-2-[3-[bis(1-methylethyl)-amino]1-phenylpropyl]-4-methylphenol [R-(R*,R*)]-2,3dihydroxybutanedioate (1:1) (salt). The empirical formula of tolterodine tartrate is CHNO, and its molecular weight is 475.6. The structural formula of tolterodine tartrate is represented below:
Tolterodine tartrate is a white, crystalline powder. The pKa value is 9.87 and the solubility in water is 12 mg/mL. It is soluble in methanol, slightly soluble in ethanol, and practically insoluble in toluene. The partition coefficient (Log D) between n-octanol and water is 1.83 at pH 7.3.
Detrol (Tolterodine) Tablets for oral administration contain 1 or 2 mg of tolterodine tartrate. The inactive ingredients are colloidal anhydrous silica, calcium hydrogen phosphate dihydrate, cellulose microcrystalline, hypromellose, magnesium stearate, sodium starch glycolate (pH 3.0 to 5.0), stearic acid, and titanium dioxide.
Detrol (Tolterodine) Clinical Pharmacology
Tolterodine is a competitive muscarinic receptor antagonist. Both urinary bladder contraction and salivation are mediated via cholinergic muscarinic receptors.
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, which exhibits an antimuscarinic activity similar to that of tolterodine, contributes significantly to the therapeutic effect. Both tolterodine and the 5-hydroxymethyl metabolite exhibit a high specificity for muscarinic receptors, since both show negligible activity or affinity for other neurotransmitter receptors and other potential cellular targets, such as calcium channels.
Tolterodine has a pronounced effect on bladder function. Effects on urodynamic parameters before and 1 and 5 hours after a single 6.4 mg dose of tolterodine immediate release were determined in healthy volunteers. The main effects of tolterodine at 1 and 5 hours were an increase in residual urine, reflecting an incomplete emptying of the bladder, and a decrease in detrusor pressure. These findings are consistent with an antimuscarinic action on the lower urinary tract.
Detrol (Tolterodine) Clinical Studies
Detrol (Tolterodine) Tablets were evaluated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency in four randomized, double-blind, placebo-controlled, 12-week studies. A total of 853 patients received Detrol (Tolterodine) 2 mg twice daily and 685 patients received placebo. The majority of patients were Caucasian (95%) and female (78%), with a mean age of 60 years (range, 19 to 93 years). At study entry, nearly all patients perceived they had urgency and most patients had increased frequency of micturitions and urge incontinence. These characteristics were well balanced across treatment groups for the studies.
The efficacy endpoints for study 007 (see ) included the change from baseline for:
The efficacy endpoints for studies 008, 009, and 010 (see ) were identical to the above endpoints with the exception that the number of incontinence episodes was per 24 hours (averaged over 7 days).
Detrol (Tolterodine) Indications And Usage
Detrol (Tolterodine) Tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.
Detrol (Tolterodine) Contraindications
Detrol (Tolterodine) Tablets are contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. Detrol (Tolterodine) is also contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients, or to fesoterodine fumarate extended-release tablets which, like Detrol (Tolterodine) , are metabolized to 5-hydroxymethyl tolterodine.
Detrol (Tolterodine) Warnings
Anaphylaxis and angioedema requiring hospitalization and emergency medical treatment have occurred with the first or subsequent doses of Detrol (Tolterodine) . In the event of difficulty in breathing, upper airway obstruction, or fall in blood pressure, Detrol (Tolterodine) should be discontinued and appropriate therapy promptly provided.
Detrol (Tolterodine) Precautions
Carcinogenicity studies with tolterodine were conducted in mice and rats. At the maximum tolerated dose in mice (30 mg/kg/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.
No mutagenic effects of tolterodine were detected in a battery of in vitro tests, including bacterial mutation assays (Ames test) in 4 strains of and in 2 strains of 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.
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 were seen. Based on AUC values, the systemic exposure was about 15-fold higher in animals than in humans. In male mice, a dose of 30 mg/kg/day did not induce any adverse effects on fertility.
Efficacy in the pediatric population has not been demonstrated.
Two pediatric phase 3 randomized, placebo-controlled, double-blind, 12-week studies were conducted using tolterodine extended release (Detrol (Tolterodine) LA) capsules. A total of 710 pediatric patients (486 on Detrol (Tolterodine) LA and 224 on placebo) aged 5–10 years with urinary frequency and urge urinary incontinence were studied. The percentage of patients with urinary tract infections was higher in patients treated with Detrol (Tolterodine) LA (6.6%) compared to patients who received placebo (4.5%). Aggressive, abnormal and hyperactive behavior and attention disorders occurred in 2.9% of children treated with Detrol (Tolterodine) LA compared to 0.9% of children treated with placebo.
Detrol (Tolterodine) Adverse Reactions
The Phase 2 and 3 clinical trial program for Detrol (Tolterodine) Tablets included 3071 patients who were treated with Detrol (Tolterodine) (N=2133) or placebo (N=938). The patients were treated with 1, 2, 4, or 8 mg/day for up to 12 months. No differences in the safety profile of tolterodine were identified based on age, gender, race, or metabolism.
The data described below reflect exposure to Detrol (Tolterodine) 2 mg bid in 986 patients and to placebo in 683 patients exposed for 12 weeks in five Phase 3, controlled clinical studies. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and approximating rates.
Sixty-six percent of patients receiving Detrol (Tolterodine) 2 mg bid reported adverse events versus 56% of placebo patients. The most common adverse events reported by patients receiving Detrol (Tolterodine) were dry mouth, headache, constipation, vertigo/dizziness, and abdominal pain. Dry mouth, constipation, abnormal vision (accommodation abnormalities), urinary retention, and xerophthalmia are expected side effects of antimuscarinic agents.
Dry mouth was the most frequently reported adverse event for patients treated with Detrol (Tolterodine) 2 mg bid in the Phase 3 clinical studies, occurring in 34.8% of patients treated with Detrol (Tolterodine) and 9.8% of placebo-treated patients. One percent of patients treated with Detrol (Tolterodine) discontinued treatment due to dry mouth.
The frequency of discontinuation due to adverse events was highest during the first 4 weeks of treatment. Seven percent of patients treated with Detrol (Tolterodine) 2 mg bid discontinued treatment due to adverse events versus 6% of placebo patients. The most common adverse events leading to discontinuation of Detrol (Tolterodine) were dizziness and headache.
Three percent of patients treated with Detrol (Tolterodine) 2 mg bid reported a serious adverse event versus 4% of placebo patients. Significant ECG changes in QT and QTc have not been demonstrated in clinical-study patients treated with Detrol (Tolterodine) 2 mg bid. Table 5 lists the adverse events reported in 1% or more of the patients treated with Detrol (Tolterodine) 2 mg bid in the 12-week studies. The adverse events are reported regardless of causality.
Detrol (Tolterodine) Overdosage
A 27-month-old child who ingested 5 to 7 Detrol (Tolterodine) Tablets 2 mg was treated with a suspension of activated charcoal and was hospitalized overnight with symptoms of dry mouth. The child fully recovered.
Detrol (Tolterodine) Dosage And Administration
The initial recommended dose of Detrol (Tolterodine) Tablets is 2 mg twice daily. The dose may be lowered to 1 mg twice daily based on individual response and tolerability. For patients with significantly reduced hepatic or renal function or who are currently taking drugs that are potent inhibitors of CYP3A4, the recommended dose of Detrol (Tolterodine) is 1 mg twice daily (see and ).
Detrol (Tolterodine) How Supplied
Bottles of 601 mg NDC 0009-4541-022 mg NDC 0009-4544-02
Bottles of 5001 mg NDC 0009-4541-032 mg NDC 0009-4544-03
Unit Dose Pack of 1401 mg NDC 0009-4541-012 mg NDC 0009-4544-01
Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature] (DTL).
Detrol (Tolterodine)
Detrol (Tolterodine) Patient Information Detrol (de-trol)(tolterodine Tartrate Tablets)
Detrol (Tolterodine) is a prescription medicine for used to treat the following symptoms due to a condition called :
Detrol (Tolterodine) LA (tolterodine tartrate extended release capsules) did not help the symptoms of overactive bladder when studied in children.
Overactive bladder happens when you cannot control your bladder muscle. When the muscle contracts too often or cannot be controlled, you get symptoms of overactive bladder, which are leakage of urine (urge urinary incontinence), needing to urinate right away (urgency), and needing to urinate often (frequency).
Do not take Detrol (Tolterodine) if you:
Before starting Detrol (Tolterodine) , tell your doctor about all of your medical and other conditions that may affect the use of Detrol (Tolterodine) , including:
Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Other medicines can affect how your body handles Detrol (Tolterodine) . Your doctor may use a lower dose of Detrol (Tolterodine) if you are taking:
Ask your doctor or pharmacist for a list of these medicines, if you are not sure.
Know the medicines you take. Keep a list of them with you to show your doctor or pharmacist each time you get a new medicine.
Medicines like Detrol (Tolterodine) can cause blurred vision or drowsiness. Use caution while driving or doing other dangerous activities until you know how Detrol (Tolterodine) affects you.
Detrol (Tolterodine) may cause allergic reactions that may be serious. Symptoms of a serious allergic reaction may include swelling of the face, lips, throat or tongue. If you experience these symptoms, you should stop taking Detrol (Tolterodine) and get emergency medical help right away.
The most common side effects with Detrol (Tolterodine) are:
Tell your doctor if you have any side effects that bother you or that do not go away.
These are not all the side effects with Detrol (Tolterodine) . For a complete list, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
Medicines are sometimes prescribed for conditions that are not mentioned in the patient information leaflet. Only use Detrol (Tolterodine) the way your doctor tells you. Do not give Detrol (Tolterodine) to other people even if they have the same symptoms you have. It may harm them.
This leaflet summarizes the most important information about Detrol (Tolterodine) . If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Detrol (Tolterodine) that is written for health professionals. You can also visit on the Internet, or call 1-888-4-Detrol (Tolterodine) (1-888-433-8765).
Detrol (Tolterodine)
Detrol (Tolterodine) Principal Display Panel - Mg Bottle Label
Detrol (Tolterodine) Principal Display Panel - Mg Bottle Label
