Tolterodine Tartrate
FDA Drug Information • Also known as: Detrol, Detrol La, Tolterodine Tartrate, Tolterodine Tartrate Extended Release
- Brand Names
- Detrol, Detrol La, Tolterodine Tartrate, Tolterodine Tartrate Extended Release
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
DESCRIPTION This product contains 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). It has the following structural formula: C 26 H 37 NO 7 M.W. 475.6 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. Each tolterodine tartrate tablet, for oral administration, contains 1 mg or 2 mg of tolterodine tartrate. In addition, each tablet contains the following inactive ingredients: corn starch, croscarmellose sodium, hypromellose, lactose monohydrate, microcrystalline cellulose, polyethylene glycol, sodium stearyl fumarate, and titanium dioxide. tolterodine figure
What Is Tolterodine Tartrate Used For?
INDICATIONS AND USAGE Tolterodine tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.
Dosage and Administration
DOSAGE AND ADMINISTRATION The initial recommended dose of tolterodine tartrate 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 tolterodine tartrate is 1 mg twice daily (see PRECAUTIONS , General ; PRECAUTIONS , Reduced Hepatic and Renal Function , and PRECAUTIONS, Drug Interactions ).
Side Effects (Adverse Reactions)
ADVERSE REACTIONS The Phase 2 and 3 clinical trial program for tolterodine tablets included 3071 patients who were treated with 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 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 tolterodine 2 mg BID reported adverse events versus 56% of placebo patients. The most common adverse events reported by patients receiving 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 tolterodine 2 mg BID in the Phase 3 clinical studies, occurring in 34.8% of patients treated with tolterodine and 9.8% of placebo-treated patients. One percent of patients treated with 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 tolterodine 2 mg BID discontinued treatment due to adverse events versus 6% of placebo patients. The most common adverse events leading to discontinuation of tolterodine were dizziness and headache. Three percent of patients treated with 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 tolterodine 2 mg BID. Table 5 lists the adverse events reported in 1% or more of the patients treated with tolterodine 2 mg BID in the 12 week studies. The adverse events are reported regardless of causality. Table 5: Incidence1(%) of Adverse Events Exceeding Placebo Rate and Reported in > 1% of Patients Treated With Tolterodine Tablets (2 mg BID) in 12 week, Phase 3 Clinical Studies Body System Adverse Event % Tolterodine N = 986 % Placebo N = 683 Autonomic Nervous Accommodation abnormal 2 1 Dry mouth 35 10 General Chest pain 2 1 Fatigue 4 3 Headache 7 5 Influenza-like symptoms 3 2 Central/Peripheral Nervous Vertigo/dizziness 5 3 Gastrointestinal Abdominal pain 5 3 Constipation 7 4 Diarrhea 4 3 Dyspepsia 4 1 Urinary Dysuria 2 1 Skin/Appendages Dry skin 1 0 Musculoskeletal Arthralgia 2 1 Vision Xerophthalmia 3 2 Psychiatric Somnolence 3 2 Metabolic/Nutritional Weight gain 1 0 Resistance Mechanism Infection 1 0 1. in nearest integer Postmarketing Surveillance The following events have been reported in association with tolterodine use in worldwide postmarketing experience: General : anaphylaxis and angioedema; Cardiovascular : tachycardia, palpitations, peripheral edema; Central/Peripheral Nervous : confusion, disorientation, memory impairment, hallucinations. Reports of aggravation of symptoms of dementia (e.g., confusion, disorientation, delusion) have been reported after tolterodine therapy was initiated in patients taking cholinesterase inhibitors for the treatment of dementia. Because these spontaneously reported events are from the worldwide postmarketing experience, the frequency of events and the role of tolterodine in their causation cannot be reliably...
Warnings and Precautions
WARNINGS Anaphylaxis and angioedema requiring hospitalization and emergency medical treatment have occurred with the first or subsequent doses of tolterodine tablets. In the event of difficulty in breathing, upper airway obstruction, or fall in blood pressure, tolterodine tablets should be discontinued and appropriate therapy promptly provided.
Drug Interactions
Drug Interactions CYP3A4 Inhibitors Ketoconazole, an inhibitor of the drug-metabolizing enzyme CYP3A4, significantly increased plasma concentrations of tolterodine when coadministered to subjects who were poor metabolizers (see CLINICAL PHARMACOLOGY , Variability in Metabolism and Drug-Drug Interactions ). For patients receiving 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, the recommended dose of tolterodine is 1 mg twice daily (see DOSAGE AND ADMINISTRATION ).
Contraindications
CONTRAINDICATIONS Tolterodine tablets are contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. Tolterodine tablets are also contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients, or to fesoterodine fumarate extended-release tablets which, like tolterodine tablets, are metabolized to 5-hydroxymethyl tolterodine.
Pregnancy and Breastfeeding
Pregnancy Teratogenic Effects Pregnancy Category C At oral doses of 20 mg/kg/day (approximately 14 times the human exposure), no anomalies or malformations were observed in mice. When given at doses of 30 to 40 mg/kg/day, tolterodine has been shown to be embryolethal, reduce fetal weight, and increase the incidence of fetal abnormalities (cleft palate, digital abnormalities, intra-abdominal hemorrhage, and various skeletal abnormalities, primarily reduced ossification) in mice. At these doses, the AUC values were about 20 to 25 fold higher than in humans. Rabbits treated subcutaneously at a dose of 0.8 mg/kg/day achieved an AUC of 100 mcg
Nursing Mothers Tolterodine is excreted into the milk in mice. Offspring of female mice treated with tolterodine 20 mg/kg/day during the lactation period had slightly reduced body weight gain. The offspring regained the weight during the maturation phase. It is not known whether tolterodine is excreted in human milk; therefore, tolterodine should not be administered during nursing. A decision should be made whether to discontinue nursing or to discontinue tolterodine in nursing mothers.
Overdosage
OVERDOSAGE A 27 month-old child who ingested 5 to 7 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. Management of Overdosage Overdosage with tolterodine can potentially result in severe central anticholinergic effects and should be treated accordingly. ECG monitoring is recommended in the event of overdosage. In dogs, changes in the QT interval (slight prolongation of 10% to 20%) were observed at a suprapharmacologic dose of 4.5 mg/kg, which is about 68 times higher than the recommended human dose. In clinical trials of normal volunteers and patients, QT interval prolongation was observed with tolterodine immediate-release at doses up to 8 mg (4 mg BID) and higher doses were not evaluated (see PRECAUTIONS , Patients With Congenital or Acquired QT Prolongation ).
How Supplied
HOW SUPPLIED Tolterodine Tartrate Tablets, 1 mg, are available as white, round, unscored, biconvex, film-coated tablets, debossed with “93” on one side and “0010” on the other side containing 1 mg tolterodine tartrate, packaged in bottles of 60 (NDC 0093-0010-06) and 500 (NDC 0093-0010-05) tablets. Tolterodine Tartrate Tablets, 2 mg, are available as white, round, unscored, biconvex, film-coated tablets, debossed “93” on one side and “18” on the other side containing 2 mg tolterodine tartrate, packaged in bottles of 60 (NDC 0093-0018-06) and 500 (NDC 0093-0018-05) tablets. PHARMACIST: Dispense in a tight container as defined in the USP, with a child-resistant closure (as required). Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature]. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. Manufactured In India By: Cipla Ltd. Goa, India Manufactured For: TEVA PHARMACEUTICALS USA, INC. North Wales, PA 19454 Rev. D 4/2015
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.