FDA

Tolterodine Tartrate

Approved 23 Feb 2015OralTablet

The FDA lists this product in 34 strengths and forms.

Indications

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

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.

Warnings and precautions

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.

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 ).

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

At a glance

Brand name: Tolterodine Tartrate
Route: Oral
Dosage form: Tablet
Applicant: Ivax Sub Teva Pharms
Status: Prescription
FDA approval: 23 Feb 2015
Application: ANDA077006-002

Contraindications

Warnings and precautions

Interactions

Pregnancy and breastfeeding

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

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: Incidence in nearest integer (%) 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 % TolterodineN = 986 % PlaceboN = 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 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 determined.

Tolterodine Tartrate

Indications

Contraindications

Warnings and precautions

Interactions

Pregnancy and breastfeeding

At a glance

Two medicines in one question?

Tolterodine Tartrate

Indications

Contraindications

Warnings and precautions

Interactions

Pregnancy and breastfeeding

At a glance

Two medicines in one question?

Adverse reactions

Composition

Strengths and forms

Official product information