Detrol

Product Type: HUMAN PRESCRIPTION DRUG

Route: ORAL

Dosage Form:

NDC: 58151-099

Application: NDA020771

Effective: 20230215

INDICATIONS AND USAGE DETROL Tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.

DOSAGE AND ADMINISTRATION The initial recommended dose of DETROL 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 is 1 mg twice daily (see PRECAUTIONS, General , PRECAUTIONS, Reduced Hepatic and Renal Function , and PRECAUTIONS, Drug Interactions ).

CONTRAINDICATIONS DETROL Tablets are contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. DETROL 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, are metabolized to 5-hydroxymethyl tolterodine.

WARNINGS Anaphylaxis and angioedema requiring hospitalization and emergency medical treatment have occurred with the first or subsequent doses of DETROL. In the event of difficulty in breathing, upper airway obstruction, or fall in blood pressure, DETROL should be discontinued and appropriate therapy promptly provided.

ADVERSE REACTIONS The Phase 2 and 3 clinical trial program for DETROL Tablets included 3071 patients who were treated with DETROL (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 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 2 mg bid reported adverse events versus 56% of placebo patients. The most common adverse events reported by patients receiving DETROL 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 2 mg bid in the Phase 3 clinical studies, occurring in 34.8% of patients treated with DETROL and 9.8% of placebo-treated patients. One percent of patients treated with DETROL 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 2 mg bid discontinued treatment due to adverse events versus 6% of placebo patients. The most common adverse events leading to discontinuation of DETROL were dizziness and headache. Three percent of patients treated with DETROL 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 2 mg bid. Table 5 lists the adverse events reported in 1% or more of the patients treated with DETROL 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 DETROL Tablets (2 mg bid) in 12-week, Phase 3 Clinical Studies Body System Adverse Event % DETROL N=986 % Placebo N=683 Autonomic Nervous accommodation abnormal dry mouth 2 35 1 10 General chest pain fatigue headache influenza-like symptoms 2 4 7 3 1 3 5 2 Central/Peripheral Nervous vertigo/dizziness 5 3 Gastrointestinal abdominal pain constipation diarrhea dyspepsia 5 7 4 4 3 4 3 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 Post-marketing Surveillance The following events have been reported in association with tolterodine use in worldwide post-marketing 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 post-marketing experience, the frequency of events and the role of tolterodine in their causation cannot be reliably determined.