1 INDICATIONS AND USAGE Trospium Chloride Extended-Release Capsules are a muscarinic antagonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.

Trospium Chloride Extended-Release Capsules are a muscarinic antagonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.

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6 ADVERSE REACTIONS The most common adverse reactions (greater than or equal to 1%) with trospium chloride extended-release capsules are dry mouth (10.7%) and constipation (8.5%).

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Slate Run Pharmaceuticals, LLC at 1-888-341-9214 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the 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 clinical practice.

The data described below reflect exposure to trospium chloride extended-release capsules in 578 patients for 12 weeks in two Phase 3 double-blind, placebo controlled trials (n=1,165).

These studies included overactive bladder patients of ages 21 to 90 years, of which 86% were female and 85% were Caucasian.

Patients received 60 mg daily doses of trospium chloride extended-release capsules.

Patients in these studies were eligible to continue treatment with trospium chloride extended-release capsules 60 mg for up to one year.

From both these controlled trials combined, 769 and 238 patients received treatment with trospium chloride extended-release capsules for at least 24 and 52 weeks, respectively.

There were 157 (27.2%) trospium chloride extended-release capsules patients and 98 (16.7%) placebo patients who experienced one or more double-blind treatment-emergent adverse events (TEAEs) that were assessed by the investigator as at least possibly related to study medication.

The most common TEAEs were dry mouth and constipation which, when reported, commonly occurred early in treatment (often within the first week).

In the two Phase 3 studies, constipation, dry mouth, and urinary retention led to discontinuation in 1%, 0.7%, and 0.5% of patients treated with trospium chloride extended-release capsules 60 mg daily, respectively.

In the placebo group, there were no discontinuations due to dry mouth or urinary retention and one due to constipation.

The incidence of serious adverse events was similar among patients receiving trospium chloride extended-release capsules and patients receiving placebo.

No treatment-emergent serious adverse events in either treatment group were judged by the investigators as being possibly related to the study medication.

Table 1 lists those treatment emergent adverse events from the trials that were assessed by the investigator as possibly related to study medication, reported in at least 1% of trospium chloride extended-release capsules patients, and were more common for the trospium chloride extended-release capsules group than for placebo.

Table 1: Incidence of treatment-emergent adverse events reported in at least 1% of patients judged by the investigator as at least possibly related to treatment and more common for the Trospium Chloride Extended-Release Capsules group than for placebo MedDRA Preferred term Number of patients (%) Placebo N=587 Trospium Chloride Extended-Release Capsules N=578 Dry mouth 22 (3.7) 62 (10.7) Constipation 9 (1.5) 49 (8.5) Dry eye 1 (0.2) 9 (1.6) Flatulence 3 (0.5) 9 (1.6) Nausea 2 (0.3) 8 (1.4) Abdominal pain 2 (0.3) 8 (1.4) Dyspepsia 4 (0.7) 7 (1.2) Urinary tract infection 5 (0.9) 7 (1.2) Constipation aggravated 3 (0.5) 7 (1.2) Abdominal distension 2 (0.3) 6 (1.0) Nasal dryness 0 (0.0) 6 (1.0) Additional adverse events reported in less than 1% of trospium chloride extended-release capsules treated patients and more common for trospium chloride extended-release capsules than placebo, judged by the investigator at least possibly related to treatment were: vision blurred, feces hard, back pain, somnolence, urinary retention, and dry skin.

Table 2 lists all treatment-emergent adverse events for the trials reported in at least 2% of all trospium chloride extended-release capsules patients and more common for the trospium chloride extended-release capsules group than for placebo without regard to the investigator’s judgment on drug relatedness.

Table 2: Incidence of treatment-emergent adverse events reported in at least 2% of patients regardless of reported relationship to treatment and more common for the Trospium Chloride Extended-Release Capsules group than for placebo MedDRA Preferred term Number of patients (%) Placebo N=587 Trospium Chloride Extended-Release Capsules N=578 Dry mouth 22 (3.7) 64 (11.1) Constipation 10 (1.7) 52 (9.0) Urinary tract infection 29 (4.9) 42 (7.3) Nasopharyngitis 10 (1.7) 17 (2.9) Influenza 9 (1.5) 13 (2.2) Additional adverse events reported in less than 2% of trospium chloride extended-release capsules treated patients and twice as frequent for trospium chloride extended-release capsules compared to placebo, regardless of reported relationship to treatment were: tachycardia, dry eyes, abdominal pain, dyspepsia, abdominal distension, constipation aggravated, nasal dryness, and rash.

In the open-label treatment phase, the most common TEAEs reported in the 769 patients with at least 6 months exposure to trospium chloride extended-release capsules were: constipation, and dry mouth.

Urinary tract infection and rash was also reported in several patients, including one of each judged by the investigator to be possibly related to treatment.

Several adverse events were reported as severe in the open-label treatment phase, including one urinary tract infection, two urinary retention events, and one aggravated constipation.

6.2 Post-marketing Experience The following adverse reactions have been identified during post-approval use of trospium chloride.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal – gastritis; Cardiovascular – palpitations, supraventricular tachycardia, chest pain, syncope, “hypertensive crisis”; Immunological – Stevens-Johnson syndrome, anaphylactic reaction, angioedema; Nervous System – dizziness, confusion, vision abnormal, hallucinations, somnolence, and delirium; Musculoskeletal – rhabdomyolysis; General – rash.