FESOTERODINE FUMARATE (Page 2 of 7)

5.6 Worsening of Myasthenia Gravis Symptoms

Fesoterodine fumarate extended-release tablets should be used with caution in patients with myasthenia gravis due to the risk of worsening of symptoms of the disease.

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in labeling:

6.1 Clinical Trials Experience

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.

Adult Overactive Bladder (OAB)

The safety of fesoterodine fumarate extended-release tablets were evaluated in Phase 2 and 3 controlled trials in a total of 2859 patients with overactive bladder, of which 2288 were treated with fesoterodine fumarate extended-release tablets. Of this total, 782 received fesoterodine fumarate extended-release tablets 4 mg/day, and 785 received fesoterodine fumarate extended-release tablets 8 mg/day with treatment periods of 8- or 12-weeks. Approximately 80% of these patients had greater than 10-weeks of exposure to fesoterodine fumarate extended-release tablets in these trials.

A total of 1964 patients participated in two 12-week, Phase 3 efficacy and safety studies and subsequent open-label extension studies. In these two studies combined, 554 patients received fesoterodine fumarate extended-release tablets 4 mg/day and 566 patients received fesoterodine fumarate extended-release tablets 8 mg/day.

In Phase 2 and 3 placebo-controlled trials combined, the incidences of serious adverse events in patients receiving placebo, fesoterodine fumarate extended-release tablets 4 mg, and fesoterodine fumarate extended-release tablets 8 mg were 1.9%, 3.5%, and 2.9%, respectively. All serious adverse events were judged to be not related or unlikely to be related to study medication by the investigator, except for four patients receiving fesoterodine fumarate extended-release tablets who reported one serious adverse reaction each: angina, chest pain, gastroenteritis, and QT prolongation on ECG.

The most commonly reported adverse event in patients treated with fesoterodine fumarate extended-release tablets was dry mouth. The incidence of dry mouth was higher in those taking 8 mg/day (35%) and in those taking 4 mg/day (19%), as compared to placebo (7%). Dry mouth led to discontinuation in 0.4%, 0.4%, and 0.8% of patients receiving placebo, fesoterodine fumarate extended-release tablets 4 mg, and fesoterodine fumarate extended-release tablets 8 mg, respectively. For those patients who reported dry mouth, most had their first occurrence of the event within the first month of treatment.

The second most commonly reported adverse event was constipation. The incidence of constipation was 2% in those taking placebo, 4% in those taking 4 mg/day, and 6% in those taking 8 mg/day.

Table 4 lists adverse events, regardless of causality, that were reported in the combined Phase 3, randomized, placebo-controlled trials at an incidence greater than placebo and in 1% or more of patients treated with fesoterodine fumarate extended-release tablets 4 mg or 8 mg once daily for up to 12-weeks.

Table 4: Adverse Events with an Incidence Exceeding the Placebo Rate and Reported by ≥1% of Patients from Double-Blind, Placebo-Controlled Phase 3 Trials of 12-weeks Treatment Duration
ALT = alanine aminotransferase; GGT = gamma glutamyltransferase
System organ class/Preferred term Placebo N=554 % Fesoterodine fumarate extended-release tablets 4 mg/day N=554 % Fesoterodine fumarate extended-release tablets 8 mg/day N=566 %
Gastrointestinal disorders Dry mouth Constipation Dyspepsia Nausea 720.51.3 18.84.21.60.7 34.662.31.9
Abdominal pain upper 0.5 1.1 0.5
Infections Urinary tract infection 3.1 3.2 4.2
Upper respiratory tract infection 2.2 2.5 1.8
Eye disorders Dry eyes 0 1.4 3.7
Renal and urinary disorders Dysuria Urinary retention 0.70.2 1.31.1 1.61.4
Respiratory disorders Cough Dry throat 0.50.4 1.60.9 0.92.3
General disorders Edema peripheral 0.7 0.7 1.2
Musculoskeletal disorders Back pain 0.4 2 0.9
Psychiatric disorders Insomnia 0.5 1.3 0.4
Investigations ALT increased GGT increased 0.90.4 0.50.4 1.21.2
Skin disorders Rash 0.5 0.7 1.1

Patients also received fesoterodine fumarate extended-release tablets for up to three years in open-label extension phases of one Phase 2 and two Phase 3 controlled trials. In all open-label trials combined, 857, 701, 529, and 105 patients received fesoterodine fumarate extended-release tablets for at least 6 months, 1 year, 2 years, and 3 years, respectively. The adverse events observed during long-term, open-label studies were similar to those observed in the 12-week, placebo-controlled studies, and included dry mouth, constipation, dry eyes, dyspepsia, and abdominal pain. Similar to the controlled studies, most adverse events of dry mouth and constipation were mild to moderate in intensity. Serious adverse events, judged to be at least possibly related to study medication by the investigator and reported more than once during the open-label treatment period of up to 3 years, included urinary retention (3 cases), diverticulitis (3 cases), constipation (2 cases), irritable bowel syndrome (2 cases), and electrocardiogram QT corrected interval prolongation (2 cases).

Pediatric use information is approved for Pfizer Inc.’s TOVIAZ® (fesoterodine fumarate) extended-release tablets. However, due to Pfizer Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.

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