ADVERSE REACTIONS
Clinical Trials Experience
The safety of Toviaz was evaluated in Phase 2 and 3 controlled trials in a total of 2859 patients with overactive bladder, of which 2288 were treated with fesoterodine. Of this total, 782 received Toviaz 4 mg/day, and 785 received Toviaz 8 mg/day in Phase 2 or 3 studies with treatment periods of 8 or 12 weeks. Approximately 80% of these patients had >10 weeks exposure to Toviaz 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 Toviaz 4 mg/day and 566 patients received Toviaz 8 mg/day.
In Phase 2 and 3 placebo-controlled trials combined, the incidences of serious adverse events in patients receiving placebo, Toviaz 4 mg, and Toviaz 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 Toviaz who reported one serious adverse event each: angina, chest pain, gastroenteritis, and QT prolongation on ECG.
The most commonly reported adverse event in patients treated with Toviaz 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, Toviaz 4 mg, and Toviaz 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 1 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 Toviaz 4 or 8 mg once daily for up to 12 weeks.
Table 1: 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
System organ class/Preferred term |
Placebo N=554 % |
Toviaz 4 mg/day N=554 % |
Toviaz 8 mg/day N=566 % |
ALT = alanine aminotransferase; GGT = gamma glutamyltransferase |
Gastrointestinal disorders |
|
|
|
Dry mouth |
7.0 |
18.8 |
34.6 |
Constipation |
2.0 |
4.2 |
6.0 |
Dyspepsia |
0.5 |
1.6 |
2.3 |
Nausea |
1.3 |
0.7 |
1.9 |
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 |
0.7 |
1.3 |
1.6 |
Urinary retention |
0.2 |
1.1 |
1.4 |
Respiratory disorders |
|
|
|
Cough |
0.5 |
1.6 |
0.9 |
Dry throat |
0.4 |
0.9 |
2.3 |
General disorders |
|
|
|
Edema peripheral |
0.7 |
0.7 |
1.2 |
Musculoskeletal disorders |
|
|
|
Back pain |
0.4 |
2.0 |
0.9 |
Psychiatric disorders |
|
|
|
Insomnia |
0.5 |
1.3 |
0.4 |
Investigations |
|
|
|
ALT increased |
0.9 |
0.5 |
1.2 |
GGT increased |
0.4 |
0.4 |
1.2 |
Skin disorders |
|
|
|
Rash |
0.5 |
0.7 |
1.1 |
Patients also received Toviaz 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 Toviaz 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).
Post-marketing Experience
The following events have been reported in association with fesoterodine use in worldwide post-marketing experience:
Eye disorders:
Blurred vision;
Cardiac disorders:
Palpitations;
General disorders and administrative site conditions:
Hypersensitivity reactions, including angioedema with airway obstruction, face edema;
Skin and subcutaneous tissue disorders
: Urticaria, pruritus.
Because these spontaneously reported events are from the worldwide post-marketing experience, the frequency of events and the role of fesoterodine in their causation cannot be reliably determined.
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REPORTS OF SUSPECTED TOVIAZ SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Toviaz. The information is not vetted and should not be considered as verified clinical evidence.
Possible Toviaz side effects / adverse reactions in 83 year old female
Reported by a physician from United States on 2011-10-05
Patient: 83 year old female weighing 75.8 kg (166.7 pounds)
Reactions: Hepatic Enzyme Increased
Suspect drug(s):
Toviaz
Dosage: 8mg daily oral
Administration route: Oral
Indication: Urinary Incontinence
Start date: 2010-11-23
End date: 2011-04-05
Toviaz
Dosage: 8mg daily oral
Administration route: Oral
Indication: Urinary Incontinence
Start date: 2011-06-07
End date: 2011-08-21
Other drugs received by patient: Citalopram Hydrobromide; Boniva; Dicyclomine; Doxazosin Mesylate; Lisinopril; Omeprazole; Sucralfate; Acetaminophen and Hydrocodone Bitartrate; Bupropion HCL
Possible Toviaz side effects / adverse reactions in 74 year old male
Reported by a consumer/non-health professional from Switzerland on 2011-10-11
Patient: 74 year old male
Reactions: Mania, Drug Interaction
Suspect drug(s):
Toviaz
Other drugs received by patient possibly interacting with the suspect drug: Toviaz
Dosage: 4 mg, 1x/day
Administration route: Oral
Start date: 2011-08-08
End date: 2011-08-22
Toviaz
Dosage: 8 mg, 1x/day
Administration route: Oral
Start date: 2011-08-24
End date: 2011-08-29
Seroquel
Dosage: 75 mg, 1x/day
Administration route: Oral
Indication: Bipolar Disorder
Other drugs received by patient: Depakene; Venlafaxine; Aspirin; Antabuse; Acidum Folicum Streuli; Diovan HCT; Lescol
Possible Toviaz side effects / adverse reactions in 67 year old female
Reported by a consumer/non-health professional from Netherlands on 2011-10-18
Patient: 67 year old female
Reactions: Bacterial Infection, DRY Skin, Erythema
Suspect drug(s):
Toviaz
Other drugs received by patient: Micardis; Acetylsalicylic Acid; Thyrax
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