TOVIAZ® (fesoterodine fumarate) 6 ADVERSE REACTIONS

(fesoterodine fumarate)

Prescribing Information

6 ADVERSE REACTIONS

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

•: Angioedema [see Warnings and Precautions (5.1)]
•: Urinary Retention [see Warnings and Precautions (5.2)]
•: Decreased Gastrointestinal Motility [see Warnings and Precautions (5.3)]

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 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 Toviaz. Of this total, 782 received Toviaz 4 mg/day, and 785 received Toviaz 8 mg/day with treatment periods of 8- or 12-weeks. Approximately 80% of these patients had greater than 10-weeks of 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 reaction 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 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 Toviaz 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
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).

Pediatric Neurogenic Detrusor Overactivity (NDO)

The safety of Toviaz was evaluated in a total of 131 pediatric patients with NDO. Patients received Toviaz 4 mg or Toviaz 8 mg orally once daily in two clinical trials (Studies 3 and 4).

Study 3 was a Phase 3 study in pediatric patients with NDO from 6 years to 17 years of age and weighing greater than 25 kg. This study consisted of a 12-week efficacy phase, in which 84 patients received Toviaz, followed by a 12-week safety extension phase, in which 103 patients received Toviaz. Of the 103 patients who received Toviaz in the safety extension phase, 67 continued Toviaz from the efficacy phase and 36 switched from an active comparator in the efficacy phase to Toviaz in the safety extension phase.

Study 4 (N=11) was an 8-week, Phase 2 pharmacokinetic (PK) and safety study in pediatric patients with NDO from 8 years to 17 years of age.

The most commonly reported adverse reactions in pediatric patients with NDO who received Toviaz 4 mg or 8 mg in Study 3 (≥2%) were diarrhea, UTI, dry mouth, constipation, abdominal pain, nausea, weight increased and headache.

Table 5 lists the adverse reactions reported at an incidence greater than or equal to 2% in either treatment group in the Study 3 efficacy phase.

Table 5: Adverse Reactions Reported in ≥2% of Patients With NDO Aged 6 Years to 17 Years in the 12-Week Efficacy Phase of Study 3
Preferred term	Toviaz 4 mg (N=42) %	Toviaz 8 mg (N=42) %
* Includes abdominal pain and abdominal pain upper
Diarrhea	11.9	7.1
Urinary tract infection	9.5	2.4
Dry mouth	7.1	9.5
Constipation	7.1	7.1
Abdominal pain*	7.1	4.8
Nausea	4.8	2.4
Weight increased	4.8	0
Headache	4.8	7.1

Ophthalmological Adverse Reactions

Ophthalmological adverse reactions, including myopia, accommodation disorder and blurred vision, were reported in 8 of 131 (6.1%) pediatric patients with NDO who received Toviaz 4 mg or Toviaz 8 mg in Study 3 (both efficacy and safety extension phases) and Study 4. The ophthalmological adverse reactions did not result in discontinuation of Toviaz in any patient.

Increases in Heart Rate

Increases in heart rate were reported in pediatric patients with NDO who received Toviaz 4 mg and Toviaz 8 mg in Study 3. The mean heart data are described in Table 6.

Table 6: Mean Baseline and Mean Changes From Baseline in Heart Rate in Pediatric Patients Weighing Greater Than 25 kg in Study 3
Study visit	Mean heart rate in beats per minute* (mean change from baseline)
Study visit	Toviaz 4 mg	Toviaz 8 mg
* Heart rate expressed as the mean of the baseline measurement and the mean at each study visit and mean changes from baseline at each study visit by original treatment group in patients with complete follow-up at all study visits.
Baseline	88.6	84.2
Week 4	93.8 (+5.2)	94.0 (+9.8)
Week 12	94.8 (+6.2)	94.0 (+9.8)
Week 24	90.4 (+1.8)	90.8 (+6.5)

The proportion of patients with heart rates greater than the 99th percentile for age also increased from baseline in patients who received Toviaz 4 mg and Toviaz 8 mg in Study 3. These data are described in Table 7.

Table 7: Proportion of Pediatric Patients With Heart Rate Greater Than the 99th Percentile for Age and Weighing Greater Than 25 kg in Study 3
Study visit	Proportion of patients with heart rate >99th percentile for age
Study visit	Toviaz 4 mg	Toviaz 8 mg
* Week 12 comprises patients who received Toviaz for 12 weeks after being originally randomized to Toviaz 4 mg and 8 mg and patients originally randomized to active comparator and subsequently transitioned to Toviaz 4 mg and 8 mg for 12 weeks.
Baseline	2.4%	2.4%
Week 4	8.1%	12.2%
Week 12*	7.5%	11.5%
Week 24	3.3%	2.7%

Increases from baseline in the proportion of patients with a heart rate greater than the 99th percentile for age were most pronounced in patients less than 12 years of age who received Toviaz 8 mg.

Increases in heart rate in patients who received Toviaz 4 mg and Toviaz 8 mg in Study 3 were not associated with clinical symptoms and did not result in discontinuation of therapy with Toviaz.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Toviaz. 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.

Cardiac disorders: Palpitations

Central nervous system disorders: Dizziness, headache, somnolence

Eye disorders: Blurred vision

Gastrointestinal disorders: Hypoaesthesia oral

General disorders and administrative site conditions: Hypersensitivity reactions, including angioedema with airway obstruction, face edema

Psychiatric disorders: Confusional state

Skin and subcutaneous tissue disorders: Urticaria, pruritus

Medication Guide

MEDICATION GUIDE

Patient Information TOVIAZ® (TOH-vee-as) (fesoterodine fumarate) extended-release tablets, for oral use
Read the Patient Information that comes with TOVIAZ before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment.
What is TOVIAZ? TOVIAZ is a prescription medicine used: • in adults to treat symptoms of a condition called overactive bladder (OAB), including urge urinary incontinence (leaking or wetting accidents due to a strong need to urinate), urinary urgency (having a strong need to urinate right away), or urinary frequency (having to urinate too often). • in children 6 years of age and older with a body weight greater than 55 pounds (25 kg) to treat neurogenic detrusor overactivity (NDO). TOVIAZ is used to increase the amount of urine your bladder can hold and reduce urine leakage. It is not known if TOVIAZ is safe and effective in children younger than 6 years of age or with a body weight 55 pounds (25-kg) or less.
Who should not take TOVIAZ? Do not take TOVIAZ if you: • are allergic to TOVIAZ or any of its ingredients. See the end of this leaflet for a complete list of ingredients. • are allergic to tolterodine tartrate tablets or tolterodine tartrate extended-release capsules. • are not able to empty your bladder (urinary retention). • have delayed or slow emptying of your stomach (gastric retention). • have an eye problem called uncontrolled narrow-angle glaucoma.
Before you take TOVIAZ, tell your healthcare provider about all your medical conditions, including if you: • have problems emptying your bladder or you have a weak urine stream. • have any stomach or intestinal problems, or problems with constipation. • are receiving treatment for an eye problem called narrow-angle glaucoma. • have a condition called Myasthenia Gravis. • have kidney problems. • have liver problems. • are pregnant or plan to become pregnant. It is not known if TOVIAZ will harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant. • are breastfeeding or plan to breastfeed. It is not known if TOVIAZ passes into your breast milk. You should talk to your healthcare provider about the best way to feed your baby while taking TOVIAZ. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal products. TOVIAZ may affect the way other medicines work, and other medicines may affect how TOVIAZ works. Especially tell your healthcare provider if you are taking antimuscarinic, antibiotics, or antifungal medicines. Know all the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist each time you get a new medicine.
How should I take TOVIAZ? • Take TOVIAZ exactly as your healthcare provider tells you to take it. • Your healthcare provider may lower your dose of TOVIAZ if you are an adult with severe kidney problems. • Your healthcare provider may lower or stop your dose of TOVIAZ if you are a child 6 years of age and older with a body weight greater than 77 pounds (35 kg) and have severe kidney problems or are taking certain medicines. • Take TOVIAZ with liquid and swallow the tablet whole. Do not chew, divide, or crush the tablet. • Take TOVIAZ with or without food. • If you miss a dose of TOVIAZ, begin taking TOVIAZ again the next day. Do not take 2 doses of TOVIAZ in the same day. • If you take too much TOVIAZ, call your healthcare provider or go to an emergency department right away.
What should I avoid while taking TOVIAZ? • TOVIAZ can cause blurred vision, dizziness, and drowsiness. Do not drive, operate machinery, or do other dangerous activities until you know how TOVIAZ affects you. • Use caution in hot environments. Decreased sweating and severe heat illness can happen when medicines such as TOVIAZ are used in a hot environment. • Drinking alcohol while taking medicines such as TOVIAZ may cause increased drowsiness.
What are the possible side effects of TOVIAZ? TOVIAZ may cause serious side effects, including: • serious allergic reactions. Symptoms of a serious allergic reaction may include swelling of the face, lips, throat, or tongue. If you have any of these symptoms, you should stop taking TOVIAZ and get emergency medical help right away. • inability to empty bladder (urinary retention). TOVIAZ may increase your chances of not being able to empty your bladder if you have bladder outlet obstruction. Tell your healthcare provider right away if you are unable to empty your bladder. • central nervous system (CNS) effects. Talk to your healthcare provider right away if you get any of these side effects: headache, dizziness, and drowsiness. • worsening of Myasthenia Gravis symptoms. The most common side effects of TOVIAZ in adults include: • dry mouth • constipation The most common side effects of TOVIAZ in children 6 years of age and older include:
• diarrhea • urinary tract infection	• dry mouth • constipation	• stomach pain • nausea	• weight gain • headache
Talk to your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of TOVIAZ. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store TOVIAZ? • Store TOVIAZ at room temperature between 68° to 77°F (20° to 25°C). • Protect the medicine from moisture by keeping the bottle closed tightly. • Keep TOVIAZ and all medicines out of the reach of children.
General information about the safe and effective use of TOVIAZ. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TOVIAZ for a condition for which it was not prescribed. Do not give TOVIAZ to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about TOVIAZ that is written for health professionals.
What are the ingredients in TOVIAZ? Active ingredient: fesoterodine fumarate. Inactive ingredients: glyceryl behenate, hypromellose, indigo carmine aluminum lake, lactose monohydrate, soya lecithin, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide, and xylitol. This product's labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com. LAB-0382-14.0 For more information, go to www.TOVIAZ.com or call 1-877-9-TOVIAZ (1-877)-986-8429.
This Patient Information has been approved by the U.S. Food and Drug Administration.				Revised: 2/2024

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