Toviaz

Last updated on RxList: 6/30/2021
Toviaz Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Toviaz?

Toviaz (fesoterodine fumarate) is a muscarinic receptor antagonist, which reduces spasms of the bladder muscles, used to treat overactive bladder with symptoms of urinary frequency, urgency, and incontinence.

What Are Side Effects of Toviaz?

Common side effects of Toviaz include:

  • dry mouth,
  • dry eyes,
  • constipation,
  • dizziness,
  • drowsiness,
  • blurred vision,
  • stomach pain or upset,
  • cough,
  • dry throat,
  • back pain, or
  • sleep problems (insomnia).

Tell your doctor if you have unlikely but serious side effects of Toviaz including:

Dosage for Toviaz

The recommended starting dose of Toviaz is 4 mg once daily. Based upon individual response and tolerability, the dose may be increased to 8 mg once daily.

What Drugs, Substances, or Supplements Interact with Toviaz?

Toviaz may interact with arsenic trioxide, conivaptan, antibiotics, antifungals, antidepressants, anti-malaria medications, heart rhythm medicines, HIV/AIDS medicines, medicine to prevent or treat nausea and vomiting, medicines to treat psychiatric disorders, migraine headache medicines, or narcotics. Tell your doctor all medications you use.

Toviaz During Pregnancy or Breastfeeding

During pregnancy, Toviaz should be used only when prescribed. It is unknown if this drug passes into breast milk and the effect on a nursing infant is unknown. Consult your doctor before breastfeeding.

Additional Information

Our Toviaz (fesoterodine fumarate) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Urinary Incontinence in Women: Types, Causes, and Treatments for Bladder Control See Slideshow
Toviaz Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using fesoterodine and call your doctor at once if you have:

  • chest pain, fast or uneven heart rate;
  • swelling of your hands or feet;
  • severe stomach pain or constipation;
  • confusion, hallucinations;
  • little or no urination;
  • pain or burning when you urinate; or
  • signs of dehydration--feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin.

Adults who are 75 years or older may be more likely to have side effects from this medicine.

Common side effects may include:

  • dry mouth; or
  • constipation.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Toviaz (Fesoterodine Fumarate Extended-Release Tablets)

Toviaz Professional Information

SIDE EFFECTS

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

  • Angioedema [see WARNINGS AND PRECAUTIONS]
  • Urinary Retention [see WARNINGS AND PRECAUTIONS]
  • Decreased Gastointestinal Motility [see WARNINGS AND PRECAUTIONS]

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 %
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
ALT = alanine aminotransferase; GGT = gamma glutamyltransferase

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) %
Diarrhea 11.9 7.1
Urinary tract infection 9.5 2.4
Dry mouth 7.1 9.5
Constipation 7.1 7.1
A Abdominal pain† 7.1 4.8
Nausea 4.8 2.4
Weight increased 4.8 0
Headache 4.8 7.1
†Includes abdominal pain and abdominal pain upper

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 minute1 (mean change from baseline)
Toviaz 4 mg Toviaz 8 mg
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)
1 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.

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
Toviaz 4 mg Toviaz 8 mg
Baseline 2.4% 2.4%
Week 4 8.1% 12.2%
Week 12* 7.6% 11.4%
Week 24 3.3% 2.7%
* 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.

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.

Post-marketing 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

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

Skin and subcutaneous tissue disorders: Urticaria, pruritus

DRUG INTERACTIONS

Antimuscarinic Drugs

Coadministration of Toviaz with other antimuscarinic agents that produce dry mouth, constipation, urinary retention, and other anticholinergic pharmacological effects may increase the frequency and/or severity of such effects. Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility.

CYP3A4 Inhibitors

Doses of Toviaz greater than 4 mg are not recommended in adult patients taking strong CYP3A4 inhibitors, such as ketoconazole, itraconazole, and clarithromycin [see DOSAGE AND ADMINISTRATION]. The Toviaz dose in pediatric patients taking strong CYP3A4 inhibitors is recommended to be reduced to 4 mg once daily in patients >35 kg and is not recommended in patients weighing greater than 25 kg and up to 35 kg [see DOSAGE AND ADMINISTRATION].

In a study in adults, coadministration of the strong CYP3A4 inhibitor ketoconazole with fesoterodine led to approximately a doubling of the maximum concentration (Cmax) and area under the concentration versus time curve (AUC) of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of fesoterodine. Compared with CYP2D6 extensive metabolizers not taking ketoconazole, further increases in the exposure to 5-HMT were observed in subjects who were CYP2D6 poor metabolizers taking ketoconazole [see CLINICAL PHARMACOLOGY.]

There is no clinically relevant effect of moderate CYP3A4 inhibitors on the pharmacokinetics of fesoterodine. Following blockade of CYP3A4 by coadministration of the moderate CYP3A4 inhibitor fluconazole 200 mg twice a day for 2 days, the average (90% confidence interval) increase in Cmax and AUC of the active metabolite of fesoterodine was approximately 19% (11%-28%) and 27% (18%-36%) respectively. No dosing adjustments are recommended in the presence of moderate CYP3A4 inhibitors (e.g., erythromycin, fluconazole, diltiazem, verapamil and grapefruit juice).

The effect of weak CYP3A4 inhibitors (e.g. cimetidine) was not examined; it is not expected to be in excess of the effect of moderate inhibitors [see CLINICAL PHARMACOLOGY].

CYP3A4 Inducers

No dosing adjustments are recommended in the presence of CYP3A4 inducers, such as rifampin and carbamazepine. Following induction of CYP3A4 by coadministration of rifampin 600 mg once a day, Cmax and AUC of the active metabolite of fesoterodine decreased by approximately 70% and 75%, respectively, after oral administration of Toviaz 8 mg. The terminal half-life of the active metabolite was not changed.

CYP2D6 Inhibitors

The interaction with CYP2D6 inhibitors was not tested clinically. In poor metabolizers for CYP2D6, representing a maximum CYP2D6 inhibition, Cmax and AUC of the active metabolite are increased 1.7-and 2-fold, respectively.

No dosing adjustments are recommended in the presence of CYP2D6 inhibitors.

Drugs Metabolized By Cytochrome P450

In vitro data indicate that at therapeutic concentrations, the active metabolite of fesoterodine does not have the potential to inhibit or induce Cytochrome P450 enzyme systems [see CLINICAL PHARMACOLOGY].

Oral Contraceptives

In the presence of fesoterodine, there are no clinically significant changes in the plasma concentrations of combined oral contraceptives containing ethinyl estradiol and levonorgestrel [see CLINICAL PHARMACOLOGY].

Warfarin

A clinical study has shown that fesoterodine 8 mg once daily has no significant effect on the pharmacokinetics or the anticoagulant activity (PT/INR) of warfarin 25 mg. Standard therapeutic monitoring for warfarin should be continued [see CLINICAL PHARMACOLOGY].

Drug-Laboratory Test Interactions

Interactions between Toviaz and laboratory tests have not been studied.

Read the entire FDA prescribing information for Toviaz (Fesoterodine Fumarate Extended-Release Tablets)

© Toviaz Patient Information is supplied by Cerner Multum, Inc. and Toviaz Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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