Toviaz (fesoterodine fumarate)

Toviaz may cause allergic reactions that may be serious. Symptoms of a serious allergic reaction may include swelling of the face, lips, throat or tongue. If you experience these symptoms, you should stop taking Toviaz and get emergency medical help right away.

The most common side effects of Toviaz are:

• Dry mouth
• Constipation

Toviaz may cause other less common side effects, including:

• Dry eyes
• Trouble emptying the bladder

Tell your doctor if you have any side effects that bother you or that do not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

These are not all of the possible side effects of Toviaz. For a complete list, ask your doctor.

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.

The daily dose of Toviaz should not exceed 4 mg in the following populations:

• Patients with severe renal impairment (CL_CR <30 mL/min).
• Patients taking potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, and clarithromycin.

Toviaz is not recommended for use in patients with severe hepatic impairment (Child-Pugh C).

Toviaz should be taken with liquid and swallowed whole. Toviaz can be administered with or without food, and should not be chewed, divided, or crushed.

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 patients taking potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, and clarithromycin. Coadministration of the potent 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.
• 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.

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 2fold, 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.

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.

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.

Drug-Laboratory Test Interactions

• Interactions between Toviaz and laboratory tests have not been studied.

• There are no data with the use of Toviaz in pregnant women to inform a drug associated risk for birth defects or miscarriage.
• There is no information on the presence of fesoterodine in human milk, the effects on the breastfed child, or the effects on milk production.
• The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Toviaz and any potential adverse effects on the breastfed child from Toviaz or from the underlying maternal condition.