TOVIAZ® (fesoterodine fumarate) 13 NONCLINICAL TOXICOLOGY

(fesoterodine fumarate)

Prescribing Information

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity

No evidence of drug-related carcinogenicity was found in 24-month studies with oral administration to mice and rats. The highest tolerated doses in mice (females 45 to 60 mg/kg/day, males 30 to 45 mg/kg/day) correspond to 11 to 19 times (females) and 4 to 9 times (males) the estimated human AUC values reached with fesoterodine 8 mg, which is the Maximum Recommended Human Dose (MRHD). In rats, the highest tolerated dose (45 to 60 mg/kg/day) corresponds to 3 to 8 times (females) and 3 to 14 times (males) the estimated human AUC at the MRHD.

Mutagenesis

Fesoterodine was not mutagenic or genotoxic in vitro (Ames tests, chromosome aberration tests) or in vivo (mouse micronucleus test).

Impairment of Fertility

Fesoterodine had no effect on male reproductive function or fertility at doses up to 45 mg/kg/day in mice. At 45 mg/kg/day, a lower number of corpora lutea, implantation sites and viable fetuses was observed in female mice administered fesoterodine for 2-weeks prior to mating and continuing through day 7 of gestation. The maternal No-Observed-Effect Level (NOEL) and the NOEL for effects on reproduction and early embryonic development were both 15 mg/kg/day. At the NOEL, the systemic exposure, based on AUC, was 0.6 to 1.5 times higher in mice than in humans at the MRHD, whereas based on peak plasma concentrations, the exposure in mice was 5 to 9 times higher.

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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