DailyMed Label: fesoterodine fumarate

DailyMed Label: fesoterodine fumarate

2023

DailyMed Prescription

fesoterodine fumarate

fesoterodine fumarate

Lupin Pharmaceuticals, Inc.

NDC: 68180-618

NDC: 68180-619

NDC: 68180-618

NDC: 68180-618

NDC: 68180-619

NDC: 68180-619

Fesoterodine fumarate extended-release tablet contains fesoterodine fumarate and is an extended-release tablet. Fesoterodine is rapidly de-esterified to its active metabolite (R)-2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethyl-phenol, or 5-hydroxymethyl tolterodine, which is a muscarinic receptor antagonist. Chemically, fesoterodine fumarate is designated as (R-(+)-2-(-3-Diisopropylamino-1-phenylpropyl)-4-hydroxymethyl-phenylisobutyrate ester hydrogen fumarate. The empirical formula is C 30 H 41 NO 7 and its molecular weight is 527.66. The structural formula is: The asterisk (*) indicates the chiral carbon. Fesoterodine fumarate is a white to off-white powder, which is very slightly soluble in water. Each fesoterodine fumarate extended-release tablets contains either 4 mg or 8 mg of fesoterodine fumarate and the following inactive ingredients: FD&C Blue #2 aluminium lake, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, polyvinyl alcohol, soya lecithin, talc, titanium dioxide and xylitol.

Fesoterodine fumarate is indicated for the treatment of: Overactive bladder (OAB) in adults with symptoms of urge urinary incontinence, urgency, and frequency. ( 1.1 )

OAB in Adults : The recommended starting dosage is 4 mg orally once daily. Based upon individual response and tolerability, increase to the maximum dosage of 8 mg once daily. ( 2.1 ) Adult Patients with Renal or Hepatic Impairment: Refer to the full prescribing information for recommended dosage. ( 2.3 ) Dosage Modifications Due to Strong CYP3A4 Inhibitors : Refer to the full prescribing information for recommended dosage. ( 2.5 ) Administration : Swallow whole with liquid. Do not chew, divide, or crush. Take with or without food. ( 2.6 )

Extended-release tablets: 4 mg and 8 mg ( 3 )

Known or suspected hypersensitivity to fesoterodine fumarate or any of its ingredients or to tolterodine tartrate tablets or tolterodine tartrate extended-release capsules. ( 4 ) Urinary retention ( 4 ) Gastric retention ( 4 ) Uncontrolled narrow-angle glaucoma. ( 4 )

Angioedema : Promptly discontinue fesoterodine fumarate and provide appropriate therapy. ( 5.1 ). Urinary Retention : Fesoterodine fumarate is not recommended in patients with clinically significant bladder outlet obstruction because of the risk of urinary retention. ( 5.2 )   Decreased Gastrointestinal Motility : Fesoterodine fumarate is not recommended for use in patients with decreased gastrointestinal motility, such as those with severe constipation. ( 5.3 ) Worsening of Narrow Angle Glaucoma : Use fesoterodine fumarate with caution in patients being treated for narrow-angle glaucoma ( 5.4 ) Central Nervous System Effects : Somnolence has been reported with fesoterodine fumarate. Advise patients not to drive or operate heavy machinery until they know how fesoterodine fumarate affects them ( 5.5 ) Worsening of Myasthenia Gravis Symptoms : Use fesoterodine fumarate with caution in patients with myasthenia gravis. ( 5.6 )

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

Coadministration of fesoterodine fumarate 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.

Risk Summary There are no available data with the use of fesoterodine fumarate in pregnant women and adolescents to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of fesoterodine to pregnant mice and rabbits during organogenesis resulted in fetotoxicity at maternal exposures that were 6 and 3 times respectively the maximum recommended human dose (MRHD) of 8 mg/day, based on AUC (see Data) . The background risk of major birth defects and miscarriage for the indicated population are unknown. However, in the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data No dose-related teratogenicity was observed in reproduction studies performed in mice and rabbits. In mice at 6 to 27 times the expected exposure at the maximum recommended human dose (MRHD) of 8 mg based on AUC (75 mg/kg/day, oral), increased resorptions and decreased live fetuses were observed. One fetus with cleft palate was observed at each dose (15, 45, and 75 mg/kg/day), at an incidence within the background historical range. In rabbits treated at 3 to 11 times the MRHD (27 mg/kg/day, oral), incompletely ossified sternebrae (retardation of bone development) and reduced survival were observed in fetuses. In rabbits at 9 to 11 times the MRHD (4.5 mg/kg/day, subcutaneous), maternal toxicity and incompletely ossified sternebrae were observed in fetuses (at an incidence within the background historical range). In rabbits at 3 times the MRHD (1.5 mg/kg/day, subcutaneous), decreased maternal food consumption in the absence of any fetal effects was observed. Oral administration of 30 mg/kg/day fesoterodine to mice in a pre- and post-natal development study resulted in decreased body weight of the dams and delayed ear opening of the pups. No effects were noted on mating and reproduction of the F 1 dams or on the F 2 offspring.

Fesoterodine fumarate extended-release tablets, 4 mg are light blue, oval, film-coated tablets, debossed with 'LU' on one side and 'R71' on the other side. They are supplied as follows: Bottles of 30               NDC 68180-618-06 Bottles of 90               NDC 68180-618-09 Fesoterodine fumarate extended-release tablets, 8 mg are blue, oval, film-coated tablets, debossed with 'LU' on one side and 'R72' on the other side. They are supplied as follows: Bottles of 30               NDC 68180-619-06 Bottles of 90               NDC 68180-619-09 Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from moisture.

Fesoterodine is a competitive muscarinic receptor antagonist. After oral administration, fesoterodine is rapidly and extensively hydrolyzed by nonspecific esterases to its active metabolite, 5-hydroxymethyl tolterodine, which is responsible for the antimuscarinic activity of fesoterodine. Muscarinic receptors play a role in contractions of urinary bladder smooth muscle. Inhibition of these receptors in the bladder is presumed to be the mechanism by which fesoterodine produces its effects.

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.

The efficacy of fesoterodine fumarate extended-release tablets was evaluated in two, Phase 3, randomized, double-blind, placebo-controlled, 12-week studies for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Entry criteria required that patients have symptoms of overactive bladder for ≥ 6-months duration, at least 8 micturitions per day, and at least 6 urinary urgency episodes or 3 urge incontinence episodes per 3-day diary period. Patients were randomized to a fixed dose of fesoterodine fumarate extended-release tablets, 4 or 8 mg/day or placebo. In one of these studies, 290 patients were randomized to an active control arm (an oral antimuscarinic agent). For the combined studies, a total of 554 patients received placebo, 554 patients received fesoterodine fumarate extended-release tablets, 4 mg/day, and 566 patients received fesoterodine fumarate extended-release tablets 8 mg/day. The majority of patients were Caucasian (91%) and female (79%) with a mean age of 58 years (range 19 to 91 years). The primary efficacy endpoints were the mean change in the number of urge urinary incontinence episodes per 24 hours and the mean change in the number of micturitions (frequency) per 24 hours. An important secondary endpoint was the mean change in the voided volume per micturition. Results for the primary endpoints and for mean change in voided volume per micturition from the two 12-week clinical studies of fesoterodine fumarate extended-release tablets are reported in Table 10. Table 10: Mean baseline and change from baseline to Week 12 for urge urinary incontinence episodes, number of micturitions, and volume voided per micturition vs. = versus a Only those patients who were urge incontinent at baseline were included for the analysis of number of urge incontinence episodes per 24 hours: In Study 1, the number of these patients was 211, 199, and 223 in the placebo, fesoterodine fumarate extended-release tablets, 4 mg/day and fesoterodine fumarate extended-release tablets , 8 mg/day groups, respectively. In Study 2, the number of these patients was 205, 228, and 218, respectively. Study 1 Study 2 Parameter Placebo N=279 Fesoterodine Fumarate Extended-Release Tablets 4 mg/day N=265 Fesoterodine Fumarate Extended-Release Tablets 8 mg/day N=276 Placebo N=266 Fesoterodine Fumarate Extended-Release Tablets 4 mg/day N=267 Fesoterodine Fumarate Extended-Release Tablets 8 mg/day N=267 Number of urge incontinence episodes per 24 hours a Baseline 3.7 3.8 3.7 3.7 3.9 3.9 Change from baseline -1.20 -2.06 -2.27 -1.00 -1.77 -2.42 p-value vs. placebo - 0.001 <0.001 - <0.003 <0.001 Number of micturitions per 24 hours Baseline 12.0 11.6 11.9 12.2 12.9 12.0 Change from baseline -1.02 -1.74 -1.94 -1.02 -1.86 -1.94 p-value vs. placebo - <0.001 <0.001 - 0.032 <0.001 Voided volume per micturition (mL) Baseline 150 160 154 159 152 156 Change from baseline 10 27 33 8 17 33 p-value vs. placebo - <0.001 <0.001 - 0.150 <0.001 Figures 1-4: The following figures show change from baseline over time in number of micturitions and urge urinary incontinence episodes per 24 h in the two studies. Figure 1: Change in Number of Micturitions per 24 h (Study 1) Figure 2: Change in Urge Incontinence Episodes per 24 h (Study 1) Figure 3: Change in Number of Micturitions per 24 h (Study 2) Figure 4: Change in Urge Incontinence Episodes per 24 h (Study 2) A reduction in number of urge urinary incontinence episodes per 24 hours was observed for both doses as compared to placebo as early as two weeks after starting fesoterodine fumarate therapy. Pediatric use information is approved for Pfizer Inc.'s TOVIAZ ®   (fesoterodine fumarate) extended-release tablets. However, due to Pfizer Inc.'s marketing exclusivity rights, this drug product is not labeled with that information.

Patient Information Fesoterodine Fumarate (fes″ oh ter′ oh deen fue′ ma rate)  Extended-release Tablets, for oral use Rx Only Read the Patient Information that comes with fesoterodine fumarate extended-release tablets 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 Fesoterodine Fumarate Extended-Release Tablets? Fesoterodine fumarate extended-release tablets 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). It is not known if fesoterodine fumarate extended-release tablets are 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 Fesoterodine Fumarate Extended-Release Tablets? Do not take fesoterodine fumarate extended-release tablets if you: are allergic to fesoterodine fumarate extended-release tablets 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 fesoterodine fumarate extended-release tablets, 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 fesoterodine fumarate extended-release tablets 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 fesoterodine fumarate extended-release tablets passes into breast milk. You should talk to your healthcare provider about the best way to feed your baby while taking fesoterodine fumarate extended-release tablets. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal products. Fesoterodine fumarate extended-release tablets may affect the way other medicines work, and other medicines may affect how fesoterodine fumarate extended-release tablets 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 Fesoterodine Fumarate Extended-Release Tablets? Take fesoterodine fumarate extended-release tablets exactly as your healthcare provider tells you to take it. Your healthcare provider may lower your dose of fesoterodine fumarate extended-release tablets if you are an adult with severe kidney problems. Take fesoterodine fumarate extended-release tablets with liquid and swallow the tablet whole. Do not chew, divide, or crush the tablet. Take fesoterodine fumarate extended-release tablets with or without food. If you miss a dose of fesoterodine fumarate extended-release tablets, begin taking fesoterodine fumarate extended-release tablets again the next day. Do not take 2 doses of fesoterodine fumarate extended-release tablets in the same day. If you take too much fesoterodine fumarate extended-release tablets, call your healthcare provider or go to an emergency department right away. What should I avoid while taking Fesoterodine fumarate Extended-release Tablets? Fesoterodine fumarate extended-release tablets can cause blurred vision, dizziness, and drowsiness. Do not drive, operate machinery, or do other dangerous activities until you know how fesoterodine fumarate extended-release tablets affects you. Use caution in hot environments. Decreased sweating and severe heat illness can happen when medicines such as fesoterodine fumarate extended-release tablets are used in a hot environment. Drinking alcohol while taking medicines such as fesoterodine fumarate extended-release tablets may cause increased drowsiness. What are the possible side effects of Fesoterodine Fumarate Extended-Release Tablets? Fesoterodine fumarate extended-release tablets 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 fesoterodine fumarate extended-release tablets and get emergency medical help right away. inability to empty bladder (urinary retention). Fesoterodine fumarate extended-release tablets 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 fesoterodine fumarate extended-release tablets in adults include: dry mouth constipation 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 fesoterodine fumarate extended-release tablets. 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 Fesoterodine Fumarate Extended-Release Tablets? Store fesoterodine fumarate extended-release tablets at 25°C (77°F). Protect the medicine from moisture by keeping the bottle closed tightly. Keep fesoterodine fumarate extended-release tablets and all medicines out of the reach of children. General information about the safe and effective use of Fesoterodine Fumarate Extended-Release Tablets. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use fesoterodine fumarate extended-release tablets for a condition for which it was not prescribed. Do not give fesoterodine fumarate extended-release tablets 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 fesoterodine fumarate extended-release tablets that is written for health professionals. What are the ingredients in Fesoterodine Fumarate Extended-Release Tablets? Active ingredient: fesoterodine fumarate Inactive ingredients: FD&C Blue #2 aluminium lake, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, polyvinyl alcohol, soya lecithin, talc, titanium dioxide and xylitol. Pediatric use information is approved for Pfizer Inc.'s TOVIAZ ® (fesoterodine fumarate) extended-release tablets. However, due to Pfizer Inc.'s marketing exclusivity rights, this drug product is not labeled with that information. This product's labeling may have been updated. For the most recent full prescribing information, please visit www.lupinpharmaceuticals.com. The brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products. For more information go to www.lupinpharmaceuticals.com or call Lupin Pharmaceuticals, Inc. at 1-800-399-2561. This Patient Information has been approved by the U.S. Food and Drug Administration. Manufactured for: Lupin Pharmaceuticals, Inc. Baltimore, Maryland 21202 United States Manufactured by: Lupin Limited Goa 403 722 INDIA. Revised: March 2022

Rx Only NDC 68180-618-06 Fesoterodine Fumarate Extended-Release Tablets, 4 mg Container Label of 30 Tablets image 6 Rx Only NDC 68180-619-06 Fesoterodine Fumarate Extended-Release Tablets, 8 mg Container Label of 30 Tablets image 7