ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following clinically significant adverse reaction is described elsewhere in the labeling:Urinary retention [see Warnings and Precautions (5.1)] Urinary retention [see Warnings and Precautions (5.1)] Most common adverse reactions (>=2%) reported with GEMTESA were headache, urinary tract infection, nasopharyngitis, diarrhea, nausea, and upper respiratory tract infection. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Urovant Sciences, Inc., at 1-833-876-8268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.The safety of GEMTESA was evaluated in 12-week, double-blind, placebo- and active-controlled study (Study 3003) in patients with OAB [see Clinical Studies (14)]. total of 545 patients received GEMTESA. The majority of the patients were Caucasian (78%) and female (85%) with mean age of 60 years (range 18 to 93 years).Adverse reactions that were reported in Study 3003 at an incidence greater than placebo and in >=2% of patients treated with GEMTESA are listed in Table 1.Table 1: Adverse Reactions, Exceeding Placebo Rate, Reported in >=2% of Patients Treated with GEMTESA 75 mg for up to 12 Weeks in Study 3003GEMTESA 75 mg (%)Placebo (%)Number of Patients545540Headache22 (4.0)13 (2.4)Nasopharyngitis15 (2.8)9 (1.7)Diarrhea12 (2.2)6 (1.1)Nausea12 (2.2)6 (1.1)Upper respiratory tract infection11 (2.0)4 (0.7)Other adverse reactions reported in <2% of patients treated with GEMTESA included:Gastrointestinal disorders: dry mouth, constipationInvestigations: residual urine volume increasedRenal and urinary disorders: urinary retentionVascular disorders: hot flushGEMTESA was also evaluated for long-term safety in an extension study (Study 3004) in 505 patients who completed the 12-week study (Study 3003). Of the 273 patients who received GEMTESA 75 mg once daily in the extension study, 181 patients were treated for total of one year.Adverse reactions reported in >=2% of patients treated with GEMTESA 75 mg for up to 52 weeks in the long-term extension study, and not already listed above, were urinary tract infection (6.6%) and bronchitis (2.9%).. 6.2 Postmarketing Experience. The following adverse reactions have been identified during post-approval use of vibegron. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure. The following adverse events have been reported in association with vibegron use in worldwide postmarketing experience:Urologic disorders: urinary retentionSkin and subcutaneous tissue disorders: pruritus, rash, drug eruption, eczemaGastrointestinal disorders: constipation.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. CarcinogenesisNo carcinogenicity was observed in long-term studies conducted in mice and rats treated with daily oral doses of vibegron for approximately years. In the mouse carcinogenicity study, CD-1 mice were treated with daily oral doses of vibegron up to 90 mg/kg/day in males and up to 150 mg/kg/day in females, corresponding to estimated systemic exposures (AUC) 21- and 55-fold higher, respectively, than in humans treated with the recommended daily dose of GEMTESA. In the rat carcinogenicity study, Sprague Dawley rats were treated with daily oral doses of vibegron up to 30 mg/kg/day in males and up to 180 mg/kg/day in females, corresponding to systemic exposures (AUC) 18- and 117-fold higher, respectively, than in humans treated with the recommended daily dose of GEMTESA.. MutagenesisVibegron was not mutagenic in in vitro microbial reverse mutation assays, showed no evidence of genotoxic activity in an in vitro human peripheral blood lymphocyte chromosomal aberration assay, and did not increase the frequency of micronucleated polychromatic erythrocytes in an in vivo rat bone marrow micronucleus assay.. Impairment of FertilityIn fertility/general reproductive toxicity studies conducted in rats, females were treated with daily oral doses of 0, 30, 100, 300, or 1000 mg/kg/day vibegron and males were treated with daily oral doses of 0, 10, 30, or 300 mg/kg/day vibegron. No effects on fertility were observed in female or male rats at doses up to 300 mg/kg/day, associated with systemic exposure (AUC) at least 274-fold higher than in humans treated with the recommended daily dose of GEMTESA. General toxicity, decreased fecundity, and decreased fertility were observed in female rats at 1000 mg/kg/day, associated with estimated systemic exposure 1867-fold higher than in humans treated with the recommended daily dose of GEMTESA.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Vibegron is selective human beta-3 adrenergic receptor agonist. Activation of the beta-3 adrenergic receptor increases bladder capacity by relaxing the detrusor smooth muscle during bladder filling.. 12.2 Pharmacodynamics. Vibegrons exposure-response relationship and the time course of pharmacodynamic response are not fully characterized.. Blood PressureIn 4-week, randomized, placebo-controlled, ambulatory blood pressure study in OAB patients (n=200), daily treatment with GEMTESA 75 mg was not associated with clinically significant changes in blood pressure. Subjects enrolled in this study had mean age of 59 years and 75% were female. Thirty-five percent of subjects had pre-existing hypertension at baseline and 29% of all subjects were taking at least concomitant antihypertensive medication.. Cardiac ElectrophysiologyGEMTESA does not prolong the QT interval to any clinically relevant extent at single dose 5.3 times the approved recommended dose.. 12.3 Pharmacokinetics. Mean vibegron Cmax and AUC increased in greater than dose-proportional manner up to 600 mg (8 times the approved recommended dosage). Steady state concentrations are achieved within days of once daily dosing. The mean accumulation ratio (Rac) was 1.7 for Cmax and 2.4 for AUC0-24hr.. AbsorptionMedian vibegron Tmax is approximately to hours.Oral administration of 75 mg vibegron tablet crushed and mixed with 15 mL of applesauce resulted in no clinically relevant changes in vibegron pharmacokinetics when compared to administration of an intact 75 mg vibegron tablet.. Effect of FoodNo clinically significant differences in vibegron pharmacokinetics were observed following administration of high-fat meal (53% fat, 869 calories [32.1 protein, 70.2 carbohydrate, and 51.1 fat]).. DistributionThe mean apparent volume of distribution is 6304 liters. Human plasma protein binding of vibegron is approximately 50%. The average blood-to-plasma concentration ratio is 0.9.. EliminationVibegron has an effective half-life of 30.8 hours across all populations.. MetabolismMetabolism plays minor role in the elimination of vibegron. CYP3A4 is the predominant enzyme responsible for in vitro metabolism.. ExcretionFollowing radiolabeled dose, approximately 59% of the dose (54% as unchanged) was recovered in feces and 20% (19% as unchanged) in urine.. Specific PopulationsNo clinically significant differences in the pharmacokinetics of vibegron were observed based on age (18 to 93 years), sex, race/ethnicity (Japanese vs. non-Japanese), mild (eGFR 60 to <90 mL/min/1.73 m2), moderate (eGFR 30 to <60 mL/min/1.73 m2), and severe (eGFR 15 to <30 mL/min/1.73 m2) renal impairment, or moderate (Child-Pugh B) hepatic impairment. The effect of more severe renal impairment (eGFR <15 mL/min/1.73 m2) with or without hemodialysis or severe (Child-Pugh C) hepatic impairment on vibegron pharmacokinetics was not studied.. Drug Interaction Studies. Clinical Studies. Digoxin: Concomitant administration of vibegron increased digoxin Cmax and AUC by 21% and 11%, respectively.. Other Drugs: No clinically significant differences in vibegron pharmacokinetics were observed when used concomitantly with ketoconazole (P-gp and strong CYP3A4 inhibitor), diltiazem (P-gp and moderate CYP3A4 inhibitor), rifampin (strong CYP3A4 inducer), or tolterodine. No clinically significant differences in the pharmacokinetics of the following drugs were observed when used concomitantly with vibegron: tolterodine, tolterodine 5-hydroxy metabolite, metoprolol, combined oral contraceptive (ethinyl estradiol, levonorgestrel), or warfarin.. In Vitro Studies. Cytochrome P450 (CYP) Enzymes: Vibegron is CYP3A4 substrate. Vibegron did not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4. Vibegron did not induce CYP1A2, CYP2B6, or CYP3A4.. Transporter Systems: Vibegron is P-gp substrate. Vibegron did not inhibit P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, or MATE2K at clinically relevant concentrations.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. The efficacy of GEMTESA was evaluated in 12-week, double-blind, randomized, placebo-controlled, and active-controlled trial (Study 3003, NCT03492281) in patients with OAB (urge urinary incontinence, urgency, and urinary frequency). Patients were randomized 5:5:4 to receive either GEMTESA 75 mg, placebo, or active control orally, once daily for 12 weeks. For study entry, patients had to have symptoms of OAB for at least months with an average of or more micturitions per day and at least urge urinary incontinence (UUI) per day, or an average of or more micturitions per day and an average of at least urgency episodes per day. Urge urinary incontinence was defined as leakage of urine of any amount because the patient felt an urge or need to urinate immediately. The study population included OAB medication-naive patients as well as patients who had received prior therapy with OAB medications.The co-primary endpoints were change from baseline in average daily number of micturitions and average daily number of UUI episodes at week 12. Additional endpoints included change from baseline in average daily number of need to urinate immediately (urgency) episodes and average volume voided per micturition.A total of 1,515 patients received at least one daily dose of placebo (n=540), GEMTESA 75 mg (n=545), or an active control treatment (n=430). The majority of patients were Caucasian (78%) and female (85%) with mean age of 60 (range 18 to 93) years.Table shows changes from baseline at week 12 for average daily number of micturitions, average daily number of UUI episodes, average daily number of need to urinate immediately (urgency) episodes, and average volume voided per micturition.Table 2: Mean Baseline and Change from Baseline at Week 12 for Micturition Frequency, Urge Urinary Incontinence Episodes, Need to Urinate Immediately (Urgency) Episodes, and Volume Voided per MicturitionParameterGEMTESA 75 mgPlaceboAverage Daily Number of MicturitionsBaseline mean (n)11.3 (526)11.8 (520)Change from BaselineLeast squares mean adjusted for treatment, baseline, sex, geographical region, study visit, and study visit by treatment interaction term. (n)-1.8 (492)-1.3 (475)Difference from Placebo-0.595% Confidence Interval-0.8, -0.2p-value<0.001Average Daily Number of UUI EpisodesBaseline mean (n)3.4 (403)3.5 (405)Change from Baseline (n)-2.0 (383)-1.4 (372)Difference from Placebo-0.695% Confidence Interval-0.9, -0.3p-value<0.0001Average Daily Number of Need to Urinate Immediately (Urgency) EpisodesBaseline mean (n)8.1 (526)8.1 (520)Change from Baseline (n)-2.7 (492)-2.0 (475)Difference from Placebo-0.795% Confidence Interval-1.1, -0.2p-value0.002Average Volume Voided (mL) per MicturitionBaseline mean (n)155 (524)148 (514)Change from Baseline (n)23 (490)2 (478)Difference from Placebo2195% Confidence Interval14, 28p-value<0.0001Figures and show the mean change from baseline over time in average daily number of micturitions and mean change from baseline over time in average daily number of UUI episodes, respectively.Figure 1: Mean (SE) Change from Baseline in the Average Daily Number of MicturitionsFigure 2: Mean (SE) Change from Baseline in the Average Daily Number of UUI Episodes in Patients with At Least Average Daily UUI Episode at Baseline. Figure 1. Figure 2.

CLINICAL TRIALS EXPERIENCE SECTION.

6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.The safety of GEMTESA was evaluated in 12-week, double-blind, placebo- and active-controlled study (Study 3003) in patients with OAB [see Clinical Studies (14)]. total of 545 patients received GEMTESA. The majority of the patients were Caucasian (78%) and female (85%) with mean age of 60 years (range 18 to 93 years).Adverse reactions that were reported in Study 3003 at an incidence greater than placebo and in >=2% of patients treated with GEMTESA are listed in Table 1.Table 1: Adverse Reactions, Exceeding Placebo Rate, Reported in >=2% of Patients Treated with GEMTESA 75 mg for up to 12 Weeks in Study 3003GEMTESA 75 mg (%)Placebo (%)Number of Patients545540Headache22 (4.0)13 (2.4)Nasopharyngitis15 (2.8)9 (1.7)Diarrhea12 (2.2)6 (1.1)Nausea12 (2.2)6 (1.1)Upper respiratory tract infection11 (2.0)4 (0.7)Other adverse reactions reported in <2% of patients treated with GEMTESA included:Gastrointestinal disorders: dry mouth, constipationInvestigations: residual urine volume increasedRenal and urinary disorders: urinary retentionVascular disorders: hot flushGEMTESA was also evaluated for long-term safety in an extension study (Study 3004) in 505 patients who completed the 12-week study (Study 3003). Of the 273 patients who received GEMTESA 75 mg once daily in the extension study, 181 patients were treated for total of one year.Adverse reactions reported in >=2% of patients treated with GEMTESA 75 mg for up to 52 weeks in the long-term extension study, and not already listed above, were urinary tract infection (6.6%) and bronchitis (2.9%).

LACTATION SECTION.

8.2 Lactation. Risk SummaryThere are no data on the presence of vibegron in human milk, the effects of the drug on the breastfed infant, or the effects on milk production. When single oral dose of radiolabeled vibegron was administered to postnatal nursing rats, radioactivity was observed in milk (see Data). When drug is present in animal milk, it is likely that the drug will be present in human milk.The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for GEMTESA and any potential adverse effects on the breastfed infant from GEMTESA or from the underlying maternal condition.. Data. Animal DataIn lactational transfer study, lactating rats were treated with single oral dose of 10 mg/kg radiolabeled [3H] vibegron on postpartum day 10. Levels of radioactivity were determined in milk and plasma collected at 1, 4, 12, and 24 after dosing. The Cmax of total radioactivity in milk and plasma were observed at and hours after dosing, respectively, with maximum milk-to-plasma concentration ratio of 2.2 observed at 12 hours after dosing. Vibegron elimination from milk showed similar trend as that from plasma. The radioactivity concentration in milk at 24 hours after administration was approximately 25% of the Cmax.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. CarcinogenesisNo carcinogenicity was observed in long-term studies conducted in mice and rats treated with daily oral doses of vibegron for approximately years. In the mouse carcinogenicity study, CD-1 mice were treated with daily oral doses of vibegron up to 90 mg/kg/day in males and up to 150 mg/kg/day in females, corresponding to estimated systemic exposures (AUC) 21- and 55-fold higher, respectively, than in humans treated with the recommended daily dose of GEMTESA. In the rat carcinogenicity study, Sprague Dawley rats were treated with daily oral doses of vibegron up to 30 mg/kg/day in males and up to 180 mg/kg/day in females, corresponding to systemic exposures (AUC) 18- and 117-fold higher, respectively, than in humans treated with the recommended daily dose of GEMTESA.. MutagenesisVibegron was not mutagenic in in vitro microbial reverse mutation assays, showed no evidence of genotoxic activity in an in vitro human peripheral blood lymphocyte chromosomal aberration assay, and did not increase the frequency of micronucleated polychromatic erythrocytes in an in vivo rat bone marrow micronucleus assay.. Impairment of FertilityIn fertility/general reproductive toxicity studies conducted in rats, females were treated with daily oral doses of 0, 30, 100, 300, or 1000 mg/kg/day vibegron and males were treated with daily oral doses of 0, 10, 30, or 300 mg/kg/day vibegron. No effects on fertility were observed in female or male rats at doses up to 300 mg/kg/day, associated with systemic exposure (AUC) at least 274-fold higher than in humans treated with the recommended daily dose of GEMTESA. General toxicity, decreased fecundity, and decreased fertility were observed in female rats at 1000 mg/kg/day, associated with estimated systemic exposure 1867-fold higher than in humans treated with the recommended daily dose of GEMTESA.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. Mean vibegron Cmax and AUC increased in greater than dose-proportional manner up to 600 mg (8 times the approved recommended dosage). Steady state concentrations are achieved within days of once daily dosing. The mean accumulation ratio (Rac) was 1.7 for Cmax and 2.4 for AUC0-24hr.. AbsorptionMedian vibegron Tmax is approximately to hours.Oral administration of 75 mg vibegron tablet crushed and mixed with 15 mL of applesauce resulted in no clinically relevant changes in vibegron pharmacokinetics when compared to administration of an intact 75 mg vibegron tablet.. Effect of FoodNo clinically significant differences in vibegron pharmacokinetics were observed following administration of high-fat meal (53% fat, 869 calories [32.1 protein, 70.2 carbohydrate, and 51.1 fat]).. DistributionThe mean apparent volume of distribution is 6304 liters. Human plasma protein binding of vibegron is approximately 50%. The average blood-to-plasma concentration ratio is 0.9.. EliminationVibegron has an effective half-life of 30.8 hours across all populations.. MetabolismMetabolism plays minor role in the elimination of vibegron. CYP3A4 is the predominant enzyme responsible for in vitro metabolism.. ExcretionFollowing radiolabeled dose, approximately 59% of the dose (54% as unchanged) was recovered in feces and 20% (19% as unchanged) in urine.. Specific PopulationsNo clinically significant differences in the pharmacokinetics of vibegron were observed based on age (18 to 93 years), sex, race/ethnicity (Japanese vs. non-Japanese), mild (eGFR 60 to <90 mL/min/1.73 m2), moderate (eGFR 30 to <60 mL/min/1.73 m2), and severe (eGFR 15 to <30 mL/min/1.73 m2) renal impairment, or moderate (Child-Pugh B) hepatic impairment. The effect of more severe renal impairment (eGFR <15 mL/min/1.73 m2) with or without hemodialysis or severe (Child-Pugh C) hepatic impairment on vibegron pharmacokinetics was not studied.. Drug Interaction Studies. Clinical Studies. Digoxin: Concomitant administration of vibegron increased digoxin Cmax and AUC by 21% and 11%, respectively.. Other Drugs: No clinically significant differences in vibegron pharmacokinetics were observed when used concomitantly with ketoconazole (P-gp and strong CYP3A4 inhibitor), diltiazem (P-gp and moderate CYP3A4 inhibitor), rifampin (strong CYP3A4 inducer), or tolterodine. No clinically significant differences in the pharmacokinetics of the following drugs were observed when used concomitantly with vibegron: tolterodine, tolterodine 5-hydroxy metabolite, metoprolol, combined oral contraceptive (ethinyl estradiol, levonorgestrel), or warfarin.. In Vitro Studies. Cytochrome P450 (CYP) Enzymes: Vibegron is CYP3A4 substrate. Vibegron did not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4. Vibegron did not induce CYP1A2, CYP2B6, or CYP3A4.. Transporter Systems: Vibegron is P-gp substrate. Vibegron did not inhibit P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, or MATE2K at clinically relevant concentrations.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryThere are no available data on GEMTESA use in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.In animal studies, no effects on embryo-fetal development were observed following administration of vibegron during the period of organogenesis at exposures approximately 275-fold and 285-fold greater than clinical exposure at the recommended daily dose of GEMTESA, in rats and rabbits, respectively. Delayed fetal skeletal ossification was observed in rabbits at approximately 898-fold clinical exposure, in the presence of maternal toxicity. In rats treated with vibegron during pregnancy and lactation, no effects on offspring were observed at 89-fold clinical exposure. Developmental toxicity was observed in offspring at approximately 458-fold clinical exposure, in the presence of maternal toxicity. No effects on offspring were observed at 89-fold clinical exposure (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies carry some risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.. Data. Animal DataIn an embryo-fetal developmental toxicity study, pregnant rats were treated with daily oral doses of 0, 30, 100, 300, or 1000 mg/kg/day vibegron during the period of organogenesis (Days to 20 of gestation). These doses were associated with systemic exposures (AUC) 0-, 9-, 89-, 275-, and 1867-fold higher, respectively, than in humans treated with the recommended daily dose of GEMTESA. No embryo-fetal developmental toxicity was observed at doses up to 300 mg/kg/day. Treatment with the high dose of 1000 mg/kg/day was discontinued due to maternal toxicity.In an embryo-fetal developmental toxicity study, pregnant rabbits were treated with daily oral doses of 0, 30, 100, or 300 mg/kg/day vibegron during the period of organogenesis (Days to 20 of gestation). These doses were associated with systemic exposures (AUC) 0-, 86-, 285-, and 898-fold higher, respectively, than in humans treated with the recommended daily dose of GEMTESA. No embryo-fetal developmental toxicity was observed at doses of vibegron up to 100 mg/kg/day. Maternal toxicity (decreased food consumption), reduced fetal body weight, and an increased incidence of delayed skeletal ossification, were observed at 300 mg/kg/day.In pre- and post-natal developmental toxicity study, pregnant or lactating rats were treated with daily oral doses of 0, 30, 100, or 500 mg/kg/day vibegron from day of gestation through day 20 of lactation. These doses were associated with estimated systemic exposures (AUC) 0-, 9-, 89-, and 458-fold higher, respectively, than in humans treated with the recommended daily dose of GEMTESA. No developmental toxicity was observed in F1 offspring at doses up to 100 mg/kg/day. Maternal toxicity was observed during lactation (decreased body weight gain) at doses >=100 mg/kg/day and during gestation (decreased body weight gain and food consumption) at 500 mg/kg/day. Developmental toxicity was observed in F1 offspring (increased stillborn index, lethality, reduced viability and weaning indices, decreased body weight and body weight gains, low physical development differentiation indices, and effects on sensory function and reflexes) at 500 mg/kg/day.

SPL PATIENT PACKAGE INSERT SECTION.

PATIENT INFORMATIONGEMTESA [gem tes ah] (vibegron)tablets, for oral useThis Patient Information has been approved by the U.S. Food and Drug Administration.Approved: 12/2020What is GEMTESAGEMTESA is prescription medicine for adults used to treat the following symptoms due to condition called overactive bladder:urge urinary incontinence: strong need to urinate with leaking or wetting accidentsurgency: the need to urinate right awayfrequency: urinating oftenIt is not known if GEMTESA is safe and effective in children.Do not take GEMTESA if you:are allergic to vibegron or any of the ingredients in GEMTESA. See the end of this leaflet for complete list of ingredients in GEMTESA. Before you take GEMTESA, tell your doctor about all of your medical conditions, including if you:have liver problems.have kidney problems.have trouble emptying your bladder or you have weak urine stream.take medicines that contain digoxin.are pregnant or plan to become pregnant. It is not known if GEMTESA will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.are breastfeeding or plan to breastfeed. It is not known if GEMTESA passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take GEMTESA.Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Know the medicines you take. Keep list of them to show your doctor and pharmacist when you get new medicine.How should take GEMTESATake GEMTESA exactly as your doctor tells you to take it.Take GEMTESA tablet, by mouth, time day with or without food.Swallow GEMTESA tablets whole with glass of water.You may also crush GEMTESA tablets, mix with tablespoon (about 15 mL) of applesauce, and take right away with glass of water.What are the possible side effects of GEMTESAGEMTESA may cause serious side effects including:inability to empty your bladder (urinary retention). GEMTESA may increase your chances of not being able to empty your bladder, especially if you have bladder outlet obstruction or take other medicines for treatment of overactive bladder. Tell your doctor right away if you are unable to empty your bladder.The most common side effects of GEMTESA include:urinary tract infectionheadachenasal congestion, sore throat or runny nosediarrheanauseaupper respiratory tract infectionThese are not all the possible side effects of GEMTESA. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should store GEMTESAStore GEMTESA at room temperature between 68F to 77F (20C to 25C).Safely throw away medicine that is no longer needed in your household trash.You may also dispose of the unused medicine through take-back option, if available. See www.fda.gov/drugdisposal for more information.Keep GEMTESA and all medicines out of the reach of children.General information about the safe and effective use of GEMTESA.Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use GEMTESA for condition for which it was not prescribed. Do not give GEMTESA to other people, even if they have the same symptoms that you have. It may harm them.You can ask your doctor or pharmacist for information about GEMTESA that is written for health professionals.What are the ingredients in GEMTESAActive ingredient: vibegron Inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, mannitol, and microcrystalline cellulose. The light green film coating contains FD&C Blue No. - aluminum lake, hypromellose, iron oxide yellow, lactose monohydrate, titanium dioxide, and triacetin.Manufactured for and Distributed by: Urovant Sciences, Inc. Irvine, CA 92617GEMTESA(R) is trademark of Urovant Sciences GmbH, registered in the U.S. and other countries. All other trademarks are the property of their respective owners.Patented: see https://www.urovant.com/about/product-patents (C) 2020 Urovant Sciences GmbH. All rights reserved.For more information, go to www.GEMTESA.com or call 1-833-876-8268.. urge urinary incontinence: strong need to urinate with leaking or wetting accidents. urgency: the need to urinate right away. frequency: urinating often. are allergic to vibegron or any of the ingredients in GEMTESA. See the end of this leaflet for complete list of ingredients in GEMTESA.. have liver problems.. have kidney problems.. have trouble emptying your bladder or you have weak urine stream.. take medicines that contain digoxin.. are pregnant or plan to become pregnant. It is not known if GEMTESA will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.. are breastfeeding or plan to breastfeed. It is not known if GEMTESA passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take GEMTESA.. Take GEMTESA exactly as your doctor tells you to take it.. Take GEMTESA tablet, by mouth, time day with or without food.. Swallow GEMTESA tablets whole with glass of water.. You may also crush GEMTESA tablets, mix with tablespoon (about 15 mL) of applesauce, and take right away with glass of water.. inability to empty your bladder (urinary retention). GEMTESA may increase your chances of not being able to empty your bladder, especially if you have bladder outlet obstruction or take other medicines for treatment of overactive bladder. Tell your doctor right away if you are unable to empty your bladder.. urinary tract infection. headache. nasal congestion, sore throat or runny nose. diarrhea. nausea. upper respiratory tract infection. Store GEMTESA at room temperature between 68F to 77F (20C to 25C).. Safely throw away medicine that is no longer needed in your household trash.. You may also dispose of the unused medicine through take-back option, if available. See www.fda.gov/drugdisposal for more information.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. Pediatric use: Safety and effectiveness in pediatric patients have not been established. (8.4)End-stage Renal Disease with or without Hemodialysis: Not recommended. (8.6)Severe Hepatic Impairment: Not recommended. (8.7). 8.1 Pregnancy. Risk SummaryThere are no available data on GEMTESA use in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.In animal studies, no effects on embryo-fetal development were observed following administration of vibegron during the period of organogenesis at exposures approximately 275-fold and 285-fold greater than clinical exposure at the recommended daily dose of GEMTESA, in rats and rabbits, respectively. Delayed fetal skeletal ossification was observed in rabbits at approximately 898-fold clinical exposure, in the presence of maternal toxicity. In rats treated with vibegron during pregnancy and lactation, no effects on offspring were observed at 89-fold clinical exposure. Developmental toxicity was observed in offspring at approximately 458-fold clinical exposure, in the presence of maternal toxicity. No effects on offspring were observed at 89-fold clinical exposure (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies carry some risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.. Data. Animal DataIn an embryo-fetal developmental toxicity study, pregnant rats were treated with daily oral doses of 0, 30, 100, 300, or 1000 mg/kg/day vibegron during the period of organogenesis (Days to 20 of gestation). These doses were associated with systemic exposures (AUC) 0-, 9-, 89-, 275-, and 1867-fold higher, respectively, than in humans treated with the recommended daily dose of GEMTESA. No embryo-fetal developmental toxicity was observed at doses up to 300 mg/kg/day. Treatment with the high dose of 1000 mg/kg/day was discontinued due to maternal toxicity.In an embryo-fetal developmental toxicity study, pregnant rabbits were treated with daily oral doses of 0, 30, 100, or 300 mg/kg/day vibegron during the period of organogenesis (Days to 20 of gestation). These doses were associated with systemic exposures (AUC) 0-, 86-, 285-, and 898-fold higher, respectively, than in humans treated with the recommended daily dose of GEMTESA. No embryo-fetal developmental toxicity was observed at doses of vibegron up to 100 mg/kg/day. Maternal toxicity (decreased food consumption), reduced fetal body weight, and an increased incidence of delayed skeletal ossification, were observed at 300 mg/kg/day.In pre- and post-natal developmental toxicity study, pregnant or lactating rats were treated with daily oral doses of 0, 30, 100, or 500 mg/kg/day vibegron from day of gestation through day 20 of lactation. These doses were associated with estimated systemic exposures (AUC) 0-, 9-, 89-, and 458-fold higher, respectively, than in humans treated with the recommended daily dose of GEMTESA. No developmental toxicity was observed in F1 offspring at doses up to 100 mg/kg/day. Maternal toxicity was observed during lactation (decreased body weight gain) at doses >=100 mg/kg/day and during gestation (decreased body weight gain and food consumption) at 500 mg/kg/day. Developmental toxicity was observed in F1 offspring (increased stillborn index, lethality, reduced viability and weaning indices, decreased body weight and body weight gains, low physical development differentiation indices, and effects on sensory function and reflexes) at 500 mg/kg/day.. 8.2 Lactation. Risk SummaryThere are no data on the presence of vibegron in human milk, the effects of the drug on the breastfed infant, or the effects on milk production. When single oral dose of radiolabeled vibegron was administered to postnatal nursing rats, radioactivity was observed in milk (see Data). When drug is present in animal milk, it is likely that the drug will be present in human milk.The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for GEMTESA and any potential adverse effects on the breastfed infant from GEMTESA or from the underlying maternal condition.. Data. Animal DataIn lactational transfer study, lactating rats were treated with single oral dose of 10 mg/kg radiolabeled [3H] vibegron on postpartum day 10. Levels of radioactivity were determined in milk and plasma collected at 1, 4, 12, and 24 after dosing. The Cmax of total radioactivity in milk and plasma were observed at and hours after dosing, respectively, with maximum milk-to-plasma concentration ratio of 2.2 observed at 12 hours after dosing. Vibegron elimination from milk showed similar trend as that from plasma. The radioactivity concentration in milk at 24 hours after administration was approximately 25% of the Cmax.. 8.4 Pediatric Use. The safety and effectiveness of GEMTESA in pediatric patients have not been established.. 8.5 Geriatric Use. Of 526 patients who received GEMTESA in the clinical studies for OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency, 242 (46%) were 65 years of age or older, and 75 (14%) were 75 years of age or older [see Clinical Studies (14)]. No overall differences in safety or effectiveness of GEMTESA have been observed between patients 65 years of age and older and younger adult patients.. 8.6 Renal Impairment. No dosage adjustment for GEMTESA is recommended for patients with mild, moderate, or severe renal impairment (eGFR 15 to <90 mL/min/1.73 m2). GEMTESA has not been studied in patients with eGFR <15 mL/min/1.73 m2 (with or without hemodialysis) and is not recommended in these patients [see Clinical Pharmacology (12.3)].. 8.7 Hepatic Impairment. No dosage adjustment for GEMTESA is recommended for patients with mild to moderate hepatic impairment (Child-Pugh and B). GEMTESA has not been studied in patients with severe hepatic impairment (Child-Pugh C) and is not recommended in this patient population [see Clinical Pharmacology (12.3)].