prolongation, including patients with a known history of qt prolongation and patients taking medications known to prolong the qt interval. (5.6) 5.1 angioedema and anaphylactic reactions angioedema of the face, lips, tongue, and/or larynx have been reported with solifenacin succinate. in some cases, angioedema occurred after the first dose, however, cases have been reported to occur hours after the first dose or after multiple doses. anaphylactic reactions have also been reported in patients treated with solifenacin succinate. angioedema associated with upper airway swelling and anaphylactic reactions may be life-threatening. solifenacin succinate is contraindicated in patients with a known or suspected hypersensitivity to solifenacin succinate [see contraindications (4 )]. if involvement of the tongue, hypopharynx, or larynx occurs, promptly discontinue solifenacin succinate and provide appropriate therapy and/or measures necessary to ensure a patent airway. 5.2 urinary retention the use of solifenacin succinate, like other antimuscarinic drugs, in patients with clinically significant bladder outlet obstruction including patients with urinary retention, may result in further urinary retention and kidney injury. the use of solifenacin succinate is not recommended in patients with clinically significant bladder outlet obstruction and is contraindicated in patients with urinary retention [see contraindications (4 )]. 5.3 gastrointestinal disorders the use of solifenacin succinate, like other antimuscarinic drugs, in patients with conditions associated with decreased gastrointestinal motility may result in further decreased gastrointestinal motility. solifenacin succinate is contraindicated in patients with gastric retention [see contraindications (4 )]. the use of solifenacin succinate is not recommended in patients with conditions associated with decreased gastrointestinal motility. 5.4 central nervous system effects solifenacin succinate is associated with antimuscarinic central nervous system (cns) adverse reactions [see adverse reactions (6.2 )]. a variety of cns antimuscarinic adverse reactions have been reported, including headache, confusion, hallucinations, and somnolence. monitor patients for signs of antimuscarinic cns adverse reactions, particularly after beginning treatment or increasing the dose. advise patients not to drive or operate heavy machinery until they know how solifenacin succinate affects them. if a patient experiences antimuscarinic cns adverse reactions, consider dose reduction or drug discontinuation. 5.5 controlled narrow-angle glaucoma solifenacin succinate should be used with caution in patients being treated for narrow-angle glaucoma [see contraindications ( 4)]. 5.6 qt prolongation in patients at high risk of qt prolongation in a study of the effect of solifenacin succinate on the qt interval conducted in 76 healthy women [see clinical pharmacology ( 12.2 )], solifenacin succinate 30 mg (three times the largest maximum recommended dose in adult patients) was associated with a mean increase in the fridericia-corrected qt interval of 8 msec (90% ci, 4, 13). the qt prolonging effect appeared less with solifenacin succinate 10 mg than with solifenacin succinate 30 mg, and the effect of solifenacin succinate 30 mg did not appear as large as that of the positive control moxifloxacin at its therapeutic dose. the use of solifenacin succinate is not recommended in patients at high risk of qt prolongation, including patients with a known history of qt prolongation and patients who are taking medications known to prolong the qt interval.

1.73 m 2 ) [see use in specific populations ( 8.6 )]. 2.3 dosing recommendations in patients with hepatic impairment do not exceed 5 mg once daily in patients with moderate hepatic impairment (child-pugh b). do not use solifenacin succinate tablet in patients with severe hepatic impairment (child-pugh c) [see use in specific populations ( 8.7 )]. 2.4 dosing recommendations in patients taking cyp3a4 inhibitors do not exceed 5 mg once daily when solifenacin succinate tablets are administered with strong cyp3a4 inhibitors such as ketoconazole [see drug interactions (7.1 )].

ities), urinary retention, and dry eyes. the incidence of dry mouth and constipation in patients treated with solifenacin succinate was higher in the 10 mg dose group compared to the 5 mg dose group. in the four 12-week double-blind clinical trials, severe fecal impaction, colonic obstruction, and intestinal obstruction were reported in one patient each, all in the solifenacin succinate 10 mg group. angioneurotic edema was reported in one patient taking solifenacin succinate 5 mg. compared to 12 weeks of treatment with solifenacin succinate, the incidence and severity of adverse reactions were similar in patients who remained on drug for up to 12 months in study 5 [see clinical studies ( 14 )]. the most frequent adverse reaction leading to study discontinuation was dry mouth (1.5%). table 1 lists the rates of identified adverse reactions, in the four randomized, placebo-controlled trials at an incidence greater than placebo and in 1% or more of patients treated with solifenacin succinate 5 or 10 mg once daily for up to 12 weeks. table 1: adverse reactions reported by ≥ 1% of patients and exceeding placebo in studies 1, 2, 3 and 4 placebo (%) solifenacin succinate 5 mg (%) solifenacin succinate 10 mg (%) number of patients 1216 578 1233 gastrointestinal disorders dry mouth 4.2 10.9 27.6 constipation 2.9 5.4 13.4 nausea 2.0 1.7 3.3 dyspepsia 1.0 1.4 3.9 abdominal pain upper 1.0 1.9 1.2 vomiting nos 0.9 0.2 1.1 infections and infestations urinary tract infection nos 2.8 2.8 4.8 influenza 1.3 2.2 0.9 pharyngitis nos 1.0 0.3 1.1 nervous system disorders dizziness 1.8 1.9 1.8 eye disorders vision blurred 1.8 3.8 4.8 dry eyes nos 0.6 0.3 1.6 renal and urinary disorders urinary retention 0.6 0 1.4 general disorders and administration site conditions edema lower limb 0.7 0.3 1.1 fatigue 1.1 1.0 2.1 psychiatric disorders depression nos 0.8 1.2 0.8 respiratory, thoracic and mediastinal disorders cough 0.2 0.2 1.1 vascular disorders hypertension nos 0.6 1.4 0.5 6.2 postmarketing experience the following adverse reactions have been identified during post-approval use of solifenacin succinate in the u.s. and/or outside of the u.s. 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. general disorders and administration site conditions : peripheral edema, hypersensitivity reactions (including angioedema with airway obstruction, rash, pruritus, urticaria, anaphylactic reaction); nervous system disorders: dizziness, headache, confusion, hallucinations, delirium, somnolence; cardiac disorders: qt prolongation, torsade de pointes, atrial fibrillation, tachycardia, palpitations; hepatobiliary disorders: liver disorders mostly characterized by abnormal liver function tests, ast (aspartate aminotransferase), alt (alanine aminotransferase), ggt (gamma-glutamyl transferase); renal and urinary disorders: renal impairment, urinary retention; metabolism and nutrition disorders : decreased appetite, hyperkalemia; skin and subcutaneous tissue disorders: exfoliative dermatitis, erythema multiforme, dry skin; eye disorders: glaucoma; gastrointestinal disorders: gastroesophageal reflux disease, ileus, vomiting, abdominal pain, dysgeusia, sialadenitis; respiratory, thoracic and mediastinal disorders: dysphonia, nasal dryness; musculoskeletal and connective tissue disorders : muscular weakness.

nacin succinate to pregnant mice resulted in the recovery of radiolabel in the fetus indicating that solifenacin-related product can cross the placental barrier. in pregnant mice, administration of solifenacin succinate at a dose of 250 mg/kg/day (7.9 times the systemic exposure at the mrhd of 10 mg), resulted in an increased incidence of cleft palate and increased maternal lethality. administration of solifenacin succinate to pregnant mice during organogenesis at greater than or equal to 3.6 times (100 mg/kg/day and greater) the systemic exposure at the mrhd, resulted in reduced fetal body weights and reduced maternal body weight gain. no embryo-fetal toxicity or teratogenicity was observed in fetuses from pregnant mice treated with solifenacin succinate at a dose of 30 mg/kg/day (1.2 times the systemic exposure at the mrhd). administration of solifenacin succinate to pregnant rats and rabbits at a dose of 50 mg/kg/day (< 1 times and 1.8 times the systemic exposure at the mrhd, respectively), resulted in no findings of embryo-fetal toxicity. oral pre- and post-natal administration of solifenacin succinate at 100 mg/kg/day (3.6 times the systemic exposure at the mrhd) during the period of organogenesis through weaning, resulted in reduced peripartum and postnatal survival, reduced body weight gain by the pups, and delayed physical development (eye opening and vaginal patency). an increase in the percentage of male offspring was also observed in litters from offspring (f2 generation) exposed to maternal doses of 250 mg/kg/day. there were no effects on natural delivery in mice treated with 1.2 times (30 mg/kg/day) the expected systemic exposure at the mrhd. 8.2 lactation risk summary there is no information on the presence of solifenacin in human milk, the effects on the breastfed child, or the effects on milk production. solifenacin is present in mouse milk [see data]. when a 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 mother’s clinical need for solifenacin succinate and any potential adverse effects on the breastfed child from solifenacin succinate or from the underlying maternal condition. data animal data oral administration of 14 c-solifenacin succinate to lactating mice resulted in the recovery of radioactivity in maternal milk. lactating female mice orally administered solifenacin succinate at a maternally toxic dose of 100 mg/kg/day (3.6 times the systemic exposure at the mrhd) had increased postpartum pup mortality, pups with reduced body weights, or delays in the onset of reflex and physical development. pups from lactating dams orally administered solifenacin succinate at a dose of 30 mg/kg/day (1.2 times the systemic exposure at the mrhd) had no discernible adverse findings. the concentrations of solifenacin in animal milk does not necessarily predict the concentration of drug in human milk. 8.4 pediatric use the safety and effectiveness of solifenacin succinate tablets have not been established in pediatric patients. 8.5 geriatric use in placebo-controlled clinical studies, similar safety and effectiveness were observed between geriatric patients (623 patients ≥ 65 years and 189 patients ≥ 75 years) and younger adult patients (1188 patients < 65 years) treated with solifenacin succinate [see clinical pharmacology ( 12.3 )]. 8.6 renal impairment solifenacin plasma concentrations are greater in patients with severe renal impairment compared to subjects with normal renal function [see clinical pharmacology ( 12.3 )]. because increased solifenacin plasma concentrations increase the risk of antimuscarinic adverse reactions, the maximum recommended dose of solifenacin succinate in patients with severe renal impairment (clcr < 30 ml/min/1.73 m 2 ) is 5 mg once daily [see dosage and administration ( 2.2 )]. the recommended dose in patients with mild or moderate renal impairment is the same as in patients with normal renal function. 8.7 hepatic impairment solifenacin plasma concentrations are greater in patients with moderate hepatic impairment compared to subjects with normal hepatic function [see clinical pharmacology ( 12.3 )]. because increased solifenacin plasma concentrations increase the risk of antimuscarinic adverse reactions, the maximum recommended dose of solifenacin succinate in patients with moderate hepatic impairment (child-pugh b) is 5 mg once daily [see dosage and administration (2.3 )] and solifenacin succinate is not recommended for use in patients with severe hepatic impairment (child-pugh c). 8.8 gender the pharmacokinetics of solifenacin is not significantly influenced by gender.

ce resulted in the recovery of radiolabel in the fetus indicating that solifenacin-related product can cross the placental barrier. in pregnant mice, administration of solifenacin succinate at a dose of 250 mg/kg/day (7.9 times the systemic exposure at the mrhd of 10 mg), resulted in an increased incidence of cleft palate and increased maternal lethality. administration of solifenacin succinate to pregnant mice during organogenesis at greater than or equal to 3.6 times (100 mg/kg/day and greater) the systemic exposure at the mrhd, resulted in reduced fetal body weights and reduced maternal body weight gain. no embryo-fetal toxicity or teratogenicity was observed in fetuses from pregnant mice treated with solifenacin succinate at a dose of 30 mg/kg/day (1.2 times the systemic exposure at the mrhd). administration of solifenacin succinate to pregnant rats and rabbits at a dose of 50 mg/kg/day (< 1 times and 1.8 times the systemic exposure at the mrhd, respectively), resulted in no findings of embryo-fetal toxicity. oral pre- and post-natal administration of solifenacin succinate at 100 mg/kg/day (3.6 times the systemic exposure at the mrhd) during the period of organogenesis through weaning, resulted in reduced peripartum and postnatal survival, reduced body weight gain by the pups, and delayed physical development (eye opening and vaginal patency). an increase in the percentage of male offspring was also observed in litters from offspring (f2 generation) exposed to maternal doses of 250 mg/kg/day. there were no effects on natural delivery in mice treated with 1.2 times (30 mg/kg/day) the expected systemic exposure at the mrhd.

19 to 79 years. the 30 mg dose of solifenacin succinate (three times the highest recommended dose) was chosen for use in this study because this dose results in a solifenacin exposure that covers those observed upon coadministration of 10 mg solifenacin succinate with strong cyp3a4 inhibitors (e.g., ketoconazole, 400 mg). due to the sequential dose escalating nature of the study, baseline ecg measurements were separated from the final qt assessment (of the 30 mg dose level) by 33 days. the median difference from baseline in heart rate associated with the 10 and 30 mg doses of solifenacin succinate compared to placebo was -2 and 0 beats/minute, respectively. because a significant period effect on qtc was observed, the qtc effects were analyzed utilizing the parallel placebo control arm rather than the pre-specified intra-patient analysis. representative results are shown in table 2. table 2: qtc changes in msec (90% ci) from baseline at t max (relative to placebo) 1 drug/dose fridericia method (using mean difference) solifenacin succinate 10 mg 2 (-3,6) solifenacin succinate 30 mg 8 (4,13) 1. results displayed are those derived from the parallel design portion of the study and represent the comparison of group 1 to time-matched placebo effects in group 2. moxifloxacin was included as a positive control in this study and, given the length of the study, its effect on the qt interval was evaluated in 3 different sessions. the placebo-subtracted mean changes (90% ci) in qtcf for moxifloxacin in the three sessions were 11 (7, 14), 12 (8, 17), and 16 (12, 21), respectively. the qt interval prolonging effect of the highest solifenacin succinate dose (three times the maximum therapeutic dose) studied was not as large as that of the positive control moxifloxacin at its recommended dose. however, the confidence intervals overlapped, and this study was not designed to draw direct statistical conclusions between the drugs or the dose levels. 12.3 pharmacokinetics absorption after oral administration of solifenacin succinate in healthy volunteers, peak plasma concentrations (c max ) of solifenacin were reached within 3 to 8 hours after administration and, at steady-state, ranged from 32.3 to 62.9 ng/ml for the 5 and 10 mg solifenacin succinate tablets, respectively. the absolute bioavailability of solifenacin is approximately 90%, with plasma concentrations of solifenacin proportional to the dose administered. effect of food solifenacin succinate may be administered without regard to meals. a single 10 mg dose administration of solifenacin succinate with food increased c max and auc of solifenacin by 4% and 3%, respectively. distribution solifenacin is approximately 98% (in vivo) bound to human plasma proteins, principally to α1-acid glycoprotein. solifenacin is highly distributed to non-cns tissues, having a mean steady-state volume of distribution of 600 l. elimination the elimination half-life (t 1/2 ) of solifenacin following chronic dosing is approximately 45 to 68 hours. metabolism solifenacin is extensively metabolized in the liver. the primary pathway for elimination is by way of cyp3a4; however, alternate metabolic pathways exist. the primary metabolic routes of solifenacin are through n-oxidation of the quinuclidin ring and 4r-hydroxylation of the tetrahydroisoquinoline ring. one pharmacologically active metabolite (4r-hydroxy solifenacin), occurring at low concentrations and unlikely to contribute significantly to clinical activity, and three pharmacologically inactive metabolites (n-glucuronide and the n-oxide and 4r-hydroxy¬n-oxide of solifenacin) have been found in human plasma after oral dosing. excretion following the administration of 10 mg of 14 c-solifenacin succinate to healthy volunteers, 69% of the radioactivity was recovered in the urine and 23% in the feces over 26 days. less than 15% (as mean value) of the dose was recovered in the urine as intact solifenacin. the major metabolites identified in urine were n-oxide of solifenacin, 4r-hydroxy solifenacin, and 4r-hydroxy-n-oxide of solifenacin and, in feces, 4r-hydroxy solifenacin. specific populations geriatric patients multiple dose studies of solifenacin succinate in geriatric volunteers (65 to 80 years) showed that cmax, auc and t1/2 values of solifenacin were 20 to 25% higher compared to the younger adult volunteers (18 to 55 years). [see use in specific populations (8.5)]. patients with renal impairment in studies with solifenacin succinate 10 mg, there was a 2.1-fold increase in auc and a 1.6-fold increase in t1/2 of solifenacin in patients with severe renal impairment compared to subjects with normal renal function [see use in specific populations (8.6)]. patients with hepatic impairment in studies with solifenacin succinate 10 mg, there was a 2-fold increase in the t 1/2 and a 35% increase in auc of solifenacin in patients with moderate hepatic impairment compared to subjects with normal hepatic function [see use in specific populations (8.7)]. solifenacin succinate has not been studied in patients with severe hepatic impairment. drug interaction studies strong cyp3a4 inhibitors in a crossover study, following blockade of cyp3a4 by coadministration of the strong cyp3a4 inhibitor, ketoconazole 400 mg once daily for 21 days, the mean c max and auc of solifenacin increased by 1.5 and 2.7-fold, respectively [see dosage and administration (2.4) and drug interactions (7.1)]. cyp3a4 inducers because solifenacin is a substrate of cyp3a4, inducers of cyp3a4 may decrease the concentration of solifenacin. warfarin in a crossover study, subjects received a single oral dose of warfarin 25 mg on the 10th day of dosing with either solifenacin succinate 10 mg or matching placebo once daily for 16 days. for r-warfarin, when it was coadministered with solifenacin succinate, the mean c max increased by 3% and auc decreased by 2%. for s-warfarin, when it was coadministered with solifenacin succinate, the mean c max and auc increased by 5% and 1%, respectively. oral contraceptives in a crossover study, subjects received 2 cycles of 21 days of oral contraceptives containing 30 ug ethinyl estradiol and 150 ug levonorgestrel. during the second cycle, subjects received additional solifenacin succinate 10 mg or matching placebo once daily for 10 days starting from the 12th day of receipt of oral contraceptives. for ethinyl estradiol, when it was administered with solifenacin succinate, the mean cmax and auc increased by 2% and 3%, respectively. for levonorgestrel, when it was administered with solifenacin succinate, the mean cmax and auc decreased by 1%. digoxin in a crossover study, subjects received digoxin (loading dose of 0.25 mg on day 1, followed by 0.125 mg from days 2 to 8) for 8 days. consecutively, they received solifenacin succinate 10 mg or matching placebo with digoxin 0.125 mg for an additional 10 days. when digoxin was coadministered with solifenacin succinate, the mean c max and auc increased by 13% and 4%, respectively. drugs metabolized by cytochrome p450 enzymes in vitro studies demonstrated that, at therapeutic concentrations, solifenacin does not inhibit cyp1a1/2, 2c9, 2c19, 2d6, or 3a4 derived from human liver microsomes.

following chronic dosing is approximately 45 to 68 hours. metabolism solifenacin is extensively metabolized in the liver. the primary pathway for elimination is by way of cyp3a4; however, alternate metabolic pathways exist. the primary metabolic routes of solifenacin are through n-oxidation of the quinuclidin ring and 4r-hydroxylation of the tetrahydroisoquinoline ring. one pharmacologically active metabolite (4r-hydroxy solifenacin), occurring at low concentrations and unlikely to contribute significantly to clinical activity, and three pharmacologically inactive metabolites (n-glucuronide and the n-oxide and 4r-hydroxy¬n-oxide of solifenacin) have been found in human plasma after oral dosing. excretion following the administration of 10 mg of 14 c-solifenacin succinate to healthy volunteers, 69% of the radioactivity was recovered in the urine and 23% in the feces over 26 days. less than 15% (as mean value) of the dose was recovered in the urine as intact solifenacin. the major metabolites identified in urine were n-oxide of solifenacin, 4r-hydroxy solifenacin, and 4r-hydroxy-n-oxide of solifenacin and, in feces, 4r-hydroxy solifenacin. specific populations geriatric patients multiple dose studies of solifenacin succinate in geriatric volunteers (65 to 80 years) showed that cmax, auc and t1/2 values of solifenacin were 20 to 25% higher compared to the younger adult volunteers (18 to 55 years). [see use in specific populations (8.5)]. patients with renal impairment in studies with solifenacin succinate 10 mg, there was a 2.1-fold increase in auc and a 1.6-fold increase in t1/2 of solifenacin in patients with severe renal impairment compared to subjects with normal renal function [see use in specific populations (8.6)]. patients with hepatic impairment in studies with solifenacin succinate 10 mg, there was a 2-fold increase in the t 1/2 and a 35% increase in auc of solifenacin in patients with moderate hepatic impairment compared to subjects with normal hepatic function [see use in specific populations (8.7)]. solifenacin succinate has not been studied in patients with severe hepatic impairment. drug interaction studies strong cyp3a4 inhibitors in a crossover study, following blockade of cyp3a4 by coadministration of the strong cyp3a4 inhibitor, ketoconazole 400 mg once daily for 21 days, the mean c max and auc of solifenacin increased by 1.5 and 2.7-fold, respectively [see dosage and administration (2.4) and drug interactions (7.1)]. cyp3a4 inducers because solifenacin is a substrate of cyp3a4, inducers of cyp3a4 may decrease the concentration of solifenacin. warfarin in a crossover study, subjects received a single oral dose of warfarin 25 mg on the 10th day of dosing with either solifenacin succinate 10 mg or matching placebo once daily for 16 days. for r-warfarin, when it was coadministered with solifenacin succinate, the mean c max increased by 3% and auc decreased by 2%. for s-warfarin, when it was coadministered with solifenacin succinate, the mean c max and auc increased by 5% and 1%, respectively. oral contraceptives in a crossover study, subjects received 2 cycles of 21 days of oral contraceptives containing 30 ug ethinyl estradiol and 150 ug levonorgestrel. during the second cycle, subjects received additional solifenacin succinate 10 mg or matching placebo once daily for 10 days starting from the 12th day of receipt of oral contraceptives. for ethinyl estradiol, when it was administered with solifenacin succinate, the mean cmax and auc increased by 2% and 3%, respectively. for levonorgestrel, when it was administered with solifenacin succinate, the mean cmax and auc decreased by 1%. digoxin in a crossover study, subjects received digoxin (loading dose of 0.25 mg on day 1, followed by 0.125 mg from days 2 to 8) for 8 days. consecutively, they received solifenacin succinate 10 mg or matching placebo with digoxin 0.125 mg for an additional 10 days. when digoxin was coadministered with solifenacin succinate, the mean c max and auc increased by 13% and 4%, respectively. drugs metabolized by cytochrome p450 enzymes in vitro studies demonstrated that, at therapeutic concentrations, solifenacin does not inhibit cyp1a1/2, 2c9, 2c19, 2d6, or 3a4 derived from human liver microsomes.

th 50 mg/kg/day (< 1 times the exposure at the mrhd) and female rats treated with 100 mg/kg/day (1.7 times the exposure at the mrhd) of solifenacin succinate. 13.2 animal toxicology and/or pharmacology juvenile animal toxicology data dose-related increased mortality without preceding clinical signs occurred in juvenile mice treated before weaning for a duration of 12 weeks, from day 10 after birth, with doses that achieved a pharmacological effect. animals dosed from postnatal day 10 onwards had higher mortality compared to the mortality in adult mice. no increased frequency in mortality was observed in juvenile mice that were treated after weaning for a duration of 4 weeks, from day 21 after birth onwards. plasma exposure at postnatal day 10 was higher than in adult mice; the systemic exposure at postnatal day 21 was comparable to the systemic exposure in adult mice.

the exposure at the mrhd) and female rats treated with 100 mg/kg/day (1.7 times the exposure at the mrhd) of solifenacin succinate.

ian (93%) and female (80%) with a mean age of 58 years. the primary endpoint in all four trials was the mean change from baseline to 12 weeks in number of micturitions/24 hours. secondary endpoints included mean change from baseline to 12 weeks in number of incontinence episodes/24 hours, and mean volume voided per micturition. the efficacy of solifenacin succinate was similar across patient age groups and gender. the mean reduction in the number of micturitions per 24 hours was significantly greater with solifenacin succinate 5 mg (2.3; p < 0.001) and solifenacin succinate 10 mg (2.7; p < 0.001) compared to placebo (1.4). the mean reduction in the number of incontinence episodes per 24 hours was significantly greater with solifenacin succinate 5 mg (1.5; p < 0.001) and solifenacin succinate 10 mg (1.8; p < 0.001) treatment groups compared to the placebo treatment group (1.1). the mean increase in the volume voided per micturition was significantly greater with solifenacin succinate 5 mg (32.3 ml; p < 0.001) and solifenacin succinate 10 mg (42.5 ml; p < 0.001) compared with placebo (8.5 ml). the results for the primary and secondary endpoints in the four individual 12-week clinical studies of solifenacin succinate are reported in tables 3 through 6. table 3: mean changes from baseline to week 12 in efficacy endpoints in study 1 parameter placebo (n=253) mean (se) solifenacin succinate 5 mg (n=266) mean (se) solifenacin succinate 10 mg (n=264) mean (se) urinary frequency (number of micturitions/24 hours) 1 baseline reduction p value vs. placebo 12.2 (0.26) 1.2 (0.21) 12.1 (0.24) 2.2 (0.18) < 0.001 12.3 (0.24) 2.6 (0.20) < 0.001 number of incontinence episodes/24 hours 2 baseline reduction p value vs. placebo 2.7 (0.23) 0.8 (0.18) 2.6 (0.22) 1.4 (0.15) < 0.01 2.6 (0.23) 1.5 (0.18) < 0.01 volume voided per micturition [ml] 2 baseline increase p value vs. placebo 143.8 (3.37) 7.4 (2.28) 149.6 (3.35) 32.9 (2.92) < 0.001 147.2 (3.15) 39.2 (3.11) < 0.001 1. primary endpoint 2. secondary endpoint table 4: mean changes from baseline to week 12 in efficacy endpoints in study 2 1. primary endpoint 2. secondary endpoint table 5: mean changes from baseline to week 12 in efficacy endpoints in study 3 parameter placebo (n=309) mean (se) solifenacin succinate 10 mg (n=306) mean (se) urinary frequency (number of micturitions/24 hours) 1 baseline reduction p value vs. placebo 11.5 (0.18) 1.5 (0.15) 11.7 (0.18) 3.0 (0.15) < 0.001 number of incontinence episodes/24 hours 2 baseline reduction p value vs. placebo 3.0 (0.20) 1.1 (0.16) 3.1 (0.22) 2.0 (0.19) < 0.001 volume voided per micturition [ml] 2 baseline increase p value vs. placebo 190.3 (5.48) 2.7 (3.15) 183.5 (4.97) 47.2 (3.79) < 0.001 1. primary endpoint 2. secondary endpoint table 6: mean changes from baseline to week 12 in efficacy endpoints in study 4 parameter placebo (n=309) mean (se) solifenacin succinate 10 mg (n=306) mean (se) urinary frequency (number of micturitions/24 hours) 1 baseline reduction p value vs. placebo 11.5 (0.18) 1.5 (0.15) 11.7 (0.18) 3.0 (0.15) < 0.001 number of incontinence episodes/24 hours 2 baseline reduction p value vs. placebo 3.0 (0.20) 1.1 (0.16) 3.1 (0.22) 2.0 (0.19) < 0.001 volume voided per micturition [ml] 2 baseline increase p value vs. placebo 190.3 (5.48) 2.7 (3.15) 183.5 (4.97) 47.2 (3.79) < 0.001 1. primary endpoint 2. secondary endpoint

gastrointestinal motility. solifenacin succinate tablets has been associated with constipation and dry mouth. advise patients to contact their health care providers if they experience severe abdominal pain or become constipated for 3 or more days [see warnings and precautions ( 5.3 )]. central nervous system effects because solifenacin succinate tablets, like other antimuscarinic agents, may cause central nervous system effects or blurred vision, advise patients to exercise caution in decisions to engage in potentially dangerous activities until the drug’s effect on the patient has been determined [see warnings and precautions ( 5.4 )]. narrow-angle glaucoma inform patients that solifenacin succinate tablets, like other antimuscarinics, may cause worsening of the glaucoma condition in patients with narrow-angle glaucoma [see warnings and precautions ( 5.5 )]. dry skin inform patients that solifenacin succinate tablets, like other antimuscarinics, may cause dry skin due to decreased sweating. heat prostration due to decreased sweating can occur when solifenacin succinate tablets are used in a hot environment [see adverse reactions ( 6.2 )]. manufactured for: camber pharmaceuticals, inc. piscataway, nj 08854 by: annora pharma pvt. ltd. sangareddy - 502313, telangana, india. revised: 04/2022 camber-logo