FDA

Vesicare LS

Approved 26 May 2020OralSuspension

Indications

VESIcare LS ® is indicated for the treatment of neurogenic detrusor overactivity (NDO) in pediatric patients aged 2 years and older. VESIcare LS is a muscarinic antagonist indicated for the treatment of neurogenic detrusor overactivity in pediatric patients aged 2 years and older. ( 1 )

Contraindications

VESIcare LS is contraindicated in patients:

With gastric retention [see Warnings and Precautions ( 5.3 )] ,
With uncontrolled narrow-angle glaucoma [see Warnings and Precautions ( 5.5 )] , and
Who have demonstrated hypersensitivity to solifenacin succinate or the inactive ingredients in VESIcare LS oral suspension. Reported adverse reactions have included anaphylaxis and angioedema [see Adverse Reactions ( 6.2 )] .
Gastric retention. ( 4 , 5.3 )
Uncontrolled narrow-angle glaucoma. ( 4 , 5.5 )
Hypersensitivity to this product or any of its components. ( 4 , 5.1 , 6.2 )

Warnings and precautions

Angioedema and Anaphylactic Reactions : Promptly discontinue VESIcare LS and provide appropriate therapy. ( 5.1 )
Urinary Retention : VESIcare LS is not recommended for use in patients with clinically significant bladder outlet obstruction in the absence of clean intermittent catherization. ( 5.2 )
Gastrointestinal Disorders : VESIcare LS is not recommended for use in patients with decreased gastrointestinal motility. ( 5.3 )
Central Nervous System Effects : Somnolence has been reported with solifenacin succinate. Advise patients not to drive or operate heavy machinery until they know how VESIcare LS affects them. ( 5.4 )
Controlled Narrow-Angle Glaucoma : Use VESIcare LS with caution in patients being treated for narrow-angle glaucoma. ( 5.5 )
QT Prolongation in Patients at High Risk of QT Prolongation : VESIcare LS is not recommended for use in patients at high risk of QT 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.

At a glance

Brand name: Vesicare LS
Active substance: solifenacin succinate
Route: Oral
Dosage form: Suspension
Applicant: Astellas
Status: Discontinued
FDA approval: 26 May 2020
Application: NDA209529-001

Contraindications

VESIcare LS is contraindicated in patients:

With gastric retention [see Warnings and Precautions ( 5.3 )] ,
With uncontrolled narrow-angle glaucoma [see Warnings and Precautions ( 5.5 )] , and
Who have demonstrated hypersensitivity to solifenacin succinate or the inactive ingredients in VESIcare LS oral suspension. Reported adverse reactions have included anaphylaxis and angioedema [see Adverse Reactions ( 6.2 )] .
Gastric retention. ( 4 , 5.3 )
Uncontrolled narrow-angle glaucoma. ( 4 , 5.5 )
Hypersensitivity to this product or any of its components. ( 4 , 5.1 , 6.2 )

Warnings and precautions

Angioedema and Anaphylactic Reactions : Promptly discontinue VESIcare LS and provide appropriate therapy. ( 5.1 )
Urinary Retention : VESIcare LS is not recommended for use in patients with clinically significant bladder outlet obstruction in the absence of clean intermittent catherization. ( 5.2 )
Gastrointestinal Disorders : VESIcare LS is not recommended for use in patients with decreased gastrointestinal motility. ( 5.3 )
Central Nervous System Effects : Somnolence has been reported with solifenacin succinate. Advise patients not to drive or operate heavy machinery until they know how VESIcare LS affects them. ( 5.4 )
Controlled Narrow-Angle Glaucoma : Use VESIcare LS with caution in patients being treated for narrow-angle glaucoma. ( 5.5 )
QT Prolongation in Patients at High Risk of QT Prolongation : VESIcare LS is not recommended for use in patients at high risk of QT prolongation, including patients with a known history of QT prolongation and patients taking medications known to prolong the QT interval. ( 5.6 )

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

There are no studies with the use of solifenacin succinate in pregnant women or adolescents to inform a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes. No adverse developmental outcomes were observed in animal reproduction studies with oral administration of solifenacin succinate to pregnant mice during the period of organogenesis at a dose resulting in 1.2 times the systemic exposure at the maximum recommended human dose (MRHD) of 10 mg/day.

However, administration of doses 3.6 times and greater than the MRHD during organogenesis produced maternal toxicity in the pregnant mice and resulted in developmental toxicity and reduced fetal body weights in offspring [see Data ] . In the U.S. general population, the estimated background risk of major birth defects or miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Oral administration of 14 C-solifenacin 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.

Adverse reactions

Angioedema and Anaphylactic Reactions [see Warnings and Precautions ( 5.1 )]
Urinary Retention [see Warnings and Precautions ( 5.2 )]
Gastrointestinal Disorders [see Warnings and Precautions ( 5.3 )]
Central Nervous System Effects [see Warnings and Precautions ( 5.4 )]
QT Prolongation in Patients at High Risk of QT Prolongation [see Warnings and Precautions ( 5.6 )] The most common adverse reactions (> 2%) were constipation, dry mouth and urinary tract infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a 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 VESIcare LS oral suspension was evaluated in two open-label trials (Studies 1 and 2) [see Clinical Studies ( 14 )] . The two studies included 95 pediatric patients aged 2 to 17 years with neurogenic detrusor overactivity (NDO) who were 53% female, 58% White, 34% Asian and 2% Black.

Treatment was initiated at the weight-based starting recommended dose and was titrated up or down in 2.5 mg increments over 12 weeks to the lowest effective dose (not to exceed the maximum recommended dose). Subsequent to the dose titration period, patients continued their optimized dose for a 40-week maintenance period (mean exposure duration 301 days, range 1 to 413 days). The most commonly reported adverse reactions were constipation, dry mouth, urinary tract infection, abdominal pain, urinalysis bacterial test positive, and somnolence.

The incidence of adverse reactions was similar between patients taking the starting recommended dose and patients taking the maximum recommended dose with the exception of constipation, which was reported, in 8.5% of patients taking the maximum recommended dose compared to 0% of patients taking the starting recommended dose. Table 2 lists the adverse reactions reported in Studies 1 and 2 at an incidence equal to or greater than 1%.

Table 2: Adverse Reactions Reported in ≥ 1% of Neurogenic Detrusor Overactivity (NDO) Patients Aged 2 to 17 Years Taking VESIcare LS Oral Suspension in Studies 1 and 2 Adverse Reaction Percentage (%) of Patients Reporting Adverse Reactions N=95 Constipation

7.4 Dry mouth

3.2 Urinary tract infection

2.1 Abdominal pain

1.1 Urinalysis bacterial test positive

1.1 Somnolence

1.1 Adverse reactions reported in ≥ 1% of solifenacin succinate-treated adult patients and at an incidence greater than in placebo-treated adult patients in clinical adult trials were: Gastrointestinal disorders : dry mouth, constipation, nausea, dyspepsia, upper abdominal pain, vomiting Infections and infestations : urinary tract infection, influenza, pharyngitis Nervous system disorders : dizziness Eye disorders : blurred vision, dry eyes Renal and urinary disorders : urinary retention General disorders and administration site conditions : lower limb edema, fatigue Psychiatric disorders : depression Respiratory, thoracic and mediastinal disorders : cough Vascular disorders : hypertension

6.2Postmarketing Experience

The following adverse reactions have been identified during post-approval use of solifenacin succinate. 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.

Vesicare LS

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Vesicare LS

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.2Urinary Retention

5.3Gastrointestinal Disorders

5.4Central Nervous System Effects

5.5Controlled Narrow-Angle Glaucoma VESIcare

Interactions

7.1Strong CYP3A4 Inhibitors

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information