Solifenacin Succinate

Pronunciation

Class: Genitourinary Smooth Muscle Relaxants
Chemical Name: (1S)-(3R)-1-azabicyclo[2.2.2]oct-3-yl-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate cmpd. with butanedioic acid (1:1)
Molecular Formula: C23H26N2O2•C4H6O4
CAS Number: 242478-38-2
Brands: Vesicare

Introduction

Genitourinary antispasmodic agent; an antimuscarinic agent.1

Uses for Solifenacin Succinate

Overactive Bladder

Relief of symptoms associated with voiding (e.g., urge urinary incontinence, urgency, frequency).1

Slideshow: How to Manage Your Overactive Bladder

Solifenacin Succinate Dosage and Administration

Administration

Oral Administration

Administer orally once daily with liquids without regard to meals.1 8

Swallow tablets whole.1 8

Dosage

Available as solifenacin succinate; dosage expressed in terms of the salt.1

Adults

Overactive Bladder
Oral

Initially, 5 mg once daily.1 If well tolerated, may increase to 10 mg once daily.1

Prescribing Limits

Adults

Overactive Bladder
Oral

Maximum 10 mg daily.1

Special Populations

Hepatic Impairment

Maximum 5 mg daily in patients with moderate hepatic impairment (Child-Pugh class B).1 (See Elimination: Special Populations, under Pharmacokinetics.)

Use not recommended in patients with severe hepatic impairment (Child-Pugh class C).1

Renal Impairment

Maximum 5 mg daily in patients with severe renal impairment (Clcr <30 mL/minute).1 (See Elimination: Special Populations, under Pharmacokinetics.)

Cautions for Solifenacin Succinate

Contraindications

  • Urinary retention, gastric retention, or uncontrolled angle-closure glaucoma.1

  • Known hypersensitivity to solifenacin succinate or any ingredient in the formulation.1

Warnings/Precautions

Sensitivity Reactions

Angioedema

Angioedema reported in at least 1 patient.1 9

General Precautions

Urinary Retention

Risk of urinary retention; use with caution in patients with clinically important bladder outflow obstruction.1

Decreased GI Motility

Use with caution in patients with decreased GI motility1 (e.g., patients with severe constipation, ulcerative colitis, or myasthenia gravis) or obstructive GI disorders.9

Fecal impaction, colonic obstruction, and intestinal obstruction reported rarely with 10-mg daily dosage.1

Prolongation of QT Interval

30-mg daily dosage associated with more pronounced prolongation of QT interval than 10-mg daily dosage.1 (See Prescribing Limits under Dosage and Administration.) Consider this observation when deciding to use solifenacin in patients with history of QT interval prolongation or receiving drugs that prolong QT interval.1

Controlled Angle-closure Glaucoma

Use with caution in patients being treated for angle-closure glaucoma.1 (See Contraindications under Cautions.)

Specific Populations

Pregnancy

Category C.1

Lactation

Distributed into milk in mice; not known whether distributed into human milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.9

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1 (See Elimination: Special Populations, under Pharmacokinetics.)

Hepatic Impairment

Use with caution.1 (See Hepatic Impairment under Dosage and Administration and see Elimination: Special Populations, under Pharmacokinetics.)

Use not recommended in patients with severe hepatic impairment (Child-Pugh class C).1

Renal Impairment

Use with caution.1 (See Renal Impairment under Dosage and Administration and see Elimination: Special Populations, under Pharmacokinetics.)

Common Adverse Effects

Dry mouth, constipation.1

Interactions for Solifenacin Succinate

Metabolized principally by CYP3A4.1 Does not inhibit CYP1A1/2, 2C9, 2C19, 2D6, or 3A4.1

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased plasma solifenacin concentrations).1 Do not exceed 5 mg daily when used concomitantly with potent inhibitors of CYP3A4.1 (See Specific Drugs under Interactions.)

Inducers of CYP3A4: Potential pharmacokinetic interaction (altered solifenacin pharmacokinetics).1

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP1A1/2, CYP2C9, CYP2C19, CYP2D6, or CYP3A4: Pharmacokinetic interaction unlikely

Drugs Affected by GI Motility

Potential pharmacokinetic interaction (altered absorption because of decreased GI motility).10 (See Decreased GI Motility under Cautions.)

Specific Drugs

Drug

Interaction

Comments

Anticholinergic agents

Possible additive anticholinergic effects9

Digoxin

No substantial effect on digoxin pharmacokinetics1

Hormonal contraceptives

No substantial changes in plasma concentrations of ethinyl estradiol or levonorgestrel1

Ketoconazole

Increased plasma solifenacin concentrations1

Do not exceed a solifenacin succinate dosage of 5 mg daily1

Warfarin

No substantial effect on warfarin pharmacokinetics1

Solifenacin Succinate Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is approximately 90%.1 6

Peak plasma concentrations achieved within 3–8 hours after administration.1

Food

Food does not affect pharmacokinetics of solifenacin.1 7

Special Populations

Increased plasma concentrations reported in geriatric patients, patients with moderate hepatic impairment (Child-Pugh class B), and patients with severe renal impairment (Clcr <30 mL/minute).1 (See Special Populations under Dosage and Administration and see Elimination: Special Populations, under Pharmacokinetics.)

Distribution

Extent

Highly distributed to tissues outside the CNS.1

Distributed into milk in mice; not known whether distributed into human milk.1

Plasma Protein Binding

Approximately 98% (mainly to α1-acid glycoprotein).1

Elimination

Metabolism

Extensively metabolized in the liver, mainly via CYP3A4.1

Elimination Route

Excreted in urine (approximately 69%) and in feces (approximately 23%); unchanged drug accounts for <15% of recovered radioactivity.1

Half-life

45–68 hours following long-term administration.1

Special Populations

Prolonged half-life in geriatric patients, patients with moderate hepatic impairment (Child-Pugh class B), and patients with severe renal impairment (Clcr <30 mL/minute).1 (See Special Populations under Dosage and Administration.)

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).1

Actions

  • Potent and selective antimuscarinic agent.1 2

  • Inhibits contraction of the detrusor muscle of the bladder, resulting in decreased bladder activity.2

  • Demonstrates binding specificity for muscarinic M3 receptors in vitro and functional selectivity for urinary bladder over secretory (e.g., salivary) glands.2

Advice to Patients

  • Risk of blurred vision, constipation, dry mouth, and heat prostration (when used in a hot environment).1 Use caution when driving or performing dangerous activities until effects on vision are known.8 Consult a clinician if severe abdominal pain occurs or if constipation persists for ≥3 days.1

  • Importance of taking solifenacin succinate with liquids and swallowing the tablet whole.1 8 If a dose is skipped, resume therapy the next day; do not take 2 doses in the same day.8

  • Importance of reading manufacturer’s patient information leaflet before initiating therapy.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Solifenacin Succinate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

5 mg

Vesicare

Yamanouchi (also promoted by GlaxoSmithKline)

10 mg

Vesicare

Yamanouchi (also promoted by GlaxoSmithKline)

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

VESIcare 10MG Tablets (ASTELLAS): 30/$170.09 or 90/$481.91

VESIcare 5MG Tablets (ASTELLAS): 30/$184.00 or 90/$526.99

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Yamanouchi. VESIcare (solifenacin succinate) tablets prescribing information. Paramus, NJ; 2004 Nov.

2. Chilman-Blair K. Solifenacin: Treatment of overactive bladder. Drugs Today. 2004; 40:343-53. [PubMed 15190387]

3. Chapple CR, Rechberger T, Al-Shukri S et al. Randomized, double-blind placebo- and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder. BJU Int. 2004; 93:303-10. [IDIS 532014] [PubMed 14764127]

4. Cardozo L, Lisec M, Millard R et al. Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder. J Urol. 2004; 172:1919-24. [IDIS 522716] [PubMed 15540755]

5. Kelleher CJ, Cardozo L, Chapple CR et al. Improved quality of life in patients with overactive bladder symptoms treated with solifenacin. BJU Int. 2005; 95:81-5. [IDIS 532015] [PubMed 15638900]

6. Kuipers ME, Krauwinkel WJJ, Mulder H et al. Solifenacin demonstrates high absolute bioavailability in healthy men. Drugs R D. 2004; 5:73-81. [PubMed 15293866]

7. Uchida T, Krauwinkel WJ, Mulder H et al. Food does not affect the pharmacokinetics of solifenacin, a new muscarinic receptor antagonist: results of a randomized crossover trial. Br J Clin Pharmacol. 2004; 58:4-7. [IDIS 519282] [PubMed 15206986]

8. Yamanouchi. VESIcare (solifenacin succinate) patient information. Paramus, NJ; 2004 Nov.

9. Astellas Pharma, Durham, NC: Personal communication.

10. Novartis. Enablex (darifenacin hydrobromide) extended-release tablets prescribing information. East Hanover, NJ; 2004 Dec.

Hide
(web2)