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Included as part of the PRECAUTIONS section.

Angioedema

Angioedema of the face, lips, tongue, and/or larynx have been reported with solifenacin. In some cases angioedema occurred after the first dose. Angioedema associated with upper airway swelling may be life threatening. If involvement of the tongue, hypopharynx, or larynx occurs, solifenacin should be promptly discontinued and appropriate therapy and/or measures necessary to ensure a patent airway should be promptly provided.

Urinary Retention

VESIcare (solifenacin succinate) , like other anticholinergic drugs, should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention [see CONTRAINDICATIONS].

Gastrointestinal Disorders

VESIcare (solifenacin succinate) , like other anticholinergics, should be used with caution in patients with decreased gastrointestinal motility [see CONTRAINDICATIONS].

Controlled Narrow-Angle Glaucoma

VESIcare (solifenacin succinate) should be used with caution in patients being treated for narrow-angle glaucoma [see CONTRAINDICATIONS].

Hepatic Impairment

VESIcare (solifenacin succinate) should be used with caution in patients with hepatic impairment. Doses of VESIcare (solifenacin succinate) greater than 5 mg are not recommended in patients with moderate hepatic impairment (Child-Pugh B). VESIcare (solifenacin succinate) is not recommended for patients with severe hepatic impairment (Child-Pugh C) [see DOSAGE AND ADMINISTRATION and Use In Specific Populations].

Renal Impairment

VESIcare (solifenacin succinate) should be used with caution in patients with renal impairment. Doses of VESIcare (solifenacin succinate) greater than 5 mg are not recommended in patients with severe renal impairment (CLcr < 30 mL/min) [see DOSAGE AND ADMINISTRATION and Use in Specific Populations].

Patients with Congenital or Acquired QT Prolongation

In a study of the effect of solifenacin on the QT interval in 76 healthy women [see CLINICAL PHARMACOLOGY] the QT prolonging effect appeared less with solifenacin 10 mg than with 30 mg (three times the maximum recommended dose), and the effect of solifenacin 30 mg did not appear as large as that of the positive control moxifloxacin at its therapeutic dose. This observation should be considered in clinical decisions to prescribe VESIcare (solifenacin succinate) for patients with a known history of QT prolongation or patients who are taking medications known to prolong the QT interval.

Patient Counseling Information

See FDA-approved patient labeling (PATIENT INFORMATION).

Patients should be informed that antimuscarinic agents such as VESIcare (solifenacin succinate) have been associated with constipation and blurred vision. Patients should be advised to contact their physician if they experience severe abdominal pain or become constipated for 3 or more days. Because VESIcare (solifenacin succinate) may cause blurred vision, patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until the drug's effect on the patient's vision has been determined. Heat prostration (due to decreased sweating) can occur when anticholinergic drugs, such as VESIcare (solifenacin succinate) , are used in a hot environment. Patients should read the patient leaflet entitled “Patient Information VESIcare (solifenacin succinate) ” before starting therapy with VESIcare (solifenacin succinate) .

Patients should be informed that solifenacin may produce angioedema, which could result in life-threatening airway obstruction. Patients should be advised to promptly discontinue solifenacin therapy and seek immediate attention if they experience edema of the tongue or laryngopharynx, or difficulty breathing.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No increase in tumors was found following the administration of solifenacin succinate to male and female mice for 104 weeks at doses up to 200 mg/kg/day (5 and 9 times, respectively, of the exposure at the maximum recommended human dose [MRHD] of 10 mg), and male and female rats for 104 weeks at doses up to 20 and 15 mg/kg/day, respectively ( < 1 times the exposure at the MRHD).

Solifenacin succinate was not mutagenic in the in vitro Salmonella typhimurium or Escherichia coli microbial mutagenicity test or chromosomal aberration test in human peripheral blood lymphocytes with or without metabolic activation, or in the in vivo micronucleus test in rats.

Solifenacin succinate had no effect on reproductive function, fertility or early embryonic development of the fetus in male and female mice treated with 250 mg/kg/day (13 times the exposure at the MRHD) of solifenacin succinate, and in male rats treated with 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.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women.

Reproduction studies have been performed in mice, rats and rabbits. After oral administration of ¹⁴C-solifenacin succinate to pregnant mice, drug-related material was shown to cross the placental barrier. No embryotoxicity or teratogenicity was observed in mice treated with 1.2 times (30 mg/kg/day) the expected exposure at the maximum recommended human dose [MRHD] of 10 mg. Administration of solifenacin succinate to pregnant mice at 3.6 times and greater (100 mg/kg/day and greater) the exposure at the MRHD, during the major period of organ development resulted in reduced fetal body weights. Administration of 7.9 times (250 mg/kg/day) the MRHD to pregnant mice resulted in an increased incidence of cleft palate. In utero and lactational exposures to maternal doses of solifenacin succinate of 3.6 times (100 mg/kg/day) the MRHD resulted in reduced peripartum and postnatal survival, reductions in body weight gain, and delayed physical development (eye opening and vaginal patency). An increase in the percentage of male offspring was also observed in litters from offspring exposed to maternal doses of 250 mg/kg/day. No embryotoxic effects were observed in rats at up to 50 mg/kg/day ( < 1 times the exposure at the MRHD) or in rabbits at up to 1.8 times (50 mg/kg/day) the exposure at the MRHD. Because animal reproduction studies are not always predictive of human response, VESIcare (solifenacin succinate) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

The effect of VESIcare (solifenacin succinate) on labor and delivery in humans has not been studied.

There were no effects on natural delivery in mice treated with 1.2 times (30 mg/kg/day) the expected exposure at the maximum recommended human dose [MRHD] of 10 mg. Administration of solifenacin succinate at 3.6 times (100 mg/kg/day) the exposure at the MRHD or greater increased peripartum pup mortality.

Nursing Mothers

After oral administration of 14C-solifenacin succinate to lactating mice, radioactivity was detected in maternal milk. There were no adverse observations in mice treated with 1.2 times (30 mg/kg/day) the expected exposure at the maximum recommended human dose [MRHD]. Pups of female mice treated with 3.6 times (100 mg/kg/day) the exposure at the MRHD or greater revealed reduced body weights, postpartum pup mortality or delays in the onset of reflex and physical development during the lactation period.

It is not known whether solifenacin is excreted in human milk. Because many drugs are excreted in human milk, VESIcare (solifenacin succinate) should not be administered during nursing. A decision should be made whether to discontinue nursing or to discontinue VESIcare (solifenacin succinate) in nursing mothers.

Pediatric Use

The safety and effectiveness of VESIcare (solifenacin succinate) in pediatric patients have not been established.

Geriatric Use

In placebo-controlled clinical studies, similar safety and effectiveness were observed between older (623 patients ≥ 65 years and 189 patients ≥ 75 years) and younger patients (1188 patients < 65 years) treated with VESIcare (solifenacin succinate) .

Multiple dose studies of VESIcare (solifenacin succinate) in elderly volunteers (65 to 80 years) showed that Cmax, AUC and t½ values were 20-25% higher as compared to the younger volunteers (18 to 55 years).

Renal Impairment

VESIcare (solifenacin succinate) should be used with caution in patients with renal impairment. There is a 2.1-fold increase in AUC and 1.6-fold increase in t½ of solifenacin in patients with severe renal impairment. Doses of VESIcare (solifenacin succinate) greater than 5 mg are not recommended in patients with severe renal impairment (CLcr < 30 mL/min) [see WARNINGS AND PRECAUTIONS; DOSAGE AND ADMINISTRATION].

Hepatic Impairment

VESIcare (solifenacin succinate) should be used with caution in patients with reduced hepatic function. There is a 2-fold increase in the t½ and 35% increase in AUC of solifenacin in patients with moderate hepatic impairment. Doses of VESIcare (solifenacin succinate) greater than 5 mg are not recommended in patients with moderate hepatic impairment (Child-Pugh B). VESIcare (solifenacin succinate) is not recommended for patients with severe hepatic impairment (Child-Pugh C) [see WARNINGS AND PRECAUTIONS; DOSAGE AND ADMINISTRATION].

Gender

The pharmacokinetics of solifenacin is not significantly influenced by gender.

Last reviewed on RxList: 5/18/2011
This monograph has been modified to include the generic and brand name in many instances.