Bladder Outflow Obstruction
VESIcare, like other anticholinergic drugs, should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention.
Gastrointestinal Obstructive Disorders and Decreased GI Motility
VESIcare, like other anticholinergics, should be used with caution in patients with decreased gastrointestinal motility.
Controlled Narrow-Angle Glaucoma
VESIcare should be used with caution in patients being treated for narrow-angle glaucoma. (See CONTRAINDICATIONS)
Reduced Renal Function
VESIcare should be used with caution in patients with reduced renal function. Doses of VESIcare greater than 5 mg are not recommended in patients with severe renal impairment (CLcr <30 mL/min). (See CLINICAL PHARMACOLOGY, DOSAGE AND ADMINISTRATION)
Reduced Hepatic Function
VESIcare should be used with caution in patients with reduced hepatic function. Doses of VESIcare greater than 5 mg are not recommended in patients with moderate hepatic impairment (Child-Pugh B). VESIcare is not recommended for patients with severe hepatic impairment (Child-Pugh C). (See CLINICAL PHARMACOLOGY, DOSAGE AND ADMINISTRATION)
Do not exceed a 5 mg daily dose of VESIcare when administered with therapeutic doses of ketoconazole or other potent CYP3A4 inhibitors. (See CLINICAL PHARMACOLOGY, DOSAGE AND ADMINISTRATION)
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, Cardiac Electrophysiology), 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 for patients with a known history of QT prolongation or patients who are taking medications known to prolong the QT interval.
Information for Patients
Patients should be informed that antimuscarinic agents such as VESIcare 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 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, are used in a hot environment. Patients should read the patient leaflet entitled “Patient Information VESIcare” before starting therapy with VESIcare.
Carcinogenesis, Mutagenesis, Impairment of Fertility
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.
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 human exposure at the maximum recommended human dose [MRHD], respectively), and male and female rats for 104 weeks at doses up to 20 and 15 mg/kg/day, respectively (<1 times exposure at the MRHD).
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 exposure at the MRHD) of solifenacin succinate, and in male rats treated with 50 mg/kg/day (<1 times exposure at the MRHD) and female rats treated with 100 mg/kg/day (1.7 times exposure at the MRHD) of solifenacin succinate.
Teratogenic Effects, Pregnancy Category
Pregnancy Category C
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 30 mg/kg/day (1.2 times exposure at the maximum recommended human dose [MRHD]). Administration of solifenacin succinate to pregnant mice at doses of 100 mg/kg and greater (3.6 times exposure at the MRHD), during the major period of organ development resulted in reduced fetal body weights. Administration of 250 mg/kg (7.9 times exposure at 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 100 mg/kg/day and greater (3.6 times exposure at 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 exposure at the MRHD) or in rabbits at up to 50 mg/kg/day (1.8 times exposure at the MRHD). There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, VESIcare should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Labor and Delivery
The effect of VESIcare on labor and delivery in humans has not been studied.
There were no effects on natural delivery in mice treated with 30 mg/kg/day (1.2 times exposure at the maximum recommended human dose [MRHD]). Administration of solifenacin succinate at 100 mg/kg/day (3.6 times exposure at the MRHD) or greater increased peripartum pup mortality.
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 30 mg/kg/day (1.2 times exposure at the maximum recommended human dose [MRHD]). Pups of female mice treated with 100 mg/kg/day (3.6 times 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 should not be administered during nursing. A decision should be made whether to discontinue nursing or to discontinue VESIcare in nursing mothers.
The safety and effectiveness of VESIcare in pediatric patients have not been established.
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 (See CLINICAL PHARMACOLOGY, Pharmacokinetics in Special Populations).