Clinical 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.

VESIcare has been evaluated for safety in 1811 patients in randomized, placebo-controlled trials. Expected adverse reactions of antimuscarinic agents are dry mouth, constipation, blurred vision (accommodation abnormalities), urinary retention, and dry eyes. The incidence of dry mouth and constipation in patients treated with VESIcare was higher in the 10 mg 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 VESIcare 10 mg group. Angioneurotic edema has been reported in one patient taking VESIcare 5 mg. Compared to 12 weeks of treatment with VESIcare, the incidence and severity of adverse reactions were similar in patients who remained on drug for up to 12 months.

The most frequent adverse reaction leading to study discontinuation was dry mouth (1.5%). Table 1 lists the rates of identified adverse reactions, derived from all reported adverse events, in randomized, placebocontrolled trials at an incidence greater than placebo and in 1% or more of patients treated with VESIcare 5 or 10 mg once daily for up to 12 weeks.

Table 1: Percentages of Patients with Identified Adverse Reactions, Derived from All Adverse Events Exceeding Placebo Rate and Reported by 1% or More Patients for Combined Pivotal Studies

Post-Marketing Experience

Because these spontaneously reported events are from the worldwide postmarketing experience, the frequency of events and the role of solifenacin in their causation cannot be reliably determined.

The following events have been reported in association with solifenacin use in worldwide postmarketing experience:

General: peripheral edema, hypersensitivity reactions, including angioedema with airway obstruction, rash, pruritus, urticaria, and anaphylactic reaction;

Central Nervous: headache, confusion, hallucinations,delirium and somnolence;

Cardiovascular: QT prolongation; Torsade de Pointes;

Hepatic: liver disorders mostly characterized by abnormal liver function tests, AST (aspartate aminotransferase) , ALT (alanine aminotransferase), GGT (gamma-glutamyl transferase);

Renal: renal impairment;

Metabolism and nutrition disorders: decreased appetite, hyperkalemia;

Dermatologic: exfoliative dermatitis and erythema multiforme;

Eye disorders: glaucoma;

Gastrointestinal disorders: gastroesophageal reflux disease and ileus;

Respiratory, thoracic and mediastinal disorders: dysphonia;

Musculoskeletal and connective tissue disorders: muscular weakness;

Read the VESIcare (solifenacin succinate) Side Effects Center for a complete guide to possible side effects »

Potent CYP3A4 Inhibitors

Following the administration of 10 mg of VESIcare in the presence of 400 mg of ketoconazole, a potent inhibitor of CYP3A4, the mean Cmax and AUC of solifenacin increased by 1.5 and 2.7-fold, respectively. Therefore, it is recommended not to exceed a 5 mg daily dose of VESIcare when administered with therapeutic doses of ketoconazole or other potent CYP3A4 inhibitors [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY]. The effects of weak or moderate CYP3A4 inhibitors were not examined.

CYP3A4 Inducers

There were no in vivo studies conducted to evaluate the effect of CYP3A4 inducers on VESIcare. In vitro drug metabolism studies have shown that solifenacin is a substrate of CYP3A4. Therefore, inducers of CYP3A4 may decrease the concentration of solifenacin.

Drugs Metabolized by Cytochrome P450

At therapeutic concentrations, solifenacin does not inhibit CYP1A1/2, 2C9, 2C19, 2D6, or 3A4 derived from human liver microsomes.

Warfarin

Solifenacin has no significant effect on the pharmacokinetics of R-warfarin or S-warfarin [see CLINICAL PHARMACOLOGY].

Oral Contraceptives

In the presence of solifenacin there are no significant changes in the plasma concentrations of combined oral contraceptives (ethinyl estradiol/levonorgestrel) [see CLINICAL PHARMACOLOGY].

Digoxin

Solifenacin had no significant effect on the pharmacokinetics of digoxin (0.125 mg/day) in healthy subjects [see CLINICAL PHARMACOLOGY].

Last reviewed on RxList: 4/15/2013
This monograph has been modified to include the generic and brand name in many instances.