VESICARE- solifenacin succinate tablet, film coated
Astellas Pharma Technologies, Inc.
1 INDICATIONS AND USAGE
VESIcare� is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.
2 DOSAGE AND ADMINISTRATION
2.1 Dosing Information
The recommended dose of VESIcare is 5 mg once daily. If the 5 mg dose is well tolerated, the dose may be increased to 10 mg once daily.
VESIcare should be taken with water and swallowed whole. VESIcare can be administered with or without food.
2.2 Dose Adjustment in Patients with Renal Impairment
For patients with severe renal impairment (CLcr < 30 mL/min), a daily dose of VESIcare greater than 5 mg is not recommended [see Warnings and Precautions (5.7); Use in Specific Populations (8.6)].
2.3 Dose Adjustment in Patients with Hepatic Impairment
For patients with moderate hepatic impairment (Child-Pugh B), a daily dose of VESIcare greater than 5 mg is not recommended. Use of VESIcare in patients with severe hepatic impairment (Child-Pugh C) is not recommended [see Warnings and Precautions (5.6); Use in Specific Populations (8.7)].
2.4 Dose Adjustment in Patients Taking CYP3A4 Inhibitors
When administered with potent CYP3A4 inhibitors such as ketoconazole, a daily dose of VESIcare greater than 5 mg is not recommended [see Drug Interactions (7.1)].
3 DOSAGE FORMS AND STRENGTHS
The 5 mg tablets are round, light yellow, debossed with 150.
The 10 mg tablets are round, light pink, debossed with 151.
4 CONTRAINDICATIONS
VESIcare is contraindicated in patients with:
urinary retention [see Warnings and Precautions (5.2)],
gastric retention [see Warnings and Precautions (5.3)],
uncontrolled narrow-angle glaucoma [see Warnings and Precautions (5.5)], and
in patients who have demonstrated hypersensitivity to the drug
OVERDOSAGE
Overdosage with VESIcare can potentially result in severe anticholinergic effects and should be treated accordingly. The highest dose ingested in an accidental overdose of solifenacin succinate was 280 mg in a 5-hour period. This case was associated with mental status changes. Some cases reported a decrease in the level of consciousness.
Intolerable anticholinergic side effects (fixed and dilated pupils, blurred vision, failure of heel-to-toe exam, tremors and dry skin) occurred on day 3 in normal volunteers taking 50 mg daily (5 times the maximum recommended therapeutic dose) and resolved within 7 days following discontinuation of drug.
In the event of overdose with VESIcare, treat with gastric lavage and appropriate supportive measures. ECG monitoring is also recommended.
11 DESCRIPTION
VESIcare (solifenacin succinate) is a muscarinic receptor antagonist. Chemically, solifenacin succinate is butanedioic acid, compounded with (1S)-(3R)-1-azabicyclo[2.2.2]oct-3-yl 3,4-dihydro-1-phenyl-2(1H)-iso-quinolinecarboxylate (1:1) having an empirical formula of C23 H26 N2 O2 �C4 H6 O4 , and a molecular weight of 480.55.
Solifenacin succinate is a white to pale-yellowish-white crystal or crystalline powder. It is freely soluble at room temperature in water, glacial acetic acid, dimethyl sulfoxide, and methanol. Each VESIcare tablet contains 5 or 10 mg of solifenacin succinate and is formulated for oral administration. In addition to the active ingredient solifenacin succinate, each VESIcare tablet also contains the following inert ingredients: lactose monohydrate, corn starch, hypromellose 2910, magnesium stearate, talc, polyethylene glycol 8000 and titanium dioxide with yellow ferric oxide (5 mg VESIcare tablet) or red ferric oxide (10 mg VESIcare tablet).
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Solifenacin is a competitive muscarinic receptor antagonist. Muscarinic receptors play an important role in several major cholinergically mediated functions, including contractions of urinary bladder smooth muscle and stimulation of salivary secretion.
