Solifenacin: uses, appearance and warnings

Solifenacin succinate is indicated for the treatment of adults with overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Solifenacin succinate is a muscarinic antagonist indicated for the treatment of adults with overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. ( 1 )

The 5 mg tablets are white or almost white round film-coated tablets, debossed with “C2” on one side and blank on the other side. The 10 mg tablets are white or almost white round film-coated tablets, debossed with “C77” on one side and blank on the other side. Tablets: 5 mg and 10 mg. ( 3 )

Solifenacin succinate tablets are supplied as round, film-coated tablets, available in bottles as follows: Each 5 mg tablet is white or almost white and debossed with “C2” on one side and blank on the other side, and is available as follows: Bottle of 30 NDC 72303-0831-1 Bottle of 90 NDC 72303-0831-2 Each 10 mg tablet is white or almost white and debossed with “C77” on one side and blank on the other side, and is available as follows: Bottle of 30 NDC 72303-0832-1 Bottle of 90 NDC 72303-0832-2 Store at 20ºC to 25ºC (68ºF-77ºF) with excursions permitted from 15ºC to 30ºC (59°F-86ºF) [see USP Controlled Room Temperature].

Solifenacin succinate is contraindicated in patients: With urinary retention [see Warnings and Precautions ( 5.2 )] , With gastric retention [see Warnings and Precautions ( 5.3 )] , With uncontrolled narrow-angle glaucoma [see Warnings and Precautions ( 5.5 )] , and Who have demonstrated hypersensitivity to solifenacin succinate or the inactive ingredients in Solifenacin succinate tablets. Reported adverse reactions have included anaphylaxis and angioedema [see Adverse Reactions ( 6.2 )] . Urinary retention. ( 4 , 5.2 ) Gastric retention. ( 4 , 5.3 ) Uncontrolled narrow-angle glaucoma. ( 4 , 5.5 ) Hypersensitivity to this product or any of its components. ( 4 , 5.1 , 6.2 )

Angioedema and Anaphylactic Reactions : Promptly discontinue Solifenacin succinate tablets and provide appropriate therapy. ( 5.1 ) Urinary Retention : Solifenacin succinate tablets are not recommended for use in patients with clinically significant bladder outlet obstruction. ( 5.2 ) Gastrointestinal Disorders : Solifenacin succinate tablets are not recommended for use in patients with decreased gastrointestinal motility. ( 5.3 ) Central Nervous System Effects : Somnolence has been reported with solifenacin succinate. Advise patients not to drive or operate heavy machinery until they know how solifenacin succinate affects them. ( 5.4 ) Controlled Narrow-Angle Glaucoma : Use Solifenacin succinate tablets with caution in patients being treated for narrow-angle glaucoma. ( 5.5 ) QT Prolongation in Patients at High Risk of QT Prolongation : Solifenacin succinate tablets are not recommended for use in patients at high risk of QT prolongation, including patients with a known history of QT prolongation and patients taking medications known to prolong the QT interval. ( 5.6 ) 5.1 Angioedema and Anaphylactic Reactions Angioedema of the face, lips, tongue, and/or larynx have been reported with solifenacin succinate. In some cases, angioedema occurred after the first dose, however, cases have been reported to occur hours after the first dose or after multiple doses. Anaphylactic reactions have also been reported in patients treated with solifenacin succinate. Angioedema associated with upper airway swelling and anaphylactic reactions may be life-threatening. Solifenacin succinate tablets are contraindicated in patients with a known or suspected hypersensitivity to solifenacin succinate [see Contraindications ( 4 )] . If involvement of the tongue, hypopharynx, or larynx occurs, promptly discontinue Solifenacin succinate tablets and provide appropriate therapy and/or measures necessary to ensure a patent airway. 5.2 Urinary Retention The use of Solifenacin succinate tablets, like other antimuscarinic drugs, in patients with clinically significant bladder outlet obstruction including patients with urinary retention, may result in further urinary retention and kidney injury. The use of Solifenacin succinate tablets is not recommended in patients with clinically significant bladder outlet obstruction and is contraindicated in patients with urinary retention [see Contraindications ( 4 )] . 5.3 Gastrointestinal Disorders The use of Solifenacin succinate tablets, like other antimuscarinic drugs, in patients with conditions associated with decreased gastrointestinal motility may result in further decreased gastrointestinal motility. Solifenacin succinate tablets are contraindicated in patients with gastric retention [see Contraindications ( 4 )] . The use of Solifenacin succinate tablets is not recommended in patients with conditions associated with decreased gastrointestinal motility. 5.4 Central Nervous System Effects Solifenacin succinate is associated with antimuscarinic central nervous system (CNS) adverse reactions [see Adverse Reactions ( 6.2 )] . A variety of CNS antimuscarinic adverse reactions have been reported, including headache, confusion, hallucinations, and somnolence. Monitor patients for signs of antimuscarinic CNS adverse reactions, particularly after beginning treatment or increasing the dose. Advise patients not to drive or operate heavy machinery until they know how solifenacin succinate affects them. If a patient experiences antimuscarinic CNS adverse reactions, consider dose reduction or drug discontinuation. 5.5 Controlled Narrow-Angle Glaucoma Solifenacin succinate should be used with caution in patients being treated for narrow-angle glaucoma [see Contraindications ( 4 )] . 5.6 QT Prolongation in Patients at High Risk of QT Prolongation In a study of the effect of solifenacin succinate on the QT interval conducted in 76 healthy women [see Clinical Pharmacology ( 12.2 )] , solifenacin succinate 30 mg (three times the largest maximum recommended dose in adult patients) was associated with a mean increase in the Fridericia-corrected QT interval of 8 msec (90% CI, 4, 13). The QT prolonging effect appeared less with solifenacin succinate 10 mg than with solifenacin succinate 30 mg, and the effect of solifenacin succinate 30 mg did not appear as large as that of the positive control moxifloxacin at its therapeutic dose. The use of Solifenacin succinate tablets is not recommended in patients at high risk of QT prolongation, including patients with a known history of QT prolongation and patients who are taking medications known to prolong the QT interval.

The most common adverse reactions (> 4% in Solifenacin succinate tablets-treated patients and > placebo-treated patients) were dry mouth and constipation at both 5 mg and 10 mg doses; and urinary tract infection and blurred vision at the 10 mg dose. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact HEC Pharm USA Inc. at 1-800-610-5709 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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. Solifenacin succinate has been evaluated for safety in 1811 adult patients in four randomized, placebo-controlled trials (Studies 1-4) [see Clinical Studies ( 14 )] . …

CYP3A4 Inhibitors : Do not exceed the 5 mg dose of Solifenacin succinate tablets with concomitant use of strong CYP3A4 inhibitors. ( 7.1 ) 7.1 Strong CYP3A4 Inhibitors Solifenacin is a substrate of CYP3A4. Concomitant use of ketoconazole, a strong CYP3A4 inhibitor, significantly increased the exposure of solifenacin [see Clinical Pharmacology ( 12.3 )] . The dosage of Solifenacin succinate tablets greater than 5 mg once daily is not recommended when concomitantly used with strong CYP3A4 inhibitors [see Dosage and Administration ( 2.4 )] .