SOLIFENACIN Drug Interactions: What You Need to Know

INTERACTIONS Inhibitors of CYP3A4 may increase the concentration of solifenacin succinate tablets (7.1). Inducers of CYP3A4 may decrease the concentration of solifenacin succinate tablets (7.2).

7.1 Potent CYP3A4 Inhibitors Following the administration of 10 mg of solifenacin succinate tablets in the presence of 400 mg of ketoconazole, a potent inhibitor of CYP3A4, the mean C max 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 solifenacin succinate tablets when administered with therapeutic doses of ketoconazole or other potent CYP3A4 inhibitors <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)]</span>. The effects of weak or moderate CYP3A4 inhibitors were not examined.

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

7.3 Drugs Metabolized by Cytochrome P450 At therapeutic concentrations, solifenacin does not inhibit CYP1A1/2, 2C9, 2C19, 2D6, or 3A4 derived from human liver microsomes.

7.4 Warfarin Solifenacin has no significant effect on the pharmacokinetics of R -warfarin or S -warfarin <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3)]</span>.

7.5 Oral Contraceptives In the presence of solifenacin there are no significant changes in the plasma concentrations of combined oral contraceptives (ethinyl estradiol/levonorgestrel) <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3)]</span>.

7.6 Digoxin Solifenacin had no significant effect on the pharmacokinetics of digoxin (0.125 mg/day) in healthy subjects <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3)]</span>.

Solifenacin succinate tablets are 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 ).

AND PRECAUTIONS

• 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 Tablets. Advise patients not to drive or operate heavy machinery until they know how Solifenacin Succinate Tablets affect 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 <span class="opacity-50 text-xs">[see Contraindications ( 4 )]</span> .

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 Tablets are associated with antimuscarinic central nervous system (CNS) adverse reactions <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.2 )]</span> . 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 Tablets affect them. If a patient experiences antimuscarinic CNS adverse reactions, consider dose reduction or drug discontinuation.

5.5 Controlled Narrow-Angle Glaucoma Solifenacin Succinate Tablets should be used with caution in patients being treated for narrow-angle glaucoma <span class="opacity-50 text-xs">[see Contraindications ( 4 )]</span> .

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 <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.2 )]</span> , 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.