<p>Concomitant medication with other medicinal products with anticholinergic properties may result in more pronounced therapeutic effects and undesirable effects. An interval of approximately one week should be allowed after stopping treatment with Solifenacin Succinate before commencing other anticholinergic therapy. The therapeutic effect of Solifenacin may be reduced by concomitant administration of cholinergic receptor agonists. Solifenacin can reduce the effect of medicinal products that stimulate the motility of the gastrointestinal tract, such as Metoclopramide and Cisapride. In vitro studies have demonstrated that at therapeutic concentrations, Solifenacin does not inhibit CYP1A1/2, 2C9, 2C19, 2D6, or 3A4 derived from human liver microsomes. Therefore, Solifenacin is unlikely to alter the clearance of drugs metabolized by these CYP enzymes. Solifenacin is metabolized by CYP3A4. Simultaneous administration of Ketoconazole (200 mg/day), a potent CYP3A4 inhibitor, resulted in a two-fold increase of the AUC of Solifenacin, while Ketoconazole at a dose of 400 mg/day resulted in a three-fold increase of the AUC of Solifenacin. Therefore, the maximum dose of Solifenacin Succinate should be restricted to 5 mg when used simultaneously with Ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors (e.g. Ritonavir, Nelfinavir, Itraconazole).<br />
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Simultaneous treatment of Solifenacin and a potent CYP3A4 inhibitor is contra-indicated in patients with severe renal impairment or moderate hepatic impairment. The effects of enzyme induction on the pharmacokinetics of Solifenacin and its metabolites have not been studied as well as the effect of higher affinity CYP3A4 substrates on Solifenacin exposure. Since Solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates with higher affinity (e.g. Verapamil, Diltiazem) and CYP3A4 inducers (e.g. Rifampicin, Phenytoin, Carbamazepine).<br />
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Effect of Solifenacin on the pharmacokinetics of other medicinal products:</p>

<ul>
	<li><strong>Oral Contraceptives</strong>: Intake of Solifenacin showed no pharmacokinetic interaction on combined oral contraceptives (Ethinylestradiol/Levonorgestrel).</li>
	<li><strong>Warfarin</strong>: Intake of Solifenacin did not alter the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.</li>
	<li><strong>Digoxin</strong>: Intake of Solifenacin showed no effect on the pharmacokinetics of digoxin.</li>
	<li><strong>Effects on ability to drive and use machines</strong>: Since Solifenacin, like other anticholinergics may cause blurred vision and, uncommonly, somnolence and fatigue, the ability to drive and use machines may be negatively affected.</li>
</ul>