Due to the combined use with other anticholinergic drugs, it is possible to develop pronounced drug reactions, as well as side effects. After discontinuation of Vesicare use, it is required to maintain an interval (about 1 week) before using the following drugs for cholinolytic treatment.
The therapeutic effect of solifenacin can be weakened in the case of combination with agonists of acetylcholine terminals. The substance may impair the properties of drugs that stimulate the peristalsis of the gastrointestinal tract (eg, cisapride or metoclopramide).
Metabolism solifenacin is carried out with the help of the enzyme CYP3A4. When combined with ketoconazole (intake of 200 mg per day), which is a potent inhibitor of the element CYP3A4, an increase in the AUC level of the substance is doubled. When combined with ketoconazole in a daily dose of 400 mg, this figure is tripled. Consequently, the size of the maximum dosage of drugs in the case of a combination with ketoconazole and drug doses of other strong inhibitors of the CYP3A4 enzyme is limited to 5 mg.
The combination of Vesicare with powerful inhibitors of the enzyme CYP3A4 is prohibited for persons with liver failure (moderate degree) or kidney (severe).
There is no information on studies of the effect of induction enzymes on the pharmacokinetics of solifenacin with its degradation products, and in addition on the activity of substrates having the enhanced affinity of the element CYP3A4 and its decay products with the exposure index of the solifenacin component.
Because the metabolism of solifenacin is carried out with the help of the enzyme CYP3A4, drug interactions with other substrates of this enzyme with increased affinity (among them diltiazem with verapamil), and in addition with inducers of the enzyme CYP3A4 (among them phenytoin with rifampicin and carbamazepine) can be observed.