Interaction between Phenytoin and Tolvaptan
Major Metabolism

ID DDInter1460 and DDInter1833
Interaction Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of tolvaptan, which is primarily metabolized by the isoenzyme. When tolvaptan was administered with the potent CYP450 3A4 inducer rifampin, tolvaptan peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 85%.
Management Concomitant use of tolvaptan with potent CYP450 3A4 inducers should generally be avoided. If coadministration is necessary, a dosage increase of tolvaptan may be required. Patient response should be closely monitored and the dosage adjusted accordingly.
References
Alternative for Phenytoin N03A
Trimethadione
Mephenytoin
Clonazepam
Paramethadione
Methsuximide
Topiramate
Vigabatrin
Ezogabine
Gabapentin
Pregabalin
Lamotrigine
More
Alternative for Tolvaptan C03X
Conivaptan

Potential Metabolism Interactions

Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.