Drug Interactions between esketamine and mephenytoin

ADJUST DOSING INTERVAL: Phenytoin bioavailability may decrease to subtherapeutic levels when the suspension is given concomitantly with enteral feedings. The mechanism may be related to phenytoin binding to substances in the enteral formula (e.g., calcium, protein) and/or binding to the tube lumen. Data have been conflicting and some studies have reported no changes in phenytoin levels, while others have reported significant reductions.

MONITOR: Acute consumption of alcohol may increase plasma phenytoin levels. Chronic consumption of alcohol may decrease plasma phenytoin levels. The mechanism of this interaction is related to induction of phenytoin metabolism by ethanol during chronic administration. Other hydantoin derivatives may be similarly affected by ethanol.

MANAGEMENT: Some experts have recommended interrupting the feeding for 2 hours before and after the phenytoin dose, giving the phenytoin suspension diluted in water, and flushing the tube with water after administration; however, this method may not entirely avoid the interaction and is not always clinically feasible. Patients should be closely monitored for clinical and laboratory evidence of altered phenytoin efficacy and levels upon initiation and discontinuation of enteral feedings. Dosage adjustments or intravenous administration may be required until therapeutic serum levels are obtained. In addition, patients receiving phenytoin therapy should be warned about the interaction between phenytoin and ethanol and they should be advised to notify their physician if they experience worsening of seizure control or symptoms of toxicity, including drowsiness, visual disturbances, change in mental status, nausea, or ataxia.

GENERALLY AVOID: Concomitant use of esketamine with central nervous system (CNS) depressants such as alcohol may increase sedation and impairment of attention, judgment, thinking, reaction speed, and psychomotor skills.

ADJUST DOSING INTERVAL: Nausea and vomiting may occur following intranasal administration of esketamine. In clinical studies, nausea and vomiting were reported in approximately 25% and 10% of esketamine-treated patients, respectively.

MANAGEMENT: Patients receiving esketamine should be advised to avoid or limit the consumption of alcohol. In addition, to help prevent nausea and vomiting, patients should be advised not to eat for at least 2 hours before intranasal administration of esketamine and not to drink liquids for at least 30 minutes prior to administration.