Drug Interactions between Beqvez 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: Coadministration with other hepatotoxic agents such as alcohol may increase the risk of liver injury and decrease the therapeutic efficacy of liver-directed adeno-associated virus (AAV) vector fidanacogene elaparvovec, designed to help replace missing and coagulation factor IX. Increased transaminase levels from AAV therapy have been attributed to immune-mediated injury of transduced hepatocytes, which may decrease their therapeutic efficacy. In addition, alcohol may impact liver enzyme elevation as well as reduce the activity of coagulation factor IX. In a prospective, open-label, single-arm, multinational clinical study of adult male patients with moderately severe to severe hemophilia B (n=45) receiving a single dose of fidanacogene elaparvovec (5 x 10[11] vector genomes [vg]/kg), increased transaminase levels greater than or equal to 1.5 times baseline were reported in 29 patients. Of these patients, 28 received treatment with corticosteroids due to increased transaminases and/or a decline in factor IX activity, with a mean initiation time to corticosteroid therapy reported at 45 days.

MANAGEMENT: According to the manufacturer, for the first year after administration of fidanacogene elaparvovec, alcohol consumption should be limited.