Rufinamide + Divalproex Sodium Interaction

Description

Therefore, increased monitoring of valproate and concomitant drug concentrations and dosage adjustment are indicated whenever enzyme-inducing or inhibiting drugs are introduced or withdrawn ( 7.1 ) • Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives, methotrexate: Monitoring of valproate concentrations is recommended ( 7.1 ) • Co-administration of valproate can affect the pharmacokinetics of other drugs (e.g., diazepam, ethosuximide, lamotrigine, phenytoin) by inhibiting their metabolism or protein binding displacement ( 7.2 ) • Patients stabilized on rufinamide should begin valproate therapy at a low dose, and titrate to clinically effective dose ( 7.2 ) • Dosage adjustment of amitriptyline/nortriptyline, propofol, warfarin, and zidovudine may be necessary if used concomitantly with divalproex sodium extended-release tablets ( 7.2 ) • Topiramate: Hyperammonemia and encephalopathy ( 5.10 , 7.3 ) • Cannabidiol: ALT and/or AST elevation ( 7.4 ) 7.1 Effects of Co-Administered Drugs on Valproate Clearance Drugs that affect the level of expression of hepatic enzymes, particularly those that elevate levels of glucuronosyltransferases (such as ritonavir), may increase the clearance of valproate. Rufinamide Based on a population pharmacokinetic analysis, rufinamide clearance was decreased by valproate. Rufinamide concentrations were increased by < 16% to 70%, dependent on concentration of valproate (with the larger increases being seen in pediatric patients at high doses or concentrations of valproate).