Divalproex Sodium Er Interactions

Clonazepam: The concomitant use of valproate and clonazepam may induce absence status in patients with a history of absence type seizures.

Source: FDA drug label - divalproex sodium er

Diazepam: Valproate displaces diazepam from its plasma albumin binding sites and inhibits its metabolism. Co-administration of valproate (1,500 mg daily) increased the free fraction of diazepam (10 mg) by 90% in healthy volunteers (n=6). Plasma clearance and volume of distribution for free diazepam were reduced by 25% and 20%, respectively, in the presence of valproate.

Source: FDA drug label - divalproex sodium er

Ethosuximide: Valproate inhibits the metabolism of ethosuximide. Administration of a single ethosuximide dose of 500 mg with valproate (800 to 1,600 mg/day) to healthy volunteers (n=6) was accompanied by a 25% increase in elimination half-life of ethosuximide and a 15% decrease in its total clearance as compared to ethosuximide alone. Patients receiving valproate and ethosuximide, especially along with other anticonvulsants, should be monitored for alterations in serum concentrations of both drugs.

Source: FDA drug label - divalproex sodium er

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.

Source: FDA drug label - divalproex sodium er

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). Patients stabilized on rufinamide before being prescribed valproate should begin valproate therapy at a low dose, and titrate to a clinically effective dose [see Dosage and Administration (2.6)].

Source: FDA drug label - divalproex sodium er

Tolbutamide: From in vitro experiments, the unbound fraction of tolbutamide was increased from 20% to 50% when added to plasma samples taken from patients treated with valproate.

Source: FDA drug label - divalproex sodium er