Valproic Acid

Epoxide hydrolase inhibitor; increases carbamazepine-10,11-epoxide plasma concentrations. Dosage adjustment and plasma level monitoring required.

Carbapenem antibiotic causing clinically significant reduction in serum valproic acid concentration, potentially resulting in loss of seizure control.

Concomitant use results in reduction of valproic acid concentrations below therapeutic range, increasing risk of breakthrough seizures. Generally not recommended.

Carbapenem antibiotic causing clinically significant reduction in serum valproic acid concentration, potentially resulting in loss of seizure control.

Co-administration reduces valproic acid concentrations below therapeutic range, increasing risk of breakthrough seizures. Generally not recommended.

May decrease valproic acid concentrations, increasing risk of breakthrough seizures. Concomitant use should be avoided.

Co-administration reduces valproic acid concentrations below therapeutic range, increasing risk of breakthrough seizures. Use is generally not recommended.

Co-administration may reduce valproic acid concentrations below therapeutic range, increasing risk of breakthrough seizures. Mechanism may involve carbapenem inhibition of valproic acid glucuronide metabolite hydrolysis.

Valproic acid increases phenobarbital serum levels. Phenobarbital blood levels should be closely monitored and dosage adjustments made as clinically indicated.

Concomitant administration with topiramate has been associated with hyperammonemia, a potentially serious condition.

Concurrent use may decrease carnitine concentrations and increase risk of carnitine depletion-associated adverse reactions including hypoglycemia, muscle aches, fatigue, and confusion.

May exacerbate urea cycle disorder and antagonize efficacy by inhibiting N-acetylglutamate synthesis, a cofactor for carbamyl phosphate synthetase.

Associated with hypothermia and hyperammonemia with and without encephalopathy; monitor blood ammonia levels.

Severe thrombocytopenia and gastrointestinal bleeding reported with concomitant use of VORINOSTAT and other HDAC inhibitors. Monitor platelet count every 2 weeks for first 2 months.

Decreases protein binding and inhibits metabolism of valproate, increasing valproate free fraction 4-fold. Monitoring of valproate concentrations recommended.

Dosage adjustment may be necessary if used concomitantly with valproic acid.

Salicylic acid can increase serum valproic acid levels through displacement from protein binding.

Salicylic acid can displace protein-bound valproic acid, leading to increased serum levels.

Salicylic acid can displace protein-bound valproic acid, leading to increased serum valproic acid levels.

Decreases plasma levels of valproic acid by approximately 14%. Delaying cholestyramine administration by 3 hours may lessen the interaction.

Valproate can affect pharmacokinetics by inhibiting metabolism or protein binding displacement. Dosage adjustment may be necessary.

High doses of folic acid may decrease serum levels of this anticonvulsant drug.

May affect valproate clearance. Monitoring of valproate concentrations recommended.

Valproate can affect pharmacokinetics by inhibiting metabolism or protein binding displacement. Dosage adjustment may be necessary.

Enzyme inhibitor that can decrease valproate clearance. Increased monitoring of valproate and concomitant drug concentrations and dosage adjustment indicated.

May increase or decrease plasma phenytoin concentrations; effects are unpredictable.

UGT inhibitor that may increase ganaxolone exposure and risk of adverse reactions; consider reduction of ZTALMY dosage when initiating valproic acid.

May induce hyperammonemia. Monitor ammonia levels closely when used concomitantly in patients with UCDs.

Valproate can affect pharmacokinetics by inhibiting metabolism or protein binding displacement. Dosage adjustment may be necessary.

May affect valproate clearance. Monitoring of valproate concentrations recommended.

Mefloquine may reduce seizure control by lowering plasma levels of anticonvulsant. Monitor blood levels and adjust dosage appropriately.

Moderate CYP3A4 inhibitor that may increase nimodipine plasma concentration and blood pressure lowering effect. Blood pressure monitoring and dose reduction of nimodipine may be necessary.

Dosage adjustment may be necessary if used concomitantly with valproic acid.

Salicylate can displace protein-bound valproic acid, increasing serum valproic acid levels.

Valproic acid decreases barbiturate metabolism. Barbiturate blood levels should be monitored and dosage adjustments made as needed.

Valproic acid appears to decrease barbiturate metabolism. Barbiturate blood levels should be monitored and dosage adjustments made as indicated.

Enzyme-inducing drug that can increase valproate clearance and double clearance rate. Increased monitoring of valproate and concomitant drug concentrations and dosage adjustment indicated.

May increase or decrease phenytoin serum levels; monitoring of phenytoin levels recommended.

Impairs folate absorption and increases metabolism of circulating folate.

High doses of folic acid may result in decreased serum levels of valproic acid.

Enzyme-inducing drug that can increase valproate clearance and double clearance rate. Increased monitoring of valproate and concomitant drug concentrations and dosage adjustment indicated.

Dosage adjustment may be necessary if used concomitantly with valproic acid.

Enzyme-inducing drug that can increase valproate clearance. Increased monitoring of valproate and concomitant drug concentrations and dosage adjustment indicated.

May increase valproate clearance by elevating hepatic glucuronosyltransferase levels. Increased monitoring of valproate concentrations indicated.

Patients stabilized on rufinamide should begin valproate therapy at a low dose and titrate to clinically effective dose.

May decrease endogenous BH4 levels by inhibiting dihydrofolate reductase, potentially increasing phenylalanine levels.

May increase plasma ammonia level; monitor ammonia levels closely.

Dosage adjustment may be necessary if used concomitantly with valproic acid.

Dosage adjustment may be necessary if used concomitantly with valproic acid.

Mean steady-state valproic acid concentrations were not different with concomitant gabapentin, and gabapentin pharmacokinetics were not affected.

Valproic acid 600 mg/day had no influence on lacosamide 400 mg/day pharmacokinetics, and lacosamide had no influence on valproic acid pharmacokinetics.

No clinically significant reduction in valproic acid plasma concentrations observed with concomitant use. No dosage adjustment recommended.

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

Lorazepam Concomitant administration of valproate (500 mg BID) and lorazepam (1 mg BID) in normal male volunteers (n = 9) was accompanied by a 17% decrease in the plasma clearance of lorazepam.

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.