Sometimes medications affect the way others are absorbed or excreted, or how effectively they work. The fact that valproic acid is often added to a regimen of other antiepileptic drugs makes the question of interactions especially important. When prescribing valproic acid, question patients or family members extensively about the use of prescription and OTC medications, herbal products, vitamins, alcohol, and other substances. Usually all necessary medications can be used, but the dosages may need to be adjusted to achieve therapeutic levels.

Effects of valproic acid on other drugs
Valproic acid inhibits certain liver enzymes and can cause the levels of Felbatol (felbamate), Lamictal (lamotrigine), Mysoline (primidone), and phenobarbital to increase markedly—in some cases, more than double. If a person taking phenobarbital is also given valproic acid, a rapid rise in phenobarbital levels can lead to extreme tiredness, slurred speech, and other signs of intoxication.

Valproic acid has more complex, variable, and less significant effects on Tegretol (carbamazepine), Zarontin (ethosuximide), Ativan (lorazepam), and Dilantin (phenytoin). Valproic acid inhibits epoxide hydrolase, thereby increasing levels of the epoxide metabolite of Tegretol. It can inhibit metabolism of Zarontin and Ativan, leading to higher levels of these medications. It also can displace Dilantin from protein binding sites and slightly increase the free Dilantin level. In each case, side effects may increase slightly.

Coagulation tests should be carefully checked if patients taking anticoagulants such as Coumadin (warfarin) begin taking valproic acid.

Effects of other drugs on valproic acid
Enzyme-inducing antiepileptic drugs, including carbamazepine, phenytoin, phenobarbital, and primidone, will markedly increase the metabolism (and thus the clearance) of Depakote.

Moderate or rapid introduction of Lamictal in a patient taking valproic acid, especially a child, can significantly increase the chances of a potentially life-threatening rash (Stevens-Johnson syndrome).

If valproic acid and Klonopin (clonazepam) are given together to a patient with a history of absence seizures, prolonged absence seizures (absence status) may occur.

Aspirin (acetylsalicylic acid, ASA) can increase some metabolites of valproic acid that may contribute to side effects.

Patients taking valproic acid along with testosterone-type androgens should be regularly checked for liver problems.

AED Interaction Sheets:
Seizure drugs are often affected by drug-drug interactions. Print these informative sheets for practical help.

• Interaction sheet for valproic acid (Depakene, Depakote and Depakote ER)