Which drugs or supplements interact with valproic acid?

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Valproic acid has numerous suspected or proven drug interactions. Valproic acid can reduce the number of platelets or inhibit the ability of platelets to stick together and form a blood clot. Therefore, it may exaggerate the effects of other medications which inhibit the stickiness of platelets or inhibit other steps in the clotting of blood. This can lead to abnormal bleeding due to the inability of blood to clot. Such medications include warfarin (Coumadin), heparin or low-molecular weight heparin (Lovenox), clopidogrel (Plavix), ticlopidine (Ticlid), and nonsteroidal antiinflammatory drugs (NSAIDs) such as ibuprofen (Motrin, Advil), naproxen (Naprosyn, Aleve), indomethacin (Indocin), nabumetone (Relafen), diclofenac (Voltaren, Cataflam, Arthrotec), ketorolac (Toradol) and aspirin.

Aspirin and felbamate (Felbatol) can reduce the elimination of valproic acid and result in elevated blood concentrations of valproic acid and toxicity due to the valproic acid.

Rifampin (Rifadin, Rimactane), carbamazepine (Tegretol), phenytoin (Dilantin) can increase the elimination of valproic acid, thereby reducing blood concentrations. Since this can result in loss of seizure control and seizures, adjustments in the dose of valproic acid may be necessary if these medications are begun.

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Cholestyramine (Questran) can reduce the absorption of valproic acid from the intestine and reduce its effectiveness. Therefore, valproic acid should be taken at least 2 hours before or 6 hours after doses of cholestyramine.

Valproic acid can significantly decrease the elimination of lamotrigine (Lamictal), ethosuximide (Zarontin), diazepam (Valium), zidovudine (AZT) and phenobarbital, thereby increasing their concentrations in blood and leading to toxicity. Valproic acid also increases the blood levels of warfarin and phenytoin by displacing them from blood proteins that they bind to. Since increased blood concentrations of these drugs may lead to an increase in side effects, the dose of warfarin and phenytoin may need to be altered when they are taken with valproic acid.