DRUG INTERACTIONS: 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.
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.
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.
PREGNANCY: The use of valproic acid during pregnancy has been associated with fetal abnormalities such as spina bifida, cardiovascular abnormalities, and neural tube defects. The risk of spina bifida in the offspring of mothers taking valproic acid during pregnancy is 1%-2%. Valproic acid also may cause reduced clotting in the mother and baby. Because of the risk of harm to the newborn, valproic acid should only be used by pregnant women when its benefits outweigh the risks.
NURSING MOTHERS: The concentration of valproic acid in breast milk of women taking valproic acid is 1-10%. Although the effect on the nursing infant, is not certain, nursing mothers probably should not breastfeeding if they are taking valproic acid.
Medically reviewed by Eni Williams, PharmD
Reference: FDA Prescribing Information
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