valproic acid, divalproex, Depakote, Depakote ER, Depakene, Depacon, Stavzor
Omudhome Ogbru, PharmD
Omudhome Ogbru, PharmD
Dr. Ogbru received his Doctorate in Pharmacy from the University of the Pacific School of Pharmacy in 1995. He completed a Pharmacy Practice Residency at the University of Arizona/University Medical Center in 1996. He was a Professor of Pharmacy Practice and a Regional Clerkship Coordinator for the University of the Pacific School of Pharmacy from 1996-99.
Medical and Pharmacy Editor:
GENERIC NAME: valproic acid, divalproex
BRAND NAME: Depakote, Depakote ER, Depakene, Depacon, Stavzor
DRUG CLASS AND MECHANISM: Valproic acid and its derivative, divalproex, are oral drugs that are used for the treatment of convulsions, migraines and bipolar disorder. The active ingredient in both products is valproic acid. Divalproex is converted to valproic acid in the stomach. Scientists do not know the mechanism of action of valproic acid. The most popular theory is that valproic acid exerts its effects by increasing the concentration of gamma-aminobutyric acid (GABA) in the brain. GABA is a neurotransmitter, a chemical that nerves use to communicate with one another. The FDA approved valproic acid in February, 1978 and divalproex in March 1983.
GENERIC AVAILABLE: Yes
STORAGE: Valproic acid should be stored at room temperature, 15-30 C (59-86 F).
DOSING: For seizures, therapy is initiated at 10-15 mg/kg/day and increased by 5-10 mg/kg/day every week to achieve the desired response. Response usually is seen when the blood concentration of valproic acid is 50-100 mcg/mL.
For acute mania due to bipolar disorder, treatment is started at 750 mg per day of delayed-release tablets in divided doses. The dose should be increased rapidly to achieve the desired effect. The maximum dose is 60 mg/kg/day.
The recommended dose for prevention of migraines is 250 mg twice daily of delayed-release tablets. The maximum recommended dose is 1000 mg/day. When using extended release tablets, the recommended dose is 500-1000 mg given once daily.
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.
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.
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.
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