Valproic Acid (Depakote, Depakene, Depacon, Abbott)
Valproic Acid is particularly useful for the primary generalized epilepsies, including true grand mal, absence not responsive to ethosuximide, and atonic seizures. It also has some action in partial and secondarily generalized seizures. This makes it a "broad spectrum" antiepileptic medication.
Advantages of valproic acid are efficacy for generalized seizures and the broad spectrum, which sometimes covers more than one seizure type with one medication.
Disadvantages include significant GI upset in many patients, the need to ease people into the drug slowly to avoid side effects, and a relatively high incidence of liver problems, which requires monitoring of liver tests in the blood. Liver problems are particularly a danger in children under five years of age on multiple medications.
Typical doses for adults are in the range of 250 - 1000 mg three times a day (750 - 3000 mg per day). Depakote-ER can be used for a twice-daily extended release pill, and Depacon for intravenous use in emergencies.
Summary Data for Valproic Acid
Pill sizes:
Depakene 250 mg (orange capsule)
Depakote 125 mg (blue-white sprinkle capsule)
Depakote 125 mg (dark orange tab, not scored)
Depakote 250 mg (peach tab, not scored)
Depakote 500 mg (pink tab, not scored)
Depakote-ER 250 mg (extended-release tab)
Depakote-ER 500 mg (extended-release tab)
Liquid for oral: 250 mg/5ml syrup.
Injectable: Depacon 100 mg/ml.
Typical adult starting dose: 125 mg three time a day. Increase every 3 - 7 days by 125 mg daily.
Load in emergency: Depacon 10 - 15 mg/kg or a dose equivalent to the oral dose. Load over 1 hour.
Typical adult dose: 750 - 4000 mg/d
Typical pediatric dose: 15 - 60 mg/kg/d divided in 2 - 4 doses.
Metabolism: Liver metabolism by the glucuronidation system.
Half-life: 8-15 hours.
Therapeutic plasma concentrations: 50 - 125 mcg/ml.
Pregnancy: Category D -- known to cause birth defects in humans.
Drugs that raise VPA levels: aspirin (also can increase bleeding risk), cimetidine, erythromycins, felbamate, fluoxitene, isoniazid.
Drugs that lower VPA levels: carbamazepine, cholestyramine, lamotrigine, phenobarbital, phenytoin, rifampin, ritonavir.
VPA increases effects of: carbamazepine (increased epoxide), coumadin, ethosuximide, felbamate, lamotrigine, nonsteroidal anti-inflammatory drugs such as ibuprofen, naproxyn, etc. (increased bleeding risk), phenobarbital, phenytoin (increases free levels), primidone, zidovudine.
VPA decreases effects of other drugs: clozapine.
Dangerous Side Effects
liver toxicity, blood toxicity, pancreatitis, birth defects (especially open spine)
Common Side Effects
GI upset, tremor, significant weight gain, thinning or loss of hair.
Other Side Effects
Rash, weight loss, water retention and lowered sodium, increased bleeding/bruising, sensitivity to the sun, blurred vision, headaches, joint aches and pains, behavior and personality changes, menstrual irregularities, sexual dysfunction, elevation of blood ammonia levels.