What is valproic acid, and how does it work (mechanism of action)?
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.
What brand names are available for valproic acid?
Depakote, Depakote ER, Depakote Sprinkle, Depakene, Depacon, Stavzor
Is valproic acid available as a generic drug?
GENERIC AVAILABLE: Yes
Do I need a prescription for valproic acid?
What are the side effects of valproic acid?
The most common side effects with valproic acid therapy are:
Divalproex may have a lower incidence of stomach upset, and taking
valproic acid or divalproex with food can reduce the stomach upset. Valproic
acid also causes skin reactions such as
alopecia (loss of hair), rash, itching
and sensitivity to sunlight.
The most serious side effects due to valproic acid are liver injury,
pancreatitis and abnormal bleeding. Liver injury is most common in the first 6
months of treatment. It also is more common in children, especially children
less than two years old. Persons taking more than one type of anticonvulsant
seem to be at higher risk. Symptoms of liver damage include jaundice, malaise,
weakness, swelling in the face, loss of appetite and vomiting. Pancreatitis due
to valproic acid can occur early in treatment or after several years of use.
Symptoms of pancreatitis are unexplained weight loss, nausea, vomiting and
severe abdominal pain. Valproic acid inhibits the formation of blood clots by
interfering with the clot-promoting effects of platelets. This can cause
Antiepileptic medications have been associated with an increased risk of
suicidal thinking and behavior. Anyone considering the use of antiepileptic
drugs must balance this risk of suicide with the clinical need for the
antiepileptic drug. Patients who begin antiepileptic therapy should be closely
observed for clinical worsening, suicidal thoughts or unusual changes in
Vascular (Multi-Infarct) Dementia
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What is the dosage for valproic acid?
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.
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Which drugs or supplements interact with valproic acid?
Valproic acid has numerous suspected or proven
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
drugs (NSAIDs) such as ibuprofen (Motrin, Advil), naproxen (Naprosyn, Aleve),
indomethacin (Indocin), nabumetone (Relafen), diclofenac (Voltaren, Cataflam,
Arthrotec), ketorolac (Toradol) and
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
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.
Is valproic acid safe to take if I’m pregnant or breastfeeding?
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 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
What else should I know about valproic acid?
What preparations of valproic acid are available?
- Delayed release tablets: 125, 250 and 500 mg.
- Extended release
tablets: 250 and 500 mg.
- Sprinkle capsules: 125 mg.
- Capsules: 250 mg.
- Syrup: 250
- Injection: 100 mg/5 ml.
How should I keep valproic acid stored?
Valproic acid should be stored at room temperature, 15 C – 30 C (59 F – 86 F).