Divalproex sodium
Definition
Divalproex sodium is an anticonvulsant (antiseizure) drug. It is also used to treat mania and to help prevent migraine headaches. It is sold under multiple brand names in the United States, including Depacon, Depakene, Depakote, and Depakote sprinkle.
Purpose
Divalproex sodium is effective in the treatment of epilepsy, particularly for preventing simple, complex (petit mal), absence, mixed, and tonic-clonic (grand mal) seizures . Divalproex sodium is also used to treat the manic phase of bipolar disorder (also called manic-depressive disorder) in adults, and to prevent migraine headache in adults.
Description
Divalproex sodium is chemically compounded from sodium valproate and valproic acid in a 1:1 ratio.
Divalproex sodium is thought to work by increasing the levels of a brain neurotransmitter called gamma-aminobutyric acid (GABA). GABA is an inhibitory neurotransmitter, which means that its presence makes it harder for nerve cells (neurons) in the brain to become activated (fire). It is believed that increasing GABA's inhibitory action on brain neurons accounts for the ability of divalproex sodium to decrease seizures, curb manic behaviors, and decrease the frequency of migraine headaches.
Divalproex sodium was discovered to decrease the likelihood of seizure in 1963. In 1978, the United States Food and Drug Administration approved it for this use. Other uses for divalproex sodium were researched and approved subsequently, including use against mania (1995) and use to decrease migraine headache frequency. Divalproex sodium's 1995 approval as an anti-mania medication was considered an exciting advance, since it represented the first new drug introduced for this use in 25 years.
Recommended dosage
Divalproex sodium is available in tablets of 125 mg, 250 mg, and 500 mg. Divalproex sodium is also available in 125-mg capsules, and in a 500-mg extended release tablet. A syrup is also available, containing 250 mg active drug per 5 mL.
Divalproex sodium therapy is usually started at 10–15 mg per kg of body weight per day. Dosages are then increased until seizures seem to be well controlled. This is usually achieved at averages under 60 mg per kg per day.
To treat mania, divalproex sodium is usually started at a daily dose of about 750 mg.
For migraine prevention, divalproex sodium is started at 250 mg, twice per day. In some patients, this dose will have to be raised to a total of 1,000 mg per day.
Precautions
A greater risk of liver damage exists in patients with kidney disease, known liver disease, Addison's disease, blood diseases, children under the age of two, patients with organic brain diseases (such as Alzheimer's, Parkinson's, slow virus infections, Huntington's chorea, multiple sclerosis, etc.), patients with metabolic disorders present at birth, patients with severe seizure disorders and accompanying mental retardation , and patients who are taking several other anticonvulsant drugs.
Because divalproex sodium can affect a patient's blood by dropping the platelet (a type of blood cell that affects clotting) count and interfering with coagulation (clotting) capability, both platelet count and coagulation parameters should be verified before starting the medication and at intervals throughout its use.
Divalproex sodium is known to cause an increased risk of birth defects when taken during pregnancy. An individual and her health care provider must weigh the potential risks and benefits of using this medication during pregnancy. Women who take this medicine should not breast-feed, since a small amount will pass into the breast milk
Divalproex sodium causes drowsiness and impairs alertness in some individuals. Patients just beginning to use the medication should avoid driving and using dangerous machinery until they determine how the drug affects them. The sedative effects are increased in the presence of alcohol, so patients should avoid drinking while taking medicines containing divalproex sodium.
Side effects
Some of the more common side effects of divalproex sodium include mild stomach cramps, change in menstrual cycle, diarrhea, loss of hair, indigestion, decreased appetite, nausea and vomiting, trembling in the hands and arms, and weight loss or weight gain. These side effects usually go away as the patient's body becomes accustomed to the medication.
Less common side effects include severe stomach cramps or continued nausea and vomiting, changes in mood, behavior, or thinking, double vision or seeing spots, severe fatigue , easy bruising or unusual bleeding, yellow cast to the skin or the whites of the eyes (jaundice), odd eye movements, and increased seizures. Patients who notice these symptoms should check with their doctor to see if their dosage or medication needs to be adjusted.
Rare side effects that should be checked out by a doctor include clumsiness, difficulty with balance, constipation, dizziness, drowsiness, headache, skin rash, agitation, restlessness, or irritability.
Interactions
Divalproex sodium is broken down (metabolized) in the liver. Other drugs that are metabolized in the liver can have too low or too high concentrations in the body when taken with divalproex sodium. Levels of divalproex sodium may be increased when taken with felbamate, isoniazid, salicylates (aspirin-containing medications), clarithromycin, erythromycin, and troleandomycin. Divalproex sodium may increase levels of carbamazepine , phenytoin, lamotrigine , nimodipine, phenobarbital, and zidovudine. Use with clonazepam may cause absence seizures. Cholestyramine and colestipol may reduce the absorption and the blood levels of divalproex sodium.
Resources
BOOKS
Ellsworth, Allan J., and others. Mosby's Medical Drug Reference. St. Louis: Mosby, Inc., 1999.
Mosby's Drug Consult. St. Louis: Mosby, Inc., 2002.
Rosalyn Carson-DeWitt, M.D.