Drug Name

Valproic acid ER (divalproex)

Drug Uses

Valproic acid ER is used for the treatment of seizures, bipolar disorder and prevention of migraines.

How to use

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 is usually 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 divalproex 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 divalproex delayed-release tablets. The maximum recommended dose is 1000 mg/day. When using divalproex ER tablets, the recommended dose is 500-1000 mg given once daily.

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 or valproate. Scientists do not know the mechanism of action of valproate. The most popular theory is that valproate exerts its effects by increasing the concentration of gamma-aminobutyric acid (GABA) in the brain. Gamma-aminobutyric acid is a neurotransmitter, a chemical that nerves use to communicate with one another.

Missed Dose

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

Storage

Store this medicine at room temperature in a tightly-closed container, away from heat and light.

Warnings/Precautions

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.

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. 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. 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.

Possible Side Effects

The most common side effects with Valproic acid therapy are drowsiness, dizziness, nausea, vomiting, indigestion, diarrhea, weight loss and tremors. 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 abnormal bleeding.

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 behavior.

More Information

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.