Valproic acid (val PRO ik) has been approved by the FDA to treat focal impaired awareness seizures, absence seizures, and in patients with multiple seizure types (that include absence seizures).

Your epilepsy treatment should always be discussed with your healthcare provider before use. Based on their judgment and knowledge, a drug may be prescribed for other epilepsy types not included in the indications. For more information, please see the prescribing information.

How can you take valproic acid? (Available formulations)

Valproic acid is available in a few different formulations to take by mouth either without or with food (to help prevent the medication from upsetting your stomach). You can take valproic acid as a capsule, an extended-release (long-acting) tablet, a delayed-release (releases the medication in the intestine to prevent damage to the stomach) tablet, a sprinkle capsule (capsule that contains small beads of medication that can be sprinkled on food), and a syrup (liquid).

There is also an injectable form for intravenous use when oral forms are not possible.

Who should not take valproic acid?

If you have liver problems or have or think you have a genetic liver problem caused by a mitochondrial disorder (e.g., Alpers-Huttenlocher syndrome), do not take valproic acid.

If you are allergic to divalproex sodium, valproic acid, sodium valproate, or any of the active ingredients in your formulation, you should not take this medicine.

If you have a genetic problem called urea cycle disorder, you should not take valproic acid.

Other considerations may influence whether you should take valproic acid. Tell your healthcare provider if you:

  • drink alcohol.
  • have or have had depression, mood problems, or suicidal thoughts or behavior.
  • have any other medical conditions.
  • are pregnant or plan to become pregnant.
  • are breastfeeding or plan to breastfeed.

What is important to know about taking valproic acid?

Do not stop taking valproic acid suddenly unless directed to do so by your healthcare provider.

As with all antiseizure medications, valproic acid should be withdrawn gradually to minimize the risk of causing or worsening seizures or status epilepticus. You should not stop using valproic acid suddenly unless your healthcare provider tells you to stop the medicine because of a serious side effect.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Taking valproic acid with certain other medicines may cause side effects or affect how well they work. Do not start or stop other medicines without talking to your healthcare provider. Make sure your healthcare provider knows all medications you are taking to treat your epilepsy. Also tell your healthcare provider if you take: acyclovir, anticoagulants (blood thinners) such as warfarin, amitriptyline, aspirin, cholestyramine, doripenem, ertapenem, ethosuximide, certain hormonal contraceptives, imipenem and cilastatin, medications for anxiety or mental illness, meropenem, nortriptyline, rifampin, sedatives, sleeping pills, tolbutamide, tranquilizers, and zidovudine. Your healthcare provider may need to change the doses of your medications or monitor you carefully for side effects.

Boxed warning

Valproic acid is approved by the FDA because it is safe and effective for the majority of people who take it. However, there are risks associated with all medicines. Some side effects caused by valproic acid can be very serious, and even life-threatening. It is important to be informed about these serious reactions and to be aware of their symptoms.

Serious liver damage

The use of valproic acid has been associated with serious liver damage that can cause death, especially in children younger than 2 years old or those who have certain mitochondrial disorders (e.g., Alpers-Huttenlocher Syndrome). The risk of getting this serious liver damage is more likely to happen within the first 6 months of treatment. Call your healthcare provider right away if you get any of the following symptoms:

  • nausea or vomiting that does not go away
  • loss of appetite
  • pain on the right side of your stomach (abdomen)
  • dark urine
  • swelling of your face
  • yellowing of your skin or the whites of your eyes

In some cases, liver damage may continue despite stopping the drug.

Fetal risk

See Women or those who are/plan to become pregnant for important warnings regarding risk to unborn babies.

Pancreatitis

Cases of life-threatening pancreatitis (inflamed pancreas) have been reported in both children and adults receiving valproic acid. Some of the cases have been described as hemorrhagic (uncontrollable bleeding) with a rapid progression from initial symptoms to death. Cases have been reported both shortly after initial use, as well as after several years of use. Patients and guardians should be warned that abdominal pain, nausea, vomiting, and/or anorexia (an eating disorder associated with low body weight) can be symptoms of pancreatitis that require prompt medical evaluation. If pancreatitis is diagnosed, valproic acid should ordinarily be discontinued. Alternative treatment of the underlying medical condition should be initiated as clinically indicated.

Women or those who are/plan to become pregnant
Use in pregnancy

Valproic acid may harm your unborn baby.

If you take valproic acid during pregnancy, your baby is at risk for serious birth defects that affect the brain and spinal cord and are called spina bifida or neural tube defects. These defects occur in 1 to 2 out of every 100 babies born to pregnant people who use this medicine during pregnancy. Taking folic acid supplements before getting pregnant and during early pregnancy can lower the chance of having a baby with a neural tube defect.

Other birth defects that affect the structures of the heart, head, arms, legs, and the opening where the urine comes out (urethra) on the bottom of the penis can also happen. Decreased hearing or hearing loss may also occur. If you take valproic acid during pregnancy for any medical condition, your child is at risk for having lower IQ and may be at risk for developing autism or attention-deficit/hyperactivity disorder. The risk of defects is higher for patients who take multiple antiseizure medications and for those with a family history of birth defects.

If you are of childbearing age (including from the start of puberty) you should talk to your healthcare provider about using other possible treatments instead of valproic acid. If the decision is made to use valproic acid, you should use effective birth control (contraception). Tell your healthcare provider right away if you become pregnant while taking valproic acid. You and your healthcare provider should decide if you will continue to take valproic acid while you are pregnant.

If you become pregnant while taking valproic acid, talk to your healthcare provider about registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The purpose of this registry is to collect information about the safety of antiseizure medicine during pregnancy. You can enroll in this registry by calling 1-888-233-2334.

Use during breastfeeding

While a small amount of valproic acid is present in breast milk, breastfeeding should be safe for healthy, full-term newborns. The amount of medicine the baby gets through the milk is much less than the amount that healthcare providers safely give to babies who take valproic acid for seizures. Talk to your healthcare provider about the best way to feed your baby while taking valproic acid. Your healthcare provider will consider the developmental and health benefits of breastfeeding along with your need for valproic acid and the potential effect on the infant from valproic acid or from your epilepsy.

Effect of birth control and fertility

Valproic acid does not decrease the effectiveness of hormonal contraceptives, including birth control pills, injections, implants, skin patches, and vaginal rings; however, these medications may decrease the effectiveness of valproic acid. Do not start or stop taking hormonal contraceptives until you have talked with your healthcare provider. Tell your healthcare provider if you have any changes in your menstrual pattern such as breakthrough bleeding. Stopping these medicines while you are taking valproic acid may cause side effects (such as dizziness, lack of coordination, or double vision). Starting these medicines may lessen how well valproic acid prevents seizures. To prevent pregnancy after using valproic acid, use a barrier form of birth control: condom, diaphragm, cervical cap, or contraceptive sponge.

What are the side effects of valproic acid?

Common side effects

The most common side effects that were reported in studies of valproic acid are nausea, headache, sleepiness, vomiting, weakness, tremor, dizziness, stomach pain, blurry vision, double vision, diarrhea, increased appetite, weight gain, hair loss, loss of appetite, and problems with walking or coordination.

Rare, but serious side effects
Serious reactions, including serious blood or liver problems

Rare but life-threatening reactions involving the immune system or multi-organ hypersensitivity, which can cause serious blood or liver problems have been reported with valproic acid use. You may or may not have a rash with these types of reactions. Call your healthcare provider right away if you experience fever, frequent infections, severe muscle pain, swelling of your face, eyes, lips, or tongue, swollen lymph glands, unusual bruising or bleeding, weakness, fatigue, yellowing of your skin, or the white part of your eyes, trouble walking or seeing, seizures happening more often, or pain/tenderness in the area toward the top of your stomach (enlarged liver/spleen).

Suicidal thoughts or behaviors

Studies have found that people who take antiseizure medications including valproic acid may have suicidal thoughts or behaviors, which occur in approximately 1 in 500 patients. If you experience any thoughts or impulses to hurt yourself, you should contact your healthcare provider immediately.

Bleeding problems

Problems with blood clotting are more likely in people who take large amounts of valproic acid. Tell your healthcare provider right away if you experience red or purple spots on your skin, bruising, pain, and swelling into your joints due to bleeding, or bleeding from your mouth or nose. Your healthcare provider may order some blood tests before prescribing valproate and may recheck occasionally as well as before any elective surgery.

Hyperammonemia and encephalopathy

Valproic acid can cause high levels of ammonia in your blood, which is known as hyperammonemia. When valproic acid is taken with topiramate, it may cause hyperammonemia and encephalopathy (brain malfunctions). If you have symptoms such as feeling tired, vomiting, or changes in mental status, tell your healthcare provider. Hyperammonemia may occur without a low body temperature (hypothermia). This is defined as a drop in your body temperature to less than 95°F and may present with symptoms like feeling tired, confusion, or coma. This serious reaction may occur more commonly in patients who are also taking topiramate.

Somnolence in the elderly

Drowsiness or sleepiness (somnolence) in the elderly can occur when taking valproic acid. This extreme drowsiness may cause you to eat or drink less than you normally would. Tell your healthcare provider if you are not able to eat or drink as you normally do. Your healthcare provider may start you at a lower dose of valproic acid.