Divalproex Sodium-ER


Depakote ER is a different form of the same medicine. The "ER" stands for "extended-release," which means that the time it takes the pills to dissolve and release the medicine is longer. Most people need to take regular Depakote two, three, or even four times a day because the pills release all their medicine within a few hours. It's hard to remember to take pills that often. Depakote ER is designed so that the pills can be taken only once a day. So it's a lot easier to remember and more convenient.

Another advantage of Depakote ER is that the amount of medicine in the blood stays more even than when regular Depakote is used. Having an even level of medicine in the blood may reduce side effects from very high levels and seizures from very low levels.

When you read about Depakote or Depakote ER, you will also see the word valproate (val-PRO-ate). This is the name of the medicine in Depakote ER after it has changed into the form that actually works in the body. A few other seizure medicines also are changed into valproate, so they work in the same way as Depakote and Depakote ER. The other valproate medicines in the United States are Depakene, Depacon (given by injection), and valproic acid.

Depakote ER became available in the United States in 2000. It is not available in Canada, the UK, or Australia. There is no generic (non–brand name) form of Depakote ER.

Depakote (DEH-pah-kote) is a brand name used in the United States for a type of medicine called divalproex (di-VAL-pro-eks) sodium. In the United States, Depakote ER is sold by Abbott Laboratories. The name or appearance may be different in various countries but usually the dose (measured in milligrams, abbreviated "mg") will be the same. These descriptions apply to the U.S. versions.

Please see package insert.


Updated: 16/10/2023

Brand Name(s)

Depakote ER

Used to Treat

Absence Seizures
Focal Aware Onset Seizure


Depakote ER 250mg

White ovaloid tablets with Abbott logo and "HF".

Depakote ER 500mg

Gray ovaloid tablets with Abbott logo and "HC".

Package Insert

Frequently Asked Questions

    How to take and store Divalproex Sodium-ER?

    Depakote ER tablets should be swallowed whole, not chewed or crushed. Most doctors recommend taking them with food to avoid an upset stomach, but they also can be taken without food. Because food affects the way medicine is used by the body, try to be consistent day in and day out. A person who usually takes Depakote with meals should do that all the time.

    As the doctor increases the amount of Depakote ER, you may be given a different kind of pills than the ones you've been using. You may start out using 250-mg tablets and then switch to 500-mg tablets. If this happens, be careful to use the correct number. Don't automatically continue to use the same number of pills as before.

    Store Depakote ER at room temperature and keep the pills away from light and dampness. Don't keep them in the bathroom if it's damp there. And of course keep them where children can't get at them.

    What if I forget?

    In general, tell patients that if they forget a dose, they should take it as soon as they remember. If it is almost time for the next dose, they should delay that dose instead of taking two doses close together. Since Depakote ER is generally taken once every 24 hours, they should allow an interval of about 12 hours before taking the second dose, and then resume a 24-hour schedule the next day.

    Patients who often forget doses may benefit from using a special pillbox or watch with an alarm.

    How does Divalproex Sodium-ER affect the brain?

    Brain cells need to work (fire) at a certain rate to function normally. During a seizure, brain cells are forced to work much more rapidly than normal. Depakote ER helps prevent brain cells from working as fast as a seizure requires them to. In this way, seizures can be stopped when they are just beginning.

    We don't completely understand how Depakote ER works. Doctors think that it may work in several ways at once. That could be why it works for so many different kinds of seizures.

    How does the body digest Divalproex Sodium-ER?

    After medicine is swallowed, it must be absorbed into the blood so it can move throughout the body. The process of absorbing, digesting, and excreting a medicine or food is called metabolism. The way the body metabolizes a particular medicine affects how often it must be taken. It also determines whether it will interact with other medicines or be affected by conditions such as liver disease.

    Depakote ER tablets use special coatings to release the medicine over a longer time than regular Depakote. After the outside film coating dissolves in the stomach, the outer layer of the tablet's contents begins to absorb fluid. It forms a layer of gel that releases the medicine slowly.

    The highest level of medicine in the blood is reached in 7 to 14 hours after Depakote ER is taken. The highest levels are not as high as with regular Depakote, and the lowest levels are not as low. This difference may reduce side effects at the highest levels and improve seizure control when the levels are lowest.

    If the same amount is taken, the body absorbs only about 89% as much medication from Depakote ER as from regular Depakote. This means that most people who change from regular Depakote to Depakote ER need to take a slightly higher amount each day to have the same effect.

    Like many other medicines, Depakote ER is broken down (digested) in the liver. People with liver disease should not take it. Anyone who also takes other medicines that are digested in the liver need to be careful. How well each medicine works and how quickly it leaves the body may be changed.

    This is why the doctor needs to know about everything that a person takes—not just prescription medicines but even things like vitamins, herbs, and aspirin! These things can affect how much Depakote ER the doctor prescribes.

    How well does the Divalproex Sodium-ER work?

    Doctors have studied large numbers of people to find out how well Depakote ER and the other medicines that contain valproate control seizures. (There is hardly any difference in the way the different valproate medicines work.) They have reported that these medicines are very good at completely controlling absence seizures in many people who take them. In another group, over 80% of people with new tonic-clonic seizures and related types didn't have any seizures during the period when they were given this kind of medicine.

    These promising results are not always matched in everyday life. Sometimes people don't take all their medicine on time. Not everyone's seizures can be controlled at a dose that can be taken without side effects. Because of individual differences, there is no "best" amount for everyone. Adjustments are often needed to reduce seizures or side effects.

    In studies of seizure medicines, some people do better with medicines like Depakote ER and others do better with something else. It's difficult to forecast the results for any given person. Differences in side effects may be important in deciding which medicine is best for each person.

    If seizures continue, the doctor probably will change the amount of Depakote ER prescribed. If that doesn't work, the next step may be either to prescribe a different seizure medicine by itself or to prescribe a combination of Depakote ER and another seizure medicine. Many are available. No single combination is best for everyone. Depakote ER is often used as an "add-on" medicine for people who continue to have certain kinds of seizures while taking other seizure medicines.

    What are the most common side effects of Divalproex Sodium-ER?

    Most people who take Depakote ER don't have too much trouble with side effects. That's one of the reasons it's used so much. The most common complaints (usually not too severe) are:

    • tiredness (sometimes with slower thinking)
    • dizziness
    • upset stomach
    • vomiting
    • tremor (shaking of the hands or other parts of the body)
    • hair loss
    • weight gain
    • changes in behavior (depression in adults, irritability in children)

    If you notice any of these problems, call the doctor. Sometimes the doctor can help by changing the amount of Depakote ER prescribed. No one should stop taking Depakote ER or change the amount they take without their doctor's guidance.

    Stomach upset from Depakote ER may be less of a problem if the pills are taken on a full stomach. Stomach upset is more likely when another seizure medicine with similar side effects (for example, Tegretol) is also being used.

    Tremor (shaking of the hands or other body parts) tends to be worse when the level of Depakote ER in the blood is highest, 7 to 14 hours after the pills are taken. Anxiety or caffeine also may make it worse. Tremor may be less of a problem with Depakote ER than with regular Depakote, since the highest level of medicine in the blood usually is not quite as high.

    Weight gain affects 30% to 50% of people who take Depakote ER. It is more common in adult women but can affect anyone. The average gain for adults is 15 pounds. Exercise and a reduced-calorie diet can be very helpful. It's uncertain whether weight gain is greater when higher doses of Depakote ER are taken.

    Hair loss occurs in 5% to 10% of people who take Depakote ER. The hair almost always grows back after the Depakote ER is stopped, but it often has a different texture. (For example, it may grow in curly instead of straight.)

    People who have just started taking Depakote ER (or who have just started taking a larger amount) should be careful during activities that might be dangerous, until they know whether they are having any side effects.

    Allergic reactions

    Allergic reactions such as rashes are less common with Depakote ER than with most other seizure medicines. Even so, you should report any rash to the doctor or nurse right away, especially if treatment has just begun. It's rare for the rash to be serious, but don't ignore it. It's often necessary to switch to a different seizure medicine.

    A very small number of people who take Depakote ER develop life-threatening disorders. See Serious side effects.

    Long-term side effects

    Some people who have taken Depakote ER or other valproate medicines (such as Depakote) for many years have experienced bone loss and a few other disorders. Taking both calcium and vitamin D may help to prevent this kind of problem. Many doctors recommend a bone density test to identify which people need treatment for bone loss.

    What are the most serious side effects of Divalproex Sodium-ER?

    The risk of liver failure is much lower in children between 2 and 10. The risk is very low in older children and adults, perhaps 1 in 50,000. There is no evidence that long-term use of Depakote ER will cause gradual damage to the liver.

    Another rare reaction to Depakote ER is a disorder of the pancreas. Occasionally it is so severe that bleeding and death can occur. Both children and adults can be affected, even after several years of taking Depakote ER or another valproate medicine. Report pain in the abdomen, upset stomach, vomiting, or loss of appetite to the doctor right away.

    Problems with blood clotting are more likely in people who take large amounts of Depakote ER. Sometimes the blood returns to normal without stopping the medicine. The doctor probably will order some blood tests before prescribing Depakote ER, and will repeat them some time later and before any elective surgery.

    A complete list of all reactions to Depakote ER can be found in the package insert, but it is important to remember that only a tiny number of people have any of these serious problems.

    On July 10, 2008, an advisory panel was convened by the Food and Drug Administration (FDA) to review data that the FDA had previously collected from drug studies showing an association between many of the antiepileptic drugs (AEDs) and suicidal ideation and behavior, which together are called suicidality. According to the FDA’s Alert, among the patients with epilepsy in these drug studies, 1 out of 1000 people taking the placebo (inactive substance) showed suicidality compared to approximately 3.5 out of 1000 people who took an AED. The FDA advisory panel voted to accept the FDA's data at its meeting on July 10.

    • Taking antiepileptic medicines may increase the risk of having suicidal thoughts or actions;
      • Do not make any changes to the medication regimen without first talking with the responsible healthcare professional;
      • Pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.
    • Be aware of common warning signs that might be a signal for risk of suicide. Some of these are:
      • Talking or thinking about wanting to hurt yourself or end your life
      • Withdrawing from friends and family
      • Becoming depressed or having your depression get worse
      • Becoming preoccupied with death and dying
      • Giving away prized possessions

    We again urge patients and families to contact their doctor before stopping an epilepsy medication because this may possibly lead to seizures and worsening of mood.

    Impact of Divalproex Sodium-ER on bone health

    At this time there is no evidence to support this medication causes bone health problems.   However, it might.  It is essential that if you taking this medication, that one take supplemental calcium of 1000 milligrams per day.  Talk to your doctor about bone health.  He/She may decide to check Vitamin D levels and other tests to check for the impact of this drug on your bones.

    What else is Divalproex Sodium-ER used for?

    Often doctors find that medicines are useful for more than one purpose. Besides controlling seizures, Depakote ER has been approved by the Food and Drug Administration (FDA) for the prevention of migraine headaches. (In fact, it was used for this purpose before it was approved for epilepsy.) It does not appear to relieve headaches while they're occurring. Depakote ER is also FDA-approved for the treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features.

    Who should not take Divalproex Sodium-ER?

    People with liver disease should not take Depakote ER. Neither should anyone who has shown an allergy to Depakote or another valproate medicine in the past. Make sure the doctor knows about any liver problems, so a different medicine can be prescribed instead.

    Can Divalproex Sodium-ER be taken with other medicines?

    Sometimes one kind of medicine changes the way another kind of medicine works in the body. This is true not only for prescription medicines, but also for medicines you just pick up off the shelf at the store. For instance, aspirin (ASA) may increase the side effects from taking Depakote ER.

    If someone who is taking Depakote ER—especially a child—also starts to take the seizure medicine called Lamictal, the chances of a very dangerous rash will be increased. Adding the Lamictal slowly reduces this danger.

    Taking both Depakote ER and another seizure medicine, Klonopin, sometimes causes absence seizures to be much longer.

    Any time a doctor suggests a new prescription, be sure to talk about what other medicines you are already using. If two kinds of medicine affect each other, the doctor may want to prescribe something else or change the amount to be taken.

    How does Depakote ER affect other medicines?

    Depakote ER affects the way the body handles many other seizure medicines. Some of these are:

    • Felbatol (felbamate)
    • Lamictal (lamotrigine)
    • Mysoline (primidone)
    • phenobarbital
    What are the effects of Divalproex Sodium-ER on Children?

    Depakote ER can be effective against many types of seizures common in children:

    • absence seizures (this is one of the most effective medicines for these brief staring spells)
    • myoclonic seizures
    • tonic-clonic seizures, such as those in Lennox-Gastaut syndrome.
    • seizures triggered by flashing lights

    Valproate medicines are also effective for infantile spasms (West syndrome), but the tablet form of Depakote ER makes it unsuitable for that purpose.

    Children under 2 or 3 years of age who take valproate in any form have a much higher risk of liver failure than adults or older children. (The risk of liver failure is very low for children over 10, perhaps 1 in 50,000.) The tablet form of Depakote ER means that it's unlikely to be prescribed for very young children anyway, so this is seldom a concern. Liver damage usually occurs within the first 6 months of treatment. The first signs of it are vomiting, loss of appetite, sluggishness, and perhaps loss of seizure control, yellow skin and eyes, or swelling.

    Higher-than-usual levels of the hormone testosterone have been found in many girls who take Depakote ER when they're older than about age 10. No symptoms are apparent, but the doctor may want to watch for later problems, perhaps related to weight gain.

    A few children who take Depakote ER seem to become more irritable but this is seldom a serious problem.

    To reduce side effects, the doctor probably will prescribe a low dose of Depakote ER to start and increase it slowly. Children usually start with a dose of 5 to 10 milligrams (mg) for each kilogram (kg, about 2.2 pounds) of their body weight per day. Since the smallest Depakote ER tablet is 250 milligrams (and it cannot be divided), smaller children may need to begin by using regular Depakote or another valproate medicine. They can switch to Depakote ER when they reach a higher dosage.

    Most children do best at about 15 to 60 mg/kg per day. Children taking a combination of Depakote and another seizure medicine usually need the higher doses because of interactions between the medicines.

    If a woman takes Divalproex Sodium-ER during pregnancy will it hurt the baby?

    In the United States, the Food and Drug Administration (FDA) assigns each medication to a Pregnancy Category according to whether it has been proven to be harmful in pregnancy. Depakote ER is listed in Pregnancy Category D. This means that there is a risk to the baby, but the benefits may outweigh the risk for some women.

    In fact, a large majority of women who use Depakote ER during pregnancy have normal, healthy babies. Certain types of defects are increased (especially if Depakote ER is taken during the first 3 months of pregnancy) but they are still relatively uncommon. The risk of defects is higher for women who take more than one seizure medicine. Women with a family history of birth defects also have a higher risk.

    The babies of women taking valproic acid have a greater than usual number of minor craniofacial abnormalities, organ malformations, limb deficiencies, or developmental delay. The risk of defects is higher for women who take more than one AED and for women with a family history of birth defects.  Moreover the NEAD study showed that children born to women who took Valproic acid, had lower IQ scores than children born to women with epilepsy who tool other seizure medications.

    Women with epilepsy who are pregnant or thinking about becoming pregnant should talk to their doctor about their seizure medicines. Taking more than one seizure medicine may increase the risk of birth defects, so doctors sometimes gradually reduce the number or amount of seizure medicines taken by women planning for pregnancy. This is not done routinely, however, because it increases the risk of seizures. Some kinds of seizures can injure the baby, so do not stop using seizure medicines or reduce the amount without the doctor’s OK.

    All women who are capable of becoming pregnant should take at least 400 mcg (0.4 mg) of the vitamin called folic acid every day because it helps to prevent one type of birth defect. (The most well-known of these is spina bifida, in which the spinal cord is not completely enclosed.) These defects are more common in the babies of women who take Depakote ER during the first 4 to 6 weeks of pregnancy. If the doctor thinks a woman is at especially high risk, a much larger dose of folic acid—4000 mcg (4 mg) per day—may be recommended. There's no proof that the folic acid will prevent the defects, however, so the doctor may recommend a check-up later in pregnancy.

    About 20% to 35% of women have seizures more often during pregnancy because of changes in hormones or changes in how their seizure medicine is handled by the body. It is helpful for the doctor to check the levels of medicine in the blood regularly during pregnancy so that the dosage can be adjusted if necessary.

    Breast-feeding by mothers taking Depakote ER 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 doctors safely give to babies who take Depakote for seizures.

    What are the effects of Divalproex Sodium-ER on Seniors

    Doctors have prescribed Depakote ER and other valproate medicines to people over 65 for many years with good results. These seniors do have a few special problems, however.

    Most seniors take more medicines than younger people, so there’s a greater risk that the medicines may affect each other. Usually seniors can continue to take all the medicines they need, including Depakote ER, without trouble if the doctor changes the amount of some of them to make up for the way they affect each other.

    Seniors also tend to be more sensitive than younger adults to medicines and their side effects. For instance, many seniors have a problem with sleepiness, depression, weight gain, or shaking of the hands even before they start taking Depakote ER. These are common side effects of this medicine, so these problems may become worse and cause real trouble. Because the level of medicine in the blood is more steady with Depakote ER than with other valproate medicines, however, side effects like tremor may be less of a problem when Depakote ER is used.

    Seniors also face more danger from some side effects because they are more likely to be seriously hurt if they fall or have another kind of accident.

    To reduce side effects, the doctor probably will prescribe a very low dose of medicine to start and then be cautious about any increases. The smallest tablet of Depakote ER, 250 mg, may be too large for some seniors to start with. They may begin by taking regular Depakote or another valproate medicine instead. They can change to Depakote ER later, when they're ready for a higher dose.

    It’s especially important for seniors to keep the doctor informed about any changes that they notice.

    What are the dose ranges for Divalproex Sodium-ER?

    The best amount is the amount that completely controls seizures without causing troublesome side effects. It depends on many factors, which are different for every individual. Follow the doctor's directions. Call if you have any questions.

    No one should stop taking Depakote ER or change the amount they take without talking to the doctor first. Stopping any seizure medicine all at once can cause a problem that may be life-threatening.

    Don’t use more than the doctor prescribes. If one or two extra tablets are taken by accident, call the doctor for advice. For a larger overdose, call a poison control center or emergency room right away unless you have other specific directions from your doctor.

    To avoid unwanted side effects, the doctor will prescribe a low dose to start and increase it gradually until the seizures are controlled, unless side effects get too bad first. People who change to Depakote ER after taking regular Depakote or another valproate medicine will need to take a little more Depakote ER to achieve the same effect.

    Read the package insert of Divalproex Sodium-ER

    In the United States, companies that manufacture medicines are required to publish certain kinds of information about each product. This document is commonly known as a “package insert” because it is usually included with each package of the medicine.

    You can also read these documents (also called "prescribing information") online. The U.S. package insert for Depakote capsules is found at:


    The U.S. package insert for Depakote-ER tablets is found at:

    Some of the information may differ in other countries.

    To learn how to read and understand a package insert, see "How to read a package insert."


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