Divalproex Sodium, Oral Tablet

• This drug has black box warnings. These are the most serious warnings from the Food and Drug Administration (FDA). Black box warnings alert doctors and patients about drug effects that may be dangerous.
• Liver damage warning: This drug can cause serious liver damage that can be fatal, especially in children younger than 2 years old and anyone with certain hereditary neurometabolic syndromes. Your risk of serious liver damage may be higher during your first 6 months of treatment with this drug. In some cases, liver damage may continue even after you stop taking the drug. Your doctor will monitor you closely for symptoms and will check your liver function before and during treatment with this drug.
• Birth defects warning: This drug may cause serious harm to your pregnancy. If you take this drug during pregnancy, your baby is at risk for serious birth defects. These include birth defects that affect the brain, spinal cord, heart, head, arms, legs, and the opening where urine comes out. These defects can happen in the first month of pregnancy, before you know you’re pregnant. This drug may also cause decreased IQ and thinking, learning, and emotional disorders in your baby.
• Pancreatitis warning: This drug can cause pancreatitis (severe inflammation in your pancreas). This condition can be fatal. This can happen shortly after you start treatment or several years after you have used the drug.

Other warnings

• Suicidal thoughts warning: Divalproex sodium may cause suicidal thoughts or actions in a small number of people, about 1 in 500. Your risk may be higher if you already have a mood disorder, such as depression or anxiety. Call your doctor right away if you have any of these symptoms, especially if they are new or worse, or if they worry you:
  • thoughts about suicide or dying
  • attempts to commit suicide
  • new or worsened depression
  • new or worsened anxiety
  • feeling agitated or restless
  • panic attacks
  • trouble sleeping
  • new or worsened irritability
  • acting aggressive or violent or being angry
  • acting on dangerous impulses
  • an extreme increase in activity and talking (mania)
  • other unusual changes in behavior or mood
• Allergic reaction: This drug can cause a severe allergic reaction (hypersensitivity). Call your doctor if you have the following symptoms. If your symptoms are severe or life-threatening, call 911 or your local emergency services or go to the nearest emergency room. These symptoms can include:
  • fever
  • trouble swallowing or breathing
  • swelling of your throat, tongue, eyes, or lips
  • hives or skin rash
  • sores in your mouth
  • blistering and peeling of your skin
  • swelling of your lymph nodes

WHEN TO CALL THE DOCTOR

Call your doctor if you take this drug and have any sudden changes in mood, behaviors, thoughts, or feelings that may lead to suicidal thoughts or actions.

Divalproex sodium is a prescription drug. It comes in three forms: oral delayed-release tablets, oral extended-release tablets, and oral sprinkle capsules.

Divalproex sodium oral tablet is available as the brand-name drugs Depakote (delayed release) and Depakote ER (extended release). It’s also available in generic forms. Generic drugs usually cost less than the brand-name version. In some cases, they may not be available in every strength or form as the brand-name drug.

Divalproex sodium may be used as part of a combination therapy. That means you may need to take it with other drugs.

Why it’s used

Divalproex sodium oral tablet is used alone or with other medications to:

• Treat seizures. These include:
  • complex partial seizures that occur by themselves or in association with other types of seizures.
  • simple and complex absence seizures.
  • multiple seizure types that include absence seizures.
• Treat the manic phase of bipolar disorder. A manic episode is a period of time where your mood is extremely strong. This may include an elevated or an irritated mood.
• Prevent migraine headaches. There is no evidence that it works to treat a migraine headache when you already have one.

How it works

Divalproex sodium oral tablet belongs to a class of drugs called anti-epileptics. A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions.

This drug works by increasing brain concentrations of a certain chemical, GABA, which reduces the excitability of your nervous system. This helps to treat seizures and manic episodes and prevent migraine headaches.

Divalproex sodium oral tablet can cause drowsiness and dizziness. Don’t drive a vehicle, use machinery, or do other activities that require alertness until you know how this drug affects you.

This drug can also cause other side effects.

More common side effects

The more common side effects that can occur with divalproex sodium include:

• nausea
• headache
• sleepiness
• vomiting
• weakness
• tremor
• dizziness
• stomach pain
• blurry or double vision
• diarrhea
• increased appetite or loss of appetite
• weight gain
• weight loss
• hair loss
• problems with walking or coordination

If these effects are mild, they may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk to your doctor or pharmacist.

Serious side effects

Call your doctor right away if you have serious side effects. Call 911 or your local emergency services or go to the nearest emergency room if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

• Bleeding problems. Symptoms can include:
  • red or purple spots on your skin
  • bruising more easily than normal
  • bleeding from your mouth or nose
• High ammonia levels in your blood. Symptoms can include:
  • feeling tired
  • vomiting
  • confusion
• Low body temperature (hypothermia). Symptoms can include:
  • drop in your body temperature to less than 95°F (35°C)
  • tiredness
  • confusion
  • coma
  • slow, shallow breathing
  • weak pulse
  • slurred speech
• Allergic (hypersensitivity) reactions, including multi-organ hypersensitivity reactions. Symptoms can include:
  • fever
  • skin rash
  • hives
  • sores in your mouth
  • blistering and peeling of your skin
  • swelling of your lymph nodes
  • swelling of your face, eyes, lips, tongue, or throat
  • trouble swallowing or breathing
  • swollen lymph nodes
  • pain and swelling around major organs, such as the liver, kidneys, heart, or muscles
• Drowsiness or sleepiness, especially in seniors
• Liver damage. Symptoms can include:
  • weakness
  • facial swelling
  • lack of appetite
  • vomiting
• Pancreatitis. Symptoms can include:
  • nausea
  • vomiting
  • severe abdominal pain
  • loss of appetite

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this information includes all possible side effects. This information is not a substitute for medical advice. Always discuss possible side effects with a healthcare provider who knows your medical history.

Divalproex sodium oral tablet can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Examples of drugs that can cause interactions with divalproex sodium are listed below.

Anesthetic drug

Taking propofol with divalproex sodium can increase the levels of propofol in your body. If you need to take these drugs together, your doctor will likely decrease your dosage of propofol.

Antiseizure drug

Taking felbamate with divalproex sodium may increase the level of divalproex sodium in your body and increase your risk of side effects. If you take felbamate with divalproex sodium, your doctor may adjust your dosage of divalproex sodium.

Antiseizure and migraine prevention drug

Taking topiramate with divalproex sodium may increase your risk of high ammonia levels in your blood, or low body temperature (hypothermia). If you’re taking these drugs together, your doctor should monitor your blood ammonia levels and temperature.

Aspirin

Taking aspirin with divalproex sodium may increase the level of divalproex sodium in your body and increase your risk of side effects. If you take aspirin with divalproex sodium, your doctor may adjust your dosage of divalproex sodium.

Blood thinner drug

Taking warfarin with divalproex sodium may increase the levels of warfarin in your body. Your doctor may monitor your INR more often if you need to take divalproex sodium together with warfarin.

Carbapenem antibiotics

Taking these drugs with divalproex sodium may decrease the level of divalproex sodium in your body. This means that it may not work as well to treat your condition. If you have to take a carbapenem antibiotic while taking divalproex sodium, your doctor will monitor your blood levels closely. Examples of these antibiotics include:

• ertapenem
• imipenem
• meropenem

HIV drug

Taking zidovudine with divalproex sodium may increase the levels of zidovudine in your body. Your doctor may monitor you more closely for side effects.

Hormonal birth control that contains estrogen

Taking some birth control medications with divalproex sodium can lower the amount of divalproex sodium in your body, making it less effective. If you need to use hormonal contraception, such as the pill, your doctor will likely monitor the amount of divalproex sodium in your body.

Mood disorder and seizure drugs

Taking certain mood disorder and seizure drugs with divalproex sodium may increase the levels of these drugs in your body. Your doctor may adjust your dosage of these medications or monitor you more closely for side effects. Examples of these drugs include:

• amitriptyline/nortriptyline
• diazepam
• ethosuximide
• lamotrigine
• phenobarbital
• phenytoin
• primidone
• rufinamide

Taking other mood disorder and seizure drugs with divalproex sodium may decrease the level of divalproex sodium in your body. This means that it may not work as well to treat your condition. Your doctor may adjust your dosage of divalproex sodium. Examples of these drugs include:

• carbamazepine
• phenobarbital
• phenytoin
• primidone

Tuberculosis drug

Taking rifampin with divalproex sodium may decrease the level of divalproex sodium in your body. This means that it may not work as well to treat your condition. If you take these drugs together, your doctor may adjust your dosage of divalproex sodium.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

This drug comes with several warnings.

Allergy warning

This drug can cause a severe allergic reaction (hypersensitivity). Symptoms may include:

• fever
• trouble swallowing or breathing
• swelling of your throat, tongue, eyes, or lips
• hives or skin rash
• sores in your mouth
• blistering and peeling of your skin
• swelling of your lymph nodes

If you develop these symptoms, call 911 or your local emergency services or go to the nearest emergency room.

Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).

Alcohol interaction warning

Divalproex sodium can cause drowsiness and dizziness. Don’t drink alcohol while taking this drug because it can increase your risks of slowed reflexes, poor judgment, and sleepiness.

Warnings for people with certain health conditions

For people with liver disease: If you have a history of liver disease, you may have a higher risk of liver failure within the first six months of treatment with this drug. Your doctor will monitor you for signs of liver damage.

For people with mitochondrial disease: If you have Alpers-Huttenlocher syndrome or have a family history of this metabolic disorder, you may have a higher risk of liver failure when taking divalproex sodium.

For people with urea cycle disorders: If you have a urea cycle disorder, you shouldn’t take this drug. It may raise your risk of hyperammonemia (high ammonia levels in your blood). This condition can be fatal.

Warnings for other groups

For pregnant women: This drug may cause serious harm to your pregnancy. If you take this drug during pregnancy, your baby is at risk for serious birth defects. These include birth defects that affect the brain, spinal cord, heart, head, arms, legs, and the opening where urine comes out. These defects can happen in the first month of pregnancy, before you know you’re pregnant. This drug may also cause decreased IQ and thinking, learning, and emotional disorders in your baby.

According to published case reports, fatal liver failure has also been observed in the children of women who used this drug while pregnant.

If you become pregnant while taking this drug, talk to your doctor about registering with the North American Antiepileptic Drug Pregnancy Registry. The purpose of this registry is to collect information about the safety of drugs used to treat seizures during pregnancy.

If you become pregnant while taking this drug, call your doctor right away. Do not stop taking the medication unless directed to by your doctor.

• For treatment of seizures and manic episodes of bipolar disorder in pregnant women: Studies show a risk of adverse effects to the fetus when the mother takes divalproex sodium. The benefits of taking the drug during pregnancy may outweigh the potential risks in certain cases.

Tell your doctor if you’re pregnant. Divalproex sodium should only be used during pregnancy by women with seizures or manic episodes whose symptoms cannot be controlled by other medications.

• For prevention of migraine headaches in pregnant women: Divalproex sodium should never be used during pregnancy for women with migraine headaches.

For women who are breastfeeding: This drug passes through breast milk and may cause side effects in a breastfeeding child. Talk with your doctor about the risks and benefits of breastfeeding while taking divalproex.

For nonpregnant women of childbearing age: If you’re planning to become pregnant and you have epilepsy or bipolar disorder, you should not use this drug unless your symptoms cannot be controlled by other medications.

If you have migraine headaches, you should not use this drug unless your symptoms cannot be controlled by other medications and you’re also using effective contraception.

Talk with your doctor to determine what’s best for you.

For seniors: Your body processes divalproex sodium more slowly. You may also experience more of a sedative effect from this medication. Extreme drowsiness may cause you to eat or drink less than you normally would. Tell your doctor if this happens.

Your doctor will monitor how much you eat and drink and check you for signs of dehydration, drowsiness, dizziness, and other side effects. They may stop giving you this drug if you aren’t eating or drinking enough or if you have extreme sleepiness.

For children: Children younger than 2 years old have an increased risk of liver damage while taking this drug, especially if they also take other drugs to treat seizures.

All possible dosages and forms may not be included here. Your dose, form, and how often you take it will depend on:

• your age
• the condition being treated
• how severe your condition is
• other medical conditions you have
• how your body reacts to the drug

Drug forms and strengths

Generic: Divalproex sodium

• Form: delayed-release oral tablet
• Strengths: 125 mg, 250 mg, 500 mg

• Form: extended-release oral tablet
• Strengths: 250 mg, 500 mg

Brand: Depakote

• Form: delayed-release oral tablet
• Strengths: 125 mg, 250 mg, 500 mg

Brand: Depakote ER

• Form: extended-release oral tablet
• Strengths: 250 mg, 500 mg

Dosage for seizures

Adult dosage (ages 18 to 64 years)

• Complex partial seizures:
  • Typical initial dosage: 10–15 mg/kg taken by mouth once per day if you’re taking extended-release tablets. For delayed-release tablets, the dosage is two to three times per day.
  • Typical dosage increases: Your doctor will likely increase your dosage at 1-week intervals by 5–10 mg/kg per day.
  • Maximum dosage: 60 mg/kg per day.
• Absence seizures:
  • Typical initial dosage: 15 mg/kg taken by mouth once per day if you’re taking extended-release tablets. For delayed-release tablets, the dosage is two to three times per day.
  • Typical dosage increases: Your doctor will likely increase your dosage at 1-week intervals by 5–10 mg/kg per day.
  • Maximum dosage: 60 mg/kg per day.

Child dosage (ages 10 to 17 years)

• Complex partial seizures:
  • Typical initial dosage: 10–15 mg/kg taken by mouth once per day if your child is taking extended-release tablets. For delayed-release tablets, the dosage is two to three times per day.
  • Typical dosage increases: Your doctor will likely increase your child’s dosage at 1-week intervals by 5–10 mg/kg per day.
  • Maximum dosage: 60 mg/kg per day.
• Absence seizures:
  • Typical initial dosage: 15 mg/kg taken by mouth once per day if your child is taking extended-release tablets. For delayed-release tablets, the dosage is two to three times per day.
  • Typical dosage increases: Your doctor will likely increase your child’s dosage at 1-week intervals by 5–10 mg/kg per day.
  • Maximum dosage: 60 mg/kg per day.

Child dosage (ages 0 to 9 years)

This medication hasn’t been studied in children younger than 10 years old. It shouldn’t be used in children in this age range.

Senior dosage (ages 65 years and older)

Your body may process this drug more slowly and you may have more of a sedative effect. Your doctor may start you on a lowered dosage and increase it slowly so that too much of this drug doesn’t build up in your body. Too much of the drug in your body can cause dangerous effects.

In general, your doctor will keep you at the lowest effective dosage that you’re able to tolerate without side effects.

Dosage for bipolar disorder mania

Adult dosage (ages 18 to 64 years)

• Typical initial dosage: For delayed-release tablets, it’s 375 mg taken by mouth twice per day, or 250 mg three times per day. For extended-release tablets, it’s 25 mg/kg taken by mouth once per day.
• Typical dosage increases: Your doctor will likely increase your dosage as quickly as possible until the drug is effective or until a desired blood level is reached.
• Maximum dosage: 60 mg/kg per day.

Child dosage (ages 0 to 17 years)

This medication did not show effectiveness in children for mania. It shouldn’t be used in people with mania who are younger than 18 years.

Senior dosage (ages 65 years and older)

Your body may process this drug more slowly and you may have more of a sedative effect. Your doctor may start you on a lowered dosage and increase it slowly so that too much of this drug doesn’t build up in your body. Too much of the drug in your body can cause dangerous effects.

In general, your doctor will keep you at the lowest effective dosage that you’re able to tolerate without side effects.

Dosage warning

There is no evidence that divalproex is effective for long-term use in mania (longer than three weeks). If your doctor would like you to take this drug for a longer period of time, they will check if you still need the drug regularly.

Dosage for migraine prevention

Adult dosage (ages 18 to 64 years)

• Typical initial dosage: For delayed-release tablets, it’s 250 mg taken twice per day. For extended-release tablets, it’s 500 mg taken once per day.
• Typical dosage increases: Your doctor will likely increase your dosage as needed.
• Maximum dosage: 1,000 mg per day.

Child dosage (ages 0 to 17 years)

This medication did not show effectiveness in children for migraine prevention. It shouldn’t be used in people with migraine headaches who are younger than 18 years.

Senior dosage (ages 65 years and older)

Your body may process this drug more slowly and you may have more of a sedative effect. Your doctor may start you on a lowered dosage and increase it slowly so that too much of this drug doesn’t build up in your body. Too much of the drug in your body can cause dangerous effects.

In general, your doctor will keep you at the lowest effective dosage that you’re able to tolerate without side effects.

Special dosage considerations

For people with liver disease: If you have liver disease, you may not be able to process this drug as well as you should. You should avoid taking divalproex sodium if you have severe liver problems.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always speak with your doctor or pharmacist about dosages that are right for you.

Divalproex sodium oral tablet is used for long-term drug treatment. For manic episodes of bipolar disorder, your doctor will decide whether this is a short-term or long-term drug treatment.

This drug comes with serious risks if you don’t take it as prescribed.

If you don’t take it at all or miss doses: If you don’t take this drug regularly, you miss doses, or you stop taking it suddenly, there can be serious risks. The condition that you’re trying to treat may not get better. You may also experience more side effects from this drug if you take it on and off.

If you stop taking it suddenly: If you’re taking this drug to treat seizures, stopping it suddenly can cause a seizure that won’t stop (status epilepticus).

If you take too much: Taking too much of this drug can cause dangerous effects, such as:

• extreme fatigue
• irregular heart rate and rhythm
• high levels of salt in your blood
• deep coma
• death

If you think you’ve taken too much of this drug, call your doctor or local poison control center. If your symptoms are severe, call 911 or your local emergency services or go to the nearest emergency room right away.

What to do if you miss a dose: If you forget to take your dose of this drug, take it as soon as you remember. If it’s just a few hours until the time for your next dose, wait and take only one dose at that time.

Never try to catch up by taking two doses at once. This could cause dangerous side effects.

How to tell if the drug is working: For treatment of seizures: You should have fewer seizures.

For treatment of manic episodes of bipolar disorder: You should see a decrease in symptoms caused by the manic phase of bipolar disorder. Your mood should be well-controlled.

For prevention of migraine headaches: You should have fewer migraine headaches.

Keep these considerations in mind if your doctor prescribes divalproex sodium for you.

General

• If this drug upsets your stomach, take it with food.
• Don’t crush or chew the tablets.

Storage

• Store delayed release tablets below 86°F (30°C).
• Store extended-release tablets at a temperature between 59°F and 86°F (15°C and 30°C).
• Don’t store this medication in moist or damp areas, such as bathrooms.

Refills

A prescription for this medication is refillable. You should not need a new prescription for this medication to be refilled. Your doctor will write the number of refills authorized on your prescription.

Travel

When traveling with your medication:

• Always carry your medication with you. When flying, never put it into a checked bag. Keep it in your carry-on bag.
• Don’t worry about airport X-ray machines. They can’t harm your medication.
• You may need to show airport staff the pharmacy label for your medication. Always carry the original prescription-labeled container with you.
• Don’t put this medication in your car’s glove compartment or leave it in the car. Be sure to avoid doing this when the weather is very hot or very cold.

Clinical monitoring

Before starting and during treatment with this drug, your doctor may check your:

• drug plasma levels (your doctor may test the levels of the drug in your body if you’re having side effects or to decide if you need a dosage adjustment)
• liver function
• body temperature
• ammonia level

Your doctor may also monitor you for signs of pancreatitis or suicidal thoughts or actions.

There are other drugs available to treat your condition. Some may be better suited for you than others. Talk to your doctor about other drug options that may work for you.

Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.