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Overview: Divalproex sodium is used for seizures, bipolar disorder, and to prevent migraine headaches. Some common side effects include headaches, feeling weak or tired, dizziness, nausea, vomiting, or stomach pain. Tell your health care provider right away if you get a new rash, bruise or bleed easily, or have mood or behavior changes. Do not start or stop any medicine without talking with your health care provider.

Uses

What is divalproex sodium used for?

Divalproex sodium is commonly used to treat the following conditions.

Divalproex sodium may also be used for other conditions as determined by your health care provider.

How does divalproex sodium work (mechanism of action)?

Divalproex sodium may work by increasing a chemical in your brain called GABA, which helps slow down the electrical activity in your brain. 

How is divalproex sodium supplied (dosage forms)?

Brands and other names

  • Depakote
  • Depakote ER
  • Depakote Sprinkles

Dosage forms and strengths

  • 125 mg, 250 mg, 500 mg delayed-release oral tablets
  • 250 mg, 500 mg extended-release oral tablets
  • 125 mg oral capsules

How should I store divalproex sodium?

Oral Tablet. Divalproex sodium tablets should be stored at room temperature, between 68 F and 77 F (20 C and 25 C). It can be exposed to temperatures between 59 F and 86 F (15 C and 30 C) for shorter periods of time, such as when you’re transporting it. Store it in a cool, dry place.

Oral Capsule. Divalproex sodium capsules should be stored below 77 F (25 C). 

Side Effects

What are the most common side effects of divalproex sodium?

The most common side effects of divalproex sodium are listed below. Tell your health care provider if you have any of these side effects that bother you.

  • Headache
  • Sleepiness or feeling unusually weak or tired
  • Nausea, vomiting, diarrhea, constipation, stomach pain
  • Tremor
  • Dizziness 
  • Changes in appetite or weight
  • Hair loss
  • Eye problems, including blurry vision, double vision, or unusual eye movements
  • Hearing a ringing sound in your ears
  • Infections, including bronchitis or flu-like symptoms
  • Swelling in your hands, feet, arms, or legs

There may be other side effects of divalproex sodium that are not listed here. Contact your health care provider if you think you are having a side effect of a medicine. In the U.S., you can report side effects to the FDA at www.fda.gov/medwatch or by calling 800-FDA-1088 (800-332-1088). In Canada, you can report side effects to Health Canada at www.health.gc.ca/medeffect or by calling 866-234-2345.

What are the serious side effects of divalproex sodium?

While less common, the most serious side effects of divalproex sodium are described below, along with what to do if they happen.

Severe Allergic Reactions. Divalproex sodium can cause allergic reactions, including a specific type of allergic reaction called DRESS. DRESS stands for drug reaction with eosinophilia and systemic symptoms. It is also sometimes called multiorgan hypersensitivity. This is a reaction that can affect multiple parts of the body, including your liver, kidneys, and heart. Stop taking the medicine and get help right away if you have any of the following symptoms of a serious allergic reaction.

  • Breathing problems or wheezing
  • Racing heart
  • Fever or general ill feeling
  • Swollen lymph nodes
  • Swelling of the face, lips, mouth, tongue, or throat
  • Trouble swallowing or throat tightness
  • Itching, skin rash, or pale red bumps on the skin called hives
  • Nausea or vomiting
  • Dizziness, feeling lightheaded, or fainting
  • Stomach cramps
  • Joint pain
  • Dark-colored urine
  • Your skin or the whites of your eyes turning yellowish in color (also called jaundice)

Liver Damage. Liver damage, also called hepatotoxicity, can happen when taking divalproex sodium. It seems to be more common within the first six months of taking it and in young children. Keep all appointments, including lab appointments, while taking this medicine. Call your health care provider right away if you have any of the following symptoms of liver damage.

  • Nausea, vomiting, or diarrhea
  • Stomach or belly pain
  • Fever
  • Weakness or unusual tiredness
  • Itching
  • Loss of appetite
  • Light-colored poop
  • Dark-colored urine (pee)
  • Your skin or the whites of your eyes turning yellowish in color (also called jaundice)
  • Swelling of your face

Inflammation of the Pancreas (Pancreatitis). Divalproex sodium may cause inflammation of the pancreas, which is called pancreatitis, or bleeding of your pancreas. Call your health care provider right away if you have symptoms of pancreas problems, including losing your appetite, vomiting or severe pain in the upper part of your belly that travels to your back.

Suicidal Thoughts and Actions. Divalproex sodium may cause suicidal thoughts or actions in a small number of people. If you are about to harm yourself, call 911 or call or text 988, the Suicide & Crisis Lifeline. Call your health care provider right away if you have any of the following symptoms.

  • New or increased thoughts of suicide or death
  • Suicide attempt
  • New or increased feelings of anxiety, depression, or other unusual changes in mood or behavior
  • Having a hard time sleeping or feeling restless
  • Crankiness, anger, aggression, or violence
  • Impulsive behavior

Bleeding. Divalproex sodium can increase your risk of bleeding. Call your health care provider right away if you have any of the following signs of severe bleeding while taking divalproex sodium. 

  • Pink, red, or brown urine (pee)
  • Vomit with blood that looks like coffee grounds
  • Red or black stools (looks like tar)
  • Coughing up blood or blood clots
  • Pain and swelling in your joints

High Ammonia Level. Divalproex sodium can increase ammonia levels in your blood. You may need a blood test to check the amount of ammonia in your blood. Tell your health care provider right away if you get any of the following symptoms of high ammonia levels. 

  • Nausea and vomiting
  • Unexplained tiredness
  • Confusion or slowed thinking
  • Slowed reaction time
  • Trouble with balance or coordination

Low Body Temperature. Divalproex sodium may lower your body temperature below normal levels. Call your health care provider right away if you have any of the following symptoms. 

  • Tiredness
  • Confusion
  • Memory loss
  • Drowsiness
  • Coma
  • Shivering

Severe Skin Reactions. Divalproex sodium can cause severe skin reactions, called Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), that can lead to death if not treated. If you get a rash, call your health care provider right away. Get emergency help if you have any of the following symptoms.

  • Painful red or purple skin that looks burned and peels off
  • Flat red rash or blisters on your skin, mouth, nose, and genitals
  • Red, painful, watery eyes
  • Flu-like symptoms including fever, chills, and muscle aches

Warnings & Precautions

Who should not use divalproex sodium?

Allergies to Ingredients. People who are allergic to any of the following should not take divalproex sodium.

  • Divalproex sodium
  • Valproic acid
  • Sodium valproate 
  • Depakote
  • Depakote ER
  • Depakote Sprinkles
  • Any of the ingredients in the specific product dispensed

Your pharmacist can tell you all of the ingredients in the specific divalproex sodium products they stock.

Liver Problems. Do not take divalproex sodium if you have liver problems or liver disease. 

Mitochondrial Disorders. Do not take divalproex sodium if you have a mitochondrial disorder. Mitochondria are found in the cells of your body and help give your cells energy. Mitochondrial disorders are genetic problems that can happen when mitochondria don’t work the way they should. Examples of mitochondrial disorders include PolG, which can cause organ problems, and Alpers-Huttenlocher syndrome, which can affect the brain, vision, muscles, and liver. 

Urea Cycle Disorder. Do not take divalproex sodium if you have a genetic condition called a urea cycle disorder. Urea cycle disorder is a group of conditions that can make it hard for your body to get rid of its waste products. 

Pregnancy. Do not take divalproex sodium for migraine prevention if you are pregnant or can become pregnant without using effective birth control. If you become pregnant, contact your health care provider right away. See the Pregnancy section for more details.

What should I know about divalproex sodium before using it?

Do not take divalproex sodium unless it has been prescribed to you by a health care provider. Take it as prescribed. Do not stop taking divalproex sodium without talking to your health care provider. Stopping divalproex sodium suddenly can cause serious side effects including seizures, including a type of seizure that does not stop (status epilepticus). If you need to stop taking divalproex sodium, your health care provider will give you instructions on how to stop the medicine.

Do not share divalproex sodium with other people, even if they have the same condition as you. It may harm them.

Keep divalproex sodium out of the reach of children.

Divalproex sodium can affect your alertness, coordination, or vision. Do not drive or do other activities that require alertness or coordination until you know how divalproex sodium affects you.

Do not crush or chew divalproex sodium tablets. They should be swallowed whole. Divalproex sodium capsules can be swallowed whole. The capsules can also be opened and poured on a small amount (about one teaspoon) of soft food, such as applesauce or pudding. The food should be swallowed right away, without chewing it. You can learn more by reading the “Instructions For Use” that come with your medicine. Ask your health care provider if you have any questions.

It is possible that you may see part of the divalproex sodium capsule or tablet in your poop. If this happens, tell your health care provider. Your health care provider may check the medicine levels in your blood to be sure you are getting the right amount.

People who are 65 and older can be at greater risk of some side effects from divalproex sodium. Talk to your health care provider about your risks if you are in this age group.

Divalproex sodium may make it difficult for you to get your partner pregnant. If you have concerns, talk to your health care provider.

What should I tell my health care provider before using divalproex sodium?

Tell your health care provider about all of your health conditions and any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements you are using. This will help them know if divalproex sodium is right for you.

In particular, make sure that you discuss any of the following.

Current and Past Health Conditions. Tell your health care provider if you have any of the following.

  • Depression, suicidal thoughts, mood or behavior problems, or thoughts of harming yourself
  • Bleeding problems
  • Drink alcohol
  • Upcoming surgery

Other Medicines and Supplements. Divalproex sodium may interact with other medicines and supplements. Before taking divalproex sodium, tell your health care provider about any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements you are using. See the Interactions section for more details.

Pregnancy. Divalproex sodium may harm an unborn baby. Do not take divalproex sodium without using effective birth control. Tell your health care provider if you are pregnant or plan to become pregnant. Your health care provider will let you know if you should take divalproex sodium while you are pregnant or trying to get pregnant. If you become pregnant while taking divalproex sodium, call your health care provider right away. You can sign up for the North American Antiepileptic Drug Pregnancy Registry by calling 888-233-2334 or at www.aedpregnancyregistry.org. This registry collects safety information about the use of antiepileptic medicines during pregnancy.

Breastfeeding. Divalproex sodium passes into breast milk. Tell your health care provider if you are breastfeeding or plan to breastfeed. Your health care provider will let you know if you should take divalproex sodium while breastfeeding.

Interactions

Does divalproex sodium interact with foods or drinks?

There are no known interactions between divalproex sodium and foods or drinks.

Do not drink alcohol while taking divalproex sodium. Both divalproex sodium and alcohol can cause liver damage. The risk of dizziness or sleepiness may also be increased if you drink alcohol while taking divalproex sodium. 

Does divalproex sodium interact with other medicines (drug interactions)?

Always tell your health care provider about any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements you are using.

In particular, make sure that you discuss if you are using any of the following before taking divalproex sodium.

  • Ethosuximide (Zarontin), felbamate (Felbatol), phenobarbital, phenytoin (Dilantin, Phenytek, and others), primidone, or rufinamide (Banzel), which is a medicine used to control seizures
  • Clonazepam (Klonopin) or diazepam (Valium and others), which is a medicine used for anxiety, muscle spasms, or seizures
  • Lamotrigine (Lamictal), which is a medicine used to control seizures and bipolar disorder
  • Carbamazepine (Carbatrol, Tegretol, and others), which is a medicine commonly used to treat seizures or nerve pain
  • Topiramate (Qudexy XR, Topamax, Trokendi XR), which is a medicine commonly used to control seizures or prevent migraine
  • Ertapenem (Invanz), imipenem/cilastatin (Primaxin), or meropenem (Merrem), which is a medicine used for bacterial infections
  • Ritonavir (Norvir) or zidovudine (Retrovir), which is a medicine commonly used to treat HIV
  • Aspirin, which is in many prescription and OTC products, including those for pain, swelling, and fever
  • Estrogen, which is found in certain birth control pills, patches, creams, rings, or vaginal suppositories 
  • Methotrexate (Trexall and others), which is a medicine commonly used for rheumatoid arthritis or certain types of cancer
  • Rifampin (Rifadin), which is a medicine commonly used to treat an infection called tuberculosis
  • Amitriptyline or nortriptyline (Pamelor), which is a medicine used to treat depression 
  • Warfarin, which is a blood thinner
  • Cannabidiol (Epidiolex), which is a medicine used to treat seizures
  • Any other medicine that causes dizziness and sleepiness, such as prescription pain medicines, sleep medicines, or medicines for anxiety

Some other medicines may alter the blood levels of divalproex sodium, and vice versa. Tell your health care provider about all medicines that you take or have recently taken.

This may not be a complete list of medicines that can interact with divalproex sodium. Always check with your health care provider.

Does interact with other drugs you are taking?

Enter your medication into the WebMD interaction checker

Overdose/Missed Dose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing , call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.