What is Divalproex ER: Uses, Warnings & Interactions

Updated May 14, 2025  •  Published Dec 30, 2020

Divalproex ER is a generic drug commonly used by neurologists and psychiatrists for seizure disorders, bipolar disorder, and migraines. The body converts divalproex into the drug valproate. This drug slows down nerves through a variety of mechanisms. Most people taking divalproex will experience side effects. Some side effects are serious, so people taking divalproex should be aware of the symptoms and contact the prescriber when they occur.

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Divalproex ER overview

BRAND NAMES:

  • Depakote ER

Generic Names:

  • Divalproex sodium ER

Uses:

  • Treats seizures and bipolar disorder. Prevents migraine headaches.

Therapeutic Classes:

  • Anticonvulsant, mood stabilizer, anti-migraine

Forms:

  • Extended-release tablet

How it’s taken:

  • By mouth

What is Divalproex ER used for?

The FDA has approved extended-release divalproex to treat manic or mixed episodes in bipolar patients and a variety of seizure types. It’s also approved as a long-term maintenance migraine treatment to reduce the incidence of migraine episodes.

What form(s) does Divalproex ER come in

  • Extended-release tablet 

    • 250 mg

    • 500 mg

What are common Divalproex ER doses?

  • For bipolar manic or mixed episodes in adults: 25–60 mg/kg taken by mouth once daily

  • For complex partial seizures in adults and children 10 years of age and older: 10–60 mg/kg taken by mouth once daily

  • For simple and complex absence seizures in adults: 15–60 mg/kg taken by mouth once daily

  • For migraine prevention in adults: 500–1,000 mg taken by mouth once daily

Common Divalproex ER prescriptions

  • Divalproex Sodium ER
    250mg tablet

  • Divalproex Sodium ER
    500mg tablet

  • Divalproex Sodium ER
    250mg tablet extended release 24 hour

  • Divalproex Sodium ER
    500mg tablet extended release 24 hour

How to take Divalproex ER

  • Take this medicine as prescribed. The dose may need to be changed several times at the start of treatment. 

  • Do not take more than prescribed. If the medicine is not working, talk to the prescriber.

  • Please read the Medication Guide that comes with this medicine.

  • Divalproex ER tablets can be taken with or without food. If the tablet causes digestive system distress, take future doses with food.

  • Swallow the tablet whole with a drink of water. Do not crush, break, or chew it.

  • If you cannot swallow a tablet, talk to the prescriber.

  • Do not stop taking doses until consulting with the prescriber.

  • Store divalproex ER tablets at room temperature out of the reach of children.

What to do if you miss a dose of Divalproex ER

  • Take a dose as soon as soon as possible. 

  • If it is almost time for your next dose, wait until then and take a regular dose. 

  • Do not take two doses to make up for a missed dose.

Divalproex ER contraindications

  • This medicine is not right for everyone. 

  • Do not use it if you have had an allergic reaction to divalproex, valproate sodium, or valproic acid. 

  • Do not use divalproex ER to prevent migraine headaches if you are pregnant.

  • Divalproex ER is also contraindicated in people with:

    • Liver disease

    • Genetic disorders that can affect liver function (mitochondrial disorders)

    • A genetic disorder called urea cycle disorder

Divalproex ER warnings

  • Tell any doctor or healthcare professional treating you about your use of divalproex ER. Valproate can interfere with some important blood tests.

  • The prescriber will need regular visits to check your progress and perform blood tests. Keep all appointments.

  • Tell the prescriber if you’re pregnant before starting divalproex. It is not safe to take this medicine during pregnancy. It could harm an unborn baby. 

  • Immediately inform the doctor if you become pregnant while on divalproex.

  • Tell your doctor if you are breastfeeding or if you have:

    • Liver disease or a history of liver disease

    • Have a mitochondrial disorder or urea cycle disorder

    • Blood disease

    • Pancreas problems

    • A viral infection (including HIV or cytomegalovirus infection)

    • A history of depression, suicide, or other mental health problems

  • Tell the prescriber about drinking alcohol before starting divalproex.

  • This medicine may cause the following problems:

    • Liver problems

    • Pancreatitis (swelling of the pancreas)

    • High ammonia levels in the blood

    • Depression or thoughts of suicide

    • Bleeding problems

    • Hypothermia (low body temperature)

  • In rare cases, divalproex can cause a serious allergic reaction that affects vital organs such as the heart, liver, or kidney. Immediately contact the prescriber if you notice symptoms such as rash, swollen lymph nodes, fever, and other signs.

  • Divalproex increases the risk of suicidal thoughts and behaviors. Talk with the prescriber right away if you notice any thoughts or behavior changes that concern you. 

  • This medicine may make you dizzy or drowsy. Do not drive or do anything else that could be dangerous until you know how this medicine affects you.

  • Divalproex can reduce male fertility. Men who are trying to have children with their partner should talk to the prescriber. 

  • Do not stop using this medicine suddenly until talking to the prescriber. Abrupt discontinuation of divalproex can bring on seizures unless the dose is gradually reduced.

  • If you notice any residue from the tablet in your stool, contact the prescriber. They may need to perform a blood test to ensure the therapy is working.

Divalproex ER interactions

  • To avoid possible drug interactions, tell the doctor about all prescription drugs, over-the-counter medications, supplements, and herbal remedies being used, particularly:

    • Other anticonvulsants, particularly carbamazepine, ethosuximide, felbamate, lamotrigine, phenobarbital, phenytoin, primidone, or topiramate

    • Carbapenem antibiotics

    • Estrogen-containing contraceptives

    • Antidepressants

    • Cannabinoids (CBD)

    • Aspirin, methotrexate, Paxlovid, propofol, rifampin, ritonavir, rufinamide, tolbutamide, warfarin, zidovudine

  • Do not drink alcohol when taking divalproex.

  • The drowsiness and other impairments caused by drugs or supplements that make you sleepy may worsen when these are taken with divalproex.

Divalproex ER side effects

Serious side effects

Talk to a doctor if you notice any signs or symptoms of a possible serious side effect, including:

  • Thoughts of hurting yourself, depression, unusual changes in behavior or moods

  • Dark urine or pale stools, loss of appetite, stomach pain, yellow skin or eyes

  • Sudden and severe stomach pain, nausea, vomiting, lightheadedness

  • Unusual bleeding, bruising, or weakness

  • Confusion, low energy, lethargy, vomiting, rapid breathing, behavior changes

  • Shivering, feeling unusually cold, cold skin, confusion, drowsiness, clumsiness, slurred speech, slow breathing

  • Blistering, peeling, red skin rash

  • Fever, rash, swollen glands in the neck, armpit, or groin

  • Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing

Less serious side effects

  • Nausea

  • Headache

  • Vomiting

  • Weakness

  • Sleepiness

  • Dizziness

  • Tremor

  • Abdominal pain

  • Vision changes

  • Diarrhea

  • Loss of appetite

  • Flu-like symptoms

  • Infection

  • Stomach upset

  • Trouble sleeping

  • Nervousness

  • Hair loss

Sources:

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