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Divalproex sodium: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Aug 17, 2022.

1. How it works

  • Divalproex sodium may be used to treat certain types of seizure, to reduce mania in people with bipolar disorder, and as a preventive treatment for migraines.
  • Experts are not exactly sure how divalproex sodium works although they suspect its activity is related to increased brain concentrations of gamma-aminobutyric acid (GABA) - a neurotransmitter in the brain that calms nervous activity.
  • Divalproex sodium belongs to the class of medicines known as antiepileptics (AEDs) or anticonvulsants. It may also be called a mood stabilizer when it is used for the treatment of bipolar disorder.

2. Upsides

  • May be used either alone or in combination with other antiepileptics for the treatment of complex partial seizures, absence seizures, and for several other types of seizure.
  • May be used to control manic episodes in people with bipolar disorder.
  • May be effective for the prevention of migraine headaches in some people.
  • Generic Divalproex is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Abdominal pain, nausea, diarrhea, constipation, dizziness, drowsiness, weakness, or weight loss. May also cause bleeding gums, bloating or swelling, cough, a tremor, hair loss, ataxia, nystagmus, skin rash, and thinking difficulties. More likely to cause drowsiness in the elderly.
  • Side effects such as an increase in liver enzymes and thrombocytopenia (a decrease in platelet numbers in the blood) are more prevalent at higher dosages.
  • Liver failure resulting in death has occurred with Divalproex treatment. Most cases have occurred during the first six months of treatment and in children under two with severe seizure or metabolic disorders, mitochondrial disease, mental retardation, or taking multiple anticonvulsants. Liver tests should be conducted before treatment and then repeated periodically thereafter.
  • Divalproex sodium may not be suitable for everyone including those with depression or other mental illness, HIV or cytomegalovirus infection, liver disease, mitochondrial disorders, or urea cycle disorders. Older people may be more sensitive to the side effects of Divalproex and require a lower starting dose and slower upward titration schedule.
  • Generally should be avoided in women who are pregnant or planning pregnancy due to the risk of major birth defects (such as neural tube defects), neurodevelopmental disorders, and decreased IQ scores following in utero exposure. However, Divalproex may be considered if there is no other suitable treatment for a woman's seizure or bipolar disorder.
  • Divalproex should not be used as a prophylactic treatment for migraine in women who are pregnant. All other women of child-bearing potential taking Divalproex as a prophylactic treatment for migraine should use effective contraception.
  • Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate short-term or long-term; symptoms include abdominal pain, nausea, vomiting, and weight loss.
  • As with other antiepileptics, Divalproex sodium may increase the risk of suicidal thoughts or behavior particularly in young adults under the age of 24. Monitor for worsening mood.
  • May cause a lowering of body temperature (hypothermia) and hypersensitivity reactions.
  • May elevate ammonia levels in the blood causing symptoms such as unexplained tiredness and vomiting and changes in mental status. Seek urgent medical advice.
  • May interact with a number of different medications including topiramate, other antiepileptics, ritonavir, carbapenem antibiotics (such as ertapenem, imipenem), and warfarin.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

  • Divalproex may be used for the treatment of absence or partial seizures, as a preventive treatment for migraine, and to treat mania associated with bipolar disorder. Divalproex may adversely and fatally affect the liver; children under two with other comorbidities are more at risk.

5. Tips

  • Swallow Divalproex whole, do not crush or chew.
  • The dosage of Divalproex depends on a number of factors including a person's age, the reason divalproex is prescribed, an individual's sensitivity to side effects, and the hydration and nutritional status of a person. Always take divalproex exactly as prescribed. Never take too much divalproex or stop suddenly without your doctor's advice. Symptoms of overdosage of Divalproex include changes in consciousness, fainting, and slow or irregular heartbeat.
  • Always take Divalproex with plenty of water and maintain good hydration throughout the day.
  • May be taken with or without food; however, food may decrease the incidence of indigestion or stomach irritation.
  • Take exactly as prescribed by your doctor. If you miss a dose, take it as soon as you remember; however, do not double up a dose if it is almost time for the next dose. Read the medication guide to familiarize yourself with the medication.
  • If Divalproex makes you drowsy, avoid driving or other hazardous tasks. Avoid alcohol as it will contribute to the drowsiness.
  • May be given once daily, unless a two to three times daily dosing schedule is deemed beneficial or the total daily dose exceeds 250mg.
  • Talk with your doctor if you notice any medication residue in your stools. You may not be getting the full dose of your medicine.
  • Be alert for changes in behavior including agitation, depressed mood, and suicide-related events, and seek medical advice if changes are apparent.
  • Contact your doctor urgently if you experience stomach pain that spreads to your back, nausea and vomiting, dark urine, facial swelling, loss of appetite, or yellowing of the skin or eyes. Also contact your doctor if you experience any mood changes, unusual bruising or bleeding, flu-like symptoms, severe skin reactions, or worsening of your symptoms.
  • Blood tests may be needed to monitor the effects of Divalproex.
  • Always tell your dentist or healthcare provider that you take Divalproex. Wearing a medical alert tag is a good idea.
  • Avoid excessive sunlight exposure or tanning beds as Divalproex may make you burn more easily. Wear sunblock and protective clothing when outdoors.
  • Divalproex is not recommended during pregnancy except when the benefits of taking the drug outweigh the risks. Tell your doctor if you inadvertently become pregnant or are intending to become pregnant so they can advise you on what to do. You should use adequate contraception while taking Divalproex. If you do become pregnant, you should enroll on the pregnancy registry, toll-free at 1-888-233-2334. Divalproex should not be used for the prevention of migraine headaches in pregnant women and women of childbearing potential who are not using effective contraception.

6. Response and effectiveness

  • It takes about four hours for divalproex sodium to reach maximum concentrations in the blood after a single dose. However, it may take several weeks for a beneficial effect to be seen, depending on the condition being treated.

7. Interactions

Medicines that interact with divalproex sodium may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with divalproex sodium. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with divalproex sodium include:

  • antibiotics such as clarithromycin, doxycycline, erythromycin
  • anticonvulsants such as lamotrigine, phenytoin, and phenobarbitone
  • antidepressants, such as desipramine, doxepin, isocarboxazid, nefazodone, phenelzine, or venlafaxine
  • antihistamines, such as azelastine, cetirizine, or levocetirizine
  • antipsychotics, such as aripiprazole, clozapine, haloperidol, or quetiapine
  • aspirin
  • carbapenem antibiotics, such as ertapenem, imipenem, or meropenem
  • clonidine
  • dextromethorphan
  • felbamate
  • folic acid
  • HIV medications such as indinavir and ritonavir
  • estrogen or progestin-containing oral contraceptives and hormonal treatments
  • medications that cause drowsiness, such as benzodiazepines, sedating antihistamines, and sleeping pills
  • methotrexate
  • metoclopramide
  • montelukast
  • muscle relaxants, such as baclofen
  • opioid analgesics such as buprenorphine, codeine, fentanyl, oxycodone, and morphine
  • rifampin
  • tramadol
  • trazodone.

Alcohol may worsen the side effects of divalproex sodium such as drowsiness, dizziness, and liver toxicity.

Note that this list is not all-inclusive and includes only common medications that may interact with divalproex sodium. You should refer to the prescribing information for divalproex sodium for a complete list of interactions.


Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use divalproex sodium only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2023 Revision date: August 17, 2022.