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Valproic acid/divalproex (Depakene®/Epival®)

Depakene®/Epival® and generic forms belong to a group of medications called “anticonvulsants” and “mood stabilizers.”

What is this medication used for?

Divalproex/valproic acid (referred to as “valproic acid” in this document) is approved by Health Canada for treatment of seizure disorders (epilepsy) in children 2 years of age and older. It is approved for treatment of manic episodes associated with bipolar disorder in adults.

When potential benefits outweigh risks, valproic acid may be prescribed “off-label” for treatment and prevention of manic episodes and depression associated with bipolar disorder, management of impulsive or aggressive behaviour, treatment of irritability associated with autism spectrum disorder, and prevention of migraine headaches. Learn more about off-label medication use:

Tell your doctor or pharmacist if you:

  • Have allergies or bad reactions to a medication.
  • Take (or plan to take) other prescription or non-prescription medications, including natural medicines. Some medications interact with valproic acid. Your doctor may adjust medication doses or monitor for side effects.
  • Have a history of pancreas, kidney or liver disease, polycystic ovarian syndrome, seizures, blood or brain disorders, serious skin reactions to medications, a urea cycle disorder or mitochondrial disease.
  • If you experience seeing, hearing or feeling things that are not there (hallucinations).
  • Miss a menstrual period, are pregnant, breast-feeding or planning a pregnancy.
  • Use alcohol or drugs. Taking valproic acid together with certain substances may cause a bad reaction. Learn more at

When will the medication start to work?

It may take 1 to 2 weeks before the benefits of valproic acid become noticeable. Improvement may be seen earlier if valproic acid is combined with other medications. A delay in response is normal.

You (or your family members) may notice clearer thoughts, less moodiness, anger, irritability, or explosive behaviour. If you experience seeing, hearing or feeling things that are not there, this may also decrease or stop entirely.

It is important that you continue taking valproic acid regularly, even if you are feeling well or there are no improvements in the first few weeks. Talk with your doctor if you feel that valproic acid has not been helpful or if side effects are too bothersome. Your doctor may recommend switching you to a different medication.

This medication is not addictive. Do not stop taking it before
talking to your doctor.

How do I take this medication?

Valproic acid is usually taken two or three times a day, at the same time(s) each day with food. Usually, you will start with a low dose and slowly increase this dose over several days or weeks, based on how you tolerate it.

Your doctor may ask you to have blood tests to measure the amount of valproic acid in your blood. Do not take your dose just before a blood test as this can affect your results. Instead, take your dose after the blood test is completed.

There are several forms of valproic acid: capsules, syrup, and enteric-coated tablets (divalproex). Valproic acid syrup may be mixed with food or liquids to help you take the medication. Valproic acid capsules and tablets should be swallowed whole and should not be crushed or chewed.

Possible common or serious side effects:

Side effects may be more common when starting a medication or after a dose increase. Talk to your doctor, nurse or pharmacist if any side effect concerns you.

  • Clumsiness, drowsiness, clouded thinking or headache.
  • Feelings of agitation, restlessness or shaking of hands.
  • Increased appetite or weight gain.
  • Stomach ache, nausea, vomiting or diarrhea.
  • Mild skin rash or skin itching.
  • Hair loss.

Contact your doctor immediately if you experience:

  • Unexplained rash, seizure, fever or excessive sweating.
  • Aggression, hyperactivity, agitation or irritability.
  • Loss of appetite, stomach pain, severe nausea or vomiting.
  • Yellow skin or eyes, itchiness, weakness, dark colored urine, or abdominal pain.
  • Swelling in the face, ankles, feet or lower legs.
  • Thoughts of hurting yourself, suicide, increased hostility or worsening symptoms.
  • In females: acne, hair growth, menstrual irregularities, or excessive weight gain.

What precautions should my doctor and I be aware of when taking this medication?

  • Many medications may interact with valproic acid, including blood thinning medications, mood stabilizers, anticonvulsants, antidepressants, anti-anxiety medications, antibiotics and several other medications. If you are (or begin) taking any other prescription, over-the-counter medication, natural health product or supplement, check with your doctor or pharmacist to see if they are safe to use.
  • While taking this medication, if you feel dizzy, drowsy or slowed down, do not drive a car or operate heavy machinery. Alcohol could make this worse. Try to avoid alcohol while taking valproic acid.

How does this medication work?

Valproic acid affects actions of the brain chemicals GABA and glutamate. This has a “stabilizing” effect on nerves, which helps reduce severe mood fluctuations, the spread of seizure activity in the brain and prevent migraine headaches. The exact way that valproic acid improves symptoms of bipolar disorder, migraine headaches, and other conditions is not known.

What special instructions should I follow while using this medication?

  • Keep all appointments with your doctor and the lab. Your doctor may order lab tests to check how you are responding and monitor for side effects.
  • Try to keep a healthy, well-balanced diet and exercise regularly. Some people may gain weight as a result of increased appetite.
  • Do not allow anyone else to use your medication.

What should I do if I forget to take a dose of this medication?

If you take valproic acid regularly and forget to take a dose, take the missed dose as soon as you remember. However, if it is within 4 hours of your next scheduled dose, skip the missed dose and continue with your regular schedule. DO NOT double your next dose to try to ‘catch up.’

How do I store this medication?

Keep this medication in the original container, stored at room temperature away from moisture and heat and protected from light. Keep this medication out of reach and sight of children.

How well does the medication work in children and adolescents?

Evidence from adults shows that valproic acid helps reduce symptoms of a manic or depressive episode associated with bipolar disorder, as well as prevent future mania or depression episodes from occurring. It may be used alone or in combination with other mood stabilizers to manage bipolar disorder. When effective, valproic acid helps to stabilize mood, control emotions and improve overall functioning. Valproic acid may be helpful for people who have symptoms of mania and depression occurring at the same time, or those who have more than four mood episodes per year. Valproic acid has been studied for migraine prevention in adults and has been shown to be significantly better than placebo (an inactive pill). Valproic acid may help manage irritability associated with autism spectrum disorder and aggressive or impulsive behavioural problems.

How long should I take the medication for?

This depends on the symptoms you have, how frequently they occur, and how long you have had them. Most people with bipolar disorder will need to take valproic acid for at least 6 months. This allows time for symptoms to stabilize and for function to improve.

Your doctor will discuss the benefits and risks of taking valproic acid with you. At this time, you can also discuss how long you might need to take this medication. If you have epilepsy or bipolar disorder and you tolerate this medication well, you may be asked to take this medication on an ongoing basis.

Do not increase, decrease, or stop taking this medication without discussing it with your doctor. If you stop taking valproic acid suddenly, it is possible that your symptoms may return or you may experience a seizure.

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