Divalproex is an anticonvulsant medication used for the management and control of certain types of seizures. It can be used alone or in combination with other seizure control medications. It is also used for people 18 years of age and older with manic depression (bipolar disorder) to treat manic episodes.

Your doctor may choose to use a medication for conditions other than the ones listed in these drug information articles. If you're unsure why you are taking this medication, contact your doctor.

The recommended adult dose of divalproex is based on weight and the final dose is determined by control of seizures with minimum of side effects. The tablets should be swallowed whole and can be taken with food to avoid stomach upset. When the dose of divalproex increases above 250 mg per day, it should be taken in divided doses. This medication should not be stopped suddenly due to the possibility of a rebound major seizure.

Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor. Do not stop taking this medication without talking with your doctor first.

It is very important that this medication be taken exactly as prescribed by your doctor. If you miss a dose, take it as soon as possible and continue on with your regular schedule. If it is almost time for your next dose, skip the missed dose and continue on with your regular dosing schedule. Do not double doses.

Epival^® is available in tablet or injectable form.

Tablets:
125 mg: Each enteric-coated, salmon-pink tablet contains divalproex sodium equivalent to valproic acid 125 mg. Nonmedicinal ingredients: cellulosic polymers, diacetylated monoglycerides, FD&C Red No. 40, povidone, pregelatinized starch (contains cornstarch), silicon dioxide, talc, titanium dioxide, and vanillin.
250 mg: Each enteric-coated, peach-coloured tablet contains divalproex sodium equivalent to valproic acid 250 mg. Nonmedicinal ingredients: cellulosic polymers, diacetylated monoglycerides, FD&C Yellow No. 6, povidone, pregelatinized starch (contains cornstarch), silicon dioxide, talc, titanium dioxide, and vanillin.
500 mg: Each enteric-coated, lavender-coloured tablet contains divalproex sodium equivalent to valproic acid 500 mg. Nonmedicinal ingredients: cellulosic polymers, D&C Red No. 30, diacetylated monoglycerides, FD&C Blue No. 2, povidone, pregelatinized starch (contains cornstarch), silicon dioxide, talc, titanium dioxide, and vanillin.
The tablets do not contain alcohol, gluten, lactose, paraben, sucrose, sulfite, or tartrazine.

Injectable: Each mL of clear, colourless solution contains valproate sodium equivalent to valproic acid 100 mg, edetate disodium 0.4 mg, and water for injection. The pH is adjusted to a range of 7.0 to 9.0 with sodium hydroxide and/or hydrochloric acid. This product does not contain preservatives.

Divalproex should not be taken by anyone who has:

• liver disease or a significant reduction in liver function
• an allergy to valproic acid or divalproex or to any of the ingredients of the medication

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor. Your health professional may be able to help you deal with some of the effects.

The following side effects may go away as your body becomes used to the medicine; check with your doctor if they continue or become bothersome.

More common:

• abdominal or stomach cramps (mild)
• change in menstrual periods
• diarrhea
• hair loss
• indgestion
• loss of appetite
• nausea and vomiting
• trembling of hands and arms
• unusual weight loss or gain

  Less common or rare:

• clumsiness or unsteadiness
• constipation
• dizziness
• drowsiness
• headache
• skin rash
• unusual excitement, restlessness, or irritability

Check with your doctor as soon as possible if any of the following side effects occur:

Less common:

• abdominal or stomach cramps (severe)
• behavioural, mood, or mental changes
• continuous, uncontrolled "back and forth" or rolling eye movements
• double-vision
• increase in seizures
• loss of appetite
• nausea or vomiting (continuing)
• spots before eyes
• swelling of face
• tiredness and weakness
• unusual bleeding or bruising
• yellow eyes or skin

Other side effects not listed above may occur in some people. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Liver: Liver failure has occurred infrequently for people taking divalproex. In most cases, this has happened during the first six months of treatment. The risk is highest for children under the age of two years, especially those who take more than one anti-seizure medication, or those who have certain medical conditions (e.g., metabolic disorders and brain disease). Children aged 3 to 10 years are also at a higher risk if they take more than one anti-seizure medication.

The following symptoms may appear before serious liver problems develop; if they do, contact your doctor at once.

• loss of seizure control
• malaise
• weakness
• lethargy
• loss of appetite
• vomiting

Occupational hazards: This medication may cause drowsiness, especially when combined with another sedating drug such as alcohol. Avoid driving or other potentially dangerous activities until you determine the effect of this medication on you.

Blood clotting: Divalproex may make it more difficult for the blood to clot. If you take this medication, take appropriate precautions and ensure that all doctors involved in your care know you use this medication. Before any surgery is performed, tests for blood clotting are necessary.

Pregnancy: In the stomach, divalproex breaks down into a substance called valproate (also known as valproic acid). Valproate has been linked to an increased risk of birth defects, including neural tube defects (e.g., spina bifida). People who need this medication to prevent major seizures should not stop taking it suddenly, as the risks posed by the seizures outweigh those posed by the medication. For those taking it to prevent minor seizures, the risks of seizures should be weighed against the risk of birth defects. If you are or may become pregnant, talk to your doctor about the risks and benefits of using this medication during pregnancy.

Breast-feeding: This medication passes into breast milk. As a general rule, women taking divalproex should not nurse.

Children: If divalproex is taken by children two years old or younger, it should be used with extreme caution and should not be used in combination with other anti-seizure medications. The benefits of seizure control should be weighed against the risk of liver failure (see above) and other problems.

• alcohol
• ASA
• carbamazepine
• cholestyramine
• chlorpromazine
• cimetidine
• felbamate
• MAO inhibitors (e.g., phenelzine)
• phenobarbital
• phenytoin
• primidone
• rifampin
• salsalate
• SSRIs (e.g., fluoxetine, fluvoxamine)
• tricyclic antidepressants (e.g., amitriptyline)

Divalproex may affect how the following medications work:

• ASA
• benzodiazepines (e.g., diazepam, lorazepam)
• carbamazepine
• lamotrigine
• phenobarbital
• phenytoin
• primidone
• tolbutamide
• warfarin
• zidovudine

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. In many cases, interactions are intended or are managed by close monitoring. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications that you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.