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How does this medication work? What will it do for me?

Divalproex belongs to the family of medications called anticonvulsants. It is used to manage and control 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 bipolar disorder to treat manic episodes.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

How should I use this medication?

The recommended adult dose of divalproex to treat seizures is based on weight and the final dose is determined by control of seizures with minimal side effects. The recommended initial dosage is 15 mg per kg of body weight per day. Your doctor may then suggest increasing at one-week intervals by 5 to 10 mg per kg of body weight per day until seizures are controlled or side effects prevent further increases. The maximum recommended dosage is 60 mg per kg of body weight per day.

When taken to treat manic episodes, the starting dose is 250 mg 3 times daily.

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.

When the dose of divalproex increases above 250 mg per day, it should be taken in divided doses.

The tablets should be swallowed whole and can be taken with or without food. This medication should not be stopped suddenly due to the possibility of a rebound major seizure.

It is important to take this medication exactly as prescribed by your doctor. If you miss a dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.

What form(s) does this medication come in?

pms-Divalproex is no longer being manufactured for sale in Canada. For brands that may still be available, search under "divalproex". This article is being kept available for reference purposes only. If you are using this medication, speak with your doctor or pharmacist for information about your treatment options.

Who should NOT take this medication?

Do not take divalproex if you:

  • are allergic to valproic acid, divalproex, or any ingredients of the medication
  • have been diagnosed with a urea cycle disorder
  • have liver disease or a significant reduction in liver function
  • have Alpers syndrome or Alpers-Huttenlocher syndrome, conditions caused by nervous system breakdown
  • have porphyria
  • are pregnant and are taking this medication for epilepsy unless there is no suitable alternative for seizure management
  • are pregnant and are taking this mediation for bipolar disorder
  • are a woman who could become pregnant and cannot follow the recommended birth control measures.
What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

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.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

  • diarrhea
  • dizziness
  • headache
  • increased appetite (possibly causing weight gain)
  • indigestion or heartburn
  • nausea
  • sleepiness
  • tiredness
  • vomiting
  • weakness

Although most of the side effects listed below don't happen very often, they could lead to serious problems if you do not seek medical attention.

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

  • changes in hair (hair loss or increased hair on face, chest, and back)
  • decreased coordination, loss of motor skills
  • difficulty speaking, reading, or understanding
  • hallucinations
  • increase in seizures
  • memory loss
  • nausea or vomiting (continuing)
  • signs of bleeding (e.g., unusual nosebleeds, bruising, blood in urine, coughing blood, bleeding gums, cuts that don't stop bleeding)
  • signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide) or other mood changes
  • signs of hypothermia (low body temperature; e.g., shivering, slurred speech, mumbling, slow and shallow breathing, weak pulse, confusion, very low energy, memory loss)
  • signs of kidney problems (e.g., nausea; vomiting; fever; swelling of arms and legs, hands, and feet; thirst; dry skin; dark urine; changed urine output; blood in the urine; weight gain; loss of appetite; drowsiness; confusion)
  • signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
  • signs of muscle damage (e.g., muscle pain, tenderness, or weakness or brown or discoloured urine) - especially if you also have a fever or a general feeling of being unwell
  • tremor
  • urinary incontinence (involuntary loss of urine)

Seek immediate medical attention if any of the following occur:

  • signs of pancreatitis (e.g., abdominal pain on the upper left side, back pain, nausea, fever, chills, rapid heartbeat, swollen abdomen)
  • severe skin reactions on a large area of the body or on the lips (e.g., ulcers, blisters, pain, redness, skin peeling)
  • signs of a serious allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, or swelling of the face and throat)
  • symptoms of high levels of ammonia in the blood (e.g., tiredness, vomiting, abnormal walking, extreme irritability, combative or bizarre behaviour, avoidance of high protein products such as meat)
  • thoughts of hurting yourself or others

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Behaviour changes: People taking this medication have occasionally experienced aggressive behaviour or hostility, anxiousness, disorientation, or decreased memory. If you experience any of these effects or notice them in a family member who is taking this medication, contact your doctor as soon as possible.

Blood clotting: This medication may make it more difficult for the blood to clot. If you take anticoagulant medications (blood thinning) medications, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. If you notice any signs of bleeding, such as frequent nosebleeds, unexplained bruising, or black and tarry stools, notify your doctor as soon as possible. Your doctor will order routine blood tests to make sure potential problems are caught early.

Drowsiness/reduced alertness: Divalproex may cause drowsiness, especially when combined with alcohol or another sedating medication. Avoid driving or other potentially dangerous activities until you determine how this medication affects you.

Multi-organ hypersensitivity reaction: A severe allergic reaction has occurred on rare occasions for some people with the use of divalproex, as well as other medications to treat seizures. This reaction involves a number of organs in the body and may be fatal if not treated quickly. Stop taking the medication and get immediate medical attention if you have symptoms of a severe allergic reaction, including fever, swollen glands, yellowing of the skin or eyes, or flu-like symptoms with skin rash or blistering.

Kidney disease: Kidney disease or reduced kidney function may cause divalproex to build up in the body, causing side effects. If you have reduced kidney function or kidney disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Liver function: Liver failure has occurred infrequently for people taking divalproex. In most cases, this has happened during the first 6 months of treatment. The risk is highest for children under the age of 2 years, especially those who take more than one antiseizure medication, or those who have certain medical conditions (e.g., metabolic disorders, brain disease, severe seizure disorders accompanied by mental retardation).

Children aged 3 to 10 years are also at a higher risk if they take more than one antiseizure medication.

Liver function tests should take place before starting treatment with divalproex. Your doctor may also perform liver function tests regularly to monitor the function of your liver. Serious liver problems may happen after symptoms such as loss of seizure control, malaise, weakness, lethargy, loss of appetite, and vomiting. People who take valproic acid should tell their doctor at once if they experience these symptoms. Increases in the levels of ammonia in the blood, with or without lethargy or coma, have been reported and may be present despite normal liver function tests.

Pancreatitis: People taking divalproex have experienced life-threatening pancreatitis (inflammation of the pancreas). These cases have occurred shortly after starting the medication and after several years of taking the medication. If you experience signs of pancreatitis such as abdominal pain on the upper left side, back pain, loss of appetite, nausea, fever, chills, rapid heartbeat, or swollen abdomen, contact your doctor immediately.

Suicidal thoughts: There is a small risk that this medication may result in thoughts of suicide. If you experience these symptoms or any other behaviour change while taking this medication, contact your doctor immediately. Family members or caregivers of people who are taking this medication should contact the person's doctor immediately if they notice unusual behaviour changes.

Stopping this medication: People who need this medication to prevent major seizures should not stop taking it suddenly as this can increase the risk of getting seizures. Do not stop taking this medication without consulting with your doctor first.

Pregnancy: There is an increased risk of serious birth defects for a child whose mother takes divalproex during pregnancy. Divalproex may cause a number of defects including a defect of the spine called spina bifida, cleft palate, heart defects, autism, or slowed or reduced mental development. This medication should not be used during pregnancy for treatment of epilepsy unless there is no other suitable alternative treatment. This medication should not be used during pregnancy for treatment of bipolar disorder. Women of child-bearing age must use effective contraception while taking this medication.

Before becoming pregnant, women who are taking divalproex should speak to their doctor. If possible, a switch to another medication to treat epilepsy should be considered. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding: This medication passes into breast milk. If you are a breast-feeding mother and are taking divalproex, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding. As a general rule, women who are taking divalproex should not breast-feed.

Children: If divalproex is taken by children 2 years old or younger, it should not be used in combination with other antiseizure medications and the doctor should monitor the child regularly. Divalproex is not recommended to treat mania for children under 18 years of age.

Seniors: People over the age of 65 may be more at risk of developing side effects from this medication and may require lower dosages.

What other drugs could interact with this medication?

There may be an interaction between divalproex and any of the following:

  • acarbose
  • alcohol
  • antihistamines (e.g., azelastine, bilastine, cetirizine, doxylamine, diphenhydramine, hydroxyzine)
  • antipsychotic medications (e.g., chlorpromazine, haloperidol, olanzapine, risperidone)
  • ASA (acetylsalicylic acid)
  • azelastine
  • barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
  • benzodiazepines (e.g., clonazepam, diazepam, lorazepam)
  • birth control pills (estrogens)
  • bismuth subsalicylate
  • brimonidine
  • cannabis
  • cholestyramine
  • chloral hydrate
  • cimetidine
  • dolutegravir
  • empagliflozin
  • ertapenem
  • erythromycin
  • estrogens (e.g., conjugated estrogen, estriol)
  • guanfacine
  • HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir)
  • imipenem
  • irinotecan
  • isoniazid
  • lemborexant
  • lithium
  • lomustine
  • mefloquine
  • methotrexate
  • minoxidil
  • monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine)
  • muscle relaxants (e.g., cyclobenzaprine, methocarbamol, orphenadrine)
  • narcotic pain medications (e.g., codeine, hydromorphone, morphine, oxycodone, tramadol)
  • meropenem
  • orlistat
  • pramipexole
  • pregabalin
  • rifampin
  • seizure medication (e.g., carbamazepine, ethosuximide, isoniazid, lamotrigine, levetiracetam, oxcarbazepine, phenytoin, primidone, rufinamide, topiramate)
  • scopolamine
  • selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, paroxetine, sertraline)
  • sodium phenylbutyrate
  • temozolomide
  • tricyclic antidepressants (e.g., amitriptyline, nortriptyline)
  • vorinostat
  • warfarin
  • zidovudine
  • zolpidem
  • zopiclone

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. 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 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.

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