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Depakote (Divalproex)

Last updated on June 2nd, 2023

Depakote 250mg and 500mg Tablets. Valproic acid (as valproate semisodium)

What Depakote is and what it is used for

The name of your medicine is Depakote 250mg or 500mg Tablets. Depakote contains a medicine called valproate semisodium. This belongs to a group of medicines called mood stabilisers. It works by stabilising the evels of chemicals in your brain that affect your mood.

Depakote can be used to manage or control mania (feeling highly excited, enthusiastic, being over-active and easily irritated or distracted) caused by bipolar disorder. Bipolar disorder is where the mood changes between feeling very high (mania) and very low (depression). Depakote can be used when lithium can not be used.

Before you take Depakote

Do not take Depakote and tell your doctor if:

  • You are allergic (hypersensitive) to valproate semisodium or any of the other ingredients of Depakote
  • Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue
  • You have liver problems
  • You or a family member has ever had liver problems caused by taking a medicine
  • You have a rare illness called porphyria which affects your metabolism

Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Depakote.

Take special care with Depakote

A small number of people being treated with mood stabilisers such as valproate semisodium have had thoughts of harming or killing themselves. If at any time you have these thoughts, immediately contact your doctor.

Check with your doctor or pharmacist before taking your medicine if:

  • You are changing from another medicine that contains valproate
  • The person taking this medicine is less than 18 years old
  • You have fits (epilepsy), brain disease or a metabolic condition affectingyour brain.
  • You have kidney problems
  • You have problems with your pancreas
  • You have an illness called ‘systemic lupus erythematosus’. This is a disease of the immune system which affects the skin, bones, joints and internal organs
  • You have a metabolic condition which results in too much ammonia in the blood (shown in blood tests)
  • You have diabetes or are being tested for diabetes. This medicine may affect the results of urine tests

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Depakote.

Weight gain

Taking Depakote may make you put on weight. Talk to your doctor about how this will affect you.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because Depakote can affect the way some other medicines work. Also, some medicines can affect the way Depakote works.

In particular, do not take and check with your doctor if you are taking any of the following:

Some medicines used for pain and inflammation called ‘salicylates’ such as aspirin.

The following medicines can affect the way Depakote works or Depakote can affect the way some of these medicines work:

  • Some medicines used to treat fits (epilepsy) such as phenobarbital, primidone, phenytoin, carbamazepine, topiramate, lamotrigine and felbamate. Your doctor may change the dose of one of your medicines and monitor your treatment closely
  • Medicines for depression
  • Medicines used to calm emotional and menta conditions such as diazepam and olanzapine
  • Zidovudine-used for HIV infection
  • Some medicines used for infections such as panipenem, imipenem.and meropenem (carbapenem antibiotics), rifampicin or erythromycin
  • Some medicines used for malaria such as mefloquine or chloroquine
  • Medicines used for thinning the blood such as warfarin. Your doctor may change your dose of the blood thinning medicine and monitor your treatment closely.
  • Temozolomide-used for cancer
  • Cimetidine – used for stomach ulcers
  • Colestyramine – used for lowering blood cholesterol levels

Pregnancy and breast-feeding

You should not take this medicine if you are pregnant or a woman of child-bearing age unless explicitly advised by your doctor.

Ask your doctor or pharmacist for advice before taking any medicine if you are pregnant or breast-feeding.

Women who could become pregnant

Before you start taking Depakote, your doctor should discuss with you the possible problems when it is taken in pregnancy.

Unplanned pregnancy is not desirable in women taking Depakote

You should use an effective method of contraception and talk to your doctor before planning pregnancy. Depakote has no effect on how well the oral contraceptive pill works.

Well before you become pregnant it is important to discuss pregnancy with your doctor and, if you have one, your specialist. This is to make sure that you and your doctor agree that you should have Depakote if you become pregnant. Women taking Depakote during pregnancy have a higher risk than other women of having a child with an abnormality. The chance of abnormalities is increased if you are also taking other medicines for epilepsy at the same time. These abnormalities include:

  • Head and face deformities including cleft palate (a gap or depression in the lip)
  • Deformities of the bones, including hip dislocation
  • Malformations of the arms and legs
  • Deformities of the tube from the bladder to the penis, where the opening is formed in a different place
  • Heart and blood vessel malformations with heart defects
  • Defects of the lining of the spinal cord
  • An abnormality of the spinal cord called ‘Spina bifida’

Women who take Depakote during pregnancy may be more likely to have a baby with spina bifida. Taking folic acid Smg each day as soon as you stop contraception may lower the risk of having a baby with spina bifida.

There is also an increased risk of other birth defects. These other defects can usually be detected in the first 3 months of the pregnancy using routine antenatal screening blood tests and ultrasound scans.

Pregnant mothers who take Depakote may have babies with blood clotting problems (such as blood not clotting or not clotting very well). This may appear as bruising or bleeding which takes a long time to stop.

Some babies born to mothers who took Depakote during pregnancy may develop less quickly than normal or have autistic disorders. These children may require additiona educational support.

Talk to your doctor before you stop taking Depakote if you want to become pregnant. Do not stop taking Depakote suddenly, as it is likely that your illness will come back.

Women who are planning to get Pregnant

If you become pregnant, think you may be pregnant or plan to become pregnant while taking Depakote, you must tell your doctor straight away.

Your doctor will give you appropriate counselling and will suggest changes to your treatment or dose

He or she will also want to check your progress while you are pregnant

It is very important that you discuss your treatment with your doctor well before you become pregnant.


If you are breast-feeding or planning to breast-feed, talk to your doctor or pharmacist before taking any medicine.


How to take Depakote

Always take Depakote exactly as your doctor has told you. Your doctor will decide your daily dose. You should check with your doctor or pharmacist if you are not sure.

How to take your medicine

Take this medicine by mouth

Swallow the tablets whole with a drink of water. Do not crush or chew them

This medicine can be taken with or after a meal

If you feel the effect of your medicine is too weak or too strong, do not change the dose yourself, but ask your doctor

How much to take

The normal dose is:

Adults including the elderly

Starting dose is 750mg on the first day. This is usually taken as 2 or 3 divided doses

The usual dose is then increased to between 1000mgand 2000mgeach day

Your doctor may decide to increase your dose depending on your illness

If you have kidney problems

Your doctor may decide to lower your dose

Children and adolescents

Children and adolescents under 18 years of age: Depakote should not be used in children and adolescents under 18 years of age for the treatment of mania


Your doctor may do regular blood tests and liver function tests before and during your treatment with this medicine.

If you take more Depakote than you should

If you or someone else has taken more Depakote than you should, talk to a doctor or go to your nearest hospital casualty department straight away. Remember to take the medicine pack with you. This is so the doctor knows what you have taken.

The following effects may happen: being sick, headache, blurred eyesight due to pupils of the eyes becoming smaller, lack of reflexes, confusion and tiredness. You may also have weak or ‘floppy’ muscles, fits (sezures), loss of consiousness, behavioura changes and breathing difficulties such as fast breathing, shortness of breath or chest pain.

If you forget to take Depakote

If you forget to take a dose at the right time, take it as soon as you remember. Do not take a double dose to make up for a forgotten dose.

If you stop taking Depakote

Keep taking your medicine until your doctor tells you to stop. Do not stop taking Depakote just because you feel better. If you stop, your illness may return.

When your doctor says that you can stop taking Depakote, your dose will be lowered gradually. Your doctor will help you to do this.

If you have any further questions on the use of this  product, ask your doctor or pharmacist.

Possible side effects

Like all medicines, Depakote can cause side effects, although not everybody gets them. Side effects are more likely to happen at the start of treatment.

Allergic reactions

If you have an allergic reaction, stop taking Depakote and see a doctor or go to a hospital straight away. The signs may include: rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue. Hands, feet or genitals may also be affected. More severe allergic reactions can lead to lymph node enlargement and possible impairment of other organs.

Stop taking Depakote and see your doctor or go to a hospital straight away if you notice a combination of any of the following serious side effects:

The following side effects may be signs of problems with your liver or pancreas and may show as a sudden illness:

  • Feeling weak, general feeling of being unwel
  • Loss of or decreased appetite (anorexia)
  • Feeling drowsy, confused or tired
  • Swelling of the feet and legs (oedema)
  • Nausea (feeling sick)
  • Vomiting (being sick)
  • Stomach pain. Sometimes may be severe and reach through to your back
  • Recurrence of fits (seizures) for patients with epilepsy
  • Yellowing of the eyes or skin

The following side effects may be signs of problems with your blood cells

  • Bruising more easily, spontaneous bruising or bleeding
  • Frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • Getting more infections than usual
  • Feeling weak, tired, faint, dizzy or having an unusually pale skin

Other serious side effects which need urgent medical attention:

  • Fits (seizures), loss or reduction of consciousness, seeing or hearing things that are not there (hallucinations)
  • Memory problems, reduced ability to perform menta tasks, being unable to concentrate
  • Difficulty in speaking or slurred speech
  • Muscle weakness, lack of co-ordination, muscle twitching or sudden jerks and shaking
  • Difficulty in walking or unusual involuntary movements, such as unusual eye movements
  • Blistering, peeling, bleeding, scaling or fluid filled patches on any part of your skin. This includes your lips, eyes, mouth, nose, genitals, hands or feet. You may also have flu-like symptoms and fever, joint aches and pains, swollen joints, headaches, chest pain and shortness of breath

Tell your doctor as soon as possible if you have any of the following side effects:

  • Unusual behaviour including being very alert, and sometimes also aggressive, hyper-active and snowing bad behaviour
  • Water retention which may cause swollen arms or legs
  • Bleeding a lot from a wound

Tell your doctor or pharmacist if any of the following side effects get serious or lasts longer than a few days

  • Hair, including body or facial hair, grows more than norma
  • Temporary hair loss
  • Acne
  • Diarrhoea
  • Night sweats or joint pain
  • Irregular periods or a lack/absence of menstrual periods
  • Breast enlargement in men
  • Loss of hearing
  • Bed wetting
  • Weight gain


Blood and urine tests may show changes in the way the kidney is working. This includes an increase in the amounts of sugar, amino acids, uric acid and phosphates. Blood tests may show changes in the amount of blood cells or levels of liver enzymes.

Tell your doctor or pharmacist if any of the following side effects gets serious or lasts longer than a few days, or if you notice any side effects not listed in this leaflet.

How to store Depakote

Keep this medicine in a safe place where children cannot see or reach it.

Do not use Depakote after the expiry date which is stated on the label after EXP. The expiry date refers to the last day of that month

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment

Further Information

What Depakote 250mg Tablets contain

Each 250mg tablet contains 269.1 mg of the active substance, valproate semisodium (equivalent to 250mg of valporic acid)

Hydrated colloidal silica, .pregelatinised starch, povidone, titanium dioxide (E171), talc; hypromellose phthalate, diacetylated monoglycerides, vanillin, sunset yellow aluminium lake (El 10)

What Depakote 500mg Tablets contain

Each 500mg tablet contains 538.2mg of the active substance, valproate semisodium (equivalent to 500mg of valporic acid)

The other ingredients are: hydrated colloidal silica, pregelatinised starch, povidone, titanium dioxide (E171), talc; hypromellose phthalate, diacetylated monoglycerides, vanillin, ponceau 4R aluminium lake (E124), indigo carmine aluminium lake (E132)

Question 1

What are the risks of birth defects for a pregnancy that began shortly after (as little as one week, at most four weeks) the mother quit taking Depakote?


The risk of birth defects from psychotropics such as valproate (Depakote) is greatest when exposure of the fetus occurs between 10 days and 2 months after fertilization. For the first two weeks or so following fertilization, there is very little risk to the developing embryo, because the placenta has not yet formed. This means that the drug cannot pass from the maternal to the infant’s blood stream.

Pregnancy and Depakote

Given the relatively short “half-life” (how long it takes for one-half of the drug to be eliminated) of Depakote – roughly 12 hours – all of the drug should have been out of the mother’s system long before the fetus could have been exposed to it. Thus, the risk of birth defects should be negligible, all other factors being equal.

Question 2

I am currently on six pills of Depakote a day. I am interested in Depakote’s interaction with other substances such as birth control pills and cigarettes.


I am not aware of specific effects on valproate (Depakote) levels due to either smoking or oral contraceptives; however, smoking is known to increase metabolism/elimination of many other psychotropic medications, leading to lower-than-expected levels. Other than carbamazepine (Tegretol), I am not aware of drugs that would increase the elimination of and thus reduce the blood levels of Depakote.


It may be that you are not absorbing the Depakote well from your GI tract, or that you happen to be a “fast metabolizer” of this drug (i.e., your liver gets rid of it before it can accumulate very much). This problem can usually be overcome by simply increasing the Depakote dose. There is also a report of antacids (such as Maalox) increasing levels of valproic acid; in theory, this could be tried (under your doctor’s supervision) to boost the Depakote levels, if a simple dosage increase doesn’t work.

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