Valproic Acid

Follow the doctor's directions. Call if you have any questions. The way the medicine is taken depends, of course, on what form the doctor has prescribed.

Depakene capsules must be swallowed whole. If they're chewed, the mouth and throat may become irritated. They are best taken on a full stomach to avoid stomach upset, but they can be taken without food. (Drink a full glass of water if taking the capsule alone.) Depakene syrup can be mixed with another liquid or food for better taste, as long as it is all consumed. Be sure to use a standard measuring spoon or dropper for accurate, consistent dosing. Because food affects the way medicine is used by the body, try to be consistent day in and day out. A person who usually takes Depakene with meals should do that all the time.

Both forms of Depakene should be stored at room temperature, away from heat, light, and dampness. (Don't keep the capsules in the bathroom if it's damp there.) Protect the syrup from freezing. Be sure to keep Depakene where children can't get it.

In general, if you forget a dose, take it as soon as you remember. If it is almost time for the next dose, delay that dose for a few hours, instead of taking two doses very close together. Then go back to the regular schedule. If you're not sure about what to do, call the doctor's office for more advice.

Do your best to follow the doctor's directions. The more often a medicine must be taken, the greater the chance of forgetting, and some people need to take Depakene three times every day. This can be difficult. If you forget doses often, it may be a good idea to get a special pillbox or watch with an alarm to remind you. You also might ask the doctor about Depakote ER, a type of valproate medicine that is taken only once a day.

Taking the right amount of seizure medicine on time every single day is the most important step in preventing seizures!

Brain cells need to work (fire) at a certain rate to function normally. During a seizure, brain cells are forced to work much more rapidly than normal. Valproic acid helps prevent brain cells from working as fast as a seizure requires them to. In this way, seizures can be stopped when they are just beginning.

We don't completely understand how valproic acid works. Doctors think that it may work in several ways at once. That could be why it works for so many different kinds of seizures.

After medicine is swallowed, it must be absorbed into the blood so it can move throughout the body. The process of absorbing, digesting, and excreting a medicine or food is called metabolism. The way the body metabolizes a particular medicine affects how often it must be taken. It also determines whether it will interact with other medicines or be affected by conditions such as liver disease.

Valproic acid is quickly absorbed by the body. The medicine takes longer to reach the blood (and the brain) if it's taken with food, but in the end the amount absorbed is about the same. The delay that occurs when valproic acid is taken with food is not important during long-term treatment, but it could have some effect when treatment is first begun. That's why it's best to be consistent.

Valproic acid is broken down (digested) in the liver. People with liver disease should not take it. Anyone who also takes other medicines that are digested in the liver (as many are) needs to be careful. How well each medicine works and how quickly it leaves the body may be changed.

This is why the doctor needs to know about everything that a person takes—not just prescription medicines but even things like vitamins, herbs, and aspirin! These things can affect how much valproic acid the doctor prescribes.

Doctors have studied large numbers of people to find out how well valproic acid and the other valproate medicines control seizures. (There is hardly any difference in the way the different valproate medicines work.) They have reported that these medicines are very good at completely controlling absence seizures in many people who take them. In another group, over 80% of people with new tonic-clonic seizures and related types didn't have any seizures during the period when they were given a medicine like valproic acid.

These promising results are not always matched in everyday life. Sometimes people don't take all their medicine on time. Not everyone's seizures can be controlled at a dose that can be taken without side effects. Because of individual differences, there is no "best" amount for everyone. Adjustments are often needed to reduce seizures or side effects.

In studies of seizure medicines, some people do better with valproic acid and others do better with something else. It's difficult to forecast the results for any given person. Differences in side effects may be important in deciding which medicine is best for each person.

If seizures continue, the doctor probably will change the amount of valproic acid prescribed. If that doesn't work, the next step may be either to prescribe a different seizure medicine by itself or to prescribe a combination of valproic acid and another seizure medicine. Many are available. No single combination is best for everyone. Valproic acid is often used as an "add-on" medicine for people who continue to have certain kinds of seizures while taking other seizure medicines.

Most people who take valproic acid don't have too much trouble with side effects. The most common complaints (usually not too severe) are:

• tiredness (sometimes with slower thinking)
• dizziness
• upset stomach
• vomiting
• tremor (shaking of the hands or other parts of the body
• hair loss
• weight gain
• changes in behavior (depression in adults, irritability in children)

If you notice any of these problems, call the doctor. Sometimes the doctor can help by changing the amount of valproic acid prescribed or prescribing a different valproate medicine. No one should stop taking valproic acid or change the amount they take without their doctor's guidance.

Stomach upset from valproic acid may be less of a problem if it is taken on a full stomach. Stomach upset is more likely when another seizure medicine with similar side effects (for example, Tegretol) is also being used.

Tremor (shaking of the hands or other body parts) tends to be worse when the level of valproate in the blood is highest, a few hours after the pills are taken. Anxiety or caffeine also may make it worse.

Weight gain affects 30% to 50% of people who take valproic acid. It is more common in adult women but can affect anyone. The average gain for adults is 15 pounds. Exercise and a reduced-calorie diet can be very helpful. It's uncertain whether weight gain is greater when higher doses of valproic acid are taken.

Hair loss occurs in 5% to 10% of people who take valproic acid. The hair almost always grows back after the valproic acid is stopped, but it often has a different texture. (For example, it may grow in curly instead of straight.)

People who have just started taking valproic acid (or who have just started taking a larger amount) should be careful during activities that might be dangerous, until they know whether they are having any side effects.

Allergic reactions
Allergic reactions such as rashes are less common with valproic acid and the other valproate medicines than with most other seizure medicines. Even so, you should report any rash to the doctor or nurse right away, especially if treatment has just begun. It's rare for the rash to be serious, but don't ignore it. It's often necessary to switch to a different seizure medicine.

A very small number of people who take valproic acid develop life-threatening disorders. Children younger than 2 years of age and other people who are taking more than one seizure medicine have the greatest risk. See Serious side effects.

Long-term side effects
Some people who have taken valproic acid for many years have experienced bone loss and a few other disorders. Taking both calcium and vitamin D may help to prevent this kind of problem. Many doctors recommend a bone density test to identify which people need treatment for bone loss.

A few people have serious reactions to valproic acid. These problems are very rare but everyone who takes this medicine should at least be aware of them because a very small number of people have died because of them.

Here's a list of warning signs that may be the start of one of these problems. If you notice any of these things, call the doctor immediately:

• weakness, sluggishness, swelling of the face, loss of appetite, vomiting, or yellowish eyes or skin, especially in a child under 2 years of age (possible liver failure)
• pain in the abdomen, upset stomach, vomiting, or loss of appetite (possible disease of the pancreas)
• easy bruising, nosebleed, or other abnormal bleeding (problems with clotting)

Tell the doctor right away if you notice any of these problems, but don't stop using the valproic acid unless the doctor says so.

The best-known and most-feared serious reaction is liver failure. This disorder usually occurs within the first 6 months of treatment. The risk of liver failure is much higher in children under 2 years of age, especially if they also take other seizure medicine or already have other serious disorders. Doctors seldom prescribe valproic acid for those with the highest risk.

The risk of liver failure is much lower in children between 2 and 10. The risk is very low in older children and adults, perhaps 1 in 50,000. There is no evidence that long-term use of valproic acid will cause gradual damage to the liver.

Another rare reaction to valproic acid is a disorder of the pancreas. Occasionally it is so severe that bleeding and death can occur. Both children and adults can be affected, even after several years of taking valproic acid. Report pain in the abdomen, upset stomach, vomiting, or loss of appetite to the doctor right away.

Problems with blood clotting are more likely in people who take large amounts of valproic acid. Sometimes the blood returns to normal without stopping the medicine. The doctor probably will order some blood tests before prescribing valproic acid, and will repeat them some time later and before any elective surgery.

A complete list of all reactions to valproic acid can be found in the package insert for brand-name Depakene, but it is important to remember that only a tiny number of people have any of these serious problems.

On July 10, 2008, an advisory panel was convened by the Food and Drug Administration (FDA) to review data that the FDA had previously collected from drug studies showing an association between many of the antiepileptic drugs (AEDs) and suicidal ideation and behavior, which together are called suicidality. According to the FDA’s Alert, among the patients with epilepsy in these drug studies, 1 out of 1000 people taking the placebo (inactive substance) showed suicidality compared to approximately 3.5 out of 1000 people who took an AED. The FDA advisory panel voted to accept the FDA's data at its meeting on July 10.

• Taking antiepileptic medicines may increase the risk of having suicidal thoughts or actions;
• Do not make any changes to the medication regimen without first talking with the responsible healthcare professional;
• Pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.
• Be aware of common warning signs that might be a signal for risk of suicide. Some of these are:
  • Talking or thinking about wanting to hurt yourself or end your life
  • Withdrawing from friends and family
  • Becoming depressed or having your depression get worse
  • Becoming preoccupied with death and dying
  • Giving away prized possessions

We again urge patients and families to contact their doctor before stopping an epilepsy medication because this may possibly lead to seizures and worsening of mood.

Long-term use of valproic acid may cause thinning of the bones.  This can predispose to fractures.  It is recommended that persons on long-term use of valproic acid take supplemental vitamin-D, 400-1000  units per day to minimize this risk.

Often doctors find that medicines are useful for more than one purpose. It is legal to prescribe medicines for ""off-label uses"" even though the Food and Drug Administration (FDA) has not formally approved such use.

The only FDA-approved use of valproic acid is the treatment of epilepsy, but it also has two off-label uses:

•     preventing migraine headaches (not treating headaches while they're occurring)
•     treating one part of the mental illness called bipolar disorder.

People with liver disease should not take valproic acid. Neither should anyone who has shown an allergy to valproic acid or another valproate medicine in the past. Make sure the doctor knows about any liver problems, so a different medicine can be prescribed instead.

Sometimes one kind of medicine changes the way another kind of medicine works in the body. This is true not only for prescription medicines, but also for medicines you just pick up off the shelf at the store. For instance, aspirin (ASA) may increase the side effects from taking valproic acid.

If someone who is taking valproic acid—especially a child—also starts to take the seizure medicine called Lamictal, the chances of a very dangerous rash will be increased. Adding the Lamictal slowly reduces this danger.

Taking both valproic acid and another seizure medicine, Klonopin, sometimes causes absence seizures to be much longer.

Any time a doctor suggests a new prescription, be sure to talk about what other medicines you are already using. If two kinds of medicine affect each other, the doctor may want to prescribe something else or change the amount to be taken.

How does valproic acid affect other medicines?
Valproic acid affects the way the body handles many other seizure medicines. Some of these are:

• Felbatol (felbamate)
• Lamictal (lamotrigine)
• Mysoline (primidone)
• phenobarbital

If a person taking one of these medicines starts taking valproic acid, the first medicine will stay in the body longer. If the person keeps taking the same amount as before, soon there will be too much of it. This may cause side effects like extreme tiredness and slurred speech. The person might seem to be drunk.

A similar thing could happen with several other seizure medicines, but the effects for people taking these would probably not be too noticeable:

• Tegretol or Carbatrol (carbamazepine)
• Zarontin (ethosuximide)
• Ativan (lorazepam)
• Dilantin or Phenytek (phenytoin)

All of these effects mean that if a person taking another seizure medicine starts taking valproic acid too, the amount of the first medicine may need to be changed. Or if a person has been taking valproic acid along with another seizure medicine, stopping either one of them means that the amount of the other one probably will have to be changed.

How do other medicines affect valproic acid?
Some other medicines do affect the way valproic acid works in the body. Make sure that the doctor is aware of all the medicines being used.

Valproic acid can be effective against many types of seizures common in children:

• absence seizures (this is one of the most effective medicines for these brief staring spells)
• myoclonic seizures
• tonic-clonic seizures, such as those in Lennox-Gastaut syndrome.
• infantile spasms
• seizures triggered by flashing lights

Children under 2 or 3 years of age who take valproic acid have a much higher risk of liver failure than adults or older children. (The risk is very low for children over 10, perhaps 1 in 50,000.) The risk is even higher for very young children who also take other seizure medicines, and it's highest of all for those with certain other serious disorders. Usually the doctor will not prescribe valproic acid or other valproate medicines for children at very high risk. Liver damage usually occurs within the first 6 months of treatment. The first signs of it are vomiting, loss of appetite, sluggishness, and perhaps loss of seizure control, yellow skin and eyes, or swelling.

Higher-than-usual levels of the hormone testosterone have been found in many girls who take valproic acid when they're older than about age 10. No symptoms are apparent, but the doctor may want to watch for later problems, perhaps related to weight gain.

A few children who take valproic acid seem to become more irritable but this is seldom a serious problem.

To reduce side effects, the doctor probably will prescribe a low dose of valproic acid to start and will increase it slowly. Children usually start with a dose of 5 to 10 milligrams (mg) for each kilogram (kg, about 2.2 pounds) of their body weight per day. This is usually given in one to three equal doses per day.

Most children do best at about 15 to 60 mg/kg per day. Children taking a combination of valproic acid and another seizure medicine usually need the higher doses because of interactions between the medicines.

Valproic acid syrup is an easy way to give a valproate medicine to small children who cannot swallow capsules. The medicine is absorbed by the body a bit more quickly than when Depakote sprinkle capsules are used, but the amount absorbed is the same.

In the United States, the Food and Drug Administration (FDA) assigns each medication to a Pregnancy Category according to whether it has been proven to be harmful in pregnancy. Valproic acid is listed in Pregnancy Category D. This means that there is a risk to the baby, but the benefits may outweigh the risk for some women.

In fact, a large majority of women who use valproic acid during pregnancy have normal, healthy babies. Certain types of defects are increased (especially if valproic acid is taken during the first 3 months of pregnancy) but they are still relatively uncommon. The risk of defects is higher for women who take more than one seizure medicine. Women with a family history of birth defects also have a higher risk.

Women with epilepsy who are pregnant or thinking about becoming pregnant should talk to their doctor about their seizure medicines. Taking more than one seizure medicine may increase the risk of birth defects, so doctors sometimes gradually reduce the number or amount of seizure medicines taken by women planning for pregnancy. This is not done routinely, however, because it increases the risk of seizures. Some kinds of seizures can injure the baby, so do not stop using seizure medicines or reduce the amount without the doctor’s OK.

All women who are capable of becoming pregnant should take at least 400 mcg (0.4 mg) of the vitamin called folic acid every day because it helps to prevent one type of birth defect. (The most well-known of these is spina bifida, in which the spinal cord is not completely enclosed.) These defects are more common in the babies of women who take valproic acid during the first 4 to 6 weeks of pregnancy. If the doctor thinks a woman is at especially high risk, a much larger dose of folic acid—4000 mcg (4 mg) per day—may be recommended. There's no proof that the folic acid will prevent the defects, however, so the doctor may recommend a check-up later in pregnancy.

About 20% to 35% of women have seizures more often during pregnancy because of changes in hormones or changes in how their seizure medicine is handled by the body. It is helpful for the doctor to check the levels of medicine in the blood regularly during pregnancy so that the dosage can be adjusted if necessary.

Breast-feeding by mothers taking valproic acid should be safe for healthy, full-term newborns. The amount of medicine the baby gets through the milk is much less than the amount that doctors safely give to babies who take valproic acid for seizures.

The babies of women taking valproic acid have a greater than usual number of minor craniofacial abnormalities, organ malformations, limb deficiencies, or developmental delay. The risk of defects is higher for women who take more than one AED and for women with a family history of birth defects.  Moreover the NEAD study showed that children born to women who took Valproic acid, had lower IQ scores than children born to women with epilepsy who tool other seizure medications.

Doctors have prescribed valproic acid to people over 65 for many years with good results. These seniors do have a few special problems, however.

Most seniors take more medicines than younger people, so there’s a greater risk that the medicines may affect each other. Usually seniors can continue to take all the medicines they need, including valproic acid, without trouble if the doctor changes the amount of some of them to make up for the way they affect each other.

Seniors also tend to be more sensitive than younger adults to medicines and their side effects. For instance, many seniors have a problem with sleepiness, depression, weight gain, or shaking of the hands even before they start taking valproic acid. These are common side effects of this medicine, so these problems may become worse and cause real trouble.

Seniors also face more danger from some side effects because they are more likely to be seriously hurt if they fall or have another kind of accident.

To reduce side effects, the doctor probably will prescribe a very low dose of valproic acid to start and then be cautious about any increases. It’s especially important for seniors to keep the doctor informed about any changes that they notice.

The best amount is the amount that completely controls seizures without causing troublesome side effects. It depends on many factors, which are different for every individual. Follow the doctor's directions. Call if you have any questions.

No one should stop taking valproic acid or change the amount they take without talking to the doctor first. Stopping any seizure medicine all at once can cause a problem that may be life-threatening.

Don’t use more than the doctor prescribes. If a little extra (such as one or two extra capsules) is taken by accident, call the doctor for advice. For a larger overdose, call a poison control center or emergency room right away unless you have other specific directions from your doctor.

To avoid unwanted side effects, the doctor will prescribe a low dose to start and increase it gradually until the seizures are controlled, unless side effects get too bad first. Most people need to take valproic acid two to four times a day.

In the United States, companies that manufacture medicines are required to publish certain kinds of information about each product. This document is commonly known as a “package insert” because it is usually included with each package of the medicine.

You can also read these documents (also called "prescribing information") online. The U.S. package insert for Depakene (valproic acid) is found at:

• http://www.rxabbvie.com/pdf/depakene.pdf

Some of the information may differ in other countries.

To learn how to read and understand a package insert, see  "How to read a package insert."