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Valproic (val-PRO-ik) acid is the generic name (non-brand name) of a widely used type of seizure medicine. The brand-name form of valproic acid in the United States and Canada is Depakene. In the UK, it is Convulex. Brand names used in other countries include Depakine, Orfiril, Valporal, and Valprosid.
In the body, valproic acid is converted to valproate, so its effects are virtually identical to those of other seizure medicines that also become valproate. These include divalproex sodium (Depakote and DepakoteER in the United States) and sodium valproate (Epilim in the UK and Australia), as well as a liquid form of valproate sodium given by injection (Depacon).
Using generic medicines rather than brand-name ones is often suggested as a way to save money. Sometimes the savings are large, but with other medicines the price differences are pretty small. Investigate and shop around before deciding whether the savings are worth any potential problems.
People who switch from brand-name Depakote or Depakene to generic valproic acid, for example, possibly risk having more seizures or side effects during the changeover, because the body does not absorb the different types in the same way. Switching from one company's generic valproic acid to another company's may have similar risks. So can switching from generic valproic acid to Depakene or Depakote.
All these risks are not fully known. For some people the effects of changing from one type to another are very small. Some use generic valproic acid successfully by always using the same company's product. Then the dosage can be adjusted to achieve the best results.
What's important is that you and the doctor should know what you're getting from the pharmacy and be able to control what type of seizure medicine you get.
Forms
Various companies make and sell valproic acid. The appearance may differ, but the dose (measured in milligrams, abbreviated "mg") usually will be the same. In the United States, it is available in two forms:
250-mg capsules
Syrup (liquid): 250 mg per 5 mL (milliliters)
How to take and store valproic acid
Capsules of valproic acid must be swallowed whole. Chewing could result in irritation of the mouth and throat. 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.) Food does affect the rate at which the medication is absorbed by the body, so it's best to be consistent about always taking it with food or not, especially when treatment is beginning.
Valproic acid 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. Both forms of valproic acid should be stored at room temperature, away from heat, light, and dampness. Don't let the syrup become frozen. Be sure to keep it where children can't get it.
What if I forget?
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.
Do your best to follow the doctor's directions. 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 switching to Depakote ER, which is taken only once a day. Doctors know that people are more likely to remember to take their pills if they don't have to take them too often.
Taking the right amount of seizure medicine on time every single day is the most important step in preventing seizures!
Valproic acid is an effective treatment for epilepsy in people of all ages. It can be used alone or with other seizure medicines to control:
absence seizures, either alone or with other seizure types
partial seizures (seizures that begin in a limited area of the brain)
Valproic acid and the other forms of valproate are highly effective seizure medicines. Their effectiveness in controlling seizures has been extensively studied in careful scientific studies involving thousands of people. (There is little difference in effectiveness between valproic acid and the other types, like Depakote, so we will use the general term "valproate.")
Valproate works against almost every type of epilepsy. It was first approved to treat absence seizures. In a number of studies, valproate has completely controlled absence seizures in a high proportion of people, and it is widely regarded as the first-choice medication for most people with absence seizures. Complete control seems more likely when the absence seizures appear alone than when they are combined with another seizure type (Sato et al., 1982).
Most experts also regard valproate as the first choice for treating generalized tonic-clonic seizures. One study (Wilder et al., 1983) compared it with Dilantin (phenytoin) in treating a group of people with newly diagnosed generalized tonic-clonic, clonic, or tonic seizures. Of the people treated with valproate, 82% had no seizures during the study period after the level of valproate in the blood reached a high enough level. The comparable figure for those who took phenytoin was 76%.
Valproate also works to control seizures triggered by flashing lights (photosensitivity) and it seems to be effective for myoclonic seizures in many situations.
Epilepsy syndromes that involve symptomatic generalized seizures, such as infantile spasms and Lennox-Gastaut syndrome, are less well controlled by valproate (or any other medication). Nevertheless, valproate is usually regarded as the first choice for treating these conditions. Some people improve enough that they can reduce their use of other seizure medicines that have more troubling side effects.
Researchers looked at whether valproate alone can be used effectively to treat partial seizures. One large study (Mattson et al., 1992) found Tegretol (carbamazepine) to be more effective than valproate in controlling complex partial seizures, but valproate was shown to be a valuable alternative. Differences in the side effects may make it a better choice for some people.
If valproic acid (valproate) alone does not fully control a person's seizures, a combination of valproic acid and another seizure medicine may be more effective. No single combination is perfect for everyone. Sometimes a series of combinations must be tried before finding what is best for that individual.
Most people who take valproic acid don't have too much trouble with side effects. That's one of the reasons it’s used so much. The most common complaints (usually not too severe) are:
tiredness (sometimes with slower thinking)
dizziness
upset stomach
vomiting
tremor
hair loss
weight gain
behavioral changes (depression in adults, irritability in children)
If these problems do not go away within several days or are really bothersome, call the doctor. Sometimes the doctor can help with these side effects by changing the prescription:
reducing the overall amount of valproic acid
prescribing smaller doses, to be taken more often
changing the amount taken at certain times, such as taking a greater proportion of the valproic acid at bedtime to reduce daytime sleepiness
prescribing the extended-release valproate product, Depakote ER, which gives a steadier level of medicine in the blood
No one should stop taking valproic acid or change the amount they take or when they take it without their doctor's guidance.
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.
Taking valproic acid on a full stomach may help to reduce stomach upset. Stomach upset from valproic acid 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 at some times than others. It 's usually most noticeable when the level of valproic acid in the blood is highest, a few hours after a dose is 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 patients taking 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.) Taking selenium (10-20 mcg per day) and zinc (25-50 mg per day) helps some people to prevent hair loss.
Allergic reactions
Allergic reactions such as rashes are less common with valproic acid and other forms of valproate than with most other seizure medicines. Even so, you should report any rash to the doctor or nurse right away, especially if valproic acid 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.
Some other rare but life-threatening disorders do occur with the use of this medication. Children younger than 2 years of age and those taking other seizure medications in addition to valproic acid are at highest risk.
Long-term side effects
Some people who have taken valproic acid or other valproate products for many years have experienced bone loss, ankle swelling, or irregular menstrual periods. Taking supplements of both calcium and vitamin D may help to prevent bone loss. Increasing numbers of doctors are advising people who have taken any form of valproate for more than 5 years to have a bone density test. If the test shows much thinning of the bones, the person may need to see a doctor who specializes in bone metabolism.
If you notice any of these symptoms, call the doctor immediately:
weakness, sluggishness, swelling of the face, loss of appetite, vomiting, or yellowing of the skin and eyes, 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, other abnormal bleeding (problems with clotting)
The best-known and most feared serious reaction is liver damage, which has been fatal for some people. This damage 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
have a severe seizure disorder with mental retardation
have another brain disease, or
have an inborn disorder of metabolism
The risk of liver failure is much lower in children between 2 and 10 and is very low in older children and adults, perhaps 1 in 50,000. This is similar to the frequency of liver failure when taking other seizure medicines, such as Dilantin (phenytoin). There is no evidence that long-term use of valproic acid will cause gradual, progressive damage to the liver.
Another rare but potentially life-threatening reaction to valproic acid is pancreatitis (inflammation of the pancreas), which occasionally progresses to bleeding and death. This reaction may occur in both children and adults, 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 when high doses of valproic acid are taken. Sometimes these problems return to normal without stopping the valproic acid. The doctor probably will order some blood tests before starting treatment with valproic acid, and will repeat them some time later and before any elective surgery.
Any time a doctor suggests a new prescription, be sure to talk about what other medicines, supplements, herbs, and vitamins are already being taken. Sometimes one kind of medicine changes the way another kind of medicine works in the body. If two kinds of medicine affect each other, the doctor may prescribe something else or change the amount to be taken.
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.
How does valproic acid affect other medicines?
Valproic acid may increase the blood level of certain other seizure medicines, including
Felbatol (felbamate)
Lamictal (lamotrigine)
Mysoline (primidone)
Phenobarbital
The levels of these medications in the blood may increase markedly—in some cases, more than double. If a person taking phenobarbital is also given valproic acid, a rapid rise in phenobarbital levels can lead to extreme tiredness, slurred speech, and other signs of intoxication.
Valproic acid has similar but less significant effects on:
Tegretol or Carbatrol (carbamazepine)
Zarontin (ethosuximide)
Ativan (lorazepam)
Dilantin or Phenytek (phenytoin)
Adding valproic acid may slightly increase side effects from each of these.
If combination therapy using valproic acid and another seizure medicine is begun, the dosage of the first medicine may need to be adjusted. Similarly, if a seizure medicine previously used in combination therapy is to be stopped, the dosage of the remaining medicine may need 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.
Several other seizure medicines cause valproic acid to leave the body much more quickly, so that higher doses may be needed to achieve the desired effect. These medicines include:
Tegretol or Carbatrol (carbamazepine)
Dilantin or Phenytek (phenytoin)
phenobarbital
Mysoline (primidone)
If Lamictal (lamotrigine) is given to someone already taking valproic acid—especially a child—the chances of a potentially life-threatening rash will be increased. Adding the Lamictal slowly reduces this danger.
If a combination of valproic acid and Klonopin (clonazepam) is given to a person who has been having absence seizures, prolonged absence seizures may occur.
Pregnancy Category D. This indicates that there is clear evidence of risk to the baby, but the benefits may outweigh the risk for pregnant women who have a serious condition that cannot be treated effectively with a safer drug.
The babies of women taking valproic acid have an increased risk of minor defects of the face or head, developmental delay, or deformities affecting the arms, legs, or organs. The risk of defects is higher for women who take more than one seizure medicine and for women with a family history of birth defects.
Taking high doses of valproic acid and having especially high levels in the blood seem to increase the risk of some defects. Preventive measures may include:
using a different seizure medicine
taking less valproic acid (with the doctor's OK)
taking smaller doses of valproic acid more times each day (or taking extended-release Depakote ER) to avoid large fluctuations in blood levels
About 20% to 35% of women have seizures more often during pregnancy because of changes in hormones or changes in how medicines are handled by the body. The doctor may recommend frequent blood tests to check the level of valproate in the blood. Then the amount taken can be adjusted as needed.
Breast-feeding by mothers taking valproic acid should be safe for healthy, full-term newborns, although a small amount (3-5%) of the medication will appear in the milk. The amount the baby gets is less than 6% of the lowest dose that a doctor might prescribe for a baby with seizures.
In the body, valproic acid is converted to valproate, so its effects are virtually identical to those of other seizure medicines that also become valproate. These include divalproex sodium (Depakote and DepakoteER in the United States) and sodium valproate (Epilim in the UK and Australia), as well as a liquid form of valproate sodium given by injection (Depacon).
Using generic medicines rather than brand-name ones is often suggested as a way to save money. Sometimes the savings are large, but with other medicines the price differences are pretty small. Investigate and shop around before deciding whether the savings are worth any potential problems.
People who switch from brand-name Depakote or Depakene to generic valproic acid, for example, possibly risk having more seizures or side effects during the changeover, because the body does not absorb the different types in the same way. Switching from one company's generic valproic acid to another company's may have similar risks. So can switching from generic valproic acid to Depakene or Depakote.
All these risks are not fully known. For some people the effects of changing from one type to another are very small. Some use generic valproic acid successfully by always using the same company's product. Then the dosage can be adjusted to achieve the best results.
What's important is that you and the doctor should know what you're getting from the pharmacy and be able to control what type of seizure medicine you get.
Forms
Various companies make and sell valproic acid. The appearance may differ, but the dose (measured in milligrams, abbreviated "mg") usually will be the same. In the United States, it is available in two forms:
250-mg capsules
Syrup (liquid): 250 mg per 5 mL (milliliters)
How to take and store valproic acid
Capsules of valproic acid must be swallowed whole. Chewing could result in irritation of the mouth and throat. 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.) Food does affect the rate at which the medication is absorbed by the body, so it's best to be consistent about always taking it with food or not, especially when treatment is beginning.
Valproic acid 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. Both forms of valproic acid should be stored at room temperature, away from heat, light, and dampness. Don't let the syrup become frozen. Be sure to keep it where children can't get it.
What if I forget?
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.
Do your best to follow the doctor's directions. 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 switching to Depakote ER, which is taken only once a day. Doctors know that people are more likely to remember to take their pills if they don't have to take them too often.
Taking the right amount of seizure medicine on time every single day is the most important step in preventing seizures!
Valproic acid is an effective treatment for epilepsy in people of all ages. It can be used alone or with other seizure medicines to control:
absence seizures, either alone or with other seizure types
partial seizures (seizures that begin in a limited area of the brain)
Valproic acid and the other forms of valproate are highly effective seizure medicines. Their effectiveness in controlling seizures has been extensively studied in careful scientific studies involving thousands of people. (There is little difference in effectiveness between valproic acid and the other types, like Depakote, so we will use the general term "valproate.")
Valproate works against almost every type of epilepsy. It was first approved to treat absence seizures. In a number of studies, valproate has completely controlled absence seizures in a high proportion of people, and it is widely regarded as the first-choice medication for most people with absence seizures. Complete control seems more likely when the absence seizures appear alone than when they are combined with another seizure type (Sato et al., 1982).
Most experts also regard valproate as the first choice for treating generalized tonic-clonic seizures. One study (Wilder et al., 1983) compared it with Dilantin (phenytoin) in treating a group of people with newly diagnosed generalized tonic-clonic, clonic, or tonic seizures. Of the people treated with valproate, 82% had no seizures during the study period after the level of valproate in the blood reached a high enough level. The comparable figure for those who took phenytoin was 76%.
Valproate also works to control seizures triggered by flashing lights (photosensitivity) and it seems to be effective for myoclonic seizures in many situations.
Epilepsy syndromes that involve symptomatic generalized seizures, such as infantile spasms and Lennox-Gastaut syndrome, are less well controlled by valproate (or any other medication). Nevertheless, valproate is usually regarded as the first choice for treating these conditions. Some people improve enough that they can reduce their use of other seizure medicines that have more troubling side effects.
Researchers looked at whether valproate alone can be used effectively to treat partial seizures. One large study (Mattson et al., 1992) found Tegretol (carbamazepine) to be more effective than valproate in controlling complex partial seizures, but valproate was shown to be a valuable alternative. Differences in the side effects may make it a better choice for some people.
If valproic acid (valproate) alone does not fully control a person's seizures, a combination of valproic acid and another seizure medicine may be more effective. No single combination is perfect for everyone. Sometimes a series of combinations must be tried before finding what is best for that individual.
Most people who take valproic acid don't have too much trouble with side effects. That's one of the reasons it’s used so much. The most common complaints (usually not too severe) are:
tiredness (sometimes with slower thinking)
dizziness
upset stomach
vomiting
tremor
hair loss
weight gain
behavioral changes (depression in adults, irritability in children)
If these problems do not go away within several days or are really bothersome, call the doctor. Sometimes the doctor can help with these side effects by changing the prescription:
reducing the overall amount of valproic acid
prescribing smaller doses, to be taken more often
changing the amount taken at certain times, such as taking a greater proportion of the valproic acid at bedtime to reduce daytime sleepiness
prescribing the extended-release valproate product, Depakote ER, which gives a steadier level of medicine in the blood
No one should stop taking valproic acid or change the amount they take or when they take it without their doctor's guidance.
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.
Taking valproic acid on a full stomach may help to reduce stomach upset. Stomach upset from valproic acid 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 at some times than others. It 's usually most noticeable when the level of valproic acid in the blood is highest, a few hours after a dose is 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 patients taking 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.) Taking selenium (10-20 mcg per day) and zinc (25-50 mg per day) helps some people to prevent hair loss.
Allergic reactions
Allergic reactions such as rashes are less common with valproic acid and other forms of valproate than with most other seizure medicines. Even so, you should report any rash to the doctor or nurse right away, especially if valproic acid 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.
Some other rare but life-threatening disorders do occur with the use of this medication. Children younger than 2 years of age and those taking other seizure medications in addition to valproic acid are at highest risk.
Long-term side effects
Some people who have taken valproic acid or other valproate products for many years have experienced bone loss, ankle swelling, or irregular menstrual periods. Taking supplements of both calcium and vitamin D may help to prevent bone loss. Increasing numbers of doctors are advising people who have taken any form of valproate for more than 5 years to have a bone density test. If the test shows much thinning of the bones, the person may need to see a doctor who specializes in bone metabolism.
If you notice any of these symptoms, call the doctor immediately:
weakness, sluggishness, swelling of the face, loss of appetite, vomiting, or yellowing of the skin and eyes, 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, other abnormal bleeding (problems with clotting)
The best-known and most feared serious reaction is liver damage, which has been fatal for some people. This damage 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
have a severe seizure disorder with mental retardation
have another brain disease, or
have an inborn disorder of metabolism
The risk of liver failure is much lower in children between 2 and 10 and is very low in older children and adults, perhaps 1 in 50,000. This is similar to the frequency of liver failure when taking other seizure medicines, such as Dilantin (phenytoin). There is no evidence that long-term use of valproic acid will cause gradual, progressive damage to the liver.
Another rare but potentially life-threatening reaction to valproic acid is pancreatitis (inflammation of the pancreas), which occasionally progresses to bleeding and death. This reaction may occur in both children and adults, 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 when high doses of valproic acid are taken. Sometimes these problems return to normal without stopping the valproic acid. The doctor probably will order some blood tests before starting treatment with valproic acid, and will repeat them some time later and before any elective surgery.
Any time a doctor suggests a new prescription, be sure to talk about what other medicines, supplements, herbs, and vitamins are already being taken. Sometimes one kind of medicine changes the way another kind of medicine works in the body. If two kinds of medicine affect each other, the doctor may prescribe something else or change the amount to be taken.
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.
How does valproic acid affect other medicines?
Valproic acid may increase the blood level of certain other seizure medicines, including
Felbatol (felbamate)
Lamictal (lamotrigine)
Mysoline (primidone)
Phenobarbital
The levels of these medications in the blood may increase markedly—in some cases, more than double. If a person taking phenobarbital is also given valproic acid, a rapid rise in phenobarbital levels can lead to extreme tiredness, slurred speech, and other signs of intoxication.
Valproic acid has similar but less significant effects on:
Tegretol or Carbatrol (carbamazepine)
Zarontin (ethosuximide)
Ativan (lorazepam)
Dilantin or Phenytek (phenytoin)
Adding valproic acid may slightly increase side effects from each of these.
If combination therapy using valproic acid and another seizure medicine is begun, the dosage of the first medicine may need to be adjusted. Similarly, if a seizure medicine previously used in combination therapy is to be stopped, the dosage of the remaining medicine may need 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.
Several other seizure medicines cause valproic acid to leave the body much more quickly, so that higher doses may be needed to achieve the desired effect. These medicines include:
Tegretol or Carbatrol (carbamazepine)
Dilantin or Phenytek (phenytoin)
phenobarbital
Mysoline (primidone)
If Lamictal (lamotrigine) is given to someone already taking valproic acid—especially a child—the chances of a potentially life-threatening rash will be increased. Adding the Lamictal slowly reduces this danger.
If a combination of valproic acid and Klonopin (clonazepam) is given to a person who has been having absence seizures, prolonged absence seizures may occur.
Pregnancy Category D. This indicates that there is clear evidence of risk to the baby, but the benefits may outweigh the risk for pregnant women who have a serious condition that cannot be treated effectively with a safer drug.
The babies of women taking valproic acid have an increased risk of minor defects of the face or head, developmental delay, or deformities affecting the arms, legs, or organs. The risk of defects is higher for women who take more than one seizure medicine and for women with a family history of birth defects.
Taking high doses of valproic acid and having especially high levels in the blood seem to increase the risk of some defects. Preventive measures may include:
using a different seizure medicine
taking less valproic acid (with the doctor's OK)
taking smaller doses of valproic acid more times each day (or taking extended-release Depakote ER) to avoid large fluctuations in blood levels
About 20% to 35% of women have seizures more often during pregnancy because of changes in hormones or changes in how medicines are handled by the body. The doctor may recommend frequent blood tests to check the level of valproate in the blood. Then the amount taken can be adjusted as needed.
Breast-feeding by mothers taking valproic acid should be safe for healthy, full-term newborns, although a small amount (3-5%) of the medication will appear in the milk. The amount the baby gets is less than 6% of the lowest dose that a doctor might prescribe for a baby with seizures.
