[Posted 05/06/2013]ISSUE: FDA is advising health care professionals and women that the anti-seizure medication valproate sodium and related products, valproic acid and divalproex sodium, are contraindicated and should not be taken by pregnant women for the prevention of migraine headaches. Based on information from a recent study, there is evidence that these medications can cause decreased IQ scores in children whose mothers took them while pregnant. Stronger warnings about use during pregnancy will be added to the drug labels, and valproate's pregnancy category for migraine use will be changed from "D" (the potential benefit of the drug in pregnant women may be acceptable despite its potential risks) to "X" (the risk of use in pregnant women clearly outweighs any possible benefit of the drug). Valproate products will remain in pregnancy category D for treating epilepsy and manic episodes associated with bipolar disorder.
BACKGROUND: Valproate products are approved for the treatment of certain types of epilepsy, the treatment of manic episodes associated with bipolar disorder, and the prevention of migraine headaches. They are also used off-label (for uses not approved by FDA) for other conditions, particularly other psychiatric conditions. This alert is based on the final results of the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study showing that children exposed to valproate products while their mothers were pregnant had decreased IQs at age 6 compared to children exposed to other anti-epileptic drugs. For additional details, see the Drug Safety Communication Data Summary section.
RECOMMENDATION: Valproate products should not be used in pregnant women for prevention of migraine headaches and should be used in pregnant women with epilepsy or bipolar disorder only if other treatments have failed to provide adequate symptom control or are otherwise unacceptable. Women who are pregnant and taking a valproate medication should not stop their medication but should talk to their health care professionals immediately. Stopping valproate treatment suddenly can cause serious and life-threatening medical problems to the woman or her baby. For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Valproic acid may cause serious or life threatening damage to the liver. The risk of developing liver damage is greatest in children who are younger than 2 years of age and in people who are taking more than one medication to prevent seizures or who have any of the following conditions: a severe seizure disorder and mental retardation; certain inherited diseases that prevent the body from changing food to energy normally; any condition that affects the ability to think, learn, and understand; or liver disease. Tell your doctor or your child's doctor if you or your child have any of these conditions. Your child should not take any other medications to control seizures while he or she is taking valproic acid. If you notice that your seizures are more severe or happen more often or if you experience any of the following symptoms, call your doctor immediately: excessive tiredness, lack of energy, weakness, stomach pain, loss of appetite, nausea, vomiting, or swelling of the face.
Valproic acid may cause serious or life-threatening damage to the pancreas. This may occur at any time during your treatment. If you experience any of the following symptoms, call your doctor immediately: stomach pain, nausea, vomiting, or loss of appetite.
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your response to valproic acid.
Talk to your doctor about the risks of taking valproic acid or of giving valproic acid to your child.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with valproic acid and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.
Before you start to take valproic acid, tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while taking valproic acid, call your doctor immediately. Valproic acid can cause birth defects. Be sure to read the manufacturer's information for women who could become pregnant. Talk to your doctor about the risk of taking valproic acid during pregnancy.
Valproic acid is used alone or with other medications to treat certain types of seizures. Valproic acid is also used to treat mania (episodes of frenzied, abnormally excited mood) in people with bipolar disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). It is also used to prevent migraine headaches, but not to relieve headaches that have already begun. Valproic acid is in a class of medications called anticonvulsants. It works by increasing the amount of a certain natural substance in the brain.
Valproic acid comes as a capsule, an extended-release (long-acting) tablet, a delayed-release (slow to begin working) tablet, a sprinkle capsule (capsule that contains small beads of medication that can be sprinkled on food), and a syrup (liquid) to take by mouth. The syrup, capsules, delayed-release tablets, and sprinkle capsules are usually taken two or more times daily. The extended-release tablets are usually taken once a day. Take valproic acid at around the same time(s) every day. Take valproic acid with food to help prevent the medication from upsetting your stomach. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take valproic acid exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Swallow the regular capsules and extended-release tablets whole; do not split, chew, or crush them.
You can swallow the sprinkle capsules whole, or you can open the capsules and sprinkle the beads they contain on a teaspoonful of soft food, such as applesauce or pudding. Swallow the mixture of food and medication beads right after you prepare it. Be careful not to chew the beads. Do not store unused mixtures of food and medication.
Do not mix the syrup into any carbonated drink.
Your doctor may start you on a low dose of valproic acid and gradually increase your dose, not more often than once a week.
Valproic acid may help to control your condition but will not cure it. Continue to take valproic acid even if you feel well. Do not stop taking valproic acid without talking to your doctor, even if you experience side effects such as unusual changes in behavior or mood. If you suddenly stop taking valproic acid, you may experience a severe, long-lasting and possibly life-threatening seizure. Your doctor will probably decrease your dose gradually.
Valproic acid is also sometimes used to treat outbursts of aggression in children with attention deficit hyperactivity disorder (ADHD; more difficulty focusing or remaining still or quiet than other people who are the same age), chorea (a group of conditions that affect the ability to control body movements), and certain conditions that affect thinking, learning, and understanding. Talk to your doctor about the possible risks of using this medication for your condition.
This medication is sometimes prescribed for other uses. Ask your doctor or pharmacist for more information.
Unless your doctor tells you otherwise, continue your normal diet. Be sure to drink plenty of water or other liquids while you are taking valproic acid.
Take the missed dose as soon as you remember it. However, if it is almost time for your next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
changes in appetite
uncontrollable shaking of a part of the body
loss of coordination
uncontrollable movements of the eyes
blurred or double vision
ringing in the ears
stuffed or runny nose
unusual bruising or bleeding
tiny purple spots on the skin
blisters or rash
difficulty breathing or swallowing
weakness in the joints
thinking about killing yourself or planning or trying to do so
Valproic acid may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online [at http://www.fda.gov/Safety/MedWatch] or by phone [1-800-332-1088].
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature, away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
coma (loss of consciousness for a period of time)
If you are taking the sprinkle capsules, you may notice the medication beads in your stool. This is normal and does not mean that you did not get the full dose of medication.
If you have diabetes and your doctor has told you to test your urine for ketones, tell the doctor that you are taking valproic acid. Valproic acid can cause false results on urine tests for ketones.
Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking valproic acid.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
Last Revised - 05/15/2013
AHFS® Consumer Medication Information. © Copyright, 2013. The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.