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Valproic acid FDA Alerts

The FDA Alerts below may be specifically about valproic acid or relate to a group or class of drugs which include valproic acid.

MedWatch Safety Alerts are distributed by the FDA and published by Drugs.com. Following is a list of possible medication recalls, market withdrawals, alerts and warnings.

Recent FDA Alerts for valproic acid

Valproate Anti-Seizure Products: Drug Safety Communication - Contraindicated for Pregnant Women for Prevention of Migraine Headaches

May 6, 2013 | Audience: Health Professional, Neurology, Pharmacy, Patient

Including valproate sodium (Depacon), divalproex sodium (Depakote, Depakote CP, and Depakote ER), valproic acid (Depakene and Stavzor), and their generics

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.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

 

[05/06/2013 - Drug Safety Communication - FDA]

Valproate Products: Drug Safety Communication - Risk of Impaired Cognitive Development in Children Exposed In Utero (During Pregnancy)

Jun 30, 2011 | Audience: OBGYN, Neurology, Psychiatry

Including valproate sodium (Depacon), divalproex sodium (Depakote, Depakote CP, and Depakote ER), valproic acid (Depakene and Stavzor), and their generics

ISSUE: FDA notified healthcare professionals that children born to mothers who take the anti-seizure medication valproate sodium or related products (valproic acid and divalproex sodium) during pregnancy have an increased risk of lower cognitive test scores than children exposed to other anti-seizure medications during pregnancy. This conclusion is based on the results of epidemiologic studies that show that children born to mothers who took valproate sodium or related products throughout their pregnancy tend to score lower on cognitive tests (IQ and other tests) than children born to mothers who took other anti-seizure medications during pregnancy. See the Drug Safety Communication for a data summary and additional information.

BACKGROUND: Valproate products are FDA-approved drugs to treat seizures, and manic or mixed episodes associated with bipolar disorder (manic-depressive disorder), and to prevent migraine headaches. They are also used off-label (for unapproved uses) for other conditions, particularly for other psychiatric conditions.

RECOMMENDATION: Healthcare professionals should inform women of childbearing age of the increased risk for adverse effects on cognitive development with prenatal valproate exposure, and should continue to counsel women of childbearing potential taking valproate about the increased risk of major malformations, including neural tube defects, when valproate is used during pregnancy. In addition, healthcare professionals should weigh the benefits and risks of valproate when prescribing this drug to women of childbearing age, particularly when treating a condition not usually associated with permanent injury or death. Alternative medications that have a lower risk of adverse birth outcomes should be considered. Patients should not stop taking valproate without talking to a healthcare professional.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:


[06/30/2011 - Drug Safety Communication - FDA]
[06/30/2011 - Questions and Answers - FDA]

Valproate Sodium and related products (valproic acid and divalproex sodium): Risk of Birth Defects

Dec 3, 2009 | Audience: Neurological and Obstetrical healthcare professionals

The FDA notified health care professionals and patients about the increased risk of neural tube defects and other major birth defects, such as craniofacial defects and cardiovascular malformations, in babies exposed to valproate sodium and related products (valproic acid and divalproex sodium) during pregnancy. Healthcare practitioners should inform women of childbearing potential about these risks, and consider alternative therapies, especially if using valproate to treat migraines or other conditions not usually considered life-threatening.

Women of childbearing potential should only use valproate if it is essential to manage their medical condition. Those who are not actively planning a pregnancy should use effective contraception, as birth defect risks are particularly high during the first trimester, before many women know they are pregnant. A valproate Medication Guide, provided with each outpatient prescription, will explain the benefits and risks of valproate and encourage patients to discuss options with their healthcare professional.

Pregnant women using valproate or other AEDs should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334; www.aedpregnancyregistry.org).

[12/03/2009 - Information for Healthcare Professionals - FDA]

    

Antiepileptic Drugs

May 5, 2009 | Audience: Neuropsychiatric healthcare professionals, other healthcare professionals, patients[UPDATE 05/05/2009] FDA notified healthcare professionals that it approved updated labeling for antiepileptic drugs used to treat epilepsy, psychiatric disorders, and other conditions (e.g., migraine and neuropathic pain syndromes). FDA also required development of a medication guide, to be issued to patients each time the product is dispensed. Since issuing safety alerts on December 16, 2008 and January 31, 2008, FDA has been working with the manufacturers of drugs in this class to better understand the suicidality risk. Eleven antiepileptic drugs were included in a pooled analysis of placebo-controlled clinical studies in which these drugs were used to treat epilepsy as well as psychiatric disorders and other conditions. The increased risk of suicidal thoughts or behavior was generally consistent among the eleven drugs, with varying mechanisms of action and across a range of indications. This observation suggests that the risk applies to all antiepileptic drugs used for any indication.

[UPDATE 12/16/2008] The FDA has completed its analysis of reports of suicidality (suicidal behavior or ideation [thoughts]) from placebo-controlled clinical trials of drugs used to treat epilepsy, psychiatric disorders, and other conditions. Based on the outcome of this review, FDA is requiring that all manufacturers of drugs in this class include a Warning in their labeling and develop a Medication Guide to be provided to patients prescribed these drugs to inform them of the risks of suicidal thoughts or actions.

[Posted 01/31/2008] FDA informed healthcare professionals that the Agency has analyzed reports of suicidality (suicidal behavior or ideation) from placebo-controlled clinical studies of eleven drugs used to treat epilepsy as well as psychiatric disorders, and other conditions. In the FDA's analysis, patients receiving antiepileptic drugs had approximately twice the risk of suicidal behavior or ideation (0.43%) compared to patients receiving placebo (0.22%). The increased risk of suicidal behavior and suicidal ideation was observed as early as one week after starting the antiepileptic drug and continued through 24 weeks. The results were generally consistent among the eleven drugs. The relative risk for suicidality was higher in patients with epilepsy compared to patients who were given one of the drugs in the class for psychiatric or other conditions.

Healthcare professionals should closely monitor all patients currently taking or starting any antiepileptic drug for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.

The drugs included in the analyses include (some of these drugs are also available in generic form):

Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
Felbamate (marketed as Felbatol)
Gabapentin (marketed as Neurontin)
Lamotrigine (marketed as Lamictal)
Levetiracetam (marketed as Keppra)
Oxcarbazepine (marketed as Trileptal)
Pregabalin (marketed as Lyrica)
Tiagabine (marketed as Gabitril)
Topiramate (marketed as Topamax)
Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)
Zonisamide (marketed as Zonegran)

Although the 11 drugs listed above were the ones included in the analysis, FDA expects that the increased risk of suicidality is shared by all antiepileptic drugs and anticipates that the class labeling changes will be applied broadly.

[December 16, 2008; UPDATED May 05, 2009 - Drug Information Page - FDA]
[January 31, 2008 - Healthcare Professional Information Sheet - FDA]

Depakote / Depakene / Depacon (divalproex sodium / valproic acid / valproate sodium)

Jun 17, 2002 | Audience: Neuropsychiatric healthcare professionalsFDA and Abbott strengthened the CONTRAINDICATIONS, WARNINGS and PRECAUTIONS sections of the label for Depakote Tablets, Depakote ER Tablets, Depakote Sprinkle Capsules, Depakene Capsules and Syrup and Depacon for Injection. Healthcare professionals were informed that hyperammonemic encephalopathy, sometimes fatal, has been reported following initiation of valproate therapy in patients with urea cycle disorders [UCD], a group of uncommon genetic abnormalities. Patient criteria to consider in evaluation for UCD prior to initiation of valproate therapy are offered.

[June, 2002 Letter - Abbott]
[June, 2002 Full, Revised Label - Abbott]

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