May 2013 Revised Depakote Drug Label Includes "Black-Box" And Warnings About These Congenital Malformations As Well As Decreased IQ Scores In Children
As indicated below, in May 2013 there was a so-called "Black-Box" warning and several other significant label revisions about serious risks for children whose mother used the following anti-seizure medications during pregnancy which were added to the Prescribing Information by FDA and the drug company AbbVie Inc. (formerly Abbott), specifically:
- Depakote (divalproex sodium) Delayed Release
- Depakote ER (Extended Release) Tablets
- Depakote Sprinkle Capsules (divalproex sodium coated particles in capsules)
- Depacon (valproate sodium) Injection
- Depakene (valproic acid) Capsules and Oral Solution
Here is a list of these recent major changes, or revisions, to the label as set forth on the DailyMed web page for Depakote:
Boxed Warning, Hepatotoxicity 05/2013
Boxed Warning, Fetal Risk 05/2013
Indications and Usage, Important Limitations (1.4) 05/2013
Contraindications, Known or Suspected Mitochondrial Disorders (4) 05/2013
Contraindications, Prophylaxis of Migraines in Pregnancy (4) 05/2013
Warnings and Precautions, Hepatotoxicity (5.1) 05/2013
Warnings and Precautions, Birth Defects (5.2) 05/2013
Warnings and Precautions, Decreased IQ (5.3) 05/2013
Warnings and Precautions, Use in Women of Childbearing Potential (5.4) 05/2013
Warnings and Precautions, Brain Atrophy (5.7) 05/2013
As regards the serious risks for children whose mother used the one of those Abbott anti-seizure medications during pregnancy, from the Boxed Warning, titled "WARNING: LIFE THREATENING ADVERSE REACTIONS":
Valproate can cause major congenital malformations, particularly neural tube defects (e.g., spina bifida). In addition, valproate can cause decreased IQ scores following in utero exposure....
Valproate should not be administered to a woman of childbearing potential unless the drug is essential to the management of her medical condition. This is especially important when valproate use is considered for a condition not usually associated with permanent injury or death (e.g., migraine). Women should use effective contraception while using valproate [see Warnings and Precautions (5.2,5.3, 5.4)].
What is most remarkable to me about this May 2013 label revision by AbbVie / Abbott was this new warning: there is a 400% (i.e., four times) increased risk of birth defects, or congenital malformations, associated with the use of Depakote, Depacon, or Depakene during pregnancy.
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In more detail, from the Prescribing Information, also referred to as the package insert or drug label, for Depakote, Depacon, and Depakene:
Warnings And Precautions
5.2 Birth Defects
Valproate can cause fetal harm when administered to a pregnant woman. Pregnancy registry data show that maternal valproate use can cause neural tube defects and other structural abnormalities (e.g., craniofacial defects, cardiovascular malformations and malformations involving various body systems). The rate of congenital malformations among babies born to mothers using valproate is about four times higher than the rate among babies born to epileptic mothers using other anti-seizure monotherapies. Evidence suggests that folic acid supplementation prior to conception and during the first trimester of pregnancy decreases the risk for congenital neural tube defects in the general population. [Emphasis added]
Of course the other added warnings about potential harm to the fetus which may occur very early in pregnancy where there is the use of Depakote, Depacon, or Depakene are very serious in nature, also:
5.3 Decreased IQ Following in utero Exposure
Valproate can cause decreased IQ scores following in uteroexposure. Published epidemiological studies have indicated that children exposed to valproate in utero have lower cognitive test scores than children exposed in uteroto either another antiepileptic drug or to no antiepileptic drugs....
5.7 Brain Atrophy
... Reports of cerebral atrophy have also been reported in children who were exposed in uteroto valproate products....
For some of the more recent developments leading up to this May 2013 label revision for Depakote, Depacon, or Depakene see our earlier article, Depakote Or Depakene Taken During Pregnancy May Cause Congenital Malformations Or Birth Defects Such As Neural Tube Defects Like Spina Bifida.
Of course, we will continue to monitor this emerging drug safety issue and report new medical findings as well as any further FDA regulatory action concerning these relatively popular Abbott / Abbvie medications for seizures, epilepsy, bipolar disorder, and (until now) migraine headaches.