Amount Of These Valproate Medications For Seizures, Epilepsy, Bipolar Disorder, And Migraines Taken During First Trimester Of Pregnancy Is A Factor
(1) Depakote Or Depakene Taken During Pregnancy May Cause Congenital Malformations Or Birth Defects Such As Neural Tube Defects Like Spina Bifida (May 31, 2013)
(2) Depacon / Depakene / Depakote: 400% Increased Risk Of Birth Defects Compared To Other Anti-Seizure Medications Used By Mothers With Epilepsy (July 12, 2013)
In the second article we reported that in May 2013 the FDA required 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
In that second article we failed to mention Stavzor (valproic acid), a lesser known medication from Noven Therapeutics, LLC which was approved by the FDA in 2008 and which had a June 2013 label change similar the the AbbVie / Abbott drugs listed above.
Now we have some new relevant medical findings to report from this recent article, "Dose dependence of fetal malformations associated with valproate", published by the Neurology medical journal, which reports on an analysis of data in the Australian Register of Antiepileptic Drugs in Pregnancy collected from 1999 to 2012.
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For this study, several Australian medical researchers looked at the specific type of fetal malformation, or birth defect, in offspring exposed to valproate drugs such as Depacon in utero. In turn, the each specific birth defect type was correlated with the dose of valproate taken by the mother in the first trimester of pregnancy.
From the Abstract for this September 2013 (published online before print in August 2013) Neurology medical journal article:
- Objective: To study the relationships between maternal valproate dose in pregnancy and the pattern of various fetal malformations.
- Results: Compared with other malformations, the mean dose of valproate taken during the first trimester was higher in mothers whose offspring had spina bifida (2,000 ± 707 vs 1,257 ± 918 mg/d) and hypospadias (2,417 ± 1,320 vs 1,235 ± 715 mg/d) (both p < 0.05). The overall mean maternal valproate dosage taken by women in the Register decreased over the last 5 years of the study period. This was paralleled by a statistically significant decrease in the rate of occurrence of spina bifida and hypospadias, but not other malformations.
- Conclusions: Human fetal malformations associated with valproate exposure during pregnancy do not all seem to bear the same quantitative relationship to drug dose, and reduction in valproate dose in earlier pregnancy is likely to offer greater dividends in protecting against spina bifida and hypospadias than against other types of fetal malformations.
The Drug Safety Monitor blog from AdverseEvents has a good article about this recent Neurolgy journal article about Depacon / Depakene / Depakote / Stavzor, "New Findings Demonstrate Specific Valproate Birth Defects Dependent on Dose Strength", and we give them a so-called "hat-tip" for drawing our attention to it.
As we stated in our previous valproate - birth defects article, 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 several medications for seizures, epilepsy, bipolar disorder, and (until recently) migraine headaches: Depacon / Depakene / Depakote / Stavzor.